Management of Myelomeningocele Study (MOMS)

• Sponsor: The George Washington University Biostatistics Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00060606
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH), Children's Hospital of Philadelphia (Other), Vanderbilt University Medical Center (Other), University of California, San Francisco (Other), University of Pittsburgh Medical Center (Other), University of Houston (Other), The University of Texas Health Science Center, Houston (Other)
• Enrollment: 183
• Locations: 3
• Arms: 2
• Duration (Months): 172
• Patients Per Site: 61
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Spina bifida (myelomeningocele) is a complex birth defect in which a portion of the spinal cord is not fully developed. The overlying bones and skin are incompletely formed and the underdeveloped area of the spinal cord is exposed on the surface of the back. Spina bifida defects are closed soon after birth to prevent further damage to the spinal cord and nerves. The Management of Myelomeningocele Study (MOMS) is a research study comparing two approaches to the treatment of babies with spina bifida: surgery before birth (prenatal surgery) and the standard closure, surgery after birth (postnatal surgery).

Condition or Disease	Intervention/Treatment	Phase
Meningomyelocele; Spinal Dysraphism	Procedure: Prenatal Myelomeningocele Repair Surgery; Procedure: Postnatal Myelomeningocele Repair Surgery	N/A

Detailed Description

Since 1997, more than 200 fetuses have had in utero closure of myelomeningocele by open maternal-fetal surgery. Preliminary clinical evidence suggests that this procedure reduces the incidence of shunt-dependent hydrocephalus and restores the cerebellum and brainstem to more normal configuration. However, clinical results of prenatal surgery for myelomeningocele are based on comparisons with historical controls and examine only efficacy, not safety. MOMS will determine if intrauterine repair of fetal myelomeningocele at 19 to 25 weeks of gestation improves outcomes as compared to standard postnatal repair. Outcomes assessed include death, the need for ventricular decompressive shunting by one year of life and neurologic function at 30 months of age.

One hundred eighty-three women, whose fetuses have spina bifida, were enrolled in the study and randomized to have either prenatal surgery or postnatal surgery. After a central screening process which included a medical record review, all women had an extensive baseline evaluation that included ultrasound, MRI, physical exam, social work evaluation, psychological screening, and education about spina bifida and prenatal surgery.

For women who were eligible following the central screening process, all screening, surgery and follow-up visits were performed at one of three MOMS Centers. The mother, if eligible, and her support person traveled (at the expense of the study) to the MOMS Center for screening and randomization.

Women assigned to have prenatal surgery were scheduled for surgery within 1 to 3 days after they were randomized. They stayed near the MOMS Center until they delivered. Women in the postnatal group traveled back to their assigned MOMS Center to deliver. Both groups delivered their babies by C-section around the 37th week of their pregnancies. Babies born to women in the postnatal surgery group had their spina bifida defects closed when they were medically stable, usually within 48 hours of birth.

Children and their parents returned to their assigned MOMS Center at 1 year and 2 ½ years of age for follow-up evaluation. Motor function, developmental progress, and bladder, kidney, and brain development were assessed.

The children were asked to return for an additional follow-up visit (MOMS2) between the ages of 6-10 years. This follow-up is to determine whether children who received the surgery before birth have better health and mental outcomes and live more independently and function more safely and appropriately in daily life than those who received the surgery after birth.

Study Design

• Study Type: Interventional
• Actual Enrollment: 183 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Myelomeningocele Repair Randomized Trial
• Study Start Date: Feb 1, 2003
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Jun 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Prenatal Surgery Group Fetal surgery to close spina bifida defect prior to 26 weeks of gestation with delivery by C-Section at approximately 37 weeks of gestation.	Procedure: Prenatal Myelomeningocele Repair Surgery; Fetal surgery to repair spina bifida defect performed prior to 26 weeks of gestation with delivery by C-section at approximately 37 weeks of gestation.
Active Comparator: Postnatal Surgery Group Standard postnatal closure of the spina bifida defect when the baby is medically stable, usually within 48 hours of birth by C-section.	Procedure: Postnatal Myelomeningocele Repair Surgery; Standard postnatal surgical closure of the spina bifida defect

Outcome Measures

Primary Outcome Measures

1. Infant Death or Need for Ventricular Shunt by 1 Year of Life [12 months of age]

2. Bayley Scales of Infant Development MDI and the Difference Between the Functional and Anatomical Level of Lesion at 30 Months of Age [30 months of age]

   Individual outcome score is the sum of the following: Rank for the Bayley score which was constructed from the Bayley Scales of Infant Development Mental Development Index standardized score for each child at 30 months. Deaths had the lowest score of 0, lower than the lowest standardized score of 49. Scores were then ranked from 1 to 182 (1 is worst,182 is best). Rank for the difference between the anatomic and functional lesion levels of the spine was generated by a plain x-ray obtained at the 12-month visit for the anatomic level and the physical examination at 30 months for the functional level. The difference between the two was calculated where a positive difference means that the child is functioning better than expected by the level of his/her lesion. Deaths received the lowest score of -25, lower than all other possible differences. The differences were then ranked from 1 to 182 (1 is worst, 182 is best). For the overall score, 2 is the worst and 364 is the best.

Secondary Outcome Measures

1. Number of Participants Walking Independently at Examination [30 months of age]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria

• Pregnant women carrying a fetus diagnosed with myelomeningocele

• Myelomeningocele lesion that starts no higher than T1 and no lower than S1 with hindbrain herniation present

• Gestational age at randomization of 19 weeks 0 days to 25 weeks 6 days

• Normal karyotype

• Singleton pregnancy

• United States resident

• Able to travel to study site for study evaluation, procedures, and visits (if randomized to prenatal surgery, must stay near center until delivery)

• Support person to travel and stay with participant

Exclusion Criteria

• Maternal insulin-dependent pregestational diabetes

• Short or incompetent cervix or cervical cerclage

• Placenta previa

• Body mass index of 35 or more

• Previous spontaneous delivery prior to 37 weeks

• Maternal HIV, Hepatitis-B or Hepatitis-C status positive

• Uterine anomaly

• Maternal medical condition which is a contraindication to surgery or general anesthesia

• Other fetal anomaly

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California at San Francisco	San Francisco	California	United States	94143
2	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
3	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• The George Washington University Biostatistics Center
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Children's Hospital of Philadelphia
• Vanderbilt University Medical Center
• University of California, San Francisco
• University of Pittsburgh Medical Center
• University of Houston
• The University of Texas Health Science Center, Houston

Investigators

• Principal Investigator: Elizabeth A Thom, PhD, George Washington University, Data and Study Coordinating Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: The George Washington University Biostatistics Center
• ClinicalTrials.gov Identifier: NCT00060606
• Other Study ID Numbers: U01HD041665; U01HD068541; U01HD41666; U01HD41667; U01HD41669
• First Posted: May 9, 2003
• Last Update Posted: Jul 7, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by The George Washington University Biostatistics Center: Maternal fetal surgery; Fetal diagnosis; Myelomeningocele; Meningomyelocele; Open neural tube defect; ONTD; Spina bifida
• Additional relevant MeSH terms: Meningomyelocele; Spina Bifida Cystica; Spinal Dysraphism; Neural Tube Defects

Study Results

Participant Flow

Arm/Group Title	Prenatal Surgery Group	Postnatal Surgery Group
Arm/Group Description	Fetal surgery to close spina bifida defect prior to 26 weeks of gestation with delivery by C-Section at approximately 37 weeks of gestation. Prenatal Myelomeningocele Repair Surgery: Fetal surgery to repair spina bifida defect performed prior to 26 weeks of gestation with delivery by C-section at approximately 37 weeks of gestation.	Standard postnatal closure of the spina bifida defect when the baby is medically stable, usually within 48 hours of birth by C-section. Postnatal Myelomeningocele Repair Surgery: Standard postnatal surgical closure of the spina bifida defect
Period Title: Overall Study
STARTED	91	92
First Primary Outcome - Shunt at 12 Mont	91	92
COMPLETED	91	91
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Prenatal Surgery Group	Postnatal Surgery Group	Total
Arm/Group Description	Prenatal Myelomeningocele Repair Surgery: Fetal surgery to repair spina bifida defect performed prior to 26 weeks of gestation with delivery by C-section at approximately 37 weeks of gestation.	Postnatal Myelomeningocele Repair Surgery: Standard postnatal surgical closure of the spina bifida defect when the baby is medically stable, usually within 48 hours of birth by C-section.	Total of all reporting groups
Overall Participants	91	92	183
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.2 (5.2)	28.7 (4.8)	28.9 (5.0)
Sex: Female, Male (Count of Participants)
Female	91 100%	92 100%	183 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White Non-Hispanic	85 93.4%	86 93.5%	171 93.4%
Black Non-Hispanic	1 1.1%	1 1.1%	2 1.1%
Hispanic	3 3.3%	4 4.3%	7 3.8%
Other	2 2.2%	1 1.1%	3 1.6%
Gestational Age at randomization (weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weeks]	23.7 (1.4)	23.9 (1.3)	23.8 (1.3)
Married (Count of Participants)
Count of Participants [Participants]	84 92.3%	86 93.5%	170 92.9%
Schooling (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.9 (1.7)	14.9 (1.7)	14.9 (1.7)
Body Mass Index at screening (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.3 (3.7)	26.3 (3.9)	26.3 (3.8)
Severe hindbrain herniation (Count of Participants)
Count of Participants [Participants]	27 29.7%	23 25%	50 27.3%
Clubfoot (Count of Participants)
Count of Participants [Participants]	24 26.4%	19 20.7%	43 23.5%
Fetal sex female (Count of Participants)
Count of Participants [Participants]	42 46.2%	57 62%	99 54.1%
Nullipara (Count of Participants)
Count of Participants [Participants]	37 40.7%	37 40.2%	74 40.4%
Previous uterine surgeries (Count of Participants)
Count of Participants [Participants]	12 13.2%	11 12%	23 12.6%
Cervical length (transvaginal) (mm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm]	39.5 (7.6)	39.4 (5.9)	39.5 (6.8)
Spina bifida lesion level L3 or lower (Count of Participants)
Count of Participants [Participants]	62 68.1%	76 82.6%	138 75.4%

Outcome Measures

1. Primary Outcome

Title	Infant Death or Need for Ventricular Shunt by 1 Year of Life
Time Frame	12 months of age

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Prenatal Surgery	Postnatal Surgery
Arm/Group Description	Fetal surgery to close spina bifida defect prior to 26 weeks of gestation with delivery by C-Section at approximately 37 weeks of gestation. Prenatal Myelomeningocele Repair Surgery: Fetal surgery to repair spina bifida defect performed prior to 26 weeks of gestation with delivery by C-section at approximately 37 weeks of gestation.	Standard postnatal closure of the spina bifida defect when the baby is medically stable, usually within 48 hours of birth by C-section. Postnatal Myelomeningocele Repair Surgery: Standard postnatal surgical closure of the spina bifida defect
Measure Participants	91	92
Count of Participants [Participants]	66 72.5%	90 97.8%

2. Primary Outcome

Title	Bayley Scales of Infant Development MDI and the Difference Between the Functional and Anatomical Level of Lesion at 30 Months of Age
Description	Individual outcome score is the sum of the following: Rank for the Bayley score which was constructed from the Bayley Scales of Infant Development Mental Development Index standardized score for each child at 30 months. Deaths had the lowest score of 0, lower than the lowest standardized score of 49. Scores were then ranked from 1 to 182 (1 is worst,182 is best). Rank for the difference between the anatomic and functional lesion levels of the spine was generated by a plain x-ray obtained at the 12-month visit for the anatomic level and the physical examination at 30 months for the functional level. The difference between the two was calculated where a positive difference means that the child is functioning better than expected by the level of his/her lesion. Deaths received the lowest score of -25, lower than all other possible differences. The differences were then ranked from 1 to 182 (1 is worst, 182 is best). For the overall score, 2 is the worst and 364 is the best.
Time Frame	30 months of age

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Prenatal Surgery	Postnatal Surgery
Arm/Group Description	Fetal surgery to close spina bifida defect prior to 26 weeks of gestation with delivery by C-Section at approximately 37 weeks of gestation. Prenatal Myelomeningocele Repair Surgery: Fetal surgery to repair spina bifida defect performed prior to 26 weeks of gestation with delivery by C-section at approximately 37 weeks of gestation.	Standard postnatal closure of the spina bifida defect when the baby is medically stable, usually within 48 hours of birth by C-section. Postnatal Myelomeningocele Repair Surgery: Standard postnatal surgical closure of the spina bifida defect
Measure Participants	91	91
Mean (Standard Deviation) [units on a scale]	199.4 (80.5)	166.6 (76.7)

3. Secondary Outcome

Title	Number of Participants Walking Independently at Examination
Time Frame	30 months of age

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Prenatal Surgery	Postnatal Surgery
Arm/Group Description	Fetal surgery to close spina bifida defect prior to 26 weeks of gestation with delivery by C-Section at approximately 37 weeks of gestation. Prenatal Myelomeningocele Repair Surgery: Fetal surgery to repair spina bifida defect performed prior to 26 weeks of gestation with delivery by C-section at approximately 37 weeks of gestation.	Standard postnatal closure of the spina bifida defect when the baby is medically stable, usually within 48 hours of birth by C-section. Postnatal Myelomeningocele Repair Surgery: Standard postnatal surgical closure of the spina bifida defect
Measure Participants	87	88
Count of Participants [Participants]	39 42.9%	21 22.8%

Adverse Events

Time Frame	Adverse events were collected from the time of randomization through 30 months of life.
Arm/Group Title	Prenatal Surgery Group		Postnatal Surgery Group
Arm/Group Description	Fetal surgery to close spina bifida defect prior to 26 weeks of gestation with delivery by C-Section at approximately 37 weeks of gestation. Prenatal Myelomeningocele Repair Surgery: Fetal surgery to repair spina bifida defect performed prior to 26 weeks of gestation with delivery by C-section at approximately 37 weeks of gestation.		Standard postnatal closure of the spina bifida defect when the baby is medically stable, usually within 48 hours of birth by C-section. Postnatal Myelomeningocele Repair Surgery: Standard postnatal surgical closure of the spina bifida defect
All Cause Mortality
	Prenatal Surgery Group		Postnatal Surgery Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/91 (4.4%)		3/92 (3.3%)
Serious Adverse Events
	Prenatal Surgery Group		Postnatal Surgery Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/91 (4.4%)		3/92 (3.3%)
General disorders
Fetal or infant death	4/91 (4.4%)		3/92 (3.3%)
Other (Not Including Serious) Adverse Events
	Prenatal Surgery Group		Postnatal Surgery Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/91 (0%)		0/92 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.