Bottom Line: In utero exposure to opioids was associated with higher risks for short- and long-term adverse outcomes including preterm birth and neurodevelopmental and physical health disorders in children. This observational study analyzed clinical and epidemiological data for a group of 8,509 mother-child pairs collected at birth starting in 1998, and 3,153 children who continued to be followed after birth up to age 21 years old. Of the 8,509 children, 454 (5.3%) had in utero opioid exposure, which was defined as maternal self-reported opioid use or a clinical diagnosis of neonatal abstinence syndrome for a child. The study reports that in utero exposure to opioids was associated with a higher likelihood of being small for gestational age and preterm birth. In utero exposure to opioids also was associated with postnatal neurodevelopmental and physical disorders, including a higher likelihood of conduct disorder or emotional disturbance diagnoses, as well as lack of normal physiological development in children before age 6 years old, and later on, a higher likelihood of attention-deficit/hyperactivity disorder. Study limitations to consider include that mothers may have used other substances, such as alcohol, cigarettes, marijuana and stimulants, which could have influenced the outcomes.