Growth and developmental outcome of infants with in-utero exposure to methadone vs buprenorphine

Bier, Jo-Ann Blaymore; Finger, Abigail; Bier, Benjamin; Johnson, Timothy A.; Coyle, Mara G.

doi:10.1038/jp.2015.22

Cited by 41 publications

(35 citation statements)

References 15 publications

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“…This association persisted for cognition up to 2 years of age (MDI 99.2 vs 82.0, p <0.01). Bier et al reported MDI scores in the normal range at 4 months of age, in a cohort of 165 methadone‐exposed infants, with no difference between those infants exposed prenatally to either low dose (<100mg/d) or high dose (≥100mg/d) methadone.…”

Section: Resultsmentioning

confidence: 99%

Childhood neurodevelopment after prescription of maintenance methadone for opioid dependency in pregnancy: a systematic review and meta‐analysis

Monnelly

Hamilton

Chappell

et al. 2018

Develop Med Child Neuro

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Aim To systematically review and meta‐analyse studies of neurodevelopmental outcome of children born to mothers prescribed methadone in pregnancy. Method MEDLINE, Embase, and PsycINFO were searched for studies published from 1975 to 2017 reporting neurodevelopmental outcomes in children with prenatal methadone exposure. Results Forty‐one studies were identified (2283 participants). Eight studies were amenable to meta‐analysis: at 2 years the Mental Development Index weighted mean difference of children with prenatal methadone exposure compared with unexposed infants was −4.3 (95% confidence interval [CI] −7.24 to −1.63), and the Psychomotor Development Index weighted mean difference was −5.42 (95% CI −10.55 to −0.28). Seven studies reported behavioural scores and six found scores to be lower among methadone‐exposed children. Twelve studies reported visual outcomes: nystagmus and strabismus were common; five studies reported visual evoked potentials of which four described abnormalities. Factors that limited the quality of some studies, and introduced risk of bias, included absence of blinding, small sample size, high attrition, uncertainty about polydrug exposure, and lack of comparison group validity. Interpretation Children born to mothers prescribed methadone in pregnancy are at risk of neurodevelopmental problems but risk of bias limits inference about harm. Research into management of opioid use disorder in pregnancy should include evaluation of childhood neurodevelopmental outcome. What this paper adds Children born to opioid‐dependent mothers prescribed methadone are at risk of neurodevelopmental impairment. Exposed infants have lower Mental Development Index and Psychomotor Development Index scores than unexposed children. Atypical visual evoked potentials, strabismus, and nystagmus have increased prevalence. Estimates of impairment may be biased by intermediate to poor quality evidence.

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Section: Resultsmentioning

confidence: 99%

Childhood neurodevelopment after prescription of maintenance methadone for opioid dependency in pregnancy: a systematic review and meta‐analysis

Monnelly

Hamilton

Chappell

et al. 2018

Develop Med Child Neuro

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“…Arlettaz et al, 3 in a retrospective study of 86 newborns exposed to methadone, reported a 13% incidence of HC less than the third percentile, but 62% were also exposed to additional drugs, primarily cocaine. Bier et al 11 reported significantly smaller HC z scores for neonates exposed to a high dose of methadone (>100 mg daily dose) compared with newborns exposed to a low dose of methadone or buprenorphine. Additionally, in a few small studies, researchers have reported smaller brain volumes and abnormal white matter development in older children (ages 9-14) who received treatment of NAS after birth compared with controls, suggesting that children may not experience "catch-up" growth in HC through early adolescence.…”

Section: Discussionmentioning

confidence: 99%

Neonatal Head Circumference in Newborns With Neonatal Abstinence Syndrome

et al. 2018

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OBJECTIVES:To compare head circumference (HC) in neonates treated for neonatal abstinence syndrome (NAS) with control neonates without antenatal opioid exposure. METHODS:Our prospective cohort study ran from April 1, 2014, through December 31, 2016. Newborns treated for NAS delivered from well-dated pregnancies ≥34 weeks' gestation were compared with newborns who were nonopioid exposed and matched for race, parity, mode of delivery, and gestational age. All mothers underwent serial antenatal urine drug testing. A minimum of 754 study participants were needed (377 in each group) to demonstrate an increase in the proportion of newborns with HCs less than or equal to the 10th percentile from 10% in controls to a minimum of 20% in NAS newborns with 90% power. RESULTS:A total of 858 neonates were enrolled (429 NAS cases and 429 controls). Mean HC for cases was 33.04 cm (±1.9 cm) compared with 33.99 cm (±2.0 cm) for controls (P < .0001). Among the 429 NAS cases, the mothers of 372 (87%) were on opioid medicationassisted treatment. For NAS cases, 30.1% (95% confidence interval: 25.8%-34.7%) had an HC less than or equal to the 10th percentile (129 of 429 neonates), and 8.2% (95% confidence interval: 5.8%-11.2%) had an HC less than or equal to the third percentile (35 of 429 neonates). Multivariate analysis was used and determined that only chronic opioid use during gestation resulting in a neonate who was NAS treated was a significant risk factor for the observed smaller HC. CONCLUSIONS: Chronic opioid use during pregnancy sufficient to cause NAS was associated with smaller HCs at birth. Most mothers were on opioid agonist medication-assisted treatment, which is currently the recommended treatment option during pregnancy.

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“…Attempts to compare the effects of different prenatal MAT regimens (methadone vs. buprenorphine and dose levels) on neurodevelopment have yielded inconsistent results. For example, the MOTHER study [16] and a retrospective cohort in Massachusetts [36] found no association, while a prospective cohort in Australia found differences in visual evoked potentials between methadone- vs. buprenorphine-exposed infants at 4 months of age, which did not persist to a 36months evaluation [37]. While there are some indications that brain function may be altered by prenatal exposure to methadone vs. buprenorphine in infancy, the small number of studies to examine this have also reported normalization of the assessed sensory function between 6 and 36 months of age [35, 37].…”

Section: Discussionmentioning

confidence: 99%

Association between prenatal opioid exposure, neonatal opioid withdrawal syndrome, and neurodevelopmental and behavioral outcomes at 5–8 months of age

Bakhireva

Holbrook

Shrestha

et al. 2019

Early Human Development

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Background: While use of prescription opioids and medication assisted therapy (MAT) for opioid use disorder in pregnancy, as well as the prevalence of neonatal opioid withdrawal syndrome (NOWS) continue to rise, little is known about outcomes for children with NOWS beyond the newborn period. Methods: We examined 1) prenatal MAT exposure vs. unexposed healthy controls [HC]; and 2) treatment for NOWS and NOWS severity on infant neurodevelopmental and behavioral outcomes at 5–8 months of age in 78 maternal-infant pairs from the ENRICH prospective cohort study. Data were obtained from 3 study visits: prenatal, delivery, and neurodevelopmental evaluation at 5–8 months of age. Neurodevelopmental outcomes included the Bayley Scales of Infant Development [BSID-III], caregiver questionnaires (Parenting Stress Index [PSI-SF], Infant Behavior Questionnaire [IBQ-R], Sensory Profile), and the experimental Still-Face Paradigm (SFP). Results: No differences in the BSID-III, PSI-SF, or IBQ-R scores were observed between MAT groups and HC; however, MAT-exposed and HC infants differed with respect to SFP self-regulation (β=−18.9; p=0.01) and Sensory Profile sensation seeking (OR=4.87; 95% CI: 1.55; 15.30) after adjusting for covariates. No significant differences between Treated-for-NOWS vs. not-Treated-for-NOWS were observed. Shorter timing to NOWS treatment initiation was associated with higher Total Stress (β=−9.08; p=0.035), while longer hospitalization was associated with higher Parent-child dysfunction (p=0.018) on PSI-SF. Conclusions: Our results provide additional evidence of little-to-no effect of MAT and pharmacological treatment of NOWS on infant neurodevelopmental and behavioral outcomes at 5–8 months of age. However, prolonged hospitalization might increase family psychosocial stress and requires further examination.

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Growth and developmental outcome of infants with in-utero exposure to methadone vs buprenorphine

Abstract: Exposure to maternal methadone dose in excess of 100 mg is associated with a reduction in infant head circumference when compared with buprenorphine or lower dose methadone, and may have a negative impact on motor skill development during early infancy.

Cited by 41 publications

References 15 publications

Childhood neurodevelopment after prescription of maintenance methadone for opioid dependency in pregnancy: a systematic review and meta‐analysis

Childhood neurodevelopment after prescription of maintenance methadone for opioid dependency in pregnancy: a systematic review and meta‐analysis

Neonatal Head Circumference in Newborns With Neonatal Abstinence Syndrome

Association between prenatal opioid exposure, neonatal opioid withdrawal syndrome, and neurodevelopmental and behavioral outcomes at 5–8 months of age

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