(264) Cardiac Autonomic Stress Response in 6- and 12-Year-Old Children After Prenatal Selective Serotonin Reuptake Inhibitor Medication Exposure: A Cohort Study

Background: Serotonin reuptake inhibitors (SRIs) are often used to treat depression during pregnancy. SRIs cross the placenta and the fetal blood-brain-barrier. Serotonin (5HT) plays a key role in the development of the autonomic stress regulation systems, and alerting central 5HT levels during critical periods of fetal nervous system development could conceivably alter stress reactivity across childhood.

Objectives: To examine cardiac autonomic stress response to a lab stress challenge at 6 and 12 years of age in children with prenatal SRI (pSRI) exposure compared with non-exposed children, controlling for maternal depression (prenatal and concurrent).

Methods: In this prospective community cohort study, Canadian mothers were recruited in 2001 in the late 2nd trimester. We excluded mothers diagnosed with psychosis or bipolar disorder. We studied the children at 6 and 12 years. Cardiac autonomic activity [heart rate (HR); parasympathetic activity, Respiratory Sinus Arrhythmia (RSA); and sympathetic activity, preejection period (PEP)] were obtained before (5 minutes) during (5 minutes) and after (5 minutes) a standard stress challenge (MacArthur Battery at 6 years, mirror tracing/math task at 12 years) in children of pSRI treated mothers (6 years: n=37, mean exposure 241.1± 69.2 days; 12 years: n=34, mean exposure 243.5± 60.6 days) and non-exposed controls (6 years: n=62, 12 years: n= 64). SRIs included Sertraline, Citalopram, Fluoxetine, Paroxetine and Venlafaxine. We used linear mixed effects regression models to examine (1) prenatal exposure group differences: medication exposed vs. non-exposed; and (2) The impact of prenatal and concurrent maternal mood, adjusted for child age.

Results: At 6 years, the overall model showed pSRI exposure was associated with a higher PEP across all time points (β = 10.79, 95% CI: 2.824 to 18.765). Post hoc testing revealed PEP at baseline was higher in pSRI exposed children compared with controls (β=11.073, 95% CI: 2.924 to 19.222). Group differences in PEP, HR and RSA were not observed in stress or recovery phases. Depressed maternal mood (prenatal and concurrent) was not associated with differences in HR, PEP or RSA. At 12 years no group differences for cardiac measure were found. No sex differences were found.

Conclusions: Elevated sympathetic activity in pSRI exposed children was found at 6 years across all study periods. Stress measures were not associated with maternal mood nor with other measures of cardiac autonomic regulation. These differences were not observed at 12 years. Whether these findings represent a developmental effect of altered fetal 5HT-related programming of stress reactivity or are related to the methods we used to study stress regulation remains to be determined.