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Early developmental trajectory of children with prenatal alcohol and opioid exposure



With significant increases in opioid use/misuse and persistent high prevalence of prenatal alcohol exposure (PAE), identifying infants at risk for long-term developmental sequelae due to these exposures remains an urgent need. This study reports on developmental outcomes in young children from a prospective cohort, ENRICH-1, which recruited pregnant women and followed up maternal–infant pairs.


Subjects were assigned to four study groups based on prenatal use of medications for opioid use disorder (MOUD), PAE, MOUD+PAE, and unexposed controls (UC). Mixed effects modeling was used to evaluate changes in the Bayley Scales of Infant Development-III (BSID-III) Cognitive, Language, and Motor scores between 6 and 20 months.


There was a significant three-way interaction (MOUD-by-PAE-by-Time) with respect to the BSID-III Cognitive (p = 0.045) and Motor (p = 0.033) scales. Significant changes between the two evaluations were observed for MOUD group in Cognitive and Language scores; for PAE group in Cognitive, Language, and Motor scores, and for MOUD+PAE group in Language scores after adjusting for child sex and family socio-economic status. The developmental scores for the UC remained stable.


Observed decline in neurodevelopmental scores during the first 2 years of life emphasizes the importance of a longitudinal approach when evaluating children with prenatal polysubstance exposure.


  • BSID-III scores were stable during the first 2 years of life for unexposed children.

  • BSID-III scores declined for children with prenatal exposures to alcohol and/or opioids.

  • Standard developmental tests may not be sensitive enough during the first year of life.

  • Findings emphasize the need for repeated evaluations of children who are at high risk.

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Fig. 1: Changes in BSID-III Cognitive, Language, and Motor Scores from 6 to 20 months by study group adjusted for child sex and family SES.

Data availability

The datasets generated and/or analyzed during the current study are not publicly available due to a lack of data-sharing acknowledgment of de-identified data in the consent and IRB protocol. The request for data sharing can be considered on a case-by-case basis with a formal data-sharing agreement between institutions.


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Research reported in this publication was supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under Award Number R01AA021771. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations



All authors have met the Pediatric Research authorship requirements. J.L. and L.N.B. conceptualized the research idea and analytical framework, provided the overall guidance and oversight, made substantial contributions to the interpretation of the data, and drafted the initial version of the manuscript. L.N.B. and J.M.S. contributed to the conceptualization of the study design for the ENRICH-1 cohort, funding acquisition, acquisition of the data, and provided oversight and supervision for all aspects of the primary data collection. J.L. oversaw collection of the neurobehavioral outcome data, scoring and validation of these data. M.H.R. and J.D. contributed to the research methodology, development of a data analysis plan (jointly with L.N.B. and J.L.), conducted formal data analyses, and contributed to drafting relevant sections of the manuscript. D.E.R. contributed to the data acquisition and data curation, quality control/quality assurance efforts, interpretation of data, literature review, and drafting of the manuscript. All authors provided revisions for important intellectual content and approved the final version of the manuscript.

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Correspondence to Ludmila N. Bakhireva.

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Lowe, J.R., DiDomenico, J., Stephen, J.M. et al. Early developmental trajectory of children with prenatal alcohol and opioid exposure. Pediatr Res (2022).

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