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Early Human Development 132 (2019) 30–36

Contents lists available at ScienceDirect

Early Human Development


journal homepage: www.elsevier.com/locate/earlhumdev

The effect of labor medications on normal newborn behavior in the first T


hour after birth: A prospective cohort study

Kajsa Brimdyra, , Karin Cadwellb, Ann-Marie Widströmb, Kristin Svenssonb,d, Rayle Phillipsc
a
Healthy Children Project, 327 Quaker Meeting House Road, East Sandwich, MA 02537, USA
b
Karolinska Institutet, Tomtebodavägen 23a, 171 65 Solna, Sweden
c
Loma Linda University, School of Medicine, 11234 Anderson St, Loma Linda, CA 92354, USA
d
Karolinska University Hospital, Eugeniavägen 3, 171 76 Solna, Sweden

A R T I C LE I N FO A B S T R A C T

Keywords: Background: Skin-to-skin contact after birth between mother and baby has immediate and long-term advantages.
Newborn behavior Widström's 9 Stages of Newborn Behavior offer an opportunity to evaluate a baby in the natural, expected and
Skin-to-skin optimal habitat. Intrapartum drugs, including fentanyl administered via epidural and synthetic oxytocin
Labor medications (synOT), have been studied in relation to neonatal outcomes with conflicting results.
Epidural
Aims: Determine the effects of common intrapartum medications on the instinctive behavior of healthy new-
Synthetic oxytocin
Widström's 9 stages
borns during the first hour after birth through a prospective cohort study.
Study design: Video record newly-born term infants during the first hour after birth while in skin-to-skin contact
with mother. Code and analyze videos using Widström's 9 Stages; compare with the labor medications mothers
received.
Subjects: Convenience sample of sixty-three low-income mothers self-selected to labor with or without in-
trapartum analgesia.
Outcome measures: Duration of time infants spend in each of Widström's 9 Stages for four cohorts: 1) exposed to
no synOT or epidural fentanyl during labor, 2) exposed to fentanyl (but not synOT), 3) exposed synOT (but not
fentanyl), 4) exposed to both fentanyl and synOT.
Results: A strong inverse correlation was found between intrapartum exposure to fentanyl and synOT and the
normal behavior of an infant, as measured by time in each Stage.
Conclusions: Intrapartum exposure to the drugs fentanyl and synOT is associated with altered newborn infant
behavior, including suckling, while in skin-to-skin contact with mother during the first hour after birth.
Widström's 9 Stages offer an opportunity to analyze newborn behavior whilst in the optimal habitat of the infant.

1. Introduction continuous, uninterrupted skin-to-skin contact after birth include in-


creased self-regulatory behaviors at 1 year of age [3] as well as possible
Worldwide, only 45% of newborns experience any skin-to-skin epigenetic gene regulation [4] and the establishment of the newborn's
contact with their mother soon after birth [1]. Infants who have been microbiome [5,6].
allowed to have the experience of early skin-to-skin contact with mo- Research shows that when healthy newborns are placed in skin-to-
thers for the first 1–2 h after birth are reported to have immediate skin contact on their mothers' chests immediately after birth, they will
health advantages including more optimal blood glucose levels, better demonstrate instinctive behaviors and, if undisturbed, will crawl to-
respirations, more optimal temperatures, and less crying [1,2]. Failure wards their mothers' breasts and begin to suckle within the first 1–2 h
to experience skin-to-skin contact and early initiation of breastfeeding after birth [7,8]. More specifically, when in skin-to-skin contact with
has been linked to increased infant mortality, with the risk of dying in mother in the first hour after birth, healthy babies go through 9 distinct
the first 28 days after birth increasing 41% for newborns who initiated and measurable stages (Widström) (Table 1, Fig. 1). Knowledge of these
breastfeeding at 2–23 h and increasing 79% for those who initiated stages provides an opportunity to observe the newborn's complex, in-
breastfeeding > 24 h after birth. Long-term advantages of immediate, stinctive behavior in its natural setting. The neonate must coordinate


Corresponding author.
E-mail addresses: kajsa@centerforbreastfeeding.org (K. Brimdyr), karin@centerforbreastfeeding.org (K. Cadwell), Ann-Marie.Widstrom@ki.se (A.-M. Widström),
Kristin.Svensson@ki.se (K. Svensson), RPhillips@llu.edu (R. Phillips).

https://doi.org/10.1016/j.earlhumdev.2019.03.019
Received 13 February 2019; Received in revised form 28 March 2019; Accepted 29 March 2019
0378-3782/ © 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/BY-NC-ND/4.0/).
K. Brimdyr, et al. Early Human Development 132 (2019) 30–36

Table 1 Researchers obtained informed consent from 96 clinically un-


Widström's 9 Stages during skin-to-skin contact immediately after birth. complicated primipara and multipara mothers in 2013: one week each
1. The birth cry is a distinct and specific cry as the baby's lungs expand for the first in May, July, August and December. Inclusion criteria for the study
time. included women who were ≥ 18 years of age, healthy, English or
2. Relaxation is a time immediately after the birth cry ends, when the baby becomes Spanish speaking as their primary language, 37 to 42 weeks pregnant,
still and has no visible movements. and who had planned a vaginal birth. Infants were eligible if they were
3. Awakening begins as the baby opens the eyes for the first time, blinks, has small
mouth movements and limited hand and shoulder motions.
full-term gestation, healthy, and had no known abnormalities. Informed
4. Activity involves larger body movements, including whole arm motions, specific consent materials were available to prospective women in both English
finger movements, shoulder motion, head lifting, and stable open eyes. and Spanish (with a translator for Spanish-only speaking participants).
5. Rest could happen at any point during the first hour, interspersed between stages or Any identifying information was removed from the collected medical
as a transition between stages.
records and given a unique code. This unique code was also linked to
6. Crawling involves the baby moving purposely towards the breast and nipple. It
could be accomplished through sliding, leaping, bobbing, or pushing. the video of the baby that was recorded during the first hour after birth.
7. Familiarization is a stage at the mother's nipple where the baby licks, tastes, touches The observational study did not change any hospital care during
and moves around the nipple and areola area. labor, birth or after birth; no hospital protocols or routines were
8. Suckling involves the baby self attaching to the nipple and initiating breastfeeding. changed by the study except to unobtrusively video record the baby
9. Sleeping is an involuntary activity of the baby around 1.5 to 2 h after birth.
during the first hour after birth while in skin-to-skin contact with the
According to Widström et al., there are 9 stages that babies go through during mother.
the first hour after birth that are innate and instinctive to the baby. Examining a Mothers determined, with their health care providers, if epidural
baby's natural and instinctive behavior during the first hour helps to eliminate anesthesia and/or synOT was to be used during labor. A list of medi-
possible iatrogenic effects the testing itself may create. cations used during labor was collected from the medical records of
study participants after the first hour video was completed.
many different state systems, including autonomic, sensory, motor and
behavioral states, in order to progress smoothly through these 9 Stages 3. Data collection procedures
within the first hour or so after birth. Many prenatal and perinatal
factors, including exposure to intrapartum medications, may affect the After birth, the full-term newborn was immediately placed in skin-
newborn's ability to coordinate and integrate these state systems and to-skin contact with the mother, who was semi-reclined on the hospital
may affect neurobehavioral organization. Research has shown that at- bed; the baby was quickly dried and mother and baby were covered
tenuated neonatal neurobehavioral organization (NNBO) when mea- with a warm blanket. The baby was to remain in skin-to-skin contact
sured soon after birth could be related to the slow initiation of optimal with the mother for at least the first hour after birth unless separation
sucking behavior [9,10]. was medically indicated. The video researcher stood behind the mo-
Although the cumulative effects of intrapartum analgesic medica- ther's head and video recorded the behaviors of the newborn during the
tions on newborns is unknown, research shows that intrapartum an- first hour after birth. Babies who were removed for examination by the
algesic medications have measurable negative outcomes, whether the nurse or by Neonatal Intensive Care Unit (NICU) staff for < 10 min but
mother received the analgesic intravenously or via epidural space [11]. then returned to the mother could remain in the study. Mother-baby
Studies indicate an association of intrapartum analgesia with an in- dyads were excluded from the study if the baby was removed by the
creased need for neonatal resuscitation [12], raised temperature and nurse or by NICU staff for more than10 min. Dyads were also removed
increased crying [13], higher rates of hypotonia and 1-min Apgar from the study if concerns for the fetus required emergency care by the
scores < 7 [14], decreased neurobehavioral scores in the first hours medical staff prior to birth or concerns for health of the mother at any
after birth and in the first month [15], and changes in the morphology point.
of the neonatal brain as measured by MRI [16]. Intrapartum analgesics Education was provided to staff using a professional video [27] and
have also been implicated in the finding of less optimal breastfeeding a workshop given by two research assistants about Widström's 9 Stages
for both initiation and duration [17–23]. Infants of women who re- of Newborn Behavior to ensure staff could recognize each stage. The
ceived > 150 micrograms of epidural fentanyl during labor have been research assistants were blinded to mother's labor medications.
found to have lower neurobehavioral scores after birth [15] and de-
creased breastfeeding duration at 6 weeks postpartum [24]. Other stu- 3.1. Statistical analysis
dies have not found an association between epidural anesthesia and
measurements of breastfeeding outcomes [25,26]. MAXQDA 11.0.2, 2013, a professional qualitative data analysis
The purpose of this observational study was to evaluate the effects software, was used to separately and independently code the video
of intrapartum medications on the instinctive behavior of a healthy recordings for Widström's 9 Stages. Analysis of the video recordings
newborn during the first hour after birth. We hypothesized that in- provided data on achievement of suckling, the final stage reached, and
trapartum narcotic medications and synthetic oxytocin (synOT) would the mean time in each of Widström's 9 Stages. SPSS version 22 was used
affect newborn behavior, as described by Widström's 9 Stages. for statistical analysis. We examined the medical record of each baby
and mother to collect the recorded demographics (i.e. gestational age,
birth weight, one-minute and five-minute Apgar scores, maternal age,
2. Methods gravida and para), as well as administered amounts of any intrapartum
medication including intravenous synOT or epidural fentanyl. For the
Loma Linda University Children's Hospital (LLUCH) is designated as purposes of analysis, the four study cohorts were: 1) mothers who had
a Baby-Friendly™ teaching hospital in Southern California with ap- received no synOT and no fentanyl (the control group), 2) mothers who
proximately 2500 births per year at the time of this study. The hospital received fentanyl without synOT, 3) mothers who received synOT
follows Step 4 of the Baby Friendly Hospital Initiative (BFHI) and without fentanyl, and 4) mothers who received both fentanyl and
routinely provides uninterrupted skin-to-skin contact for all healthy synOT. Descriptive statistics were used in all of the studies for the study
full-term newborns immediately after all vaginal and cesarean births for populations and descriptive variables; the normally distributed results
at least one hour. This study protocol was limited to vaginal births only. were reported with mean and standard deviation (SD), and the re-
The hospital practice includes a consistent formulary for medications maining results were reported with median and (interquartile) range.
used in epidurals, including fentanyl. The study protocol was approved Independent t-tests on the mean time spent in each of Widström's 9
by the Institutional Review Board of LLUCH. Stages, and to provide the standard deviation. A 95% confidence level

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K. Brimdyr, et al. Early Human Development 132 (2019) 30–36

Fig. 1. Visual illustration of the 9 Stages of Newborn Behavior while skin-to-skin during the first hour after birth, photographs copyright Healthy Children Project,
Inc. Used with permission.

was used to test statistical significance, with p < .05 being considered dyads were exposed to synOT without fentanyl, and 4) 25 dyads were
a significant result. ANOVA tests were used to compare the means of the exposed to both fentanyl and synOT. Although self-selected, the mo-
cohort groups, with pair-wise analysis using a Bonferroni correction. thers in the four cohorts did not differ in age (p = .44), number of
Independent t-tests using Levene's Test for Equality of Variances were pregnancies (p = .25) or number of births (p = .57) (Table 1). The
conducted between the control and each cohort group. resulting babies in the four cohorts did not differ in relation to birth
weight (p = .11), gestational age (p = .45), one-minute Apgar score
(p = .64), or five-minute Apgar score (p = .65) (Table 2).
4. Results

Of the 96 mothers consented into the study, 63 remained in the 4.1. The birth cry (stage 1)
study. Six were erroneously consented (five were scheduled for repeat
cesareans; one had a physical abnormality that precluded breast- Babies with no exposure to fentanyl or synOT (control group) had
feeding). Twenty-five mothers were removed from the study when they significantly longer birth cries than babies in all three other cohorts:
became high-risk during labor or during the first hour after birth, for those exposed to fentanyl without synOT (p < .001), those exposed to
reasons which had not been evident at the time of consent, and two synOT without fentanyl (p = .02), and those exposed to both fentanyl
mothers were considered medication outliers (detailed information on and synOT (p = .03). Babies exposed to fentanyl without synOT had
removed dyads are reported elsewhere [23]). Babies who were delayed significantly shorter birth cries than those in all three other cohorts:
in starting skin-to-skin care for < 10 min or removed for < 10 min were those with no exposure to fentanyl or synOT (control group)
included in the research. There was no difference in suckling between (p < .001), those exposed to synOT without fentanyl (p = .04), or
babies that were delayed or removed for < 10 minutes compared to those exposed to both fentanyl and synOT (p = .02).
those who stayed in continuous skin-to-skin contact (p = .53). There were no significant differences between the cohorts in rela-
The 63 low-risk mother-infant dyads were found to fall into four tion to the duration of the next three stages of newborn behaviors,
cohorts: 1) 10 dyads had no exposure to synOT or fentanyl (control Relaxation (Stage 2), Awakening (Stage 3), or Activity (Stage 4)
group), 2) 16 dyads were exposed to fentanyl without synOT, 3) 12 (Table 3).

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K. Brimdyr, et al. Early Human Development 132 (2019) 30–36

Table 2
Maternal-related and infant-related demographic data by cohort.
Characteristics (mean) Control cohort Cohort exposed to fentanyl without Cohort exposed to synOT without Cohort exposed to both fentanyl and
(No exposure to synOT or synOT, n = 16 fentanyl, n = 12 synOT, n = 25
fentanyl), n = 10

Mother
Age (years)a 28.8 (4.4) 26.9 (5.1) 29.2 (6.0) 30.0 (6.5)
Number of pregnanciesa 2.2 (1.3) 2.12 (1.3) 2.58 (1.8) 3.04 (1.6)
Number of birthsa 0.9 (1.0) 0.81 (0.91) 1.25 (1.4) 1.28 (1.3)

Infant
1 Minute Apgarb 8.00 (7,9) 8.0 (8,8) 8.0 (8,8.75) 8.0 (8,9)
5 Minute Apgarb 9.0 (9,9) 9.0 (9,9) 9.0 (9,9) 9.0 (9,9)
Gestational Agea 39.2 (0.7) 39.6 (0.8) 39.867 (1.1) 39.36 (1.3)
Birth Weight (g)a 3260 (417) 3518 (403) 3345 (387) 3203 (407)

a
Mean (SD).
b
Median (25 centile, 75 centile).

4.2. Rest (stage 5) babies exposed to synOT without fentanyl (mean 0.58 ± 0.51)
(p = .01).
Babies in the cohort exposed to synOT without fentanyl spent sig-
nificantly less time resting than the control cohort with no exposure to 4.6. Sleeping (stage 9)
synOT or fentanyl (p = .05), babies exposed to fentanyl without synOT
(p = .04), or babies exposed to fentanyl and synOT (p = .01) cohorts. Only one baby reached the Sleeping Stage, which is not unexpected,
since babies usually fall asleep between 1.5 and 2 h after birth. The one
4.3. Crawling (stage 6) baby was in the control cohort.

Babies in the control cohort were significantly faster at crawling to 4.7. Progress through the stages at one hour
the breast (spent less time crawling to the breast) than those in the
cohort with exposure to fentanyl without synOT (p = .05), synOT Babies exposed to both fentanyl and synOT were significantly less
without exposure to fentanyl (p < .002), or exposure to both fentanyl likely to progress through the stages, with a mean stage of 5.47 ( ± 1.4)
and synOT (p = .04). (ending at Rest/Crawling) than babies with no exposure to fentanyl or
synOT, with a mean stage of 7.10 ( ± 1.7) (p = .03) (ending at
4.4. Familiarization (stage 7) Familiarization/Suckling) or babies exposed to synOT without fentanyl,
with a mean stage of 7.17 ( ± 11) (p = .01) (ending at Familiarization/
Babies in the cohort exposed to both fentanyl and synOT spent Suckling). The final stage for babies exposed to both fentanyl and
significantly less time in the Familiarization Stage than babies in the synOT was not significantly different than those exposed to fentanyl
control cohort (p = .05), the cohort exposed to fentanyl without synOT without synOT with a mean stage of 6.63 ( ± 1.6) (ending at Crawling/
(p < .001) or the cohort exposed to synOT without fentanyl Familiarization).
(p < .001).
4.8. Removed/delayed
4.5. Suckling (stage 8)
Babies in the cohort exposed to both fentanyl and synOT were sig-
Suckling was examined in terms of whether a baby reached the nificantly more likely to have a longer delay time between the birth and
stage, and began suckling, rather than the mean duration of stage, since initiation of skin-to-skin contact or removed from the mother after skin-
many babies did not reach Stage 8. Babies exposed to both fentanyl and to-skin contact had begun. Those exposed to both fentanyl and synOT
synOT were significantly less likely to reach this stage and begin had a mean delay of 4:31.9 ( ± 04:53.3) minutes compared to babies in
suckling (mean 0.16 ± 0.37) than babies in the control cohort with no the control group, which had a mean delay of 1:13.1 ( ± 02:34.2)
exposure to fentanyl or synOT (mean 0.70 ± 0.48) (p < .001), babies (p = .01), exposure to fentanyl without synOT with a mean delay of
exposed to fentanyl without synOT (mean 0.56 ± 0.51) (p < .001) or 1:22.2 ( ± 02:16.2) (p = .02), or exposure to synOT without fentanyl

Table 3
Duration of first 7 stages of Widström's 9 stages, by cohort, mean times (SD).
Control cohort Cohort exposed to fentanyl without Cohort exposed to synOT without Cohort exposed to both fentanyl and
(No exposure to synOT or synOT, n = 16 fentanyl, n = 12 synOT, n = 25
fentanyl), n = 10

Birth cry 00:32.4 ( ± : 44.7) 00:06.8 ( ± : 06.1)a 00:17.6 ( ± : 23.0)a 00:21.1( ± : 28.6)a
Relaxation 1:18.0 ( ± 3:32) 00:41.2 ( ± 1:15.5) 00:06.3 ( ± 0:10.2) 00:37.2 ( ± 1:13)
Awakening 10:45.9 ( ± 6:17.0) 8:19.6 ( ± 5:50.8) 6:46.9 ( ± 4:17.7) 8:01.3 ( ± 06:42.5)
Activity 10:33.6 ( ± 8:15.9) 12:30.0 ( ± 12:48.0) 11:54.4 ( ± 7:01.4) 14:27.5 ( ± 9:51.6)
Rest 17:18.7 ( ± 8:57.6) 14:25.6 ( ± 10:23.9) 10:42.4 ( ± 5:41.5)a 16:52.6 ( ± 11:06.1)
Crawling 00:31.0 ( ± 1:01.1) 1:56.2 ( ± 2:48.9)a 2:38.5 ( ± 2:44.3)a 1:04.9 ( ± 2:05.6)a
Familiarization 4:21.9 ( ± 10:03.6) 6:09.6 ( ± 8:45.7) 10:52.3 ( ± 10:32.9) 1:36.4 ( ± 2:56.7)a

ANOVA tests were used to compare the means of the cohort groups, with pair-wise analysis using a Bonferroni correction. Independent t-tests using Levene's Test for
Equality of Variances were conducted between the control and each cohort group. Key: 4:21.9 means 4 min, 21.9 s.
a
Significant compared to Control Cohort.

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with a mean delay of 1:05.9 ( ± 02:16.5) (p = .02) cohorts. (control cohort) crawled more efficiently than those exposed to either
medication independently or together, with babies who were exposed
5. Discussion to synOT without fentanyl epidural taking the longest time to crawl to
the mother's breast during the Crawling Stage.
Widström et al. first documented the stages of instinctive newborn Babies exposed to synOT without fentanyl also spent significantly
behaviors that newborns go through during the first hour after birth [7] less time resting during the first hour than babies in the other cohorts.
when they are in skin-to-skin contact with their mothers. This was ex- Rest is interspersed with the other stages throughout the first hour.
panded with production of a video illustrating the behaviors [28], a Being awake during rest (awake-rest) plays an important role in con-
video with practical advice for staff on implementing skin-to-skin solidating memories, and it is hypothesized that the periods of awake
contact immediately after birth in order to support the 9 Stages [27], an rest during the first hour after birth, while in skin-to-skin contact with
expanded paper about the 9 Stages [8], and a video for parents about the mother, may consolidate the newborns initial experience with
the 9 Stages [29]. Further projects and papers have focused on specific breastfeeding and self-attachment, aiding in improved breastfeeding
elements of these Stages [21–23,30–32]. The previous papers focused and supporting increased exclusivity of breastfeeding [30].
on the behavioral sequences and highlighted the phenomenon of the 9 Babies who were exposed to both fentanyl and synOT spent the
Stages [8,33] with the proportions of newborns that experience each shortest amount of time in the Familiarization Stage. This stage has
stage, and the time at which each stage was achieved after birth [8,33]. many elements that increase a mother's oxytocin and prolactin levels,
Although these elements are essential in understanding the innate and including licking and nuzzling the mother's nipple, and massaging her
instinctive behaviors of newborns as a whole, this study, which ex- breast. Decreasing this time to a mean of 1:36.4 min (babies exposed to
amines the amount of time spend within each stage, allows us to un- both fentanyl and synOT) compared to 4:21.9 (babies not exposed to
derstand the implications of each stage independently (a long Awa- fentanyl or synOT) (p = .05), 6:09.6 min (babies exposed to fentanyl
kening Stage, for example, would push out the start time of the other but not synOT) (p < .001), or 10:52.3 min (babies exposed to synOT
stages). This also allows the Resting Stage to be analyzed in- but not fentanyl) (p < .001) could have consequences on the post-birth
dependently, since by its definition it is interspersed between the other contractions of the uterus and on the mother's milk supply.
stages. (Fig. 2). Babies exposed to both fentanyl and synOT were significantly more
The babies in the control cohort who were not exposed to epidural likely not to reach the stage of Familiarization by the end of the first
fentanyl or synthetic oxytocin had significantly longer birth cries than hour, reaching on average Stage 5.48, which is the equivalent of Rest/
did babies in either of the other three cohorts. Synthetic oxytocin alone Crawling. Babies in the control cohort (no exposure to fentanyl or
or in conjunction with epidural fentanyl was associated with shorter synOT) reached, on average, Stage 7.1 and the babies exposed to synOT
duration of a baby's initial birth cry with babies exposed to fentanyl without fentanyl reached, on average, Stage 7.17 (Familiarization/
without synOT having the shortest cry. There are many factors during Suckling).
birth that could influence the duration of birth cry, but this association The first hour after birth is a once-in-a-lifetime experience for both
deserves further study. mother and baby. This unique time is often called a “sensitive period”
Babies who had been exposed to both fentanyl and synOT were [34]. High levels of catecholamine during this time aid in attachment
more likely to be delayed in being reunited with their mothers or re- and memory for the newborn [35]. Skin-to-skin contact leads to high
moved from their mother shortly after being place in skin-to-skin con- levels of oxytocin, which aid in attachment, bonding, milk production
tact compared to babies who were not exposed or who were only ex- and milk letdown [30]. Stimulation of mother's nipples by baby's hand
posed to either fentanyl or synOT but not both. This finding adds new movements and by sucking leads to spikes in oxytocin and prolactin,
information to previous studies which found high levels of intrapartum which directly stimulate milk production. Sucking during this time,
epidural fentanyl exposure to be associated with physiologic compro- then, takes on increased importance as an instinctive and innate be-
mise in newborns shortly after birth. havior.
Babies whose mothers were not exposed to either synOT or fentanyl The finding that only 70% of unmedicated newborns self-attached

Fig. 2. The 9 Stages of Newborn Behavior per cohort over the first hour. The four cohorts are 1)control, exposed to no synOT or epidural fentanyl during labor, 2)
exposed to fentanyl (but not synOT) during labor, 3) exposed synOT (but not fentanyl) during labor, 4) exposed to both fentanyl and synOT during labor.

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