• Romuladus E Azuine, Yuelong Ji, Hsing-Yuan Chang, Yoona Kim, Hongkai Ji, Jessica DiBari, Xiumei Hong, Guoying Wang, Gopal K Singh, Colleen Pearson, Barry Zuckerman, Pamela J Surkan, and Xiaobin Wang.
• Division of Research, Office of Epidemiology and Research, Maternal and Child Health Bureau, Health Resources and Services Administration, US Department of Health and Human Services, Rockville, Maryland.
• JAMA Netw Open. 2019 Jun 5; 2 (6): e196405.

ImportanceThe opioid epidemic increasingly affects pregnant women and developing fetuses, resulting in high rates of neonatal abstinence syndrome. However, longitudinal studies that prospectively observe newborns with neonatal abstinence syndrome or with maternal opioid use and examine their long-term physical and neurodevelopmental outcomes are lacking.ObjectiveTo examine prenatal risk factors associated with maternal opioid use during pregnancy and the short-term and long-term health consequences on their children.Design, Setting, And ParticipantsThis cohort study analyzed data from the Boston Birth Cohort, an urban, low-income, multiethnic cohort that enrolled mother-newborn pairs at birth at Boston Medical Center (Boston, Massachusetts) starting in 1998, and a subset of children were prospectively observed at Boston Medical Center pediatric primary care and subspecialty clinics from birth to age 21 years. Data analysis began in June 2018 and was completed in May 2019.ExposuresIn utero opioid exposure was defined as maternal self-reported opioid use and/or clinical diagnosis of neonatal abstinence syndrome.Main Outcomes And MeasuresPregnancy outcomes, postnatal child physical health, and major neurodevelopmental disabilities, documented in maternal and child medical records.ResultsThis study included 8509 Boston Birth Cohort mother-newborn pairs for prenatal and perinatal analyses. Of those, 3153 children continued to receive pediatric care at Boston Medical Center and were included in assessing postnatal outcomes. Overall, 454 of the 8509 children (5.3%) in the Boston Birth Cohort had in utero opioid exposure. At birth, opioid exposure was associated with higher risks of fetal growth restriction (odds ratio [OR], 1.87; 95% CI, 1.41-2.47) and preterm birth (OR, 1.49; 95% CI, 1.19-1.86). Opioid exposure was associated with increased risks of lack of expected physiological development (OR, 1.80; 95% CI, 1.17-2.79) and conduct disorder/emotional disturbance (OR, 2.13; 95% CI, 1.20-3.77) among preschool-aged children. In school-aged children, opioid exposure was associated with a higher risk of attention-deficit/hyperactivity disorder (OR, 2.55; 95% CI, 1.42-4.57).Conclusions And RelevanceIn this sample of urban, high-risk, low-income mother-child pairs, in utero opioid exposure was significantly associated with adverse short-term and long-term outcomes across developmental stages, including higher rates of physical and neurodevelopmental disorders in affected children. Efforts to prevent the opioid epidemic and mitigate its health consequences would benefit from more intergenerational research.

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