The narcotic-dependent mother: Fetal and neonatal consequences

Kandall, Stephen R.; Albin, Susan; Gartner, Lawrence M.; Lee, Kwang-Sun; Eidelman, Arthur I.; Lowinson, Joyce H.

doi:10.1016/0378-3782(77)90017-2

Cited by 160 publications

(90 citation statements)

References 20 publications

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“…Further, most occurred after the first trimester, in contrast to three‐fourths of spontaneous losses during the first trimester in the general population 56, 57. This apparent underestimate is probably related to a delay by many opioid‐dependent pregnant women in seeking prenatal care until after completing the high‐risk first trimester 35, 58, 59 and insufficient reporting of time of enrollment in several studies 36, 37, 44, 45, 46. Our ability to assess the relationship between fetal death and OMAT was also limited substantially, given sparse and inconsistent patient‐level reporting of gestational timing (onset and duration) of BUP or MET treatment and important potential confounders 60, 61.…”

Section: Discussionmentioning

confidence: 99%

Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta‐analysis of safety in the mother, fetus and child

et al. 2016

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AimsTo assess the safety of buprenorphine compared with methadone to treat pregnant women with opioid use disorder.MethodsWe searched PubMed, Embase and the Cochrane Library from inception to February 2015 for randomized controlled trials (RCT) and observational cohort studies (OBS) that compared buprenorphine with methadone for treating opioid‐dependent pregnant women. Two reviewers assessed independently the titles and abstracts of all search results and full texts of potentially eligible studies reporting original data for maternal/fetal/infant death, preterm birth, fetal growth outcomes, fetal/congenital anomalies, fetal/child neurodevelopment and/or maternal adverse events. We ascertained each study's risk of bias using validated instruments and assessed the strength of evidence for each outcome using established methods. We computed effect sizes using random‐effects models for each outcome with two or more studies.ResultsThree RCTs (n = 223) and 15 cohort OBSs (n = 1923) met inclusion criteria. In meta‐analyses using unadjusted data and methadone as comparator, buprenorphine was associated with lower risk of preterm birth [RCT risk ratio (RR) = 0.40, 95% confidence interval (CI) = 0.18, 0.91; OBS RR = 0.67, 95% CI = 0.50, 0.90], greater birth weight [RCT weighted mean difference (WMD) = 277 g, 95% CI = 104, 450; OBS WMD = 265 g, 95% CI = 196, 335] and larger head circumference [RCT WMD = 0.90 cm, 95% CI = 0.14, 1.66; OBS WMD = 0.68 cm, 95% CI = 0.41, 0.94]. No treatment differences were observed for spontaneous fetal death, fetal/congenital anomalies and other fetal growth measures, although the power to detect such differences may be inadequate due to small sample sizes.ConclusionsModerately strong evidence indicates lower risk of preterm birth, greater birth weight and larger head circumference with buprenorphine treatment of maternal opioid use disorder during pregnancy compared with methadone treatment, and no greater harms.

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Section: Discussionmentioning

confidence: 99%

Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta‐analysis of safety in the mother, fetus and child

et al. 2016

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“…Accordingly, the concentration of methadone in the fetal circulation may not correlate with maternal serum drug level of women under treatment. Over the last 30 years, several researchers have reported clinical observations on the presence or absence of a correlation between the dose of methadone administered to the mother and the incidence or intensity of neonatal abstinence syndrome [1][2][3][4].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous investigations have indicated that methadone treatment programs improve maternal and neonatal outcome of this patient population; a review of this literature would be out of the scope of this report. However, a controversy exists regarding the association of methadone pharmacotherapy with neonatal abstinence syndrome (NAS) [1,2] and whether the dose administered correlates with the incidence and intensity of the syndrome [1][2][3][4]. The variability in the efficacy of methadone among nonpregnant patients could be attributed to the factors affecting its disposition, which include maternal clearance, bioavailability, and metabolism by the liver and intestine.…”

Section: Introductionmentioning

confidence: 99%

Role of P-glycoprotein in transplacental transfer of methadone

Nanovskaya

Nekhayeva

Karunaratne

et al. 2005

Biochemical Pharmacology

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Methadone is the therapeutic agent of choice for treatment of the pregnant opiate addict. However, little is known on the factors affecting its concentration in the fetal circulation during pregnancy and how it might relate to neonatal outcome. Therefore, a better understanding of the function of placental metabolic enzymes and transporters should add to the knowledge of the role of the tissue in the disposition of methadone and its relation to neonatal outcome. We hypothesized that the expression and activity of the placental efflux transporter P-glycoprotein (P-gp) would affect the transfer of methadone to the fetal circulation. Data obtained utilizing dual perfusion of placental lobule and monolayers of Be-Wo cell line indicated that methadone is extruded by P-gp. Transfer of methadone to the fetal circuit was increased by 30% in the presence of the P-gp inhibitor GF120918 while the transfer of paclitaxel, a typical substrate of the glycoprotein, was increased by 50%. In the Be-Wo cell line, methadone and paclitaxel uptake was also increased in the presence of the P-gp inhibitor cyclosporin A. Moreover, the expression of P-gp in placental brush-border membranes varied between term placentas. Taken together, these data strongly suggest that the concentration of methadone in the fetal circulation is affected by the expression and activity of P-gp. It is reasonable to speculate that placental disposition of methadone affects its concentration in the fetal circulation. If true, this may also be directly related to the incidence and intensity of neonatal abstinence syndrome (NAS).

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“…[14][15][16][17] Urine toxicology did not reveal any illicit use, but neonatal urine samples taken in the first few hours may only detect substances ingested by the mother over the preceding days or weeks, depending on the rate of elimination of the drug. However, urine analysis provides a more rapid result for a toxicology screen than either meconium or hair samples.…”

Section: Discussionmentioning

confidence: 99%

Can methadone concentrations predict the severity of withdrawal in infants at risk of neonatal abstinence syndrome?

Kuschel

2004

Archives of Disease in Childhood - Fetal and Neonatal Edition

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Aim: To assess the usefulness of cord and serum methadone concentrations at 2 days of age in predicting the severity of neonatal abstinence syndrome (NAS) in infants whose mothers received methadone during pregnancy. Methods: After informed consent, infants were enrolled if they were delivered at 35 weeks gestation or greater. Relevant information was collected from maternal notes. A sample of cord blood was taken at delivery, with a follow up sample at 48 hours of age. The samples were analysed in batches, and the results were unavailable to the attending clinical staff. Infants were treated for NAS on clinical grounds according to a standardised scoring system. Results: Twenty five of 36 eligible infants over the 21 month period of the study were enrolled. Of these, 12 required treatment for NAS. Maternal methadone dose did not predict the need for treatment. However, infants who required treatment had significantly lower methadone concentrations in cord blood than the group who did not receive treatment (31 v 88 ng/ml respectively; p = 0.029). Paired blood samples for methadone concentrations were available for 17 infants. All but one of the 12 infants who required treatment had undetectable concentrations of methadone in the postnatal sample, whereas the median postnatal methadone concentration in untreated infants was 23 ng/ml (p = 0.002). Conclusions: Methadone concentrations taken from cord blood may identify infants at greater risk of neonatal withdrawal and therefore requiring treatment.

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The narcotic-dependent mother: Fetal and neonatal consequences

Cited by 160 publications

References 20 publications

Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta‐analysis of safety in the mother, fetus and child

Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta‐analysis of safety in the mother, fetus and child

Role of P-glycoprotein in transplacental transfer of methadone

Can methadone concentrations predict the severity of withdrawal in infants at risk of neonatal abstinence syndrome?

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