(AC) Intrauterine Exposure to SSRI Antidepressants and Risk of Emotional Disorder till Age 22: A Danish National Register Study

Publication Number: 1027

Background: Depression in pregnancy is common, and selective serotonin reuptake inhibitors (SSRIs) are usually the first line of medications for treating perinatal depression. However, their effects on fetal development are less clearly understood. In recent years, animal and clinical studies suggest that potential risks to the offspring may not manifest until adolescence, once brain circuits regulating emotion have matured. However few studies have examined outcomes into adolescence. Here, we use Danish population data to test the effect of maternal SSRI use during pregnancy on offspring emotional psychopathology up to age 22.

Objectives: To test the associations between maternal SSRI antidepressant use in pregnancy and offspring emotional disorders and antidepressant usage while controlling for confounders.

Methods: SETTING: 1,094,202 single-birth Danish children born 1997-2015, and followed through 2018, using data linkages across Danish national birth, prescription, and patient registers. MAIN EXPOSURE: use of any SSRI medication within the pregnancy period. Main Outcome: first diagnosis/filled drug; each diagnostic and medication class were also examined individually. STATISTICAL ANALYSIS: Propensity score weights (primary) and matching were used to adjust for potential confounders. We also used Danish National Birth Cohort data (1997-2003) to quantify subclinical differences.

Results: 4.6% (n=1018) of exposed and 3.9% (n=42,796) of unexposed offspring had an emotional disorder diagnosis or an antidepressant prescription (propensity-score-weighted HR=1.45 [95%CI: 1.30-1.61]. Median age was earlier among exposed (9 years, interquartile range (IQR), 7-13) versus unexposed (12 years, IQR: 12-17) offspring (p < 0.01). The associations were similar when restricting the sample to pregnant mothers with a psychiatric diagnosis (HR=1.46 [1.24-1.72]). PS-weighting reduced mean differences between SSRI users and non-users on most but not all clinical and subclinical factors. Paternal use during the index pregnancy was also associated with offspring emotional disorders (HR=1.33 [1.22, 1.46]).

Conclusions: Our findings extend previous work suggesting that prenatal antidepressant exposure is associated with increased, as well as earlier onset of, emotional disorders throughout adolescence. Offspring of mothers who use SSRIs in pregnancy constitute a high-risk cohort who should be screened for psychiatric onset prior to adolescence. The associations between paternal SSRI use and offspring outcomes suggest that effects of in utero exposure may be a combination of drug-specific exposures and markers of underlying maternal illness.