SMFM Papers www.AJOG .

org

The obstetrical and neonatal impact of maternal opioid

detoxification in pregnancy
Robert D. Stewart, MD; David B. Nelson, MD; Emily H. Adhikari, MD; Donald D. McIntire, PhD; Scott W. Roberts, MD;
Jodi S. Dashe, MD; Jeanne S. Sheffield, MD

OBJECTIVE: The purpose of this study was to analyze the obstetric and detoxification at delivery had longer inpatient detoxification admissions
neonatal impact of an opioid detoxification program during pregnancy, (median 25 vs 15 days, P < .001) and were less likely to leave prior to
as well as to examine variables associated with successful opioid completion of the program than women who had relapsed at delivery
detoxification. (9% vs 33%, respectively, P < .001). Infants of mothers who were
successfully detoxified had shorter hospitalizations (median 3 vs
STUDY DESIGN: This is a retrospective cohort study of women electing
22 days, P < .001), lower maximum neonatal abstinence syndrome
inpatient detoxification and subsequently delivering at our hospital
scores (0 vs 8.3, P < .001), and were less likely to be treated for
from Jan. 1, 2006, through Dec. 31, 2011. Detoxification was
withdrawal (10% vs 80%, P < .001).
considered successful if women had no illicit drug supplementation at
the time of delivery. Maternal characteristics were ascertained by chart CONCLUSION: Opiate detoxification in pregnancy requires a significant
review and analyzed for variables associated with success. Obstetric time commitment and extended treatment, however, can be successfully
and neonatal outcomes were also assessed based on maternal suc- achieved in compliant parturients. Importantly, maternal demographics
cess at delivery. and drug histories do not portend success, supporting continued opiate
detoxification being offered to all women expressing intent.
RESULTS: Of the 95 women during the study period with complete
data, 53 (56%) were successful. There were no demographic or social Key words: drug use in pregnancy, methadone detoxification, opioid
risk factors identified associated with success. Women with successful detoxification

Cite this article as: Stewart RD, Nelson DB, Adhikari EH, et al. The obstetrical and neonatal impact of maternal opioid detoxification in pregnancy. Am J Obstet Gynecol
2013;209:267.e1-5.

M aternal opioid use during preg-

nancy is a significant public
health concern with implications for
abstinence syndrome (NAS).2 Further-
more, maternal abuse during pregnancy
places the pregnant woman at an
system irritability, respiratory distress,
and autonomic dysfunction, often re-
quiring several weeks of neonatal opiate
both maternal and fetal health. Accord- increased risk for partaking in high-risk solution.9 Opioid detoxification pro-
ing to the 2010 National Survey on Drug behavior to support her drug addiction, vides an alternative approach in well-
Use and Health, approximately 4.4% of including prostitution, theft, and violence. selected patients who desire decreased
pregnant women were current illicit These behaviors place the woman at risk opioid dosing with resultant decreases in
drug users.1 Opioid abuse in pregnancy for acquiring sexually transmitted dis- neonatal complications.10,11
has been associated with a multitude of eases, for becoming the victim of violence, For many years, our group has offered
adverse outcomes for both the mother as well as legal ramifications.3 pregnant opioid users inpatient hos-
and fetus, including preterm birth, fetal Methadone has been the recom- pitalization with slow taper of their
demise, intrauterine growth restric- mended first-line treatment for pregnant methadone dosage, with the goal of
tion, placental abruption, and neonatal women with opioid addiction since the reducing the likelihood of NAS.10,11 The
1970s, with the goal of reducing adverse main argument against such a strategy
From the Department of Obstetrics and outcomes associated with uncontrolled has been that it might predispose to
Gynecology, University of Texas Southwestern narcotic withdrawal. Because of its relapse, with women going back to illicit
Medical Center, Dallas, TX. long half-life, methadone effectively heroin use.3,7,12 As this is a valid concern
Received March 8, 2013; revised April 23, 2013; suppresses maternal cravings and can when caring for such a high-risk popu-
accepted May 13, 2013. be administered in a controlled setting lation, we sought to determine if certain
The authors report no conflict of interest. once daily. However, infants exposed patient characteristics could be used to
Presented at the 33rd annual meeting of the to methadone are at significant risk for better identify parturients likely to be
Society for Maternal-Fetal Medicine, adverse outcomes including preterm successful with methadone detoxifica-
San Francisco, CA, Feb. 11-16, 2013.
birth, small for gestational age, neonatal tion, or conversely, who might be better
Reprints not available from the authors.
intensive care unit admissions, as well as served by a methadone maintenance
0002-9378/$36.00 NAS.4-9 NAS complicates 60-90% of program. Such information would be
ª 2013 Mosby, Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ajog.2013.05.026 infants exposed to methadone in utero useful for counseling women interested
and is characterized by central nervous in opioid detoxification or maintenance.

SEPTEMBER 2013 American Journal of Obstetrics & Gynecology 267.e1

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M ATERIALS AND M ETHODS women >24 weeks’ gestation. Women Statistical analysis included Pearson
We conducted a retrospective cohort are observed in the hospital for several c2, Student t test, Cochran-Mantel-
study of all pregnant opioid users who days after all medications have been Haenszel c2 for trend, and Wilcoxon
underwent inpatient opioid detoxifica- discontinued. After completion of rank sum. P values < .05 were consid-
tion with methadone from Jan. 1, 2006, detoxification, women are offered ad- ered significant. Analysis was performed
through Dec. 31, 2011, and who subse- mission to an outpatient drug rehabili- using software (SAS 9.2; SAS Institute
quently delivered at our institution. At tation housing facility, however rates of Inc, Cary, NC). This study was approved
our hospital, pregnant women with a maternal acceptance of this program by the institutional review boards of
history of substance use are followed up were unable to be determined. Nurse the University of Texas Southwestern
by a multidisciplinary medical and social practitioners and drug counselors Medical Center and Parkland Hospital.
case management team of physicians, continue to follow up each woman
nurse practitioners, drug counselors, in conjunction with a maternal-fetal R ESULTS
and social workers. As part of this medicine specialist. All women with a During the study period, 95 women
program, inpatient hospitalization and prior or current illicit drug use, regard- delivered at our hospital with maternal
detoxification is offered to all pregnant less if they complete detoxification, elect and neonatal outcomes available for
opioid users as well as women currently methadone maintenance, or continue analysis, of whom 53 (56%) were suc-
enrolled in a methadone maintenance illicit substance use, are followed up cessful. Maternal characteristics were
program. Contraindications to detoxifi- in a dedicated clinic by these same analyzed for variables that were as-
cation include fetal growth restriction, specialists. sociated with successful detoxification.
oligohydramnios, significant maternal For the purposes of this study, suc- Maternal demographic characteristics
psychiatric illness, or a prior unsuccess- cessful detoxification was defined as are presented in Table 1. There were no
ful detoxification attempt. All other no maternal illicit drug supplementa- differences in maternal age, ethnicity, or
pregnant opioid users are offered inpa- tion at the time of delivery. This was nulliparity between those women who
tient detoxification. Prior to making determined by maternal admission of were drug free at the time of delivery as
their decision, women are noncoercively relapse, maternal urine toxicology, or compared to those who tested positive
counseled about potential benefits of fetal meconium toxicology, with any one for illicit drugs. When maternal drug
reducing fetal opioid exposure and about finding determining illicit supplemen- history was analyzed, there was no dif-
the hazards of uncontrolled maternal tation. Women who were actively un- ference in prior maternal substance
opioid use. Regardless of their decision, dergoing detoxification at the time of use. Intravenous opioid use (as opposed
women continue to receive the multi- delivery or on methadone maintenance to intranasal or oral ingestion), total
disciplinary social services offered to all at the time of delivery were considered amount of daily use, and years of use
pregnant women with a history of sub- successful. Women who underwent were not different between the 2 groups.
stance abuse. inpatient detoxification were identified Women with illicit substance use at
Women who elect to undergo detox- by records maintained by our program. delivery were more likely to have a pos-
ification are admitted to the hospital, The medical records were reviewed for itive hepatitis C antibody (64% vs 40%,
and detoxification with methadone is maternal demographics and maternal P ¼ .02) while human immunodefi-
conducted according to a previously drug history, including length of use, ciency virus, syphilis, and hepatitis B
published protocol.10 The initial dose of route of administration, and amount of seropositivity did not differ.
methadone is selected based on reported use. The maternal inpatient record was Methadone detoxification data are
history of use and any signs or symp- reviewed for pertinent data, including presented in Table 2. The median gesta-
toms of opioid withdrawal. Methadone infections such as hepatitis B or C, initial tional age upon admission for detoxifi-
is distributed twice daily with tablets methadone dosage, duration of hospi- cation was 20 weeks, and this did not
crushed in orange juice to blind women talization, and success of detoxification. differ according to success of detoxifi-
as to the dose they receive. Signs and The delivery record was reviewed for cation (P ¼ .80); nor did the maximum
symptoms of withdrawal are typically obstetrical data as well as maternal methadone dosage required, which was
treated by increasing the methadone relapse. All infants received drug testing 40 mg per day in each group (P ¼ .91).
dose by 5-mg increments as needed. If a and were followed up for evidence of The duration of hospitalization to
woman elects to undergo detoxification withdrawal. The newborn record was complete detoxification was significantly
and has previously been on methadone also reviewed for duration of hospitali- longer in those who were successful as
maintenance, her initial dose is started zation, maximum NAS score, and need opposed to those who relapsed. Those
at her maintenance dosage. The dose for opioid treatment for withdrawal women who remained free of opioid use
is then decreased by no more than symptoms. NAS scores were determined at delivery required a median of 25 days
20% every 1-3 days as tolerated, until by physical examination by trained pe- to complete detoxification as opposed
the woman is weaned from all metha- diatric providers according to the Fin- to 15 days in those women who subse-
done. Fetal surveillance is initiated in negan scoring system.4 quently relapsed (P < .001). This is

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related to the number of women who left
the detoxification program prior to TABLE 1
completion, 33% vs 9% in the relapse Selected maternal demographic data and substance abuse history of
group and the success group, respectively women undergoing opioid detoxification
(P ¼ .004). No illicit drug use Illicit drug use
Seventeen women elected to discon- at delivery at delivery
Variable n [ 53 n [ 42 P value
tinue the detoxification component of
the program and receive maintenance Age, y 25.1  5.3 25.9  5.5 .47
therapy. Sixteen of these women were Ethnicity .52
started on methadone maintenance,
Caucasian 24 (45) 21 (50)
and 1 chose buprenorphine. Those on
methadone maintenance received doses African American 4 (8) 1 (2)
ranging from 35e110 mg per day. Of the Hispanic 25 (47) 20 (48)
17 women on maintenance therapy at Nulliparous 14 (25) 13 (31) .63
delivery, 12 (71%) were supplementing
with illicit drugs, including the 1 patient Polysubstance use 19 (36) 19 (45) .35
on buprenorphine maintenance. Two Intravenous use 35 (66) 33 (78) .17
other women left the program prior to Reported use, $/d 50 [30, 80] 50 [30, 85] .96
completion, refused methadone main-
Years of use 4.6  3.9 5.0  5.2 .67
tenance, and were subsequently supple-
menting with illicit drugs at delivery. Incarceration 15 (28) 6 (14) .10
Fetal demise occurred in 3 patients. Tobacco use 42 (79) 36 (86) .41
Two of these occurred in women who Maternal coinfection
did not complete the detoxification pro-
HIV 0 0 NA
gram, refused methadone maintenance,
did not return for prenatal care, and Hepatitis C 21 (40) 27 (64) .02
were found to be using illicit drugs at Hepatitis B 0 1 (2) .26
the time the fetal demise was diagnosed. Syphilis 0 0 NA
One woman successfully completed
Data reported as n (%), mean  SD, median [First Quartile, Third Quartile].
detoxification at 15 weeks’ gestation. At
HIV, human immunodeficiency virus; NA, not applicable.
20 weeks, she developed rupture of
Stewart. Opioid detoxification in pregnancy. Am J Obstet Gynecol 2013.
membranes and subsequently delivered
a previable infant. No stillbirth or fetal
demise occurred among women hospi-
talized for detoxification. There was no mothers who were actively enrolled in at a later gestational age (39 vs 37.8
case in which an emergent delivery the inpatient detoxification program. weeks, P ¼ .008) and had larger birth-
occurred because of nonreassuring fetal The maximum NAS scores of these weights (3065 vs 2788 g, P ¼ .01),
status during antepartum surveillance. 5 neonates ranged from 8e10. Those although preterm birth and fetal growth
One woman had a twin gestation. infants born to mothers who were suc- restriction were not different between
Therefore, 93 infants were available for cessfully off drugs at delivery delivered the groups.
analysis.
The infant outcome data are shown
in Table 3. Infants born to mothers TABLE 2
without illicit supplementation at de- Variables of inpatient detoxification admission compared by illicit
livery had lower maximum NAS scores maternal drug use at delivery
(0 [0, 0] vs 8.3 [6.5, 10], P < .001), had No illicit drug Illicit drug
shorter hospitalizations (3 [2, 6] vs 22 use at delivery use at delivery
[15, 26] days, P < .001), and were less Variable n [ 53 n [ 42 P value
likely to be treated for withdrawal (10% Gestational age at program entry, wk 19.9  8.6 20.4  9.8 .80
vs 80%, P <.001). Five infants who were
Maximum methadone dosage, mg/d 40 [30, 40] 40 [30, 40] .91
born to mothers without illicit drug
use at delivery required treatment for Duration of detoxification, d 25 [17, 38] 15 [5, 21] < .001
neonatal withdrawal; 3 mothers were Left program prior to completion 5 (9) 14 (33) .004
receiving methadone maintenance at Data reported as n (%), mean  SD, median [First Quartile, Third Quartile].
doses of 35 mg, 55 mg, and 60 mg per Stewart. Opioid detoxification in pregnancy. Am J Obstet Gynecol 2013.
day. The other 2 infants were born to

SEPTEMBER 2013 American Journal of Obstetrics & Gynecology 267.e3

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programs during the antepartum period

TABLE 3 also allows for the mother-infant pair to
Infant outcomes of women electing inpatient opioid detoxification continue this rehabilitation program
compared by illicit maternal drug use at delivery into the postpartum period, providing
No illicit drug use Illicit drug use at continued support during this time. A
Variable at delivery, n [ 53 delivery, n [ 40 P value caveat to these benefits of extended
Max NAS score 0 [0, 0] 8.3 [6.5, 10] < .001 detoxification is that the patient must
Infant treated for withdrawal 5 (10) 33 (80) < .001 be motivated and willing to undergo
such an intense therapy and prolonged
Infant hospital duration, d 3 [2, 6] 22 [15, 26] < .001
hospitalization.
Gestational age at delivery 39  1.9 37.8  2.4 .008 Our results also again highlight
34 wk 4 (8) 4 (10) .69 the benefits of successful detoxification,
36 wk 5 (10) 7 (18) .27
namely fewer infants requiring treat-
ment for withdrawal or NAS, and
Birthweight percentile 3065  487 2788  516 .01 shorter infant hospitalizations. The
<10th 7 (13) 12 (30) .05 consequences of NAS include central
<3rd 1 (2) 2 (5) .40 nervous system irritability, tachypnea,
apnea, poor feeding, and failure to
5-min Apgar <4 0 1 (3) .26 thrive. While indices such as preterm
pH <7 0 0 NA birth and low birthweight did not differ
Neonatal death 0 0 NA within our study, we believe that the
benefits of successful detoxification are
Data reported as n (%), mean  SD, median [First Quartile, Third Quartile].
NA, not applicable; NAS, neonatal abstinence syndrome.
evident. Recent studies have focused on
Stewart. Opioid detoxification in pregnancy. Am J Obstet Gynecol 2013.
the severity of NAS in mothers who are
receiving methadone maintenance for
opioid addiction. These studies have
noted that there is no association be-
We further subdivided our cohorts rates of illicit substance use at delivery, tween increasing methadone doses and
into 3 groups: women who completed likely resulting in the higher maximum severity of neonatal withdrawal.5,7,8 Of
detoxification and had no illicit drug NAS scores and the markedly increased note, within these studies the average
use; women on methadone at deliverye percentage of infants requiring treat- doses used in methadone maintenance
either maintenance or undergoing de- ment for withdrawal. ranged 60e100 mg per day, with com-
toxification (no illicit drug use); and Prolonged maternal hospitalization is parisons made between methadone dose
women with illicit drug use at delivery. costly, both monetarily and emotionally, thresholds of 80e100 mg per day. In our
In doing so, there was no longer a sig- however the benefit of incurring these experience, methadone doses are asso-
nificant difference in maternal hepatitis costs is the significant reduction in infant ciated with less neonatal withdrawal,
C antibody status between those who did hospitalization and withdrawal. Previous lower NAS scores, and shorter infant
not resume illicit drug use as compared reports of patient detoxification used hospitalizations, especially in doses of
to those who resumed illicit drug use regimens that were more accelerated <20 mg per day.11 The discrepancy in
(data not shown). All other results than the program used at our institu- methadone dosage makes comparisons
remained the same. tion.12 These programs consisted of between these studies difficult. It may be
structured methadone tapers of either 3 however, that in an attempt to fully
C OMMENT or 7 days. Such rapid tapers would be suppress maternal symptoms, increas-
This study was undertaken to determine expected to have decreased success rates ingly higher doses of methadone main-
maternal factors associated with metha- and more maternal relapse rates, and tenance are well above the dosage
done detoxification success to better when compared to methadone mainte- threshold that is necessary to decrease
define admission criteria for this com- nance, they did. However, our program the rate of neonatal withdrawal.
ponent of our drug use in pregnancy slowly tapers women off of opioids based Our program of methadone detoxifi-
program as well as to improve our on maternal symptoms. The benefit cation had a success rate of 56%, which
counseling. We found that women who of extended detoxification is not only is stable from what we previously have
were not using illicit drugs at delivery that the patient is able to gradually reported.10 By comparison, recent re-
had been hospitalized approximately wean from opioids with minimal with- ports of methadone maintenance during
10 days longer than those who relapsed; drawal symptoms, but they are also able pregnancy have demonstrated compa-
however, their infants were hospitalized to have intense daily counseling and re- rable success rates of 63-82%.5,7,8,12,13
nearly 20 days less. Women who left the sources provided to them. Establishing Success within these previous studies
program prior to completion had higher relationships with drug intervention was variably defined. Similarly, high

267.e4 American Journal of Obstetrics & Gynecology SEPTEMBER 2013

www.AJOG.org SMFM Papers
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SEPTEMBER 2013 American Journal of Obstetrics & Gynecology 267.e5