Methadone is used for medication-assisted treatment of heroin addiction during pregnancy. The neurodevelopmental outcome of children with prenatal methadone exposure can be sub-optimal. We tested the hypothesis that brain development is altered among newborn infants whose mothers were prescribed methadone.20 methadone-exposed neonates born after 37 weeks' postmenstrual age (PMA) and 20 non-exposed controls underwent diffusion MRI at mean PMA of 39+ 2 and 41+ 1 weeks, respectively. An age-optimized Tract-based Spatial Statistics (TBSS) pipeline was used to perform voxel-wise statistical comparison of fractional anisotropy (FA) data between exposed and non-exposed neonates.Methadone-exposed neonates had decreased FA within the centrum semiovale, inferior longitudinal fasciculi (ILF) and the internal and external capsules after adjustment for GA at MRI (p < 0.05, TFCE corrected). Median FA across the white matter skeleton was 12% lower among methadone-exposed infants. Mean head circumference (HC) z-scores were lower in the methadone-exposed group (− 0.52 (0.99) vs 1.15 (0.84), p < 0.001); after adjustment for HC z-scores, differences in FA remained in the anterior and posterior limbs of the internal capsule and the ILF. Polydrug use among cases was common.Prenatal methadone exposure is associated with microstructural alteration in major white matter tracts, which is present at birth and is independent of head growth. Although the findings cannot be attributed to methadone per se, the data indicate that further research to determine optimal management of opioid use disorder during pregnancy is required. Future studies should evaluate childhood outcomes including infant brain development and long-term neurocognitive function.

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.

In October 2019, the British Association of Perinatal Medicine (BAPM) published a Framework1 and associated infographic2 for ‘Practice on Perinatal Management of Extreme Preterm Birth Before 27 Weeks of Gestation’. This outlined an approach, based on data from the UK and abroad, to assist clinicians in decision-making relating to perinatal care at ≤26+6 weeks gestation. Many frontline providers of delivery room care of extremely preterm infants will have completed a Resuscitation Council UK (RCUK) Newborn Life Support or Advanced Resuscitation of the Newborn Infant course. This RCUK response to the BAPM Framework highlights how this might impact on their approach.

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