Four prospective studies were included in the review with 1,598 participants (711 participants took fluoxetine or SSRIs, 154 took tricyclic antidepressants, and 733 participants were in the control group).
Exposure to tricyclic antidepressants, fluoxetine, and selective serotonin re-uptake inhibitors (SSRIs) did not increase the risk of intra-uterine death or major birth defects (morphological teratogenicity).
Decreased birth weight (growth impairment) of infants exposed to fluoxetine in the third trimester were identified in one study.
The development of children (behavioural teratogenicity) whose mothers took tricyclics or fluoxetine during gestation did not differ from that of controls.
Direct drug effects (neonatal toxicity) and withdrawal syndromes occurred in some neonates whose mothers were treated with antidepressants near term.
In the first included study, rates of major malformations were comparable across the three groups. Infants born to women treated with either fluoxetine or tricyclic antidepressants had more neonatal complications than the group exposed to nonteratogens.
In the second included study, the rate of major birth defects was not significantly different in the two fluoxetine groups compared with controls. However, in the fluoxetine groups, the presence of three or more minor anomolies were reported more frequently (15.5%) compared with controls (6.5%, p=0.03). Premature birth occurred in 14.3% of infants born to the late-exposure group compared with 4.1% of infants in the early-exposure group, and 5.9% in the control group. Poor neonatal adaptation was described in 31.5% of the infants born to the late-exposure group compared with 8.9% of the infants born to the early-exposure group. Full-term infants born to the late-exposure group had a lower mean birth weight (by an average of 188 g) and shorter birth length than infants born to either the early exposure of control groups. Maternal weight gain was an average of 3 kg less in the late-exposure group.
In the third included study, there were no differences in rates of perinatal complications. Incidence of major malformations was the same in the three groups, and mean global IQ was similar. Scores on verbal comprehension, expressive language, temperament, mood, arousability, activity level, and distractibility tests and behaviour problems did not differ in children exposed to antidepressants compared with controls. Multiple regression of the effect of the duration of antidepressant therapy (first trimester compared with entire pregnancy) revealed no significant differences on any of the neurobehavioural tests compared with the control children.
In the fourth included study, exposure to an SSRI was not associated with increased risk for major malformations or higher rates of miscarriage, stillbirth, or prematurity. Birth weights of infants and gestational ages were similar in the group with SSRI-exposure and controls. Pregnancy outcome among women who took an SSRI throughout pregnancy did not differ from those who took the drug only during the first trimester.