Maternal Buprenorphine Dose at Delivery and Its Relationship to Neonatal Outcomes

O’Connor, Alane; O’Brien, Liam M.; Alto, William A.

doi:10.1159/000441220

Cited by 19 publications

(11 citation statements)

References 11 publications

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“…Despite its reduced NOWS liability, approximately 50% of neonates born to women treated with buprenorphine during pregnancy require pharmacological treatment of NOWS (Jones et al, 2010;Bartu et al, 2012). Notably, neonatal withdrawal severity is not related to maternal buprenorphine dose (Jones et al, 2014;O'Connor et al, 2016;Shah et al, 2016). This clinical observation suggests that fetal exposure to buprenorphine or to its major, active metabolite norbuprenorphine (NorBUP) may be influenced by differences in maternal-fetal metabolism, distribution, and/or excretion of buprenorphine and NorBUP among maternal-fetal dyads.…”

Section: Introductionmentioning

confidence: 98%

In Utero Exposure to Norbuprenorphine, a Major Metabolite of Buprenorphine, Induces Fetal Opioid Dependence and Leads to Neonatal Opioid Withdrawal Syndrome

Griffin,

Caperton,

Russell

et al. 2019

J Pharmacol Exp Ther

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Buprenorphine is the preferred treatment of opioid use disorder during pregnancy but can cause fetal opioid dependence and neonatal opioid withdrawal syndrome (NOWS). Notably, withdrawal severity is independent of maternal buprenorphine dose, suggesting that interindividual variance in pharmacokinetics may influence risk and severity of NOWS. Using a rat model of NOWS, we tested the hypothesis that clinically relevant doses of the active metabolite norbuprenorphine (NorBUP) can induce in utero opioid dependence, manifested as naltrexone-precipitated withdrawal signs in the neonate. Pregnant Long-Evans rats were implanted with 14-day osmotic minipumps containing vehicle, morphine (positive control), or NorBUP (0.3-10 mg/kg per day) on gestation day 9. By 12 hours post-delivery, an intraperitoneal injection of the opioid antagonist naltrexone (1 or 10 mg/kg) or saline was administered to pups. Precipitated withdrawal signs were graded by raters blinded to treatment conditions. In a separate group, NorBUP concentrations in maternal and fetal blood and brain on gestation day 20 were determined by liquid chromatography-tandem mass spectrometry. Steady-state maternal blood concentrations of NorBUP in dams infused with 1 or 3 mg/kg per day were comparable to values reported in pregnant humans treated with buprenorphine (1.0 and 9.6 ng/ml, respectively), suggesting a clinically relevant dosing regimen. At these doses, NorBUP increased withdrawal severity in the neonate as shown by an evaluation of 10 withdrawal indicators. These findings support the possibility that NorBUP contributes to fetal opioid dependence and NOWS following maternal buprenorphine treatment during pregnancy.

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Section: Introductionmentioning

confidence: 98%

In Utero Exposure to Norbuprenorphine, a Major Metabolite of Buprenorphine, Induces Fetal Opioid Dependence and Leads to Neonatal Opioid Withdrawal Syndrome

Griffin,

Caperton,

Russell

et al. 2019

J Pharmacol Exp Ther

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“…Although two other reports have not found such an association, this may be due to the limited use of other substances in the populations that comprised those studies (Jones et al, 2014;. O’Connor et al, 2016). Regardless, buprenorphine’s effects on fetal growth remains an open question.…”

Section: Discussionmentioning

confidence: 71%

Maternal buprenorphine treatment and infant outcome

Jansson

Vélez

McConnell

et al. 2017

Drug and Alcohol Dependence

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Background and Objectives Maternal buprenorphine maintenance predisposes the infant to exhibit neonatal abstinence syndrome (NAS), but there is insufficient published information regarding the nature of NAS and factors that contribute to its severity in buprenorphine-exposed infants. Methods The present study evaluated forty-one infants of buprenorphine-maintained women in comprehensive substance use disorder treatment who participated in an open-label study examining the effects of maternal buprenorphine maintenance on infant outcomes. Modifiers of the infant outcomes, including maternal treatment and substance use disorder parameters, were also evaluated. Results Fifty-nine percent of offspring exhibited NAS that required pharmacologic management. Both maternal buprenorphine dose as well as prenatal polysubstance exposure to illicit substance use/licit substance misuse were independently associated with NAS expression. Polysubstance exposure was associated with more severe NAS expression after controlling for the effects of buprenorphine dose. Other exposures, including cigarette smoking and SRI use, were not related to outcomes. Maternal buprenorphine dose was positively associated with lower birth weight and length. Conclusions Polysubstance exposure was the most potent predictor of NAS severity in this sample of buprenorphine-exposed neonates. This finding suggests the need for interventions that reduce maternal polysubstance use during medication assisted treatment for opioid use disorder, and highlights the necessity of a comprehensive approach, beyond buprenorphine treatment alone, for the optimal care for pregnant women with opioid use disorders.

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“…Furthermore, reducing medication doses in order to limit fetal exposure has been linked to an increase in illicit drug use and its subsequent risks 7. Dosing decisions should only focus on maternal opioid cravings to prevent relapse 68. New mothers can, however, reduce NAS severity through rooming in with their neonate, providing skin-to-skin contact, breastfeeding, minimizing environmental stimuli, and comforting the baby via swaying, rocking, and providing a pacifier 37,69…”

Section: Treatment Options and Decisionsmentioning

confidence: 99%

Opioid use disorder in pregnancy

Harter¹

2019

Mental Health Clinician

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The number of pregnant people affected by the opioid epidemic in the United States continues to rise. The following key aspects of opioid use disorder in pregnancy are explored through the progression of a pregnancy via a patient case: treatment options, treatment decisions, substance use screening, dosing modifications, and other aspects of peripartum care. Many factors affect opioid use disorder treatment choices during pregnancy; however, when a pregnant person is medically eligible for a therapy and multiple options are available locally, the ultimate decision regarding treatment selection should be left up to the patient and strong support services provided. This approach to treatment results in optimal maternal and neonatal outcomes and long-term maternal engagement and retention in care.

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Maternal Buprenorphine Dose at Delivery and Its Relationship to Neonatal Outcomes

Cited by 19 publications

References 11 publications

In Utero Exposure to Norbuprenorphine, a Major Metabolite of Buprenorphine, Induces Fetal Opioid Dependence and Leads to Neonatal Opioid Withdrawal Syndrome

In Utero Exposure to Norbuprenorphine, a Major Metabolite of Buprenorphine, Induces Fetal Opioid Dependence and Leads to Neonatal Opioid Withdrawal Syndrome

Maternal buprenorphine treatment and infant outcome

Opioid use disorder in pregnancy

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