Intrapartum Epidural Fentanyl and Breastfeeding in the Immediate Postpartum Period: a Randomized, Controlled, Double-blinded Study

NCT01497509 | Withdrawn

• 1 other identifier: RCT epidural fentanyl
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Although intrapartum epidural analgesia is frequently implicated in adverse breast-feeding outcomes, many previous studies feature major design limitations that preclude widespread applicability of findings. Some fail to control for the precise pharmacologic composition of the epidural infusion, including whether or not an opioid, such as fentanyl, is even used at all in addition to local anesthetic or whether a combined spinal/epidural or purely epidural technique is used. The drugs used in epidural infusions not only have different mechanisms of action and lipophilicities but are also transferred across the placenta in varying proportions, with one study identifying an umbilical vein/maternal vein ratio of 0.94 for epidural fentanyl and 0.30 for bupivacaine, and another finding significantly different umbilical cord fentanyl concentrations among neonates whose mothers' epidural infusions contained \>150 micrograms fentanyl, \<150 micrograms, or none at all. It is also possible that the same total dose of epidural fentanyl could affect neonates differently depending upon the time course over which it was administered - namely, whether fentanyl is included in both the initial epidural bolus and the subsequent infusion or solely in the infusion. In two studies, mean umbilical vein concentrations of fentanyl did not correlate with total epidural infusion time, but both of these featured sample sizes fewer than 30, necessitating further research. Another limitation of some previous studies is defining success solely as the time to cessation of breast-feeding. Questionnaires mailed to mothers months or even years postpartum may generate unreliable data. If epidural medications truly mediate some physiologic effect upon breast-feeding, then the optimal study period is immediately post-delivery, specifically before the drugs are cleared from the maternal and neonatal circulations. After hospital discharge, many new factors - such as a mother's need to return to work or lack of social support - begin to confound the picture of breast-feeding success. Full-time employment outside the home has been significantly associated with decreased likelihood of breast-feeding at 6 months postpartum. Some studies also fail to control for intent to breast-feed at the time of hospital admission, number of infants previously breast-fed, or labor duration. Failure to account for oxytocin augmentation of labor is also problematic, as intravenous intrapartum oxytocin infusion has been shown to decrease a woman's endogenous serum oxytocin concentration on the second day postpartum in a dose-dependent fashion, which can subsequently impair milk release and, thus, decrease breast-feeding success. Epidural analgesia may worsen breast-feeding outcomes by attenuating neonatal exhibition of neurobehaviors tied to feeding, such as sucking, rooting, and swallowing, during the immediate postpartum period. This critical period is when mother and baby make their first attempts at breast-feeding and set a precedent for subsequent interactions. Neonatal feeding behavior in the early postpartum period is an important predictor of long-term breast-feeding success; those babies who feed most vigorously during their first days of life are significantly more likely to still be breast-feeding at 3 or 6 months than those who exhibit any lesser degree of breast-feeding enthusiasm. Radzyminski et al. found no significant dose-response relationship for either epidural bupivacaine or fentanyl regarding neonatal feeding behaviors, and Porter et al. found no significant effect of epidural fentanyl, mean dose 184 micrograms, upon neonatal APGAR scores, incidence of respiratory depression, or NACS scores (Neurologic and Adaptive Capacity Scores) at 2 or 24 hours post-delivery. Beilin et al. found that neonatal NACS scores were significantly lower when mothers' epidural infusions contained greater than 150 micrograms total epidural fentanyl than when they contained only bupivacaine. In this randomized, controlled, double-blinded study, we investigate whether intrapartum epidural fentanyl significantly decreases the likelihood of breast-feeding at hospital discharge and increases the incidence of neonatal deficits in latching on to the breast and audibly swallowing during the first three hours of life. We hypothesize that these effects will be dose-dependent but will have no relation to the time course over which the epidural fentanyl is administered. We also investigate whether oxytocin augmentation of labor and decreased amount of skin-to-skin contact during the first hour of life are associated with significantly decreased breast-feeding rates at hospital discharge.

Conditions

Neonatal Neurobehavior; Breastfeeding Outcomes

Outcome Measures

Primary Outcomes (1)

• Neonatal rooting, latching, sucking, and swallowing behaviors

  Neonatal feeding behaviors will be scored using the Preterm Infant Breastfeeding Behavior Scale (PIBBS), which has good interrater reliability with full-term neonates as well as pre-term.

  First 4 hours post-delivery

Secondary Outcomes (1)

• Breastfeeding outcome

  Time of hospital discharge (on average, 48 hours post-delivery)

Study Arms (2)

Patients electing to receive intrapartum epidural analgesia

EXPERIMENTAL

Drug: Bolus 10mL 0.25% bupivacaine/ep 1:600,000; infusion 10mL/hour 0.25% bupivacaine and epi 1:800,000; Drug: Bolus 10mL 0.25% bupivacaine/ epinephrine 1:600,000;infusion 10mL/hour 0.25% bupivacaine, 2 mcg/mL fentanyl, and epinephrine 1:800,000; Drug: Bolus 10mL 0.25% bupivacaine, 10mcg/mL fentanyl, and epi 1:600,000; infusion 10mL/hour 0.25% bupivacaine, 2.5 mcg/mL fentanyl, and epi 1:800,000; Drug: Bolus 10mL 0.25% bupivacaine, 5 mcg/mL fentanyl, and epi 1:600,000; infusion 10mL/hour 0.25% bupivacaine, 3.5 mcg/mL fentanyl, and epi 1:800,000

Patients electing not to receive epidural analgesia

NO INTERVENTION

Interventions

Bolus 10mL 0.25% bupivacaine/ep 1:600,000; infusion 10mL/hour 0.25% bupivacaine and epi 1:800,000 DRUG

Patients electing to receive intrapartum epidural analgesia

Bolus 10mL 0.25% bupivacaine/ epinephrine 1:600,000;infusion 10mL/hour 0.25% bupivacaine, 2 mcg/mL fentanyl, and epinephrine 1:800,000 DRUG

Patients electing to receive intrapartum epidural analgesia

Bolus 10mL 0.25% bupivacaine, 10mcg/mL fentanyl, and epi 1:600,000; infusion 10mL/hour 0.25% bupivacaine, 2.5 mcg/mL fentanyl, and epi 1:800,000 DRUG

Patients electing to receive intrapartum epidural analgesia

Bolus 10mL 0.25% bupivacaine, 5 mcg/mL fentanyl, and epi 1:600,000; infusion 10mL/hour 0.25% bupivacaine, 3.5 mcg/mL fentanyl, and epi 1:800,000 DRUG

Patients electing to receive intrapartum epidural analgesia

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Singleton pregnancy
• Maternal age 18+
• Intention to breast-feed at time of hospital admission

You may not qualify if:

• Delivery by Cesarean section
• Neonatal morbidity requiring admission to neonatal intensive care unit

Sponsors & Collaborators

• University Hospitals Cleveland Medical Center: lead

Study Sites (1)

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Location

MeSH Terms

Interventions

Bupivacaine; Epinephrine; Fentanyl

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Ethanolamines; Amino Alcohols; Alcohols; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2011
• First Posted: December 22, 2011
• Study Start: May 1, 2012
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: April 18, 2022

Record last verified: 2012-04

Locations

US (1)