Naltrexone Treatment for Pregnant Women With Opioid Use Disorder Compared With Matched Buprenorphine Control Subjects

doi:10.1016/j.clinthera.2019.07.003

Clinical Therapeutics

Volume 41, Issue 9, September 2019, Pages 1681-1689

https://doi.org/10.1016/j.clinthera.2019.07.003 Get rights and content

ABSTRACT

Purpose

The use of the opioid antagonist naltrexone (NTX) for pregnant women with opioid use disorder (OUD) remains understudied. The purpose of this pilot study was to examine pregnancy and neonatal outcomes in a cohort of NTX-treated women.

Methods

This single-center, retrospective cohort study included 6 mother–infant dyads taking NTX compared with 13 taking buprenorphine (BUP) between 2017 and 2019. Maternal demographic characteristics, any unprescribed or illicit opioid use per urine toxicology or provider report during the pregnancy or 6 months’ postdelivery, delivery outcomes, gestational age, birth weight, Apgar scores, neonatal intensive care unit admission, and neonatal abstinence syndrome (NAS) outcomes (NAS diagnosis, pharmacologic treatment, and total hospital length of stay) were compared.

Findings

Maternal and infant demographic characteristics were similar between the 2 groups, with the exception of cigarette smoking in the BUP group being more common (92% vs 33%; P = 0.02). None of the women on NTX versus 23% of the women on BUP had documented opioid misuse (P = 0.52). No infants in the NTX group had a NAS diagnosis versus 92% in the BUP group (P < 0.001). Forty-six percent of the BUP-exposed infants were treated for NAS versus 0% in the NTX group (P < 0.001). NTX-exposed infants had a shorter length of stay (mean [SD], 3.2 [1.6] vs 10.9 [8.2] days; P = 0.008).

Implications

Maintaining women on NTX during pregnancy was associated with favorable outcomes. These results support the need for larger multicenter studies sufficiently powered to detect possible differences between the medications on long-term maternal and child safety and efficacy outcomes.

Introduction

The United States is experiencing an opioid epidemic that has not spared women of childbearing age, with an estimated 5.6 per 1000 women in the United States with opioid use disorder (OUD) during pregnancy.¹ The standard of care for pregnant women with OUD is medication treatment with a long-acting opioid such as methadone (MTD) or buprenorphine (BUP), proven to decrease the risk for overdose, relapse, mortality, pregnancy loss, and preterm birth.2, 3 As rates of OUD in pregnancy continue to rise, so does the incidence of neonatal abstinence syndrome (NAS), now affecting between 5 and 20 per 1000 live births in the United States.1, 4 Infants with NAS are frequently pharmacologically treated with opioids for withdrawal, with an average hospitalization of 22 days.¹

Numerous studies have compared the 2 standard-of-care treatments for pregnant women with OUD: MTD and BUP. A systematic review and meta-analysis concluded that BUP was associated with lower risk of preterm birth, greater birth weight, larger head circumference, and less severe NAS compared with MTD.⁵ Women treated with BUP also have improved compliance with prenatal care and less unprescribed substance misuse during the pregnancy compared with MTD-treated women.⁶

In nonpregnant patients, naltrexone (NTX) is one of the three standard treatments for OUD.⁷ NTX is a pure opioid antagonist with high affinity for the mu-opioid receptor. NTX is available in an oral formulation as well as an extended-release injectable formulation,∗ which was approved to treat OUD in the United States in 2010. Currently, NTX is used by 11% of young adults with OUD, with a large increase in the past 5 years.⁸ NTX blocks the euphoric effects of opioid agonists, is devoid of abuse potential and tolerance, and has a modest adverse effect profile.⁹ It has been tested in randomized controlled trials outside of the United States, showing opioid abstinence efficacy with no reported significant adverse events.¹⁰ In addition, it is reportedly particularly helpful in select populations who are highly motivated to end their dependencies (eg, inmates).¹¹ The mortality rate associated with NTX is similar to that of MTD and BUP.10, 12 In recent years, the idea of using NTX to treat pregnant women with OUD has been proposed.¹³ As NTX is becoming an increasingly common treatment for OUD, this will likely lead to more women becoming pregnant while taking NTX. Thus, there is a critical need for maternal, fetal, and infant safety and efficacy data to inform clinicians on how to best manage these pregnancies.

Animal research with exposures 50 to 200 times the human therapeutic doses of NTX have been shown to not alter pregnancy outcomes, maternal health, or increase the rate of congenital malformations.14, 15 At doses 100 times the human dose, animal studies have shown a relation between NTX exposure and increased prenatal growth, altered pain responses, and neurobehavior.16, 17 There are limited human data on the use of NTX in pregnancy. For the oral formulations, no adverse fetal or neonatal effects have been reported.¹⁸ Previous case series with use of an NTX implant in pregnancy showed normal birth outcomes.19, 20 These preliminary reports have shown similar gestational ages and birth weights in these NTX pregnancies compared with BUP, as well as rates of NAS that are <10% with shorter lengths of hospital stay (LOS).20, 21 Birth growth parameters in a cohort of infants on NTX were larger than those who were MTD exposed.²¹

Current gaps in research include knowledge regarding the relative safety and efficacy of NTX in pregnant women, impact on maternal abstinence from unprescribed opioids throughout the pregnancy and postpartum period, and impact on the range of neonatal and childhood outcomes.

The purpose of the current study was to examine pregnancy and neonatal outcomes in a cohort of NTX-treated women. Maternal demographic characteristics and OUD history, misuse of opioids, delivery outcomes, gestational age, birth weight, Apgar scores, neonatal intensive care unit admission, and NAS outcomes were compared with a cohort treated with BUP.

This was a retrospective cohort study comparing pregnant women with OUD treated at a single academic center with NTX versus women treated with BUP. BUP was chosen for the control group due to lower addiction severity compared with MTD and similar demographic attributes as women on NTX presenting for care at our institution.5, 22 NTX pregnancies between January 1, 2017, and December 31, 2018, were identified with the use of our clinic patient lists and the Boston University Medical Campus Clinical Data Warehouse. Women who were initiated on NTX prepregnancy or in the first trimester were considered for inclusion. Pregnant women on BUP were identified based on our patient lists, matched according to month of delivery in the NTX cohort. If multiple infants were born exposed to BUP in a given month, the infant with the first birth date in that month was selected. We elected to match according to month of delivery to eliminate any potential confounding that might arise from temporal trends in treatment and outcomes. Both groups had to have care at our center for the pregnancy, delivery, and immediate postpartum period. Exclusion criteria included women who were on NTX for the treatment of alcohol use disorder.

Boston Medical Center is a tertiary care urban safety net medical center with an integrated addiction and prenatal care program called Project RESPECT (Recovery, Empowerment, Social Services, Prenatal care, Education, Community and Treatment). For pregnant women receiving BUP, women were instructed to take the sublingual medication every 12–24 hours. The mean dose at delivery of BUP was 12.4 mg (95% CI, 10.9–13.9) per day. From January 2017 to June 2018, the BUP mono-product^† was used, then starting in July 2018, all women transitioned to the combination BUP/naloxone^‡ product due to a change in clinic protocol. During labor, all women are offered regional anesthesia with an epidural for labor pain. Postpartum pain control regimens for vaginal deliveries include nonsteroidal anti-inflammatory agents (NSAIDs) and nonpharmacologic interventions. After a cesarean section (C-section), pain regimens include the scheduled IV NSAID ketorolac for 72 hours followed by the scheduled oral NSAID ibuprofen, short-acting oral opioid hydromorphone as needed, and nonpharmacologic interventions.

The Boston Medical Center NTX treatment algorithm is provided in the Figure 1. Women who become pregnant while receiving NTX are referred to Project RESPECT for consultation. After consent for treatment by the Project RESPECT team, the patient continues on extended-release NTX 380 mg every 28 days by intramuscular gluteal injection or oral NTX 50–100 mg daily. Women are transitioned from extended-release NTX to oral NTX starting at 35–37 weeks' gestational age and continued on this regimen until admission for labor or discontinued 24 hours before the scheduled C-section. Intrapartum, there is a patient-directed pain management plan with epidurals (offered per routine), IV opioids, and nitrous oxide. Women may request avoidance of opioids if desired. For vaginal deliveries, women re-start NTX at 48 hours’ postdelivery. For C-sections, re-starting of NTX is delayed until postoperative pain is controlled on NSAID medications alone.

Boston Medical Center practices a rooming-in model of care in which infants remain with their mothers on the postpartum unit until maternal discharge. The infant is then transferred to the inpatient pediatric unit for continued monitoring and NAS treatment where rooming-in is encouraged. Infants are assessed with the Eat-Sleep-Console NAS Assessment tool using a standardized NAS treatment algorithm with MTD as first-line pharmacologic treatment.²³ A NAS diagnosis was made via chart abstraction with documented signs and symptoms of opioid withdrawal by clinicians, with correlating positive opioid urine or meconium toxicology screen in the infant, and/or urine toxicology screen in the mother. Mothers were encouraged to breastfeed if they were enrolled in Project RESPECT, had attended adequate prenatal care visits (defined as attending at least 50% of recommended visits, and being seen at least twice in the 2 months before delivery), and had no illicit or unprescribed drug use close to the time of delivery assessed by urine toxicology testing.

The Project RESPECT policy is for all women to receive urine toxicology testing at each prenatal encounter and upon admission to the labor and delivery unit. The urine screening panel includes amphetamines, barbiturates, benzodiazepines, cocaine, and opiates. Confirmatory toxicology testing is sent for any positive screen, in addition to an expanded opioid panel (MTD, BUP, oxycodone, and fentanyl). Urine and meconium toxicology screening is sent from the infant after delivery. The meconium toxicology panel includes phencyclidine, cocaine, benzodiazepines, barbiturates, amphetamines, MTD, BUP, and opiates.

This study was approved by the Boston University Medical Campus Institutional Review Board. Prenatal characteristics were collected on all mothers, including demographic characteristics (maternal age, race, health insurance, and prenatal care visits), co-exposures (psychiatric medications and hepatitis C), nicotine use (defined as any amount of nicotine smoking documented in the medical record in the third trimester), OUD history (type of opioid and years of dependence), psychiatric comorbidities, any unprescribed or illicit drug use during the pregnancy or 6 months’ postdelivery (via urine toxicology or documented provider report), delivery type (vaginal/C-section), maternal LOS, congenital anomalies (by chart review), and gestational age at delivery. For the infants, Apgar scores, birth growth parameters (birth weight and head circumference), any medical diagnoses, neonatal intensive care unit admission, any breastfeeding (defined as any amount of breast milk consumed by the infant during the hospitalization), NAS outcomes (diagnosis of NAS [yes/no] defined as documented signs of opioid withdrawal requiring inpatient monitoring for 5–7 days with correlating opioid-positive toxicology screening, receipt of any pharmacologic treatment for NAS [yes/no], and total infant LOS in days), and infant discharge destination (parental custody vs nonparental custody). Data were hand-abstracted from the electronic medical record and entered into an electronic Excel database (Microsoft Corporation, Redmond, Washington).

Maternal and infant outcomes were compared between the NTX and BUP cohorts by using bivariate analyses. Two-sample t tests were used to determine differences in means of continuous measures between the NTX and BUP groups. Due to the small sample size, comparisons of categorical measures between the 2 groups were assessed by using Fisher’s exact test. Mean differences and odds ratios (ORs) were calculated by using BUP as the reference group. The sample size was insufficient for any regression modeling. All statistical analyses were performed by using SAS version 9.4 (SAS Institute, Inc, Cary, North Carolina).

Section snippets

Results

A total of 217 charts were considered for inclusion. There were 113 dyads excluded due to MTD treatment. A total of 12 NTX-maintained pregnancies were identified, of which 6 were excluded due to a primary indication of alcohol use disorder. For the remaining 6 NTX-treated patients, 3 of the women were on oral NTX and 3 were on extended-release NTX. The 92 BUP dyads were matched by infant date of delivery to yield a total of 13 control BUP dyads.

Maternal characteristics are shown in Table I. The

Discussion

We identified preliminary evidence that pregnancy and neonatal outcomes were comparable between BUP- and NTX-maintained pregnancies for women with OUD. None of the women treated with NTX had any documented misuse of opioids, and none of the infants developed signs of opioid withdrawal, resulting in significantly shorter infant LOS compared with BUP. If proven to be safe and efficacious across an array of maternal and infant outcomes, NTX continuation during pregnancy represents a novel

Conclusions

NTX pregnancy and neonatal outcomes do not seem worse than BUP treatment. Thus, it is a promising treatment option for pregnant women with OUD who are already receiving it prepregnancy. Further studies are necessary to evaluate the full range of outcomes for both the mother and infant, including relative safety, efficacy, and long-term outcomes.

Conflicts of Interest

The authors have indicated that they have no other conflicts of interest regarding the content of this article.

Acknowledgments

This work was supported by the National Institutes of Health (Eunice Kennedy Shriver National Institute of Child Health and Human Development) grant 1R01HD096798-01.

Drs. Wachman and Miller drafted the first draft of the manuscript; Dr. Wachman, Dr. Saia, Dr. Carter, Ms. Shrestha, and Dr. Jones helped to conceptualize the idea for the manuscript and plan the data collection; Dr. Valle and Ms. Shrestha helped to design and perform the data collection; and Drs. Miller and Werler planned and

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Cited by (24)

Guideline No. 443b: Opioid Use Throughout Women's Lifespan: Opioid Use in Pregnancy and Breastfeeding
2023, Journal of Obstetrics and Gynaecology Canada
To provide health care providers the best evidence on opioid use and women’s health. Areas of focus include pregnancy and postpartum care.
The target population includes all women currently using or contemplating using opioids.
Open, evidence-informed dialogue about opioid use will improve patient care.
Exploring opioid use through a trauma-informed approach provides the health care provider and patient with an opportunity to build a strong, collaborative, and therapeutic alliance. This alliance empowers women to make informed choices about their own care. It also allows for the diagnosis and possible treatment of opioid use disorders. Opioid use should not be stigmatized, as stigma leads to poor “partnered care” (i.e., the partnership between the patient and care provider). Health care providers need to understand the effect opioids can have on pregnant women and support them to make knowledgeable decisions about their health.
A literature search was designed and carried out in PubMed and the Cochrane Library databases from August 2018 until March 2023 using following MeSH terms and keywords (and variants): opioids, opioid agonist therapy, illicit drugs, fertility, pregnancy, fetal development, neonatal abstinence syndrome, and breastfeeding.
The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations).
All health care providers who care for pregnant and/or post-partum women and their newborns.
Opioid use during pregnancy often co-occurs with mental health issues and is associated with adverse maternal, fetal, and neonatal outcomes; treatment of opioid use disorder with agonist therapy for pregnant women can be safe during pregnancy where the risks outnumber the benefits.
- 1.
  Opioids are highly addictive and often prescribed for pain relief and overprescribing has contributed to the opioid epidemic in Canada (high).
- 2.
  Opioids should only be prescribed when absolutely necessary, in the lowest effective dose, and for the shortest duration necessary (high).
- 3.
  Pregnant women who use illicit opioids are at increased risk of sexually transmitted infections, being victims of and/or participating in violence and other illegal activity, concurrent mental health disorders, polysubstance use, poor nutrition, and reliance on social assistance (moderate).
- 4.
  During pregnancy, a woman’s physiological changes can affect the pharmacokinetic properties of exogenous opioids (moderate).
- 5.
  Prenatal opioid exposure has been associated with preterm birth, an infant small for gestational age, and decreased fetal heart rate, although more data are needed (low/moderate); prenatal opioid exposure can cause neonatal opioid withdrawal (high).
- 6.
  Women undergoing opioid agonist therapy may require higher doses of short-acting opioids for analgesia and, in some cases, high-affinity opioids for intrapartum and postpartum pain management (high).
- 7.
  Opioids can be safely used for pain control in labour for women on opioid agonist therapy; however, higher doses may be required in these women compared to women who are opioid-naive (moderate).
- 8.
  Use of opioid antagonists (naltrexone and naloxone) for pregnant women with opioid use disorder remains understudied, and there are gaps in knowledge concerning the safety and efficacy for use during pregnancy (very low).
- 9.
  To help pregnant women transition from injectable opioid agonist therapy or illicit opioid use to oral opioid agonist therapy in the antepartum period, methadone or slow-release oral morphine may be preferable to buprenorphine/naloxone, as these options do not require a period of opioid abstinence before beginning therapy (moderate).
- 1.
  Health care providers should only prescribe opioids when other evidence-based medical and psychosocial therapies have failed (strong, high).
- 2.
  When interpreting antepartum and intrapartum non-stress tests and fetal heart surveillance, health care providers should consider the suppression of fetal heart rate due to opioids and reduced variability and accelerations in fetal heart rate at the opioid’s biological peak (strong, moderate).
- 3.
  Health care providers should recommend against using non-prescribed opioids, illicit opioids, or other non-prescribed substances while breastfeeding (strong, moderate), but women receiving stable doses of opioid agonist therapy or opioids for chronic pain should be supported to breastfeed (strong, moderate).
- 4.
  Health care providers must have a conversation with their pregnant patients concerning the risks and benefits of prescribed opioids for chronic pain, to weigh the likelihood of increased pain when reducing or stopping medication against potential adverse effects on the pregnancy from continuing therapeutic doses of pain medication (strong, high).
- 5.
  Health care providers should titrate opioid treatment for chronic, non-cancer pain management in pregnant women to the lowest effective dose, with the understanding that the dose may need to be increased because of the metabolic changes caused by pregnancy (strong, high).
- 6.
  Delivery should take place in a centre that can provide monitoring for neonatal withdrawal and infants exposed to opiates during pregnancy should be observed carefully during the neonatal period(strong, high).
- 7.
  Health care providers should offer nicotine replacement therapy to pregnant patients with concurrent nicotine and opioid use, in conjunction with a discussion of risks and benefits, in settings where access to tobacco or cigarettes is limited (i.e. in hospital during the intrapartum and postpartum periods) as a way to reduce pain sensitivity (strong, low).
- 8.
  Health care providers should recommend epidural analgesia early in labour for women with opioid use disorder, as this may mitigate the hyperalgesia caused by chronic opioid use (strong, moderate).
- 9.
  Health care providers should conduct universal screening for substance use and opioid use disorder in pregnant patients, with their consent, using evidence-based screening tools (strong, moderate).
- 10.
  Pregnant patients with opioid use disorder should be referred to integrated care programs, when these are available and accessible (strong, moderate).
- 11.
  Obstetrical care providers should not attempt to taper the opioid dose or to detoxify (taper completely) in women with opioid use disorder during pregnancy (strong, high). However, following a discussion of the obstetrical and fetal risks of tapering or detoxification, the patient may make an informed decision to undergo this process. In this case, the opioid dose should be slowly tapered to the lowest effective dose (strong, low).
- 12.
  Health care providers should recommend treatment with opioid agonist therapy for pregnant women with opioid use disorder, initiating treatment at the lowest effective dose and increase the dose as the pregnancy progresses because of the physiological and metabolic changes associated with pregnancy (strong, high).
- 13.
  Obstetrical care providers should consider dose increases and split doses of methadone or buprenorphine for opioid use disorder to prevent withdrawal and relapse during pregnancy because of the increase in metabolism of opioids as pregnancy progresses (strong, high).
- 14.
  Women receiving stable doses of opioid agonist therapy may need their dose increased as the pregnancy progresses because of the physiological and metabolic changes during pregnancy (strong, high).
- 15.
  Health care providers can safely recommend buprenorphine/naloxone in pregnancy based on current data. Consequently, switching patients to a buprenorphine-only product is not necessary (strong, high).
- 16.
  Health care providers should screen pregnant women with opioid use disorder or a history of intravenous drug use for hepatitis C, hepatitis B, syphilis, and HIV (strong, moderate). They should also consider collecting (or having the patient collect) vaginal swabs to test for chlamydia and gonorrhea (strong, moderate).
- 17.
  For women with ongoing risk factors for hepatitis B, health care providers should offer hepatitis B vaccine on an accelerated schedule to pregnant women who are not immune to hepatitis B infection (strong, high).
- 18.
  Although there is a paucity of research on naloxone rescue medication in pregnancy, naloxone should be administered by any trained bystander or medical professional for resuscitation if opioid overdose is suspected in a pregnant patient, as preventing the mother’s death from opioid overdose is the top priority (strong, low).
Directive clinique n<sup>o</sup> 443b: Opioïdes aux différentes étapes de la vie des femmes: Grossesse et allaitement
2023, Journal of Obstetrics and Gynaecology Canada
Présenter aux professionnels de la santé les données probantes concernant l’utilisation des opioïdes et la santé des femmes. Les domaines d’intérêt sont la grossesse et les soins post-partum.
Toutes les femmes qui utilisent des opioïdes.
Un dialogue ouvert et éclairé sur l’utilisation des opioïdes améliorera les soins aux patientes.
L’exploration de l’utilisation d’opioïdes par une approche tenant compte des traumatismes antérieurs donne au professionnel de la santé et à la patiente l’occasion de bâtir une alliance solide, collaborative et thérapeutique. Cette alliance permet aux femmes de faire des choix éclairés. Elle favorise le diagnostic et le traitement possible du trouble lié à l’utilisation d’opioïdes. L’utilisation ne doit pas être stigmatisée, puisque la stigmatisation affaiblit le partenariat (le partenariat entre patiente et professionnel de la santé). Les professionnels de la santé ceus-ci doivent comprendre l’effet potentiel des opioïdes sur la santé les femmes enceintes et les aider à prendre des décisions éclairées sur leur santé.
Une recherche a été conçue puis effectuée dans les bases de données PubMed et Cochrane Library pour la période d’août 2018 à mars 2023 des termes MeSH et mots clés suivants (et variantes) : opioids, opioid agonist therapy, illicit drugs, fertility, pregnancy, fetal development, neonatal abstinence syndrome et breastfeeding.
Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Voir l’annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l’interprétation des recommandations fortes et conditionnelles [faibles]).
Tous les professionnels de la santé qui prodiguent des soins aux femmes et aux nouveaux-nés.
La consommation d'opioïdes pendant la grossesse coïncide souvent avec des problèmes de santé mentale et est associée à des conséquences néfastes pour la mère, le fœtus et le nouveau-né ; le traitement des troubles liés à la consommation d'opioïdes par agonistes peut être sûr pendant la grossesse lorsque les risques sont plus nombreux que les avantages.
- 1.
  Les opioïdes créent une forte dépendance et sont souvent prescrits pour soulager la douleur. Leur prescription excessive a contribué à l'épidémie d'opioïdes au Canada (élevée).
- 2.
  Les opioïdes ne doivent être prescrits qu'en cas d'absolue nécessité, à la dose efficace la plus faible et pour la durée la plus courte possible (élevée).
- 3.
  Les femmes enceintes qui utilisent des opioïdes illicites sont plus à risque de contracter une infection transmissible sexuellement, d’être victimes de violence, de poser des gestes violents ou de s’adonner à des activités illégales, de présenter un trouble de santé mental concomitant, de consommer plusieurs substances, d’avoir une mauvaise alimentation et de dépendre de l’aide sociale (moyenne).
- 4.
  Les changements physiologiques de la grossesse peuvent altérer les propriétés pharmacocinétiques des opioïdes exogènes (moyenne).
- 5.
  L’exposition prénatale aux opioïdes a été associée à la naissance avant terme, au nourrisson petit pour l’âge gestationnel et à une diminution de la fréquence cardiaque fœtale, mais il faut recueillir davantage de données (faible/moyenne); l’exposition prénatale aux opioïdes peut entraîner un syndrome de sevrage néonatal des opioïdes (élevée).
- 6.
  Les femmes qui suivent un traitement par agonistes opioïdes peuvent avoir besoin de plus fortes doses d’opioïdes à courte durée d’action pour l’analgésie et, dans certains cas, d’opioïdes à haute affinité pour les récepteurs opioïdes pour le traitement de la douleur per partum et post-partum (élevée).
- 7.
  Les opioïdes peuvent être utilisés en toute sécurité pour soulager la douleur pendant le travail chez les femmes qui suivent un traitement par agonistes opioïdes, mais il pourrait être nécessaire de leur administrer une dose plus forte que chez les femmes naïves aux opioïdes (moyenne).
- 8.
  L’utilisation d’antagonistes opioïdes (naltrexone et naloxone) chez les femmes enceintes présentant un trouble lié à l’utilisation d’opioïdes reste peu étudiée; par conséquent on accuse un manque de données sur l’innocuité et l’efficacité des antagonistes opioïdes chez les femmes enceintes (très faible).
- 9.
  Aider les femmes enceintes à passer d'un traitement par agonistes opioïdes injectables ou d'une consommation d'opioïdes illicites à un traitement par agonistes opioïdes oraux pendant la période ante partum, la méthadone ou la morphine orale à libération lente peuvent être préférables à la buprénorphine-naloxone, car ces options ne nécessitent pas une période de sevrage d’opioïdes avant le début du traitement (moyenne).
- 1.
  Les professionnels de la santé ne devraient prescrire des opioïdes que lorsque d'autres thérapies médicales et psychosociales fondées sur des données probantes ont échoué (forte, élevée).
- 2.
  À l’interprétation des résultats de l’examen de réactivité fœtale ante partum ou per partum et de la surveillance de la fréquence cardiaque fœtale, le professionnels de la santé doit prendre en compte le ralentissement de la fréquence cardiaque fœtale causé par les opioïdes ainsi que la diminution de la variabilité et des accélérations au pic d’action biologique de l’opioïde (forte, moyenne).
- 3.
  Les professionnels de la santé devraient recommander de ne pas utiliser d'opioïdes non prescrits, d'opioïdes illicites ou d'autres substances non prescrites pendant l'allaitement (forte, moyenne), mais les femmes recevant des doses stables d'agonistes opioïdes ou d'opioïdes pour la douleur chronique devraient être encouragées à allaiter (forte, moyenne).
- 4.
  Les professionnels de la santé doivent discuter avec leurs patientes enceintes des risques et des avantages des opioïdes prescrits pour traiter les douleurs chroniques, afin de mettre en balance la probabilité d'une augmentation de la douleur en cas de réduction ou d'arrêt de la médication et les effets indésirables potentiels sur la grossesse de la poursuite des doses thérapeutiques d'analgésiques (forte, élevée).
- 5.
  Les professionnels de la santé doivent titrer le traitement opioïde pour la gestion de la douleur chronique non cancéreuse chez les femmes enceintes à la dose efficace la plus faible, en sachant que la dose peut devoir être augmentée en raison des changements métaboliques causés par la grossesse (forte, élevée).
- 6.
  L'accouchement doit avoir lieu dans un centre qui peut assurer le suivi du sevrage néonatal et les nourrissons exposés aux opiacés pendant la grossesse doivent être observés attentivement pendant la période néonatale (forte, élevée).
- 7.
  Les professionnels de la santé doivent proposer une thérapie de remplacement de la nicotine aux patientes enceintes qui consomment simultanément de la nicotine et des opioïdes, tout en discutant des risques et des avantages, dans des contextes où l'accès au tabac ou aux cigarettes est limité (c'est-à-dire à l'hôpital pendant les périodes intrapartum et postpartum), comme moyen de réduire la sensibilité à la douleur (forte, faible).
- 8.
  Les professionnels de la santé devraient recommander une analgésie péridurale au début du travail pour les femmes souffrant d'un trouble lié à l'utilisation d'opioïdes, car cela peut atténuer l'hyperalgésie causée par l'utilisation chronique d'opioïdes (forte, moyenne).
- 9.
  Les professionnels de la santé devraient procéder à un dépistage universel de la consommation de substances et des troubles liés à l'utilisation d'opioïdes chez les patientes enceintes, avec leur consentement, en utilisant des outils de dépistage fondés sur des données probantes (forte, moyenne).
- 10.
  Les patientes enceintes souffrant de troubles liés à la consommation d'opioïdes devraient être orientées vers des programmes de soins intégrés, lorsque ceux-ci sont disponibles et accessibles (forte, moyenne).
- 11.
  Les professionnels de l’obstétricaux ne devraient pas tenter de diminuer la dose d'opioïdes ou de procéder à une désintoxication (diminution complète) chez les femmes souffrant d'un trouble lié à l'utilisation d'opioïdes pendant la grossesse (forte, élevée). Cependant, après une discussion sur les risques obstétriques et fœtaux de la réduction progressive ou de la désintoxication, la patiente peut décider en connaissance de cause de se soumettre à ce processus. Dans ce cas, la dose d'opioïdes doit être réduite lentement jusqu'à la dose efficace la plus faible (forte, faible).
- 12.
  Les professionnels de la santé doivent recommander un traitement par agoniste opioïde aux femmes enceintes souffrant d'un trouble de la consommation d'opioïdes, en commençant le traitement par la dose efficace la plus faible et en augmentant la dose au fur et à mesure de l'évolution de la grossesse, en raison des changements physiologiques et métaboliques associés à la grossesse (forte, élevée).
- 13.
  Les professionnels de l’obstétrique doivent envisager d'augmenter les doses et de fractionner les doses de méthadone ou de buprénorphine pour le traitement des troubles liés à l'utilisation d'opioïdes afin de prévenir le sevrage et la rechute pendant la grossesse, en raison de l'augmentation du métabolisme des opioïdes au fur et à mesure que la grossesse progresse (forte, élevée).
- 14.
  Les femmes recevant des doses stables d'agonistes opioïdes peuvent avoir besoin d'une augmentation de leur dose au fur et à mesure de la grossesse en raison des changements physiologiques et métaboliques survenant pendant la grosse (forte, élevée).
- 15.
  Les professionnels de la santé peuvent recommander et prescrire en toute sécurité la buprénorphine-naloxone pendant la grossesse d’après les données actuelles. Par conséquent, il n’est pas nécessaire de faire passer les patientes à un produit à base de buprénorphine seule (forte, élevée).
- 16.
  Les professionnels de la santé doit dépister l’hépatite C, l’hépatite B et le VIH chez les femmes enceintes présentant un trouble lié à l’utilisation d’opioïdes (forte, moyenne). Il doit aussi envisager les prélèvements vaginaux (ou l’autoprélèvement par la patiente) pour dépister la chlamydia et la gonorrhée (forte, moyenne).
- 17.
  Les professionnels de la santé doit offrir le vaccin contre l’hépatite B selon un calendrier accéléré aux femmes enceintes non immunisées qui présentent des facteurs de risque continus pour l’hépatite B (forte, élevée).
- 18.
  Bien qu’on accuse un manque de recherches sur le recours à la naloxone pendant la grossesse, la naloxone doit être administrée par tout témoin formé ou tout professionnel de la santé à des fins de réanimation si une surdose d’opioïdes est soupçonnée chez une patiente enceinte, car la prévention du décès maternel par surdose est la priorité absolue (forte, faible).
Opioids and Opioid Use Disorder in Pregnancy
2023, Obstetrics and Gynecology Clinics of North America
Integrated Review of the Assessment of Newborns With Neonatal Abstinence Syndrome
2021, JOGNN - Journal of Obstetric, Gynecologic, and Neonatal Nursing
Citation Excerpt :
After final assessment of eligible full-text articles, 31 were included in our review (see Supplemental Tables S1–S4). Of the identified studies, 28 were conducted in the United States, including Connecticut (Grossman et al., 2017, 2018); Kentucky and Pennsylvania (Gomez-Pomar et al., 2017); Maine (Heller et al., 2017); Maine and Massachusetts (Wachman et al., 2015); Maryland (Liu et al., 2016); Massachusetts (Allocco et al., 2016; Timpson et al., 2018; Wachman et al., 2013, 2019; Wachman, Grossman, et al., 2018; Wachman et al., 2018); New Hampshire (Holmes et al., 2016); New Mexico (Achilles & Castaneda-Lovato, 2019); New York (Levran et al., 2014); North Carolina (Blount et al., 2019; Dodds et al., 2019); Ohio (Hall et al., 2015; Wiles et al., 2015); Pennsylvania (Kraft et al., 2017; Lemon et al., 2018; Moore et al., 2018; Ng et al., 2015; Oji-Mmuo et al., 2016); Texas (Tolia et al., 2018); Washington (Parlaman et al., 2019); and seven sites combined into three categories: U.S. urban areas, U.S. rural areas, and Europe (Jones et al., 2016). One study was conducted in Canada (Chisamore et al., 2016), one in Germany (Schubach et al., 2016), and one in Iran (Fanaei et al., 2020).
To critically review and summarize current knowledge regarding the assessment of newborns with neonatal abstinence syndrome (NAS).
We searched the following databases for articles on the assessment of newborns with NAS that were published in English between January 2014 and June 2020: PubMed, CINAHL, and PsycINFO. Keywords and Medical Subject Heading terms used to identify relevant research articles included neonatal abstinence syndrome; Finnegan Scale; eat, sleep, console; epigenetics; genetics; pharmacokinetics; and measurement. We independently reviewed articles for inclusion.
We retrieved 435 articles through database searches and 17 through manual reference searches; 31 articles are included in the final review. Excluded articles were duplicates, not relevant to NAS, qualitative studies, and/or of low quality.
We used the methodology of Whittemore and Knafl to guide this integrative review. We extracted and organized data under the following headings: author, year and country, purpose, study design, participants, measurement, biomarker (if applicable), results, limitations, recommendations, and intervention.
The Finnegan Neonatal Abstinence Scale is the most widely used instrument to measure symptoms of NAS in newborns, although it is very subjective. Recently, there has been a transition from the Finnegan Neonatal Abstinence Scale to the eat, sleep, console method, which consists of structured assessment and intervention and has been shown to decrease length of hospital stay and total opioid treatment dose. Researchers examined biomarkers of NAS, including genetic markers and autonomic nervous system responses, on the variation in incidence and differential severity of NAS. In the included articles, women with opioid use disorder who were treated with naltrexone during pregnancy gave birth to newborns without NAS diagnoses. However, most women who were treated with buprenorphine gave birth to newborns with NAS diagnoses.
NAS negatively affects newborns in a multitude of ways, and the objective assessment and measurement of the newborn’s response to withdrawal remains understudied and needs further investigation.
Endogenous opiates and behavior: 2019
2021, Peptides
Citation Excerpt :
Prazosin blocked U50,488-induced reinstatement of alcohol drinking, and decreased U50,488-induced Fos expression in the orbitofrontal cortex, NAC core, ventral BNST, central and basolateral amygdalar nuclei and VTA [259]. Naltrexone and varenicline failed to alter concurrent ethanol and nicotine consumption by female alcohol-preferring rats [903]. Highlights: Mice with genome-wide deletion of neuronal POMC enhancer 1 displayed lower basal POMC and PDYN levels that was reversed by low alcohol intake, coupled with increased basal OPRM1 and OPRK1 levels unaffected by low alcohol intake [1003].
This paper is the forty-second consecutive installment of the annual anthological review of research concerning the endogenous opioid system, summarizing articles published during 2019 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides and receptors as well as effects of opioid/opiate agonists and antagonists. The review is subdivided into the following specific topics: molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors (1), the roles of these opioid peptides and receptors in pain and analgesia in animals (2) and humans (3), opioid-sensitive and opioid-insensitive effects of nonopioid analgesics (4), opioid peptide and receptor involvement in tolerance and dependence (5), stress and social status (6), learning and memory (7), eating and drinking (8), drug abuse and alcohol (9), sexual activity and hormones, pregnancy, development and endocrinology (10), mental illness and mood (11), seizures and neurologic disorders (12), electrical-related activity and neurophysiology (13), general activity and locomotion (14), gastrointestinal, renal and hepatic functions (15), cardiovascular responses (16), respiration and thermoregulation (17), and immunological responses (18).
Naltrexone use in pregnancy: a time for change
2020, American Journal of Obstetrics and Gynecology

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Pilot StudyNaltrexone Treatment for Pregnant Women With Opioid Use Disorder Compared With Matched Buprenorphine Control Subjects

ABSTRACT

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Pilot Study
Naltrexone Treatment for Pregnant Women With Opioid Use Disorder Compared With Matched Buprenorphine Control Subjects