Fifty Years of Research on Prenatal Substances: Lessons Learned for the Opioid Epidemic.

Current efforts to design research on developmental effects of prenatal opioid exposure can benefit from knowledge gained from 50 years of studies of fetal alcohol and prenatal drug exposures such as cocaine. Scientific advances in neurobiology, developmental psychopathology, infant assessments, genetics, and imaging support the principles of developmental neurotoxicology that guide research in prenatal exposures. Important to research design is accurate assessment of amount, frequency, and timing of exposure which benefits from accurate self-report and biomarkers of exposure. Identifying and control of pre- and postnatal factors that impact development are difficult and dependent on appropriate research design and selection of comparison groups and measurement of confounding, mediating, and moderating variables. Polysubstance exposure has increased due to the number of prescribed and nonprescribed substances used by pregnant women and varying combinations of drugs may have differential effects on the outcome. Multiple experimental and clinical assessments of infant behavior have been developed but predicting outcome before 18-24 months of age remains difficult. With some exceptions, prenatal substance exposure effect sizes have been small, and cognitive and behavioral effects tend to be specific rather than global. Studies require large sample sizes, adequate retention, and support for social services in at-risk samples. The ethical and legal contexts and stigma associated with drug/alcohol use disorder should be considered in order to prevent harm to families in research programs. Recognition of the pervasive use of addictive substances in this nation should lead to broad scientific efforts to understand how substances affect child outcomes and to initiate prevention and intervention where needed.