Selective Serotonin Reuptake Inhibitors Affect Neurobehavioral Development in the Human Fetus

The aim of this prospective study was to investigate whether selective serotonin reuptake inhibitors (SSRIs) utilized by pregnant women influence fetal neurobehavioral development. In this observational study we investigated developmental milestones of fetal behavior during the pregnancy of women with psychiatric disorders who took SSRIs throughout gestation (medicated group; n = 96) or who had discontinued medication early in gestation or before conception (unmedicated group; n = 37). Healthy unexposed fetuses of women without mental disorders comprised the control group (n = 130). Ultrasonographic observations of fetal behavior were made three times in pregnancy (T1-T3). Effects of SSRIs were studied over a wide range of dosages (low, standard, or high) and for different drug types. Fetuses exposed to standard or high SSRI dosages compared with control, unmedicated, or low-medicated fetuses showed significantly increased motor activity at the beginning (T1) and end of the second trimester (T2). They particularly exhibited disrupted emergence of non-rapid eye movement (non-REM; quiet) sleep during the third trimester, characterized by continual bodily activity and, thus, poor inhibitory motor control during this sleep state near term (T3). The SSRI effects on the fetus were dose related, but independent of SSRI type. The results demonstrate changes in fetal neurobehavioral development associated with standard and high SSRI dosages that are observable throughout gestation. A first-choice SSRI type was not apparent. Bodily activity at high rate during non-REM sleep in SSRI-exposed fetuses is an abnormal phenomenon, but its significance for postnatal development is unclear. Neuropsychopharmacology (2011) 36, 1961-1971; doi:10.1038/npp. 2011.67; published online 27 April 2011