Maternal methadone dose and neonatal withdrawal

Berghella, Vincenzo; Lim, Pearl J; Hill, Mary Kay; Cherpes, Jennifer; Chennat, Jennifer; Kaltenbach, Karol

doi:10.1067/s0002-9378(03)00520-9

Cited by 140 publications

(93 citation statements)

References 28 publications

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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%

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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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Section: Discussionmentioning

confidence: 99%

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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“…36 Previous studies investigating the influence of prescribed maternal methadone dose upon the development of NAS have yielded conflicting results. 9,[13][14][15][16][17][18][19] The largest of these studies included 100 infants. 15 Other studies have spanned more than a decade and been confounded by cocaine and heroin use.…”

Section: Discussionmentioning

confidence: 99%

“…9,[13][14][15][16][17][18][19] The largest of these studies included 100 infants. 15 Other studies have spanned more than a decade and been confounded by cocaine and heroin use. 9 Within our cohort of 444 infants, we observed a strong positive association between prescribed maternal methadone dose and the development of NAS.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12] There is conflicting evidence with regard to optimal maternal methadone dose in pregnancy, with some studies showing an association between maternal methadone dose and the risk of NAS and some studies showing no such relationship. 9,[13][14][15][16][17][18][19] Duration of stay may be longer for infants born to polydrug-misusing mothers, 20 and since higher doses of methadone have been associated with less polydrug use, reducing methadone during pregnancy may not be justified. 13 Australian and European data have demonstrated large consumption of healthcare resources by infants born to drug-misusing women, 2,8 but there are few data to quantify this within the UK healthcare setting.…”

Section: Introductionmentioning

confidence: 99%

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Maternal methadone use in pregnancy: factors associated with the development of neonatal abstinence syndrome and implications for healthcare resources

Dryden

Young

Hepburn

et al. 2009

BJOG

210

205

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Objectives The objectives of this study were to investigate factors associated with the development of neonatal abstinence syndrome (NAS) and to assess the implications for healthcare resources of infants born to drug-misusing women.Design Retrospective cohort study from 1 January 2004 to 31 December 2006.Setting Inner-city maternity hospital providing dedicated multidisciplinary care to drug-misusing women.Population Four hundred and fifty singleton pregnancies of drugmisusing women prescribed substitute methadone in pregnancy.Methods Case note review.Main outcome measures Development of NAS and duration of infant hospital stay.Results 45.5% of infants developed NAS requiring pharmacological treatment. The odds ratio of the infant developing NAS was independently related to prescribed maternal methadone dose rather than associated polydrug misuse. Breastfeeding was associated with reduced odds of requiring treatment for NAS (OR 0.55, 95% CI 0.34-0.88). Preterm birth did not influence the odds of the infant receiving treatment for NAS. 48.4% infants were admitted to the neonatal unit (NNU) 40% of these primarily for treatment of NAS. The median total hospital stay for all infants was 10 days (interquartile range 7-17 days). Infants born to methadone-prescribed drug-misusing mothers represented 2.9% of hospital births, but used 18.2% of NNU cot days.Conclusions Higher maternal methadone dose is associated with a higher incidence of NAS. Pregnant drug-misusing women should be encouraged and supported to breastfeed. Their infants are extremely vulnerable and draw heavily on healthcare resources.Keywords Breastfeeding, health resources, methadone, neonatal abstinence syndrome.

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