The Effect of Neuraxial Analgesia on Maternal Breastfeeding

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01074190
• Collaborator: (none)
• Enrollment: 345
• Location: 1
• Arms: 3
• Duration (Months): 83
• Patients Per Site Per Month: 4.2

Study Details

Study Description

Brief Summary

A previous randomized trial showed a possible negative association with labor neuraxial analgesia with high compared to low doses of fentanyl, and breastfeeding at 6 weeks postpartum. The significance of this study would be to validate or refute these findings. In addition, we hope to better evaluate the impact of cumulative dose of fentanyl on breastfeeding success in the initial postpartum period as well as at 6 weeks and 6 months post delivery. In order to better assess the quality of breastfeeding, we will utilize a validated breastfeeding assessment tool, LATCH (Latch, Audible swallowing, Type of Nipple, Comfort, and Help). This validated tool can assess maternal and infant variables, define areas of needed intervention, and determine priorities in providing patient teaching. The LATCH assessment has been shown to be a predictor of breastfeeding duration. We also plan to vary the dosage of fentanyl analgesia to determine the relationship between doses below 150 micrograms and changes in breastfeeding assessments. If a clear association between decreased breastfeeding and total fentanyl is identified, then regimens to reduce cumulative doses of fentanyl can be developed to improve the likelihood of breastfeeding success in mothers that desire to breastfeed.

Prior observational studies have inferred epidurals negatively affect breastfeeding by decreasing maternal plasma oxytocin release which may adversely affect infant neurobehavioral development. In a study by Beilin et al., it was reported that mothers receiving a high cumulative dose (> 150 microgram) epidural fentanyl were more likely to have stopped nursing 6 weeks postpartum compared with groups receiving no fentanyl or those receiving < 150 microgram. The study however, was underpowered to detect differences in breastfeeding prior to hospital discharge. In addition, the breastfeeding assessment tool utilized resulted in binary assessments, and therefore, a global rating of the quality of breastfeeding was not available.

Condition or Disease	Intervention/Treatment	Phase
Pain; Breastfeeding	Drug: Group 1; Drug: Group 2; Drug: Group 3	N/A

Detailed Description

Participants in this study will be asked to complete a questionnaire called the Intrinsic Motivation Inventory (IMI).

Subjects will be randomized at the time they request neuraxial analgesia to one of three groups: Group 1: patient controlled epidural analgesia (PCEA) with bupivacaine 1mg/mL; Group 2: PCEA with fentanyl 1 mcg/mL plus bupivacaine 0.8 mg/mL; Group 3: PCEA with fentanyl 2 mcg/mL plus bupivacaine 0.625 mg/mL. Labor analgesia will be initiated in all groups using fentanyl 15 mcg plus bupivacaine 2.5 mg administered intrathecally. A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.

The patient as well as individuals who evaluate the study patient will be blinded to the group assignment. Samples of maternal venous blood ½ teaspoon (2 mls) and cord blood 2ml (1/2 teaspoon) will be collected after the delivery of the fetus. Blood concentrations of fentanyl and bupivacaine will be ascertained using high performance liquid chromatography (HPLC) analysis. Success of breastfeeding using the LATCH assessment tool will be measured by the lactation nurses within 24 hrs of delivery. At 6 weeks and at 3 months postpartum, follow-up phone calls by the anesthesia service will be made to assess for duration of breastfeeding. Also, the patient's obstetrician will be contacted to obtain the patient's Edinburgh Postnatal Depression Score to assess for postpartum depression, which may be a variable in decreasing breastfeeding success.

Study Design

• Study Type: Interventional
• Actual Enrollment: 345 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Effect of Neuraxial Analgesia on Maternal Breastfeeding
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 spinal fentanyl 15 micrograms plus bupivacaine 2.5 mg followed by a patient controlled epidural analgesia (PCEA) maintenance infusion of bupivacaine 1mg/mL	Drug: Group 1; A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.; Other Names: bupivacaine 1mg/ml
Experimental: Group 2 spinal fentanyl 15 micrograms plus bupivacaine 2.5 mg spinal followed by a PCEA infusion of fentanyl 1 micrograms/mL plus bupivacaine 0.8 mg/mL	Drug: Group 2; A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.; Other Names: fentanyl 1mcg/ml plus bupivacaine 0.8 mg/ml
Active Comparator: Group 3 spinal fentanyl 15 micrograms plus bupivacaine 2.5mg followed by a PCEA infusion of fentanyl 2 micrograms/mL plus bupivacaine 0.625 mg/mL	Drug: Group 3; A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.; Other Names: fentanyl 2mcg/ml plus bupivacaine 0.625 mg/ml

Outcome Measures

Primary Outcome Measures

1. Breastfeeding at 6 Weeks Post Delivery [6 weeks post delivery]

   Breastfeeding continuing at 6 weeks after delivery of the baby.

Secondary Outcome Measures

1. Breastfeeding at 3 Months After Delivery [3 months after delivery]

   Breastfeeding at 3 months after delivery of baby

Other Outcome Measures

1. Cumulative Fentanyl Dose (Micrograms) [Time of epidural catheter removal]

   Total cumulative dose of fentanyl in micrograms

2. Plasma Fentanyl Concentration (ng/mL) [Time of epidural catheter removal]

   Blood plasma fentanyl concentraton (nanograms/milliliter).

3. Umbilical Vein Plasma Fentanyl Concentration (ng/mL) [Immediately after delivery]

   Umbilical venous blood plasma was analyzed for fentanyl concentration (ng/mL)

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age 18 and above

• English speaking

• Term gestation (> 38 weeks)

• Parous parturients presenting for attempted vaginal delivery with a cervical dilation less than 8 cm

• They must request neuraxial labor analgesia

• Have previously successfully breastfed their child postpartum for at least 6 weeks

• Are expressing an interest in exclusively breastfeeding postpartum

Exclusion Criteria:

• Under 18 years of age

• Parturients who have received parental opioids during labor or have taken opioids prenatally

• Patients whose neuraxial analgesia failed due to abnormal spinal anatomy including scoliosis or previous spinal instrumentation

• Supplemental epidural opioids during labor

• Had an expedited labor with the delivery of the fetus less than 90 minutes from the placement of the neuraxial anesthestic

• Underwent cesarean delivery

• Received general analgesia for an unanticipated postpartum procedure

• Dropout criteria include patients who wished to be taken out of the study or were lost to follow-up

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Northwestern University

Investigators

• Principal Investigator: Paloma Toledo, M.D.,MPH, Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Baumgarder DJ, Muehl P, Fischer M, Pribbenow B. Effect of labor epidural anesthesia on breast-feeding of healthy full-term newborns delivered vaginally. J Am Board Fam Pract. 2003 Jan-Feb;16(1):7-13.
• Beilin Y, Bodian CA, Weiser J, Hossain S, Arnold I, Feierman DE, Martin G, Holzman I. Effect of labor epidural analgesia with and without fentanyl on infant breast-feeding: a prospective, randomized, double-blind study. Anesthesiology. 2005 Dec;103(6):1211-7.
• Jensen D, Wallace S, Kelsay P. LATCH: a breastfeeding charting system and documentation tool. J Obstet Gynecol Neonatal Nurs. 1994 Jan;23(1):27-32.
• Rahm VA, Hallgren A, Högberg H, Hurtig I, Odlind V. Plasma oxytocin levels in women during labor with or without epidural analgesia: a prospective study. Acta Obstet Gynecol Scand. 2002 Nov;81(11):1033-9.
• Riordan J, Gross A, Angeron J, Krumwiede B, Melin J. The effect of labor pain relief medication on neonatal suckling and breastfeeding duration. J Hum Lact. 2000 Feb;16(1):7-12.

• Responsible Party: Paloma Toledo, Associate Professor of Anesthesiology, Northwestern University
• ClinicalTrials.gov Identifier: NCT01074190
• Other Study ID Numbers: STU00007275
• First Posted: Feb 24, 2010
• Last Update Posted: Apr 5, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Paloma Toledo, Associate Professor of Anesthesiology, Northwestern University: Epidural Labor Analgesia; Pain; Infant; Breastfeeding
• Additional relevant MeSH terms: Fentanyl; Bupivacaine

Study Results

Participant Flow

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	spinal fentanyl 15 micrograms plus bupivacaine 2.5 mg followed by a patient controlled epidural analgesia (PCEA) maintenance infusion of bupivacaine 1mg/mL Group 1: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.	spinal fentanyl 15 micrograms plus bupivacaine 2.5 mg spinal followed by a PCEA infusion of fentanyl 1 micrograms/mL plus bupivacaine 0.8 mg/mL Group 2: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.	spinal fentanyl 15 micrograms plus bupivacaine 2.5mg followed by a PCEA infusion of fentanyl 2 micrograms/mL plus bupivacaine 0.625 mg/mL Group 3: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.
Period Title: Overall Study
STARTED	115	115	115
COMPLETED	111	109	112
NOT COMPLETED	4	6	3

Baseline Characteristics

Arm/Group Title	Group 1	Group 2	Group 3	Total
Arm/Group Description	spinal fentanyl 15 micrograms plus bupivacaine 2.5 mg followed by a patient controlled epidural analgesia (PCEA) maintenance infusion of bupivacaine 1mg/mL Group 1: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.	spinal fentanyl 15 micrograms plus bupivacaine 2.5 mg spinal followed by a PCEA infusion of fentanyl 1 micrograms/mL plus bupivacaine 0.8 mg/mL Group 2: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.	spinal fentanyl 15 micrograms plus bupivacaine 2.5mg followed by a PCEA infusion of fentanyl 2 micrograms/mL plus bupivacaine 0.625 mg/mL Group 3: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.	Total of all reporting groups
Overall Participants	111	109	112	332
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	111 100%	109 100%	112 100%	332 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (Years of age) [Mean (Inter-Quartile Range) ]
Mean (Inter-Quartile Range) [Years of age]	33	34	34	34
Sex: Female, Male (Count of Participants)
Female	111 100%	109 100%	112 100%	332 100%
Male	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	111 100%	109 100%	112 100%	332 100%
Body Mass Index (kg/m∧ 2) (Kilograms/meters squared) [Mean (Inter-Quartile Range) ]
Mean (Inter-Quartile Range) [Kilograms/meters squared]	28	28	29	28
Number of times pregnant (Number of times pregnant) [Mean (Inter-Quartile Range) ]
Mean (Inter-Quartile Range) [Number of times pregnant]	3	3	2	3
Live Births (live births) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [live births]	1	1	1	1
Gestational Age (Days) (Days) [Mean (Inter-Quartile Range) ]
Mean (Inter-Quartile Range) [Days]	277	276	276	276
Duration of breastfeeding with last infant (Count of Participants)
Less than three months	9 8.1%	6 5.5%	9 8%	24 7.2%
3-6 months	20 18%	31 28.4%	30 26.8%	81 24.4%
Greater than 6 months	82 73.9%	72 66.1%	73 65.2%	227 68.4%
Reason for discontinuing breastfeeding with last child (Count of Participants)
Return to work	35 31.5%	30 27.5%	36 32.1%	101 30.4%
Perceived time to stop	22 19.8%	22 20.2%	20 17.9%	64 19.3%
Lack of time	3 2.7%	2 1.8%	9 8%	14 4.2%
Pregnancy	10 9%	9 8.3%	9 8%	28 8.4%
Inadequate milk production	11 9.9%	19 17.4%	14 12.5%	44 13.3%
Child eating solid foods/teething	21 18.9%	17 15.6%	19 17%	57 17.2%
Difficulty with breastfeeding	9 8.1%	10 9.2%	5 4.5%	24 7.2%
Support for breastfeeding (Count of Participants)
Weak	0 0%	2 1.8%	1 0.9%	3 0.9%
Moderate	9 8.1%	13 11.9%	18 16.1%	40 12%
Strong	101 91%	94 86.2%	93 83%	288 86.7%
Missing Data	1 0.9%	0 0%	0 0%	1 0.3%
Used an assistive device/nipple shield (Count of Participants)
Used Device	19 17.1%	22 20.2%	18 16.1%	59 17.8%
Did not use device or no response	92 82.9%	87 79.8%	94 83.9%	273 82.2%
Skin-to-skin contact in the first 24 hours (Count of Participants)
Did not remember	2 1.8%	3 2.8%	2 1.8%	7 2.1%
0-25%	35 31.5%	33 30.3%	43 38.4%	111 33.4%
25-50%	28 25.2%	41 37.6%	39 34.8%	108 32.5%
50-75%	23 20.7%	27 24.8%	25 22.3%	75 22.6%
75-100%	13 11.7%	5 4.6%	3 2.7%	21 6.3%
Missing Data	10 9%	0 0%	0 0%	10 3%
Time from delivery to initial breastfeeding (Count of Participants)
Did not remember	4 3.6%	2 1.8%	5 4.5%	11 3.3%
0 to 1 hour	90 81.1%	80 73.4%	79 70.5%	249 75%
1 to 3 hours	9 8.1%	19 17.4%	16 14.3%	44 13.3%
4 to 10 hours	4 3.6%	4 3.7%	5 4.5%	13 3.9%
Greater than 10 hours	4 3.6%	4 3.7%	7 6.3%	15 4.5%
Took a breastfeeding class or received breastfeeding education (Count of Participants)
Took breastfeeding class	62 55.9%	52 47.7%	62 55.4%	176 53%
Did not take class or no response	49 44.1%	57 52.3%	50 44.6%	156 47%
Breastfeeding motivational measurement scale (Score on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Score on a scale]	119	117	117	118
Verbal rating score for analgesia satisfaction (0-100) (score on a scale) [Mean (Full Range) ]
Mean (Full Range) [score on a scale]	91	91	86	89
Infant birth weight (Kilograms) [Mean (Full Range) ]
Mean (Full Range) [Kilograms]	3.54	3.61	3.57	3.56
Mode of Delivery (Count of Participants)
Vaginal Delivery	111 100%	107 98.2%	110 98.2%	328 98.8%
Assisted Vaginal Delivery	0 0%	1 0.9%	2 1.8%	3 0.9%
Cesarean Delivery	0 0%	1 0.9%	0 0%	1 0.3%
Breastfeeding at lactation consultant assessment n (%) (Count of Participants)
Yes	98 88.3%	96 88.1%	98 87.5%	292 88%
No	8 7.2%	9 8.3%	3 2.7%	20 6%
Consultant not available	5 4.5%	4 3.7%	11 9.8%	20 6%
LATCH score (0-2 for each factor) (Score on scale) [Mean (Full Range) ]
Latch	2	2	2	2
Audible swallowing	2	2	2	2
Type of nipple	2	2	2	2
Comfort (breast/nipple)	2	2	2	2
Hold (positioning)	1	1	1	1
Total Score maximum 0-10	8.5	8	9	8.5
Skin-to-skin contact in the first 24 hours post delivery (Count of Participants)
0-25%	72 64.9%	70 64.2%	71 63.4%	213 64.2%
25-50%	19 17.1%	2 1.8%	17 15.2%	38 11.4%
50-75%	9 8.1%	8 7.3%	11 9.8%	28 8.4%
75-100%	5 4.5%	0 0%	2 1.8%	7 2.1%

Outcome Measures

1. Primary Outcome

Title	Breastfeeding at 6 Weeks Post Delivery
Description	Breastfeeding continuing at 6 weeks after delivery of the baby.
Time Frame	6 weeks post delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	spinal fentanyl 15 micrograms plus bupivacaine 2.5 mg followed by a patient controlled epidural analgesia (PCEA) maintenance infusion of bupivacaine 1mg/mL Group 1: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.	spinal fentanyl 15 micrograms plus bupivacaine 2.5 mg spinal followed by a PCEA infusion of fentanyl 1 micrograms/mL plus bupivacaine 0.8 mg/mL Group 2: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.	spinal fentanyl 15 micrograms plus bupivacaine 2.5mg followed by a PCEA infusion of fentanyl 2 micrograms/mL plus bupivacaine 0.625 mg/mL Group 3: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.
Measure Participants	111	109	112
Currently breast feeding	100 90.1%	99 90.8%	102 91.1%
Not breastfeeding	3 2.7%	2 1.8%	6 5.4%
Lost to follow up	8 7.2%	8 7.3%	4 3.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1, Group 2, Group 3
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.34
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Breastfeeding at 3 Months After Delivery
Description	Breastfeeding at 3 months after delivery of baby
Time Frame	3 months after delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	spinal fentanyl 15 micrograms plus bupivacaine 2.5 mg followed by a patient controlled epidural analgesia (PCEA) maintenance infusion of bupivacaine 1mg/mL Group 1: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.	spinal fentanyl 15 micrograms plus bupivacaine 2.5 mg spinal followed by a PCEA infusion of fentanyl 1 micrograms/mL plus bupivacaine 0.8 mg/mL Group 2: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.	spinal fentanyl 15 micrograms plus bupivacaine 2.5mg followed by a PCEA infusion of fentanyl 2 micrograms/mL plus bupivacaine 0.625 mg/mL Group 3: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.
Measure Participants	111	109	112
Breastfeeding	94 84.7%	96 88.1%	93 83%
Not breastfeeding	6 5.4%	4 3.7%	12 10.7%
Lost to follow up	11 9.9%	9 8.3%	7 6.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1, Group 2, Group 3
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.1
	Comments
	Method	Chi-squared
	Comments

3. Other Pre-specified Outcome

Title	Cumulative Fentanyl Dose (Micrograms)
Description	Total cumulative dose of fentanyl in micrograms
Time Frame	Time of epidural catheter removal

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1	Group 2	Group 3	Total
Arm/Group Description	spinal fentanyl 15 micrograms plus bupivacaine 2.5 mg followed by a patient controlled epidural analgesia (PCEA) maintenance infusion of bupivacaine 1mg/mL Group 1: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.	spinal fentanyl 15 micrograms plus bupivacaine 2.5 mg spinal followed by a PCEA infusion of fentanyl 1 micrograms/mL plus bupivacaine 0.8 mg/mL Group 2: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.	spinal fentanyl 15 micrograms plus bupivacaine 2.5mg followed by a PCEA infusion of fentanyl 2 micrograms/mL plus bupivacaine 0.625 mg/mL Group 3: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.	Cumulative Fentanyl Group 1-3
Measure Participants	111	109	112	332
Median (Inter-Quartile Range) [fentalyl dose micrograms]	15	78	139	78

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1, Group 2, Group 3, Total
	Comments	A sample size of 315 achieves 80% power to detect a difference among groups using a 2 degrees of freedom Chi-Square Test with a significance level (alpha) of 0.05.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.1
	Comments
	Method	Chi-squared
	Comments

4. Other Pre-specified Outcome

Title	Plasma Fentanyl Concentration (ng/mL)
Description	Blood plasma fentanyl concentraton (nanograms/milliliter).
Time Frame	Time of epidural catheter removal

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1	Group 2	Group 3	Total
Arm/Group Description	spinal fentanyl 15 micrograms plus bupivacaine 2.5 mg followed by a patient controlled epidural analgesia (PCEA) maintenance infusion of bupivacaine 1mg/mL Group 1: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.	spinal fentanyl 15 micrograms plus bupivacaine 2.5 mg spinal followed by a PCEA infusion of fentanyl 1 micrograms/mL plus bupivacaine 0.8 mg/mL Group 2: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.	spinal fentanyl 15 micrograms plus bupivacaine 2.5mg followed by a PCEA infusion of fentanyl 2 micrograms/mL plus bupivacaine 0.625 mg/mL Group 3: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.	Plasma fentanyl concentrations (ng/mL) Group 1-3
Measure Participants	111	109	112	332
Median (Inter-Quartile Range) [ng/mL]	.01	.07	.13	.07

5. Other Pre-specified Outcome

Title	Umbilical Vein Plasma Fentanyl Concentration (ng/mL)
Description	Umbilical venous blood plasma was analyzed for fentanyl concentration (ng/mL)
Time Frame	Immediately after delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1	Group 2	Group 3	Total
Arm/Group Description	spinal fentanyl 15 micrograms plus bupivacaine 2.5 mg followed by a patient controlled epidural analgesia (PCEA) maintenance infusion of bupivacaine 1mg/mL Group 1: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.	spinal fentanyl 15 micrograms plus bupivacaine 2.5 mg spinal followed by a PCEA infusion of fentanyl 1 micrograms/mL plus bupivacaine 0.8 mg/mL Group 2: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.	spinal fentanyl 15 micrograms plus bupivacaine 2.5mg followed by a PCEA infusion of fentanyl 2 micrograms/mL plus bupivacaine 0.625 mg/mL Group 3: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.	Umbilical vein plasma fentanyl concentrations (ng/mL) Group 1-3
Measure Participants	111	109	112	332
Median (Inter-Quartile Range) [ng/mL]	.005	.03	.06	.03

Adverse Events

Time Frame	6 Weeks after delivery
Adverse Event Reporting Description	Subject contacted at 6 weeks to assess for adverse events.
Arm/Group Title	Group 1		Group 2		Group 3
Arm/Group Description	spinal fentanyl 15 micrograms plus bupivacaine 2.5 mg followed by a patient controlled epidural analgesia (PCEA) maintenance infusion of bupivacaine 1mg/mL Group 1: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.		spinal fentanyl 15 micrograms plus bupivacaine 2.5 mg spinal followed by a PCEA infusion of fentanyl 1 micrograms/mL plus bupivacaine 0.8 mg/mL Group 2: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.		spinal fentanyl 15 micrograms plus bupivacaine 2.5mg followed by a PCEA infusion of fentanyl 2 micrograms/mL plus bupivacaine 0.625 mg/mL Group 3: A basal infusion rate for the PCEA will be set at 8 mL/h with patient administered boluses of 8 mL every 10 minutes and a one hour limit of 32 mL. Breakthrough pain in all groups will be managed using anesthesiologist administered boluses of bupivacaine 1.25 mg/mL without fentanyl.
All Cause Mortality
	Group 1		Group 2		Group 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/111 (0%)		0/109 (0%)		0/112 (0%)
Serious Adverse Events
	Group 1		Group 2		Group 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/111 (0%)		0/109 (0%)		0/112 (0%)
Other (Not Including Serious) Adverse Events
	Group 1		Group 2		Group 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/111 (0%)		0/109 (0%)		0/112 (0%)
Nervous system disorders
Spinal headache	0/111 (0%)	0	0/109 (0%)	0	0/112 (0%)	0

Limitations/Caveats

The study was limited because few of the participants required more than 150 micrograms of fentanyl for labor analgesia. This was the cut off for reduction of breastfeeding stated by earlier studies.

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Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.