Abstract
Polysubstance use among pregnant women has increased because of the opioid epidemic and the increasing legalization of cannabis along with persistent tobacco and alcohol consumption. Previous research on prenatal substance use and the child's risk of attention-deficit/hyperactivity disorder (ADHD) has mostly focused on single-substance exposures; simultaneous examination of multiple substance use and assessment of their synergistic health consequences is needed. To assess the consequences of the use of specific substances during pregnancy, investigate whether the interaction of multiple prenatal substance exposures is associated with increases in the risk of childhood ADHD, and estimate the aggregate burden of polysubstance exposure during gestation. This cohort study analyzed data from the Boston Birth Cohort from 1998 to 2019. The sample of the present study comprised a multiethnic urban cohort of mother-child pairs who were predominantly low income. A total of 3138 children who were enrolled shortly after birth at Boston Medical Center were included and followed up from age 6 months to 21 years. Substance use during pregnancy was identified based on self-reported tobacco smoking, alcohol consumption, and use of cannabis, cocaine, or opioids in any trimester of pregnancy. Diagnostic codes for neonatal opioid withdrawal syndrome or neonatal abstinence syndrome from the International Classification of Diseases, Ninth Revision, and the International Classification of Diseases, Tenth Revision, were also used to identify opioid exposure during gestation. ADHD diagnosis in the child's electronic medical record. Among 3138 children (1583 boys [50.4%]; median age, 12 years [IQR, 9-14 years]; median follow-up, 10 years [IQR, 7-12 years]) in the final analytic sample, 486 (15.5%) had an ADHD diagnosis and 2652 (84.5%) were neurotypical. The median postnatal follow-up duration was 12 years (IQR, 9-14 years). Among mothers, 46 women (1.5%) self-identified as Asian (non-Pacific Islander), 701 (22.3%) as Hispanic, 1838 (58.6%) as non-Hispanic Black, 227 (7.2%) as non-Hispanic White, and 326 (10.4%) as other races and/or ethnicities (including American Indian or Indigenous, Cape Verdean, Pacific Islander, multiracial, other, or unknown). A total of 759 women (24.2%) reported the use of at least 1 substance during pregnancy, with tobacco being the most frequently reported (580 women [18.5%]). Cox proportional hazards models revealed that opioid exposure (60 children) had the highest adjusted hazard ratio (HR) for ADHD (2.19; 95% CI, 1.10-4.37). After including main statistical effects of all individual substances in an elastic net regression model, the HR of opioids was reduced to 1.60, and evidence of a statistical interaction between opioids and both cannabis and alcohol was found, producing 1.42 and 1.15 times higher risk of ADHD, respectively. The interaction between opioids and smoking was also associated with a higher risk of ADHD (HR, 1.17). The findings of this study suggest that it is important to consider prenatal concurrent exposure to multiple substances and their possible interactions when counseling women regarding substance use during pregnancy, the future risk of ADHD for their children, and strategies for cessation and treatment programs.
Highlights
Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental condition diagnosed in approximately 1 in 10 children as of 2016.1 Attention-deficit/hyperactivity disorder has numerous known sequelae that persist from childhood to adulthood, including increased risk of other mental health disorders,[2-5] lower employment and educational attainment,[6,7] and higher all-cause[8,9] and suicide-specific mortality,[10] despite recent improvements in treatment strategies
Cox proportional hazards models revealed that opioid exposure (60 children) had the highest adjusted hazard ratio (HR) for ADHD (2.19; 95% CI, 1.10-4.37)
Tobacco exposure during pregnancy has been found to have persistent associations with the risk of childhood ADHD,[11] with 1 study finding an adjusted hazard ratio (HR) of 1.48.12 Alcohol consumption[13-15] (1 study[13] found a relative risk of 1.55) and opioid use (1 study[16] found that heroin, oxycodone, or opioid agonists used in cessation therapies were associated with an odds ratio of 2.55) have been associated with increased risk of ADHD
Summary
Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental condition diagnosed in approximately 1 in 10 children as of 2016.1 Attention-deficit/hyperactivity disorder has numerous known sequelae that persist from childhood to adulthood, including increased risk of other mental health disorders,[2-5] lower employment and educational attainment,[6,7] and higher all-cause[8,9] and suicide-specific mortality,[10] despite recent improvements in treatment strategies. Identification of modifiable risk factors in the prenatal and early-life periods may provide new avenues for prevention efforts It may improve early detection of individuals at high risk to complement existing treatment, which could address disabilities associated with ADHD and improve long-term health outcomes. The use of cannabis has been less frequently examined; there is some evidence that cannabis is associated with quantitative attention outcomes, this association has yet to be formally extrapolated to ADHD diagnosis.[17] Many of these studies, had study design limitations, such as recall bias from the use of retrospective designs,[18] examination of specific populations that may not be generalizable to a wider range of children exposed to substances,[19-21] or lack of adjustment for additional concurrent substance use, which could have produced biased estimates.[17,22]
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