Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT01497509 |
| Other study ID # |
RCT epidural fentanyl |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 2012 |
| Est. completion date |
November 2012 |
Study information
| Verified date |
April 2012 |
| Source |
University Hospitals Cleveland Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
Description:
NACS scores do not specifically measure feeding behaviors, but rather the five general areas
of adaptive capacity, passive tone, active tone, primary reflexes, and alertness/crying/motor
activity. Conversely, the Preterm Infant Breastfeeding Behavior Scale (PIBBS)specifically
examines neonatal rooting, latching, sucking, and swallowing behaviors as well as general
activity level, thus producing a comprehensive picture of breast-feeding interactions.
Beilin et al. previously performed a randomized, controlled, double-blinded study of
multiparous women who were randomized to receive intrapartum epidural analgesia that
contained, in addition to bupivacaine, either greater than 150 micrograms total fentanyl,
less than 150 micrograms, or zero. This study had several limitations. Breast-feeding
difficulties were not assessed until 24 hours postpartum, long after the neonate would have
been expected to have fully metabolized the drugs. Like most previous studies, Beilin et al.
also did not control for skin-to-skin mother-infant contact. According to a prospective
cohort study of 21,842 mothers in 19 hospitals, the likelihood of exclusive breast-feeding
throughout the hospital stay is positively, significantly correlated with the number of
minutes of skin-to-skin contact during the first three hours postpartum, even after
controlling for intention to breast-feed at the time of hospital admission. Another
randomized, controlled, double-blinded study found no significant differences regarding
breast-feeding initiation or breast-feeding rates at 12 months postpartum among women who
received bupivacaine-only epidural analgesia, combined spinal-epidural analgesia with mean
fentanyl dose 107.3 micrograms, or epidural infusion with mean fentanyl dose 162.8
micrograms. All fentanyl was administered only as part of a continuous infusion and never in
an initial bolus, so the potentially different effects resulting from large loading doses of
fentanyl compared to gradual infusion could not be studied. The authors did not objectively
measure neonatal feeding behavior, relying solely upon maternal interviewing at 24-48 hours
post-delivery, and they studied only nulliparous women.
In a pilot study of 310 mothers who delivered at University Hospitals Case Medical Center
(Cleveland, Ohio) between September 2009 and February 2010, we found that duration of
epidural infusion was significantly correlated with decreased neonatal ability to
successfully latch onto the breast and audibly swallow during the first three hours of life.
All infusions contained identical doses of fentanyl and bupivacaine.
