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

Abstract

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.

Neonatal Drug Withdrawal

“…Methadone concentrations in cord blood and at 48 hours of age, 72 as well as the rate of decline in neonatal serum concentration, 65 appear to correlate with NAS signs. Kuschel et al 72 found that infants who required rescue treatment had lower cord blood methadone concentrations and that, in all but 1 infant, methadone concentrations were undetectable in the serum at 48 hours.…”

“…Some studies demonstrated that larger maternal methadone dosages in late pregnancy were associated with greater neonatal concentrations and increased risk of withdrawal, 8,9,[62][63][64][65][66][67][68] but others refuted a correlation. [69][70][71][72][73][74] This lack of consensus is explained in part by different approaches to the management of antenatal methadone maintenance therapy. There were substantial variations in the mean and range of daily methadone dose in the populations studied.…”

“…Kuschel et al 72 found that infants who required rescue treatment had lower cord blood methadone concentrations and that, in all but 1 infant, methadone concentrations were undetectable in the serum at 48 hours. Doberczak 65 noted that faster declines in postnatal blood methadone concentrations were associated with more severe CNS withdrawal.…”

Maternal and neonatal factors impacting response to methadone therapy in infants treated for neonatal abstinence syndrome

“…[1][2][3] Among infants exposed to chronic opiates in utero, the incidence of neonatal abstinence syndrome (NAS) ranges from 21 to 94%. [4][5][6] The onset, duration and severity of NAS may be impacted by the types and degree of fetal drug exposure and by neonatal treatment strategies, [7][8][9][10][11][12][13] use of tobacco during pregnancy, 14 gestational age 15,16 and use of maternal breast milk (MBM) as the primary source of nutrition. [17][18][19][20] The interactions of these factors and the composite impact on response to pharmacologic therapy for NAS have not been adequately elucidated in a large cohort of infants.…”

Breastfeeding and Methadone Therapy: The Maternal Experience

“…21 While pregnant and postpartum women should be counseled in ways to reduce or quit smoking due to the association of tobacco with decreased breast milk volume and adverse fetal and neonatal outcomes (e.g., sudden infant death syndrome), they should also understand that the potential health benefits of breastfeeding likely outweigh the risks of tobacco products passing into breast milk. 9,22 Clinicians should also seek to dispel women's fears that infants can "OD" on methadone-emphasizing the proportionately small transfer of methadone through milk, 10 the poor correlation between maternal methadone dose and severity of NAS symptoms, 5,[11][12][13][23][24][25] and the mechanisms through which breastfeeding can potentially protect against NAS development (e.g., skin-to-skin contact; small transfer of methadone through breast milk). [26][27][28] It is equally imperative that clinicians communicate to women the infant health risks of unprotected sex (and HIV contraction), alcohol use, and illicit drugs while breastfeeding, as these substances pass readily into breast milk.…”