Study designs of evaluations included in the review
Prospective cohort studies were eligible for inclusion.
Specific interventions included in the review
Studies that compared exposure to newer antidepressants with no exposure were eligible for inclusion. The newer antidepressants of interest included currently available selective serotonin re-uptake inhibitors (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline), serotonin-norepinephrine re-uptake inhibitors (venlafaxine), dual-action drugs (nefazodone, trazodone and mirtazapine) and selective noradrenaline re-uptake inhibitors (reboxetine and bupropion). Studies evaluating tricyclics and related drugs, monoamine oxidase inhibitors, botanicals and related compounds were excluded. The studies included in the review evaluated fluoxetine (10 to 80 mg/day, mean 25.8 and 26.8 in two other studies), fluvoxamine (10 to 60 mg/day), paroxetine (10 to 60 mg/day), sertraline (25 to 250 mg/day), venlafaxine (37.5 to 300 mg/day), and nefazodone, trazodone and bupropion (doses of these not reported). Most of the studies were conducted in Canada or the USA.
Participants included in the review
Studies of pregnant women who were exposed to the specified drugs in the first trimester of pregnancy were eligible for inclusion. Studies of women who were exposed to known teratogens or foetotoxic agents were excluded.
Outcomes assessed in the review
Studies that assessed major structural or functional malformations (including those requiring surgical correction) were eligible for inclusion. Malformations reported in the individual studies were listed according to exposure status. These included malformations in various body systems such as the heart, liver, brain, intestine and genital tract. Only outcomes for live births were considered.
How were decisions on the relevance of primary studies made?
Two reviewers independently selected the studies and resolved any disagreements through consensus.