PEDIATRICS Vol. 113 No. 2 February 2004, pp. 368-375 Philip Sanford Zeskind, PhD*, and Laura E. Stephens* * Department of Pediatrics, Carolinas Medical Center, Charlotte, North Carolina Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina

Objective. This is a prospective study of the effects of maternal use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy on newborn neurobehavioral integrity, including systematic measures of behavioral state, sleep organization, motor activity, heart rate variability (HRV), tremulousness, and startles.

Methods. The sample included 17 SSRI-exposed and 17 nonexposed, full-birth-weight newborn infants who had no obvious medical problems and were matched on maternal cigarette use, social class, and maternal age. SSRI exposure was determined by medical records and maternal self-report during a standard interview. Behavioral state, startles, and tremulousness were evaluated for 1 hour between feedings. Automated recordings of motor activity and HRV were also assessed during a 15-minute subset sleep period. HRV was subjected to spectral analysis to detect rhythms in autonomic regulation. Exposed and nonexposed infant groups were compared on measures of neurobehavioral development both before and after adjustment for gestational age as a covariate.

Results. SSRI-exposed infants had a shorter mean gestational age; were more motorically active and tremulous; and showed fewer rhythms in HRV, fewer changes in behavioral state, fewer different behavioral states, and a lower peak behavioral state. SSRI-exposed infants also had significantly more rapid eye movement sleep, which was characterized by longer continuous bouts in that state and higher numbers of spontaneous startles or sudden arousals. After effects of gestational age were covaried, significant differences continued to be found in tremulousness and all measures of state and sleep organization, but effects on startles, motor activity, and rhythms in HRV were no longer significant.

Conclusions. Results provide the first systematic evidence that women who use SSRIs during pregnancy have healthy, full-birth-weight newborn infants who show disruptions in a wide range of neurobehavioral outcomes. Effects on motor activity, startles, and HRV may be mediated through the effects of SSRI exposure on gestational age. Future research can lead to a better understanding of the effects of SSRI use during pregnancy and an improved public health outcome.