FETAL EFFECTS OF SELECTIVE SEROTONIN REUPTAKE INHIBITOR TREATMENT DURING PREGNANCY: IMMEDIATE AND LONGER TERM CHILD OUTCOMES

Abstract

It is estimated that 20% of women experience symptoms of depression during pregnancy and antidepressant medication is prescribed for between 2% and 8% of pregnant women depending on the country of report. In the UK antidepressant prescribing during pregnancy increased fourfold from 1992 to 2006, with Selective Serotonin Reuptake Inhibitors (SSRIs) most often chosen. SSRIs cross the human placenta, with fetal levels varying according to treatment type and are found in amniotic fluid. The significance of prenatal exposure to SSRIs and outcomes in terms of the physical health and the neurodevelopment of the infant and child remainunclear. Several prescribed medications are known to be human teratogens, causing increased prevalence of a range of physical and neurodevelopmental deficits in exposed infants. Research into infant outcomes following prenatal exposure is challenging. Ethical constraints do not permit the most rigorous design for investigation, i.e.randomized double-blind controlled studies. In addition, variations in drug type, timing of exposure, dose, duration of exposure, placental passage and genetic factors all require consideration alongside maternal and infant demographic influences (e.g. maternal illness, socioeconomic status). Furthermore, a specific outcome type may be associated with specific risk variables and require targeted investigation. Maternal depression itself, either directly or indirectly, has been reported to influence obstetric and neonatal outcomes. Although beyond the scope of this review, research often fails to consider fetal exposure to antidepressants. Maternal antenatal depression is an important predictor of postnatal depression which may also impact on infant neurodevelopment. Understanding the risks of maternal depression and its treatment with regard to the development of the child is of paramount importance for clinical decision making. Serotonin is known to play a role in the development and physiology of the central nervous system, the gastrointestinal and the cardiovascular systems. In the fetal brain serotonin modulates different developmental processes including neurogenesis, apoptosis and axon branching and therefore alterations in the serotonin system may directly impact on later neuronal development. The role of serotonin in fetal development raises the possibility that SSRI exposure in utero may predispose to structural birth defects and poorer longer term outcomes, however, to date such a relationship is unclear. This review aims to bring together clinical research that examines the immediate and longer term physical and developmental risks to the child that may be associated with prenatal exposure to SSRIs. The article also examines the methodological issues that may contribute to conflicting findings.