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NEST: Laparotomy vs. Drainage for Infants With Necrotizing Enterocolitis

Sponsor
NICHD Neonatal Research Network (Other)
Overall Status
Completed
CT.gov ID
NCT01029353
Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH), National Center for Research Resources (NCRR) (NIH)
529
Enrollment
22
Locations
4
Arms
115
Actual Duration (Months)
24
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will compare the effectiveness of two surgical procedures -laparotomy versus drainage - commonly used to treat necrotizing enterocolitis (NEC) or isolated intestinal perforations (IP) in extremely low birth weight infants (≤1,000 g). Infants diagnosed with NEC or IP requiring surgical intervention, will be recruited. Subjects will be randomized to receive either a laparotomy or peritoneal drainage. Primary outcome is impairment-free survival at 18-22 months corrected age.

Condition or Disease Intervention/Treatment Phase
  • Procedure: Laparotomy
  • Procedure: Drainage
 N/A

Detailed Description

Necrotizing enterocolitis (NEC) is a condition, generally affecting premature infants, in which the intestines become ischemic (lack oxygen and/or blood flow). NEC occurs in up to 5-15% of extremely low birth weight (ELBW) infants. Isolated or focal intestinal perforation (IP) is a less common condition, affecting an estimated 4% of ELBWs, in which a hole develops in the intestines leaking fluid into the abdominal cavity. Outcome for infants with NEC and/or IP is poor: 49% die and half of the surviving infants are neurodevelopmentally impaired.

Surgical options for NEC and IP include two possible procedures: peritoneal drainage, in which a tube is placed in the abdominal cavity through a small incision for fluid to drain out; or laparotomy, in which an incision is made in the abdomen and necrotic intestine is removed. Drainage may be followed by a laparotomy.

The Neonatal Research Network's observational study of 156 ELBW infants with NEC or IP (Pediatrics. 2006 Apr; 117(4): e680-7) showed comparable outcomes for the two procedures before hospital discharge, but suggested an advantage of laparotomy over drainage at 18-22 months corrected age with lower rates of death or neurodevelopmental impairment. However, the infants that underwent laparotomy were more mature; infants with drains were smaller and more premature. We hypothesize that initial laparotomy may improve an infant's long-term neurodevelopmental outcome, potentially by reducing the maximum severity or duration of inflammation.

This study included a randomized controlled trial to compare the effectiveness of laparotomy versus drainage for treating NEC or IP in extremely low birth weight infants. Target enrollment is 300 infants diagnosed with NEC or IP for randomization to receive initially either a laparotomy or drainage. Subsequent laparotomies may be performed on infants in either group, if their condition continues to deteriorate. Surviving infants will return for a follow-up assessment at 18-22 months corrected age.

This study also attempted to use a comprehensive cohort design that would have added additional information beyond the conventional randomized trial component. The cohort component included trial data among eligible, non-randomized infants with NEC/IP, who consented for the non-randomized cohort, would be collected and analyzed as a secondary specific aim. This additional cohort was called the preference cohort.

Study Design

Study Type:
Interventional
Actual Enrollment :
529 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multi-center Randomized Trial of Laparotomy vs. Drainage as the Initial Surgical Therapy for ELBW Infants With Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP): Outcomes at 18-22 Months Adjusted Age
Actual Study Start Date :
Jan 1, 2010
Actual Primary Completion Date :
Aug 1, 2019
Actual Study Completion Date :
Aug 1, 2019

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Randomized Trial: Laparotomy

Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.

Procedure: Laparotomy
Initial laparotomy will be performed. Standard procedures will be used, including inspection of the bowel with removal of diseased areas, creation of stoma(s), and other procedures deemed indicated by the surgeon.
Active Comparator: Randomized Trial: Peritoneal drain placement

Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.

Procedure: Drainage
Initial drainage will involve placing a Penrose drain in the abdomen.
Other Names:
  • Peritoneal drain

    		•
    Active Comparator: Preference Cohort: Laparotomy

    Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures.

    Procedure: Laparotomy
    Initial laparotomy will be performed. Standard procedures will be used, including inspection of the bowel with removal of diseased areas, creation of stoma(s), and other procedures deemed indicated by the surgeon.
    Active Comparator: Preference Cohort: Peritoneal drain placement

    Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.

    Procedure: Drainage
    Initial drainage will involve placing a Penrose drain in the abdomen.
    Other Names:
  • Peritoneal drain

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Death or Neurodevelopmental Impairment (NDI) [at 18-22 months corrected age]

      Death or NDI at 18-22 months corrected age

    Secondary Outcome Measures

    1. Death [by 18-22 months corrected age]

      Death by 18-22 months corrected age

    2. Survival With Neurodevelopmental Impairment (NDI) [by 18-22 months corrected age]

      NDI at 18-22 months corrected age (among survivors)

    3. Death or Moderate to Severe Cerebral Palsy [up to the follow-up visit completed within the 18-22 months corrected age window]

      Death within 18-22 months corrected age or moderate to severe cerebral palsy at 18-22 months corrected age

    4. Death or Bayley Cognitive Composite Score Less Than 85 [up to the follow-up visit completed within the 18-22 months corrected age window]

      Death within 18-22 months corrected age or Bayley cognitive composite score less than 85 at 18-22 months corrected age. Higher values of the Bayley cognitive composite score is better than lower values. Normal values are greater than or equal to 85. A moderate value is in the 70-84 range, and a severe value is <70.

    5. Death or Blindness [up to the follow-up visit completed within the 18-22 months corrected age window]

      Death within 18-22 months corrected age or blindness at 18-22 months corrected age

    6. Death or Hearing Loss [up to the follow-up visit completed within the 18-22 months corrected age window]

      Death within 18-22 months corrected age or hearing loss at 18-22 months corrected age

    7. Subsequent Laparotomy [between initial surgery and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Subsequent laparotomy after initial surgery

    8. Any Intraoperative Complications During Any Surgery [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Any intraoperative complications during any surgery

    9. Any Wound Dehiscence [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Any wound dehiscence during any surgery

    10. Any Intra-abdominal Abscess [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Any intra-abdominal abscess during any surgery

    11. Any Intestinal Stricture [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Any intestinal stricture during any surgery

    12. Any Late Onset Sepsis [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Any late onset sepsis after randomization

    13. Any Parenteral Nutrition (PN)-Associated Cholestasis [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Any Parenteral nutrition (PN)-associated cholestasis during any surgery

    14. Any Severe IVH [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Any severe IVH ater randomization

    15. Duration of Mechanical Ventilation [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Duration of mechanical ventilation while on study

    16. Duration of Parenteral Nutrition [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Duration of parenteral nutrition while on study

    17. Final Bowel Length [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Final bowel length after last surgery

    18. Time to Full Feeds [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Time to full feeds while on study

    19. Length of Hospital Stay [from randomization up to 1 year following birth]

      Length of hospital stay while on study

    20. Death or NDI Stratified by Pre-operative Diagnosis [at 18-22 months corrected age]

      Death or NDI at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

    21. Death Stratified by Pre-operative Diagnosis [by 18-22 months corrected age]

      Death within 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

    22. Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis [by 18-22 months corrected age]

      NDI at 18-22 months corrected age (among survivors). Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

    23. Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis [up to the follow-up visit completed within the 18-22 months corrected age window]

      Death within 18-22 months corrected age or moderate to severe cerebral palsy at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

    24. Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis [up to the follow-up visit completed within the 18-22 months corrected age window]

      Death within 18-22 months corrected age or Bayley cognitive composite score less than 85 at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). Higher values of the Bayley cognitive composite score is better than lower values. Normal values are greater than or equal to 85. A moderate value is in the 70-84 range, and a severe value is <70.

    25. Death or Blindness Stratified by Pre-operative Diagnosis [up to the follow-up visit completed within the 18-22 months corrected age window]

      Death within 18-22 months corrected age or blindness at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

    26. Death or Hearing Loss Stratified by Pre-operative Diagnosis [up to the follow-up visit completed within the 18-22 months corrected age window]

      Death within 18-22 months corrected age or hearing loss at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

    27. Subsequent Laparotomy Stratified by Pre-operative Diagnosis [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Subsequent laparotomy after initial surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

    28. Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Any intraoperative complications during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

    29. Any Wound Dehiscence Stratified by Pre-operative Diagnosis [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Any wound dehiscence during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

    30. Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Any intra-abdominal abscess during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

    31. Any Intestinal Stricture Stratified by Pre-operative Diagnosis [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Any intestinal stricture during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

    32. Any Late Onset Sepsis Stratified by Pre-operative Diagnosis [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Any late onset sepsis after randomization. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

    33. Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Any Parenteral nutrition (PN)-associated cholestasis during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

    34. Any Severe IVH Stratified by Pre-operative Diagnosis [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Any severe IVH ater randomization. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

    35. Duration of Mechanical Ventilation Stratified by Pre-operative Diagnosis [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Duration of mechanical ventilation while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

    36. Duration of Parenteral Nutrition Stratified by Pre-operative Diagnosis [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Duration of parenteral nutrition while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

    37. Final Bowel Length Stratified by Pre-operative Diagnosis [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Final bowel length after last surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

    38. Time to Full Feeds Stratified by Pre-operative Diagnosis [between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth]

      Time to full feeds while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

    39. Length of Hospital Stay Stratified by Pre-operative Diagnosis [from randomization up to 1 year following birth]

      Length of hospital stay while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 8 Weeks
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Infants born at ≤1,000 g birth weight

    • Infant is ≤8 0/7 weeks of age at the time of eligibility assessment

    • Pediatric surgeon decision to perform surgery for suspected NEC or IP

    • Subject is at a center able to perform both laparotomy and drainage

    Exclusion Criteria:

    • Major anomaly that influences likelihood of developing primary outcome or affects surgical treatment considerations

    • Congenital infection

    • Prior laparotomy or peritoneal drain placement

    • Prior NEC or IP

    • Infant for whom full support is not being provided

    • Follow-up unlikely

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35233
    2 University of California - Los Angeles Los Angeles California United States 90025
    3 Stanford University Palo Alto California United States 94304
    4 Yale University New Haven Connecticut United States 06504
    5 Emory University Atlanta Georgia United States 30303
    6 Indiana University Indianapolis Indiana United States 46202
    7 University of Iowa Iowa City Iowa United States 52242
    8 Tufts Medical Center Boston Massachusetts United States 02111
    9 Wayne State University Detroit Michigan United States 48201
    10 Children's Mercy Hospital Kansas City Missouri United States 64108
    11 University of New Mexico Albuquerque New Mexico United States 87131
    12 University of Rochester Rochester New York United States 14642
    13 RTI International Durham North Carolina United States 27705
    14 Duke University Durham North Carolina United States 27710
    15 Cincinnati Children's Medical Center Cincinnati Ohio United States 45267
    16 Case Western Reserve University Cleveland Ohio United States 44106
    17 Research Institute at Nationwide Children's Hospital Columbus Ohio United States 43205
    18 Univeristy of Pennsylvania Philadelphia Pennsylvania United States 19104
    19 Brown University, Women & Infants Hospital of Rhode Island Providence Rhode Island United States 02905
    20 University of Texas Southwestern Medical Center at Dallas Dallas Texas United States 75235
    21 University of Texas Health Science Center at Houston Houston Texas United States 77030
    22 University of Utah Salt Lake City Utah United States 84108

    Sponsors and Collaborators

    • NICHD Neonatal Research Network
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
    • National Center for Research Resources (NCRR)

    Investigators

    • Principal Investigator: Abbot R. Laptook, MD, Brown University, Women & Infants Hospital of Rhode Island
    • Principal Investigator: Michele C. Walsh, MD MS, Case Western Reserve University, Rainbow Babies and Children's Hospital
    • Principal Investigator: C. Michael Cotten, MD, Duke University
    • Principal Investigator: David Carlton, MD, Emory University
    • Principal Investigator: Greg Sokol, MD, Indiana University
    • Principal Investigator: Abhik Das, PhD, RTI International
    • Principal Investigator: Krisa P. Van Meurs, MD, Stanford University
    • Principal Investigator: Ivan D. Frantz III, MD, Tufts Medical Center
    • Principal Investigator: Brenda Poindexter, MD, MS, Children's Hospital Medical Center, Cincinnati
    • Principal Investigator: Waldemar A. Carlo, MD, University of Alabama at Birmingham
    • Principal Investigator: Edward F. Bell, MD, University of Iowa
    • Principal Investigator: Kristi L. Watterberg, MD, University of New Mexico
    • Principal Investigator: Myra Wyckoff, MD, University of Texas, Southwestern Medical Center at Dallas
    • Principal Investigator: Kathleen A. Kennedy, MD MPH, The University of Texas Health Science Center, Houston
    • Principal Investigator: Seetha Shankaran, MD, Wayne State University
    • Principal Investigator: Richard A. Ehrenkranz, MD, Yale University
    • Study Director: Martin K. Blakely, MD, Vanderbilt University Medical Center
    • Principal Investigator: William Truog, MD, Children's Mercy Hospital Kansas City
    • Principal Investigator: Barbara Schmidt, MD, MSc, Univeristy of Pennsylvania
    • Principal Investigator: Carl D'Angio, MD, University of Rochester
    • Principal Investigator: Uday Devaskar, MD, University of Carlifornia - Los Angeles
    • Principal Investigator: Leif Nelin, MD, Research Institute at Nationwide Children's Hospital
    • Principal Investigator: Brad Yoder, MD, University of Utah

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    NICHD Neonatal Research Network
    ClinicalTrials.gov Identifier:
    NCT01029353
    Other Study ID Numbers:
    • NICHD-NRN-0039
    • U10HD021364
    • U10HD021373
    • U10HD021385
    • U10HD027851
    • U10HD027853
    • U10HD027856
    • U10HD027871
    • U10HD027880
    • U10HD027904
    • U10HD034216
    • U10HD036790
    • U10HD040492
    • U10HD040689
    • U10HD053089
    • U10HD053109
    • U10HD053119
    • U10HD053124
    • UL1RR024139
    • UL1RR025744
    • UL1RR025764
    • UL1RR025777
    • M01RR008084
    • UL1RR024979
    • U10HD068284
    • U10HD068278
    • U10HD068270
    • U10HD068263
    • U10HD068244
    • UG1HD087226
    First Posted:
    Dec 10, 2009
    Last Update Posted:
    Nov 23, 2021
    Last Verified:
    Nov 1, 2021
    Keywords provided by NICHD Neonatal Research Network
    NICHD Neonatal Research Network
    Very Low Birth Weight (VLBW)
    Extremely Low Birth Weight (ELBW)
    Prematurity
    Laparotomy
    Drainage
    Isolated intestinal perforation
    Focal intestinal perforation
    Additional relevant MeSH terms:
    Enterocolitis
    Enterocolitis, Necrotizing
    Intestinal Perforation
    Birth Weight

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain Preference Cohort: Initial Laparotomy Preference Cohort: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the neonatal intensive care unit (NICU) or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation. Under general anesthesia in the neonatal intensive care unit (NICU) or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Period Title: Overall Study
    STARTED 148 162 100 119
    Included in ITT Analysis 146 162 100 119
    Reached Network Status 146 162 100 119
    COMPLETED 141 154 93 115
    NOT COMPLETED 7 8 7 4

    Baseline Characteristics

    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain Preference Cohort: Initial Laparotomy Preference Cohort: Initial Peritoneal Drain Total
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation. Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation. Total of all reporting groups
    Overall Participants 146 162 100 119 527
    Age (days) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [days]
    11.6
    (10)
    12.1
    (9.9)
    79.9
    (125.4)
    49.9
    (111.7)
    33.3
    (81.0)
    Sex/Gender, Customized (Count of Participants)
    Female
    66
    45.2%
    63
    38.9%
    48
    48%
    53
    44.5%
    230
    43.6%
    Male
    80
    54.8%
    98
    60.5%
    52
    52%
    66
    55.5%
    296
    56.2%
    Missing
    0
    0%
    1
    0.6%
    0
    0%
    0
    0%
    1
    0.2%
    Race/Ethnicity, Customized (Count of Participants)
    Black
    62
    42.5%
    67
    41.4%
    31
    31%
    42
    35.3%
    202
    38.3%
    Missing
    5
    3.4%
    5
    3.1%
    1
    1%
    1
    0.8%
    12
    2.3%
    Other
    6
    4.1%
    8
    4.9%
    9
    9%
    6
    5%
    29
    5.5%
    White
    73
    50%
    82
    50.6%
    59
    59%
    70
    58.8%
    284
    53.9%
    Maternal hispanic ethnicity (Count of Participants)
    Missing
    1
    0.7%
    9
    5.6%
    3
    3%
    9
    7.6%
    22
    4.2%
    No
    107
    73.3%
    120
    74.1%
    75
    75%
    95
    79.8%
    397
    75.3%
    Yes
    38
    26%
    33
    20.4%
    22
    22%
    15
    12.6%
    108
    20.5%
    Infant gestational age (weeks) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [weeks]
    25
    (1.7)
    24.9
    (1.7)
    24.6
    (1.1)
    24.5
    (1.2)
    25
    (1.7)
    Infant birth weight (gram) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [gram]
    721.2
    (138.4)
    711.4
    (135.9)
    719.8
    (150.5)
    675.6
    (161.7)
    707.6
    (146.2)
    Infant was small for gestational age (Count of Participants)
    Missing
    0
    0%
    1
    0.6%
    0
    0%
    0
    0%
    1
    0.2%
    No
    131
    89.7%
    145
    89.5%
    84
    84%
    98
    82.4%
    458
    86.9%
    Yes
    15
    10.3%
    16
    9.9%
    16
    16%
    21
    17.6%
    68
    12.9%
    Inborn status (Count of Participants)
    In born
    82
    56.2%
    90
    55.6%
    65
    65%
    75
    63%
    312
    59.2%
    Out born
    64
    43.8%
    72
    44.4%
    35
    35%
    44
    37%
    215
    40.8%
    Infant Apgar score at 1 minute (units on a scale) [Median (Full Range) ]
    Median (Full Range) [units on a scale]
    3
    3
    4
    4
    3
    Infant Apgar score at 5 minute (units on a scale) [Median (Full Range) ]
    Median (Full Range) [units on a scale]
    6
    6
    7
    7
    7
    Infant had patent ductus arteriosus (PDA) prior to enrollment (Count of Participants)
    Missing
    10
    6.8%
    15
    9.3%
    2
    2%
    4
    3.4%
    31
    5.9%
    No
    77
    52.7%
    85
    52.5%
    52
    52%
    56
    47.1%
    270
    51.2%
    Yes
    59
    40.4%
    62
    38.3%
    46
    46%
    59
    49.6%
    226
    42.9%
    Infant received postnatal steroids (Count of Participants)
    No
    119
    81.5%
    115
    71%
    67
    67%
    83
    69.7%
    384
    72.9%
    Yes
    27
    18.5%
    47
    29%
    33
    33%
    36
    30.3%
    143
    27.1%
    Infant received indomethacin before or on Randomization (Count of Participants)
    Missing
    3
    2.1%
    6
    3.7%
    3
    3%
    7
    5.9%
    19
    3.6%
    No
    69
    47.3%
    74
    45.7%
    51
    51%
    38
    31.9%
    232
    44%
    Yes
    74
    50.7%
    82
    50.6%
    46
    46%
    74
    62.2%
    276
    52.4%
    Infant received enteral feedings before or on enrollment (Count of Participants)
    Missing
    33
    22.6%
    38
    23.5%
    16
    16%
    25
    21%
    112
    21.3%
    No
    23
    15.8%
    29
    17.9%
    5
    5%
    11
    9.2%
    68
    12.9%
    Yes
    90
    61.6%
    95
    58.6%
    79
    79%
    83
    69.7%
    347
    65.8%
    Infant had early onset sepsis before or on enrollment (Count of Participants)
    Missing
    2
    1.4%
    5
    3.1%
    0
    0%
    1
    0.8%
    8
    1.5%
    No
    143
    97.9%
    151
    93.2%
    98
    98%
    117
    98.3%
    509
    96.6%
    Yes
    1
    0.7%
    6
    3.7%
    2
    2%
    1
    0.8%
    10
    1.9%
    Infant had late onset sepsis before or on enrollment (Count of Participants)
    Missing
    0
    0%
    2
    1.2%
    1
    1%
    0
    0%
    3
    0.6%
    No
    109
    74.7%
    113
    69.8%
    72
    72%
    76
    63.9%
    370
    70.2%
    Yes
    37
    25.3%
    47
    29%
    27
    27%
    43
    36.1%
    154
    29.2%
    Infant had severe intraventricular hemorrhage (IVH) (grade 3 or 4) (Count of Participants)
    Missing
    6
    4.1%
    5
    3.1%
    1
    1%
    4
    3.4%
    16
    3%
    No
    123
    84.2%
    134
    82.7%
    86
    86%
    88
    73.9%
    431
    81.8%
    Yes
    17
    11.6%
    23
    14.2%
    13
    13%
    27
    22.7%
    80
    15.2%
    Infant on vasopressors at Enrollment (Count of Participants)
    No
    105
    71.9%
    103
    63.6%
    55
    55%
    71
    59.7%
    334
    63.4%
    Yes
    41
    28.1%
    59
    36.4%
    45
    45%
    47
    39.5%
    192
    36.4%
    Missing
    0
    0%
    0
    0%
    0
    0%
    1
    0.8%
    1
    0.2%
    Infant received HFOV or HFJV at randomization (Count of Participants)
    No
    114
    78.1%
    114
    70.4%
    51
    51%
    66
    55.5%
    345
    65.5%
    Yes
    32
    21.9%
    48
    29.6%
    49
    49%
    53
    44.5%
    182
    34.5%
    Infant pH closest to enrollment (pH) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pH]
    7.2
    (0.1)
    7.2
    (0.1)
    7.2
    (0.1)
    7.2
    (0.2)
    7.2
    (0.1)
    Infant fraction of inspired oxygen (FiO2) closest to enrollment (Percent) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Percent]
    44.8
    (26.3)
    45.9
    (24.1)
    57.8
    (29.7)
    53.5
    (30.0)
    49.6
    (27.6)
    Infant mean blood pressure (mmHG) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHG]
    37.1
    (10.3)
    37.0
    (11.5)
    39.0
    (11.3)
    36.1
    (11.7)
    37.2
    (11.2)
    Infant lowest platelet count (1000 platelets per microliter) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [1000 platelets per microliter]
    155.7
    (96)
    150.4
    (80.9)
    156.2
    (91.4)
    131.5
    (79.6)
    148.7
    (87.3)
    Infant baseline risk of death or neurodevelopmental impairment (NDI) (Percent probability) [Median (Standard Deviation) ]
    Median (Standard Deviation) [Percent probability]
    63.4
    (27)
    70.7
    (23.7)
    88.1
    (20.7)
    85.8
    (23.1)
    70.3
    (25.0)
    Infant preoperative diagnosis (NEC or IP) (Count of Participants)
    IP
    104
    71.2%
    109
    67.3%
    25
    25%
    72
    60.5%
    310
    58.8%
    NEC
    42
    28.8%
    53
    32.7%
    75
    75%
    47
    39.5%
    217
    41.2%
    Maternal Age, Continuous (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    27.6
    (6.7)
    27.3
    (6.3)
    26.7
    (6.3)
    26.8
    (6.2)
    27.2
    (6.4)
    Married, Customized (Count of Participants)
    Missing
    1
    0.7%
    6
    3.7%
    4
    4%
    4
    3.4%
    15
    2.8%
    No
    81
    55.5%
    95
    58.6%
    50
    50%
    62
    52.1%
    288
    54.6%
    Yes
    64
    43.8%
    61
    37.7%
    46
    46%
    53
    44.5%
    224
    42.5%
    Maternal Education, Customized (Count of Participants)
    College graduate
    18
    12.3%
    21
    13%
    19
    19%
    25
    21%
    83
    15.7%
    High school graduate
    42
    28.8%
    38
    23.5%
    19
    19%
    25
    21%
    124
    23.5%
    Less than high school
    21
    14.4%
    28
    17.3%
    22
    22%
    12
    10.1%
    83
    15.7%
    Missing
    42
    28.8%
    51
    31.5%
    25
    25%
    38
    31.9%
    156
    29.6%
    Some college
    23
    15.8%
    24
    14.8%
    15
    15%
    19
    16%
    81
    15.4%
    Mother had private insurance (Count of Participants)
    Missing
    0
    0%
    3
    1.9%
    0
    0%
    1
    0.8%
    4
    0.8%
    No
    98
    67.1%
    113
    69.8%
    71
    71%
    65
    54.6%
    347
    65.8%
    Yes
    48
    32.9%
    46
    28.4%
    29
    29%
    53
    44.5%
    176
    33.4%
    Mother received prenatal care (Count of Participants)
    Missing
    1
    0.7%
    3
    1.9%
    6
    6%
    5
    4.2%
    15
    2.8%
    No
    3
    2.1%
    10
    6.2%
    2
    2%
    5
    4.2%
    20
    3.8%
    Yes
    142
    97.3%
    149
    92%
    92
    92%
    109
    91.6%
    492
    93.4%
    Mother received antibiotics (Count of Participants)
    Missing
    28
    19.2%
    37
    22.8%
    15
    15%
    18
    15.1%
    98
    18.6%
    No
    39
    26.7%
    42
    25.9%
    19
    19%
    19
    16%
    119
    22.6%
    Yes
    79
    54.1%
    83
    51.2%
    66
    66%
    82
    68.9%
    310
    58.8%
    Rupture of membranes > 18 hours (Count of Participants)
    Missing
    22
    15.1%
    29
    17.9%
    7
    7%
    6
    5%
    64
    12.1%
    No
    101
    69.2%
    108
    66.7%
    69
    69%
    97
    81.5%
    375
    71.2%
    Yes
    23
    15.8%
    25
    15.4%
    24
    24%
    16
    13.4%
    88
    16.7%
    Maternal hypertension (Count of Participants)
    Missing
    26
    17.8%
    31
    19.1%
    10
    10%
    13
    10.9%
    80
    15.2%
    No
    85
    58.2%
    98
    60.5%
    65
    65%
    84
    70.6%
    332
    63%
    Yes
    35
    24%
    33
    20.4%
    25
    25%
    22
    18.5%
    115
    21.8%
    Mother received antenatal magnesium (Count of Participants)
    Missing
    52
    35.6%
    68
    42%
    59
    59%
    66
    55.5%
    245
    46.5%
    No
    17
    11.6%
    21
    13%
    6
    6%
    7
    5.9%
    51
    9.7%
    Yes
    77
    52.7%
    73
    45.1%
    35
    35%
    46
    38.7%
    231
    43.8%
    Mother received steroids (Count of Participants)
    Missing
    0
    0%
    1
    0.6%
    0
    0%
    0
    0%
    1
    0.2%
    No
    22
    15.1%
    31
    19.1%
    11
    11%
    18
    15.1%
    82
    15.6%
    Yes
    124
    84.9%
    130
    80.2%
    89
    89%
    101
    84.9%
    444
    84.3%

    Outcome Measures

    1. Primary Outcome
    Title Death or Neurodevelopmental Impairment (NDI)
    Description Death or NDI at 18-22 months corrected age
    Time Frame at 18-22 months corrected age

    Outcome Measure Data

    Analysis Population Description
    Analysis of randomized trial data included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization. Analysis of preference cohort data included all eligible participants who were consented, enrolled, did not withdraw consent, and who provided outcome data.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain Preference Cohort: Laparotomy Preference Cohort: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation. Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 141 154 93 115
    No
    44
    30.1%
    46
    28.4%
    27
    27%
    28
    23.5%
    Yes
    97
    66.4%
    108
    66.7%
    66
    66%
    87
    73.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis. Model included treatment, baseline risk of death or NDI, and pre-operative diagnosis (Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP)) as covariates.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.00
    Confidence Interval (2-Sided) 95%
    0.87 to 1.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments RR: Initial Laparotomy over Peritoneal Drain. RR from robust Poisson regression with log link, reference cell coding, center as repeated measure. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis. Using Robust Poisson regression with log link and center as repeated measure, and effect coding, test for an interaction between treatment (Initial Laparotomy/Initial Peritoneal Drain) and pre-operative diagnosis (Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP)) as covariates. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-operative diagnosis as covariates.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.03
    Comments Pre-specified threshold = 0.05
    Method Robust Poisson regression
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.95, 95% credible interval of (0.82, 1.11).
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Preference Cohort: Laparotomy, Preference Cohort: Initial Peritoneal Drain
    Comments A frequentist analysis. Model included treatment, baseline risk of death or NDI, and pre-operative diagnosis (Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP)) covariates.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.97
    Confidence Interval (2-Sided) 95%
    0.75 to 1.26
    Parameter Dispersion Type:
    Value:
    Estimation Comments RR: Initial Laparotomy over Peritoneal Drain. RR from robust regression with log link, reference cell coding, center as repeated measure. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariate.
    2. Secondary Outcome
    Title Death
    Description Death by 18-22 months corrected age
    Time Frame by 18-22 months corrected age

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 146 162
    No
    105
    71.9%
    114
    70.4%
    Yes
    41
    28.1%
    48
    29.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.00
    Confidence Interval (2-Sided) 95%
    0.69 to 1.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments RR: Initial Laparotomy over Peritoneal Drain. RR from robust Poisson regression with log link, reference cell coding, center as repeated measure. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments
    Type of Statistical Test Superiority
    Comments A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.95, 95% credible interval of (0.69, 1.30).
    3. Secondary Outcome
    Title Survival With Neurodevelopmental Impairment (NDI)
    Description NDI at 18-22 months corrected age (among survivors)
    Time Frame by 18-22 months corrected age

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, survived until follow-up visit at 18-22 months, and provided sufficient information to determine if NDI occurred.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 100 106
    No
    44
    30.1%
    46
    28.4%
    Yes
    56
    38.4%
    60
    37%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis. Estimate based on model fit using only data from study survivors.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.02
    Confidence Interval (2-Sided) 95%
    0.78 to 1.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments RR: Initial Laparotomy over Peritoneal Drain. RR from robust Poisson regression with log link, reference cell coding, center as repeated measure. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis among study survivors. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.99, 95% credible interval of (0.78, 1.25).
    4. Secondary Outcome
    Title Death or Moderate to Severe Cerebral Palsy
    Description Death within 18-22 months corrected age or moderate to severe cerebral palsy at 18-22 months corrected age
    Time Frame up to the follow-up visit completed within the 18-22 months corrected age window

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 142 157
    No
    84
    57.5%
    78
    48.1%
    Yes
    58
    39.7%
    79
    48.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.83
    Confidence Interval (2-Sided) 95%
    0.66 to 1.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments RR: Initial Laparotomy over Peritoneal Drain. RR from robust Poisson regression with log link, reference cell coding, center as repeated measure. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.82, 95% credible interval of (0.65, 1.02).
    5. Secondary Outcome
    Title Death or Bayley Cognitive Composite Score Less Than 85
    Description Death within 18-22 months corrected age or Bayley cognitive composite score less than 85 at 18-22 months corrected age. Higher values of the Bayley cognitive composite score is better than lower values. Normal values are greater than or equal to 85. A moderate value is in the 70-84 range, and a severe value is <70.
    Time Frame up to the follow-up visit completed within the 18-22 months corrected age window

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 141 151
    No
    46
    31.5%
    51
    31.5%
    Yes
    95
    65.1%
    100
    61.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.03
    Confidence Interval (2-Sided) 95%
    0.89 to 1.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments RR: Initial Laparotomy over Peritoneal Drain. RR from robust Poisson regression with log link, reference cell coding, center as repeated measure. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.98, 95% credible interval of (0.84, 1.15).
    6. Secondary Outcome
    Title Death or Blindness
    Description Death within 18-22 months corrected age or blindness at 18-22 months corrected age
    Time Frame up to the follow-up visit completed within the 18-22 months corrected age window

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 142 157
    No
    101
    69.2%
    105
    64.8%
    Yes
    41
    28.1%
    52
    32.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.92
    Confidence Interval (2-Sided) 95%
    0.64 to 1.31
    Parameter Dispersion Type:
    Value:
    Estimation Comments RR: Initial Laparotomy over Peritoneal Drain. RR from robust Poisson regression with log link, reference cell coding, center as repeated measure. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.86, 95% credible interval of (0.64, 1.16).
    7. Secondary Outcome
    Title Death or Hearing Loss
    Description Death within 18-22 months corrected age or hearing loss at 18-22 months corrected age
    Time Frame up to the follow-up visit completed within the 18-22 months corrected age window

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 141 156
    No
    98
    67.1%
    105
    64.8%
    Yes
    43
    29.5%
    51
    31.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.97
    Confidence Interval (2-Sided) 95%
    0.69 to 1.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments RR: Initial Laparotomy over Peritoneal Drain. RR from robust Poisson regression with log link, reference cell coding, center as repeated measure. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.92, 95% credible interval of (0.68, 1.25).
    8. Secondary Outcome
    Title Subsequent Laparotomy
    Description Subsequent laparotomy after initial surgery
    Time Frame between initial surgery and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 145 162
    No
    110
    75.3%
    81
    50%
    Yes
    35
    24%
    81
    50%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.47
    Confidence Interval (2-Sided) 95%
    0.35 to 0.63
    Parameter Dispersion Type:
    Value:
    Estimation Comments RR: Initial Laparotomy over Peritoneal Drain. RR from robust Poisson regression with log link, reference cell coding, center as repeated measure. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.51, 95% credible interval of (0.37, 0.69).
    9. Secondary Outcome
    Title Any Intraoperative Complications During Any Surgery
    Description Any intraoperative complications during any surgery
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 145 162
    No
    116
    79.5%
    141
    87%
    Yes
    29
    19.9%
    21
    13%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.57
    Confidence Interval (2-Sided) 95%
    1.04 to 2.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments RR: Initial Laparotomy over Peritoneal Drain. RR from robust Poisson regression with log link, reference cell coding, center as repeated measure. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median relative risk of Initial Laparotomy over Initial Drainage was 1.45, 95% credible interval of (0.92, 2.31).
    10. Secondary Outcome
    Title Any Wound Dehiscence
    Description Any wound dehiscence during any surgery
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 146 162
    No
    135
    92.5%
    154
    95.1%
    Yes
    11
    7.5%
    8
    4.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.58
    Confidence Interval (2-Sided) 95%
    0.71 to 3.50
    Parameter Dispersion Type:
    Value:
    Estimation Comments RR: Initial Laparotomy over Peritoneal Drain. RR from robust Poisson regression with log link, reference cell coding, center as repeated measure. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median relative risk of Initial Laparotomy over Initial Drainage was 1.31, 95% credible interval of (0.66, 2.62).
    11. Secondary Outcome
    Title Any Intra-abdominal Abscess
    Description Any intra-abdominal abscess during any surgery
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 146 162
    No
    141
    96.6%
    158
    97.5%
    Yes
    5
    3.4%
    4
    2.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis This analysis used model identical to other by treatment analyses for binary outcome. RR estimated from robust Poisson regression with log link, reference cell coding, center as repeated measure. RR: Initial Laparotomy over Peritoneal Drain. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates. However, adjusted RR estimates could not be calculated due to the iteration limit being excessed in PROC GENMOD.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median relative risk of Initial Laparotomy over Initial Drainage was 1.16, 95% credible interval of (0.50, 2.65).
    12. Secondary Outcome
    Title Any Intestinal Stricture
    Description Any intestinal stricture during any surgery
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 146 162
    No
    139
    95.2%
    153
    94.4%
    Yes
    7
    4.8%
    9
    5.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.86
    Confidence Interval (2-Sided) 95%
    0.34 to 2.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments RR: Initial Laparotomy over Peritoneal Drain. RR from robust Poisson regression with log link, reference cell coding, center as repeated measure. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.93, 95% credible interval of (0.45, 1.91).
    13. Secondary Outcome
    Title Any Late Onset Sepsis
    Description Any late onset sepsis after randomization
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 146 160
    No
    123
    84.2%
    126
    77.8%
    Yes
    23
    15.8%
    34
    21%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.73
    Confidence Interval (2-Sided) 95%
    0.37 to 1.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments RR: Initial Laparotomy over Peritoneal Drain. RR from robust Poisson regression with log link, reference cell coding, center as repeated measure. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.75, 95% credible interval of (0.48, 1.16).
    14. Secondary Outcome
    Title Any Parenteral Nutrition (PN)-Associated Cholestasis
    Description Any Parenteral nutrition (PN)-associated cholestasis during any surgery
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 146 162
    No
    110
    75.3%
    116
    71.6%
    Yes
    36
    24.7%
    46
    28.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.90
    Confidence Interval (2-Sided) 95%
    0.70 to 1.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments RR: Initial Laparotomy over Peritoneal Drain. RR from robust Poisson regression with log link, reference cell coding, center as repeated measure. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with effect coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.91, 95% credible interval of (0.65, 1.27).
    15. Secondary Outcome
    Title Any Severe IVH
    Description Any severe IVH ater randomization
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 140 157
    No
    122
    83.6%
    132
    81.5%
    Yes
    18
    12.3%
    25
    15.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.77
    Confidence Interval (2-Sided) 95%
    0.44 to 1.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments RR: Initial Laparotomy over Peritoneal Drain. RR from robust Poisson regression with log link, reference cell coding, center as repeated measure. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.82, 95% credible interval of (0.49, 1.33).
    16. Secondary Outcome
    Title Duration of Mechanical Ventilation
    Description Duration of mechanical ventilation while on study
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 107 120
    Mean (Standard Deviation) [days]
    33.3
    (25.6)
    38.9
    (26.7)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -6.01
    Confidence Interval (2-Sided) 95%
    -12.77 to 0.75
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference (MD): Laparotomy minus Drain. MD from mixed model using PROC MIXED in SAS, center as random effect, and reference cell coding. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using a hierarchical linear regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=1000), treatment, baseline risk, and preop diagnosis parameters = Normal(mean=0, variance=10), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median difference Initial Laparotomy minus Initial Drainage was -2.68, 95% credible interval of (-7.11, 1.83).
    17. Secondary Outcome
    Title Duration of Parenteral Nutrition
    Description Duration of parenteral nutrition while on study
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 135 149
    Mean (Standard Deviation) [days]
    55.5
    (34.1)
    64.1
    (36.4)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -8.75
    Confidence Interval (2-Sided) 95%
    -17.05 to -0.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference (MD): Laparotomy minus Drain. MD from mixed model using PROC MIXED in SAS, center as random effect, and reference cell coding. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using a hierarchical linear regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=1000), treatment, baseline risk, and preop diagnosis parameters = Normal(mean=0, variance=10), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median difference Initial Laparotomy minus Initial Drainage was -3.23, 95% credible interval of (-8.08, 1.68).
    18. Secondary Outcome
    Title Final Bowel Length
    Description Final bowel length after last surgery
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 28 16
    Mean (Standard Deviation) [cm]
    74.4
    (24.6)
    68.7
    (35.7)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.59
    Confidence Interval (2-Sided) 95%
    -9.09 to 22.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference (MD): Laparotomy minus Drain. MD from mixed model using PROC MIXED in SAS, center as random effect, and reference cell coding. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using a hierarchical linear regression. The SAS procedure PROC MCMC with reference coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=1000), treatment, baseline risk, and preop diagnosis parameters = Normal(mean=0, variance=10), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median difference Initial Laparotomy minus Initial Drainage was 1.65, 95% credible interval of (-3.97, 7.23).
    19. Secondary Outcome
    Title Time to Full Feeds
    Description Time to full feeds while on study
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 92 92
    Mean (Standard Deviation) [days]
    46.9
    (45.8)
    50.6
    (27.7)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.56
    Confidence Interval (2-Sided) 95%
    -13.02 to 7.91
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference (MD): Laparotomy minus Drain. MD from mixed model using PROC MIXED in SAS, center as random effect, and reference cell coding. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using a hierarchical linear regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=1000), treatment, baseline risk, and preop diagnosis parameters = Normal(mean=0, variance=10), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median difference Initial Laparotomy minus Initial Drainage was -0.71, 95% credible interval of (-5.89, 4.48).
    20. Secondary Outcome
    Title Length of Hospital Stay
    Description Length of hospital stay while on study
    Time Frame from randomization up to 1 year following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 137 156
    Mean (Standard Deviation) [days]
    101.2
    (71.2)
    113.8
    (73.8)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A frequentist analysis.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -13.95
    Confidence Interval (2-Sided) 95%
    -30.54 to 2.63
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mean Difference (MD): Laparotomy minus Drain. MD from mixed model using PROC MIXED in SAS, center as random effect, and reference cell coding. Model included treatment, baseline risk of death or NDI, and pre-op diagnosis (NEC/IP) as covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Initial Laparotomy and Initial Peritoneal Drain were compared using a hierarchical linear regression. The SAS procedure PROC MCMC with reference cell coding was used. Center (random effect), treatment, pre-operative diagnosis, and baseline risk of death or NDI were binary covariates. Pre-operative diagnosis levels were NEC and IP. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=1000), treatment, baseline risk, and preop diagnosis parameters = Normal(mean=0, variance=10), random effect standard deviation = Half-Normal(mean=0, variance=10). The posterior median difference Initial Laparotomy minus Initial Drainage was -1.78, 95% credible interval of (-7.44, 3.87).
    21. Secondary Outcome
    Title Death or NDI Stratified by Pre-operative Diagnosis
    Description Death or NDI at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
    Time Frame at 18-22 months corrected age

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 141 154
    No
    31
    21.2%
    38
    23.5%
    Yes
    68
    46.6%
    64
    39.5%
    No
    13
    8.9%
    8
    4.9%
    Yes
    29
    19.9%
    44
    27.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.81
    Confidence Interval (2-Sided) 95%
    0.64 to 1.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.11
    Confidence Interval (2-Sided) 95%
    0.95 to 1.31
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Within pre-operative diagnosis, Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. Pre-operative diagnosis levels were NEC and IP. PROC MCMC with effect coding was used. Center (random effect), treatment, pre-operative diagnosis, baseline risk, and the treatment by Preoperative diagnosis were the covariates. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). For the NEC pre-operative diagnosis, the posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.81, 95% credible interval of (0.63, 1.00). For the IP pre-operative diagnosis, the posterior median relative risk of Initial Laparotomy over Initial Drainage was 1.09, 95% credible interval of (0.90, 1.33).
    22. Secondary Outcome
    Title Death Stratified by Pre-operative Diagnosis
    Description Death within 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
    Time Frame by 18-22 months corrected age

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 146 162
    No
    80
    54.8%
    88
    54.3%
    Yes
    24
    16.4%
    21
    13%
    No
    25
    17.1%
    26
    16%
    Yes
    17
    11.6%
    27
    16.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.77
    Confidence Interval (2-Sided) 95%
    0.52 to 1.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.28
    Confidence Interval (2-Sided) 95%
    0.79 to 2.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Within pre-operative diagnosis, Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. Pre-operative diagnosis levels were NEC and IP. PROC MCMC with effect coding was used. Center (random effect), treatment, pre-operative diagnosis, baseline risk, and the treatment by Preoperative diagnosis were the covariates. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). For the NEC pre-operative diagnosis, the posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.82, 95% credible interval of (0.53, 1.20). For the IP pre-operative diagnosis, the posterior median relative risk of Initial Laparotomy over Initial Drainage was 1.18, 95% credible interval of (0.74, 1.87).
    23. Secondary Outcome
    Title Survival With Neurodevelopmental Impairment (NDI) Stratified by Pre-operative Diagnosis
    Description NDI at 18-22 months corrected age (among survivors). Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
    Time Frame by 18-22 months corrected age

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, survived until follow-up visit at 18-22 months, and provided sufficient information to determine if NDI occurred.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 100 106
    No
    31
    21.2%
    38
    23.5%
    Yes
    44
    30.1%
    43
    26.5%
    No
    13
    8.9%
    8
    4.9%
    Yes
    12
    8.2%
    17
    10.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.73
    Confidence Interval (2-Sided) 95%
    0.42 to 1.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.11
    Confidence Interval (2-Sided) 95%
    0.85 to 1.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Within pre-operative diagnosis, Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. Pre-operative diagnosis levels were NEC and IP. PROC MCMC with effect coding was used. Center (random effect), treatment, pre-operative diagnosis, baseline risk, and the treatment by Pre-operative diagnosis were the covariates. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). For the NEC pre-operative diagnosis, the posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.76, 95% credible interval of (0.48, 1.18). For the IP pre-operative diagnosis, the posterior median relative risk of Initial Laparotomy over Initial Drainage was 1.08, 95% credible interval of (0.83, 1.42).
    24. Secondary Outcome
    Title Death or Moderate to Severe Cerebral Palsy Stratified by Pre-operative Diagnosis
    Description Death within 18-22 months corrected age or moderate to severe cerebral palsy at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
    Time Frame up to the follow-up visit completed within the 18-22 months corrected age window

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 142 157
    No
    64
    43.8%
    64
    39.5%
    Yes
    36
    24.7%
    41
    25.3%
    No
    20
    13.7%
    14
    8.6%
    Yes
    22
    15.1%
    38
    23.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.70
    Confidence Interval (2-Sided) 95%
    0.47 to 1.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.95
    Confidence Interval (2-Sided) 95%
    0.76 to 1.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Within pre-operative diagnosis, Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. Pre-operative diagnosis levels were NEC and IP. PROC MCMC with effect coding was used. Center (random effect), treatment, pre-operative diagnosis, baseline risk, and the treatment by Preoperative diagnosis were the covariates. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). For the NEC pre-operative diagnosis, the posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.73, 95% credible interval of (0.52, 0.96). For the IP pre-operative diagnosis, the posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.95, 95% credible interval of (0.68, 1.32).
    25. Secondary Outcome
    Title Death or Bayley Cognitive Composite Score Less Than 85 Stratified by Pre-operative Diagnosis
    Description Death within 18-22 months corrected age or Bayley cognitive composite score less than 85 at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP). Higher values of the Bayley cognitive composite score is better than lower values. Normal values are greater than or equal to 85. A moderate value is in the 70-84 range, and a severe value is <70.
    Time Frame up to the follow-up visit completed within the 18-22 months corrected age window

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 141 151
    No
    32
    21.9%
    42
    25.9%
    Yes
    67
    45.9%
    59
    36.4%
    No
    14
    9.6%
    9
    5.6%
    Yes
    28
    19.2%
    41
    25.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.81
    Confidence Interval (2-Sided) 95%
    0.61 to 1.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.17
    Confidence Interval (2-Sided) 95%
    1.01 to 1.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Within pre-operative diagnosis, Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. Pre-operative diagnosis levels were NEC and IP. PROC MCMC with effect coding was used. Center (random effect), treatment, pre-operative diagnosis, baseline risk, and the treatment by Preoperative diagnosis were the covariates. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). For the NEC pre-operative diagnosis, the posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.80, 95% credible interval of (0.61, 1.01). For the IP pre-operative diagnosis, the posterior median relative risk of Initial Laparotomy over Initial Drainage was 1.15, 95% credible interval of (0.94, 1.42).
    26. Secondary Outcome
    Title Death or Blindness Stratified by Pre-operative Diagnosis
    Description Death within 18-22 months corrected age or blindness at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
    Time Frame up to the follow-up visit completed within the 18-22 months corrected age window

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 142 157
    No
    76
    52.1%
    83
    51.2%
    Yes
    24
    16.4%
    22
    13.6%
    No
    25
    17.1%
    22
    13.6%
    Yes
    17
    11.6%
    30
    18.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.68
    Confidence Interval (2-Sided) 95%
    0.46 to 1.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.22
    Confidence Interval (2-Sided) 95%
    0.74 to 2.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Within pre-operative diagnosis, Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. Pre-operative diagnosis levels were NEC and IP. PROC MCMC with effect coding was used. Center (random effect), treatment, pre-operative diagnosis, baseline risk, and the treatment by Preoperative diagnosis were the covariates. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). For the NEC pre-operative diagnosis, the posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.72, 95% credible interval of (0.48, 1.05). For the IP pre-operative diagnosis, the posterior median relative risk of Initial Laparotomy over Initial Drainage was 1.12, 95% credible interval of (0.71, 1.76).
    27. Secondary Outcome
    Title Death or Hearing Loss Stratified by Pre-operative Diagnosis
    Description Death within 18-22 months corrected age or hearing loss at 18-22 months corrected age. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
    Time Frame up to the follow-up visit completed within the 18-22 months corrected age window

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 141 156
    No
    73
    50%
    81
    50%
    Yes
    26
    17.8%
    23
    14.2%
    No
    25
    17.1%
    24
    14.8%
    Yes
    17
    11.6%
    28
    17.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.73
    Confidence Interval (2-Sided) 95%
    0.51 to 1.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.25
    Confidence Interval (2-Sided) 95%
    0.82 to 1.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates. Reported results in this analysis restricted to infants with IP.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments A Bayesian analysis. Within pre-operative diagnosis, Initial Laparotomy and Initial Peritoneal Drain were compared using log-binomial regression. Pre-operative diagnosis levels were NEC and IP. PROC MCMC with effect coding was used. Center (random effect), treatment, pre-operative diagnosis, baseline risk, and the treatment by Preoperative diagnosis were the covariates. Markov chain Monte Carlo (MCMC) characteristics: three chains, 10000 tunings, 10000 burn-ins, 1000000 samples, thinning=20.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Other Statistical Analysis Priors for model parameters: intercept = Normal(mean=0, variance=100), baseline risk and preop diagnosis parameters = Normal(mean=0, variance=1), treatment and the interaction term = Normal(mean=0, variance=0.31416), random effect standard deviation = Half-Normal(mean=0, variance=10). For the NEC pre-operative diagnosis, the posterior median relative risk of Initial Laparotomy over Initial Drainage was 0.77, 95% credible interval of (0.51, 1.14). For the IP pre-operative diagnosis, the posterior median relative risk of Initial Laparotomy over Initial Drainage was 1.17, 95% credible interval of (0.76, 1.81).
    28. Secondary Outcome
    Title Subsequent Laparotomy Stratified by Pre-operative Diagnosis
    Description Subsequent laparotomy after initial surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 145 162
    No
    81
    55.5%
    58
    35.8%
    Yes
    23
    15.8%
    51
    31.5%
    No
    29
    19.9%
    23
    14.2%
    Yes
    12
    8.2%
    30
    18.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.53
    Confidence Interval (2-Sided) 95%
    0.31 to 0.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.44
    Confidence Interval (2-Sided) 95%
    0.29 to 0.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    29. Secondary Outcome
    Title Any Intraoperative Complications During Any Surgery Stratified by Pre-operative Diagnosis
    Description Any intraoperative complications during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 145 162
    No
    83
    56.8%
    95
    58.6%
    Yes
    21
    14.4%
    14
    8.6%
    No
    33
    22.6%
    46
    28.4%
    Yes
    8
    5.5%
    7
    4.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.44
    Confidence Interval (2-Sided) 95%
    0.58 to 3.57
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.63
    Confidence Interval (2-Sided) 95%
    1.06 to 2.50
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    30. Secondary Outcome
    Title Any Wound Dehiscence Stratified by Pre-operative Diagnosis
    Description Any wound dehiscence during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 146 162
    No
    99
    67.8%
    104
    64.2%
    Yes
    5
    3.4%
    5
    3.1%
    No
    36
    24.7%
    50
    30.9%
    Yes
    6
    4.1%
    3
    1.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 2.52
    Confidence Interval (2-Sided) 95%
    0.84 to 7.55
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.05
    Confidence Interval (2-Sided) 95%
    0.38 to 2.88
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    31. Secondary Outcome
    Title Any Intra-abdominal Abscess Stratified by Pre-operative Diagnosis
    Description Any intra-abdominal abscess during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 146 162
    No
    101
    69.2%
    106
    65.4%
    Yes
    3
    2.1%
    3
    1.9%
    No
    40
    27.4%
    52
    32.1%
    Yes
    2
    1.4%
    1
    0.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.78
    Confidence Interval (2-Sided) 95%
    0.82 to 3.86
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.16
    Confidence Interval (2-Sided) 95%
    0.42 to 3.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    32. Secondary Outcome
    Title Any Intestinal Stricture Stratified by Pre-operative Diagnosis
    Description Any intestinal stricture during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 146 162
    No
    101
    69.2%
    103
    63.6%
    Yes
    3
    2.1%
    6
    3.7%
    No
    38
    26%
    50
    30.9%
    Yes
    4
    2.7%
    3
    1.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.68
    Confidence Interval (2-Sided) 95%
    0.35 to 8.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.50
    Confidence Interval (2-Sided) 95%
    0.10 to 2.44
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    33. Secondary Outcome
    Title Any Late Onset Sepsis Stratified by Pre-operative Diagnosis
    Description Any late onset sepsis after randomization. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 146 160
    No
    88
    60.3%
    80
    49.4%
    Yes
    16
    11%
    27
    16.7%
    No
    35
    24%
    46
    28.4%
    Yes
    7
    4.8%
    7
    4.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.29
    Confidence Interval (2-Sided) 95%
    0.62 to 2.69
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.60
    Confidence Interval (2-Sided) 95%
    0.27 to 1.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    34. Secondary Outcome
    Title Any Parenteral Nutrition (PN)-Associated Cholestasis Stratified by Pre-operative Diagnosis
    Description Any Parenteral nutrition (PN)-associated cholestasis during any surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 146 162
    No
    79
    54.1%
    82
    50.6%
    Yes
    25
    17.1%
    27
    16.7%
    No
    31
    21.2%
    34
    21%
    Yes
    11
    7.5%
    19
    11.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.75
    Confidence Interval (2-Sided) 95%
    0.41 to 1.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.99
    Confidence Interval (2-Sided) 95%
    0.69 to 1.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    35. Secondary Outcome
    Title Any Severe IVH Stratified by Pre-operative Diagnosis
    Description Any severe IVH ater randomization. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 140 157
    No
    84
    57.5%
    84
    51.9%
    Yes
    17
    11.6%
    22
    13.6%
    No
    38
    26%
    48
    29.6%
    Yes
    1
    0.7%
    3
    1.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.43
    Confidence Interval (2-Sided) 95%
    0.04 to 4.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a robust Poisson regression model, with log link and center as repeated measure. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy over drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.81
    Confidence Interval (2-Sided) 95%
    0.44 to 1.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC GENMOD in SAS, using center as the repeated effect. Effect coding was used to represent the binary covariates.
    36. Secondary Outcome
    Title Duration of Mechanical Ventilation Stratified by Pre-operative Diagnosis
    Description Duration of mechanical ventilation while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 107 120
    IP
    34.1
    (26.6)
    42.2
    (28)
    NEC
    31
    (22.6)
    31.7
    (22.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.27
    Confidence Interval (2-Sided) 95%
    -14.10 to 11.60
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC MIXED in SAS, using center as the random effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -7.85
    Confidence Interval (2-Sided) 95%
    -15.84 to 0.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC MIXED in SAS, using center as the random effect. Effect coding was used to represent the binary covariates.
    37. Secondary Outcome
    Title Duration of Parenteral Nutrition Stratified by Pre-operative Diagnosis
    Description Duration of parenteral nutrition while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 135 149
    IP
    56.3
    (35.2)
    63.6
    (33.7)
    NEC
    53.5
    (31.3)
    65.3
    (42)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -11.57
    Confidence Interval (2-Sided) 95%
    -27.15 to 4.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC MIXED in SAS, using center as the random effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -7.63
    Confidence Interval (2-Sided) 95%
    -17.46 to 2.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC MIXED in SAS, using center as the random effect. Effect coding was used to represent the binary covariates.
    38. Secondary Outcome
    Title Final Bowel Length Stratified by Pre-operative Diagnosis
    Description Final bowel length after last surgery. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 28 16
    IP
    83.1
    (20.9)
    74.7
    (22.4)
    NEC
    62.7
    (25)
    64
    (44.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.00
    Confidence Interval (2-Sided) 95%
    -18.84 to 26.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC MIXED in SAS, using center as the random effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 9.05
    Confidence Interval (2-Sided) 95%
    -13.29 to 31.38
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC MIXED in SAS, using center as the random effect. Effect coding was used to represent the binary covariates.
    39. Secondary Outcome
    Title Time to Full Feeds Stratified by Pre-operative Diagnosis
    Description Time to full feeds while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
    Time Frame between randomization and Neonatal Research Network NRN infant status i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 92 92
    IP
    52.4
    (50.4)
    56.3
    (27.1)
    NEC
    29.6
    (18.9)
    32.3
    (21.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.13
    Confidence Interval (2-Sided) 95%
    -24.62 to 18.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC MIXED in SAS, using center as the random effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.39
    Confidence Interval (2-Sided) 95%
    -14.42 to 9.63
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC MIXED in SAS, using center as the random effect. Effect coding was used to represent the binary covariates. Reported results in this analysis restricted to infants with IP.
    40. Secondary Outcome
    Title Length of Hospital Stay Stratified by Pre-operative Diagnosis
    Description Length of hospital stay while on study. Stratification variable is pre-operative diagnosis: Necrotizing Enterocolitis (NEC) or Isolated Intestinal Perforation (IP).
    Time Frame from randomization up to 1 year following birth

    Outcome Measure Data

    Analysis Population Description
    Analysis included all eligible participants who were consented, randomized, did not withdraw consent, and who provided outcome data after randomization.
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    Measure Participants 137 156
    IP
    109.6
    (67)
    121.3
    (64.7)
    NEC
    80.2
    (77.8)
    99.2
    (87.7)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to NEC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -18.43
    Confidence Interval (2-Sided) 95%
    -48.41 to 11.55
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC MIXED in SAS, using center as the random effect. Effect coding was used to represent the binary covariates.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Randomized Trial: Initial Laparotomy, Randomized Trial: Initial Peritoneal Drain
    Comments This by treatment and by pre-operative diagnosis secondary analysis was completed by using a mixed linear regression model, using center as the random effect. Model included treatment, baseline risk of death or NDI, pre-op diagnosis (NEC/IP), and treatment by pre-op diagnosis as covariates. Reported results in this analysis restricted to model based treatment effect estimate (laparotomy minus drain) when pre-operative diagnosis is equal to IP.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -11.95
    Confidence Interval (2-Sided) 95%
    -31.96 to 8.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments The model was fit using PROC MIXED in SAS, using center as the random effect. Effect coding was used to represent the binary covariates.

    Adverse Events

    Time Frame Adverse events are monitored from randomization through study status (death, discharge or 120 days)
    Adverse Event Reporting Description
    Arm/Group Title Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain Preference Cohort: Initial Laparotomy Preference Cohort: Initial Peritoneal Drain
    Arm/Group Description Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation. Under general anesthesia in the NICU or operating room, a laparotomy will be performed following standard procedures. Place a one-fourth inch Penrose drain in the lower abdomen with local anesthesia and sedation.
    All Cause Mortality
    Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain Preference Cohort: Initial Laparotomy Preference Cohort: Initial Peritoneal Drain
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 41/146 (28.1%) 48/162 (29.6%) 48/100 (48%) 60/119 (50.4%)
    Serious Adverse Events
    Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain Preference Cohort: Initial Laparotomy Preference Cohort: Initial Peritoneal Drain
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 41/146 (28.1%) 49/162 (30.2%) 49/100 (49%) 60/119 (50.4%)
    Blood and lymphatic system disorders
    Coagulopathies 0/146 (0%) 0 0/162 (0%) 0 1/100 (1%) 1 0/119 (0%) 0
    Cardiac disorders
    Pericardial effusion 1/146 (0.7%) 1 0/162 (0%) 0 0/100 (0%) 0 0/119 (0%) 0
    Cardiopulmonary failure 0/146 (0%) 0 1/162 (0.6%) 1 0/100 (0%) 0 2/119 (1.7%) 2
    Gastrointestinal disorders
    Abdominal herniation 0/146 (0%) 0 1/162 (0.6%) 1 0/100 (0%) 0 0/119 (0%) 0
    Neonatal spontaneous intestinal perforation 3/146 (2.1%) 3 0/162 (0%) 0 2/100 (2%) 2 9/119 (7.6%) 9
    Necrotizing enterocolitis neonatal 21/146 (14.4%) 21 24/162 (14.8%) 24 35/100 (35%) 35 25/119 (21%) 25
    Intra-abdominal bleeding 1/146 (0.7%) 1 0/162 (0%) 0 0/100 (0%) 0 0/119 (0%) 0
    General disorders
    Death 4/146 (2.7%) 4 11/162 (6.8%) 11 6/100 (6%) 6 8/119 (6.7%) 8
    Multiorgan failure 1/146 (0.7%) 1 1/162 (0.6%) 1 0/100 (0%) 0 0/119 (0%) 0
    Infections and infestations
    Neonatal sepsis 10/146 (6.8%) 10 16/162 (9.9%) 16 13/100 (13%) 13 9/119 (7.6%) 9
    Fungal Infection 0/146 (0%) 0 1/162 (0.6%) 1 0/100 (0%) 0 0/119 (0%) 0
    Neonatal infection 1/146 (0.7%) 1 2/162 (1.2%) 2 0/100 (0%) 0 7/119 (5.9%) 7
    Injury, poisoning and procedural complications
    Wound dehiscence 0/146 (0%) 0 0/162 (0%) 0 1/100 (1%) 1 0/119 (0%) 0
    Metabolism and nutrition disorders
    Metabolic acidosis 0/146 (0%) 0 0/162 (0%) 0 0/100 (0%) 0 1/119 (0.8%) 1
    Nervous system disorders
    CNS injury 0/146 (0%) 0 1/162 (0.6%) 1 0/100 (0%) 0 0/119 (0%) 0
    Intracranial hemorrhage 4/146 (2.7%) 4 1/162 (0.6%) 1 0/100 (0%) 0 3/119 (2.5%) 3
    Intraventricular haemorrhage neonatal 0/146 (0%) 0 0/162 (0%) 0 1/100 (1%) 1 1/119 (0.8%) 1
    Pregnancy, puerperium and perinatal conditions
    Prematurity 3/146 (2.1%) 3 1/162 (0.6%) 1 0/100 (0%) 0 2/119 (1.7%) 2
    Renal and urinary disorders
    Renal failure neonatal 0/146 (0%) 0 1/162 (0.6%) 1 0/100 (0%) 0 0/119 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Bronchopulmonary dysplasia 1/146 (0.7%) 1 2/162 (1.2%) 2 1/100 (1%) 1 2/119 (1.7%) 2
    Neonatal respiratory distress syndrome 3/146 (2.1%) 3 1/162 (0.6%) 1 0/100 (0%) 0 7/119 (5.9%) 7
    Neonatal pneumothorax 0/146 (0%) 0 2/162 (1.2%) 2 0/100 (0%) 0 0/119 (0%) 0
    Neonatal pulmonary haemorrhage 1/146 (0.7%) 1 0/162 (0%) 0 1/100 (1%) 1 1/119 (0.8%) 1
    Other (Not Including Serious) Adverse Events
    Randomized Trial: Initial Laparotomy Randomized Trial: Initial Peritoneal Drain Preference Cohort: Initial Laparotomy Preference Cohort: Initial Peritoneal Drain
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/146 (0%) 0/162 (0%) 0/100 (0%) 0/119 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Investigators must adhere to the Neonatal Research Network Publication policies.

    Results Point of Contact

    Name/Title Martin L Blakely, MD
    Organization Vanderbilt University Medical Center
    Phone 615-936-7211
    Email martin.blakely@vumc.org
    Responsible Party:
    NICHD Neonatal Research Network
    ClinicalTrials.gov Identifier:
    NCT01029353
    Other Study ID Numbers:
    • NICHD-NRN-0039
    • U10HD021364
    • U10HD021373
    • U10HD021385
    • U10HD027851
    • U10HD027853
    • U10HD027856
    • U10HD027871
    • U10HD027880
    • U10HD027904
    • U10HD034216
    • U10HD036790
    • U10HD040492
    • U10HD040689
    • U10HD053089
    • U10HD053109
    • U10HD053119
    • U10HD053124
    • UL1RR024139
    • UL1RR025744
    • UL1RR025764
    • UL1RR025777
    • M01RR008084
    • UL1RR024979
    • U10HD068284
    • U10HD068278
    • U10HD068270
    • U10HD068263
    • U10HD068244
    • UG1HD087226
    First Posted:
    Dec 10, 2009
    Last Update Posted:
    Nov 23, 2021
    Last Verified:
    Nov 1, 2021