Antidepressant use during pregnancy and psychiatric disorders in offspring: Danish nationwide register based cohort study

Abstract

Objective To investigate the association between in utero exposure to antidepressants and risk of psychiatric disorders.Design Population based cohort study.Setting Danish national registers.Participants 905 383 liveborn singletons born during 1998-2012 in Denmark and followed from birth until July 2014, death, emigration, or date of first psychiatric diagnosis, whichever came first. The children were followed for a maximum of 16.5 years and contributed 8.1×10⁶ person years at risk.Exposures for observational studies Children were categorised into four groups according to maternal antidepressant use within two years before and during pregnancy: unexposed, antidepressant discontinuation (use before but not during pregnancy), antidepressant continuation (use both before and during pregnancy), and new user (use only during pregnancy).Main outcome measure First psychiatric diagnosis in children, defined as first day of inpatient or outpatient treatment for psychiatric disorders. Hazard ratios of psychiatric disorders were estimated using Cox regression models.Results Overall, psychiatric disorders were diagnosed in 32 400 children. The adjusted 15 year cumulative incidence of psychiatric disorders was 8.0% (95% confidence interval 7.9% to 8.2%) in the unexposed group, 11.5% (10.3% to 12.9%) in the antidepressant discontinuation group, 13.6% (11.3% to 16.3%) in the continuation group, and 14.5% (10.5% to 19.8%) in the new user group. The antidepressant continuation group had an increased risk of psychiatric disorders (hazard ratio 1.27, 1.17 to 1.38), compared with the discontinuation group.Conclusions In utero exposure to antidepressants was associated with increased risk of psychiatric disorders. The association may be attributable to the severity of underlying maternal disorders in combination with antidepressant exposure in utero. The findings suggest that focusing solely on a single psychiatric disorder among offspring in studies of in utero antidepressant exposure may be too restrictive.

Fig 1 Flowchart showing identification of study population. Antidepressant use before pregnancy was defined as prescription on any date between two years and one month before pregnancy. Antidepressant use during pregnancy was defined as prescription dispensed on any date from one month before pregnancy until delivery

Fig 2 Crude and adjusted Kaplan-Meier curves illustrating cumulative incidence of any psychiatric disorders in children according to maternal antidepressant use before and during pregnancy (n=905 383). Unexposed group: children whose mothers did not use antidepressant before or during pregnancy. Antidepressant discontinuation group: children whose mothers used antidepressants before but not during pregnancy. Antidepressant continuation group: children whose mothers used antidepressants both before and during pregnancy. New user group: children whose mothers used antidepressants during but not before pregnancy. Adjusted for maternal age at delivery, primiparity, maternal psychiatric history at delivery, inpatient and outpatient psychiatric treatment from two years before pregnancy until delivery, dispensing of other psychotropic prescriptions during pregnancy, dispensing of antiepileptic prescriptions during pregnancy, number of non-psychiatric hospital visits during pregnancy, smoking during pregnancy, place of residence, marital status, highest education, income, calendar year of delivery, and paternal psychiatric history at time of delivery