Association of preterm birth with prescription of psychotropic drugs in adolescence and young adulthood

Importance Individuals born preterm have increased risk of mental health impairment compared with individuals born at term. The associations between preterm birth and attention-deficit/hyperactivity disorder and autism are well established; for depression, anxiety, psychotic and bipolar disorder, studies show divergent results. Objective To compare the prescription of psychotropic drugs in adolescence and young adulthood between those born preterm and those born at term. Design, Setting, and Participants This cohort study used registry data to identify all Norwegians born after 23 weeks of completed gestation between 1989 and 1998. Included individuals were those without registered birth defects, alive at age 10 years, and with available maternal data. Individuals were followed up from 2004 to 2016. Psychotropic drug prescriptions received from age 10 to 23 years were compared between preterm groups and peers born at term. Individuals were compared with their siblings to control for shared family confounding. Data analyses were performed from August 2018 through February 2020. Exposures Gestational age at birth (GA) was categorized in 4 groups: extremely preterm (GA, 23 weeks and 0 days to 27 weeks and 6 days), very preterm (GA, 28 weeks and 0 days to 31 weeks and 6 days), moderately or late preterm (GA, 32 weeks and 0 days to 36 weeks and 6 days), and full term (GA, 37 weeks and 0 days to 44 weeks and 6 days). Main Outcomes and Measures Prescriptions of psychotropic drugs (ie, prescriptions specifically of psychostimulants, antidepressants, anxiolytics, hypnotics or sedatives, or antipsychotics or prescriptions of any of these 5 drugs) among preterm groups were compared with prescriptions among peers born at term and among siblings. Results Among 505 030 individuals (259 545 [51.4%] males; mean [SD] birth weight, 3533 [580] g), 762 individuals (0.2%) were extremely preterm, 2907 individuals (0.6%) were very preterm, 25 988 individuals (5.1%) were moderately or late preterm, and 475 373 individuals (94.1%) were full term. Individuals born preterm had increased risk of psychotropic drug prescription, with a dose-response association between GA and prescription. The extremely preterm group had higher rates of prescription for all drug types compared with peers born at term, with odds ratios from 1.7 (95% CI, 1.4-2.1) for antidepressants to 2.7 (95% CI, 2.1-3.4) for psychostimulants. The elevated odds of prescription of all types were less pronounced in the moderately to late preterm group, including odds ratios of 1.1 (95% CI, 1.0-1.1) for antidepressants and 1.2 (95% CI, 1.1-1.2) for psychostimulants. The increases in odds were smaller in the sibling comparison, and increases were not significant for several groups. For example, the OR for any prescription in the sibling analysis was 1.8 (95% CI, 1.2-2.8) in the very preterm group and 1.0 (95% CI, 0.9-1.1) in the moderately or late preterm group. Conclusions and Relevance This cohort study found higher rates of prescription of psychotropic drugs throughout adolescence and young adulthood among individuals with all degrees of preterm birth compared with those born at term. These results provide further evidence for an increased risk of mental health impairment among individuals born preterm and suggest that this is not restricted to the most preterm groups.publishedVersio