Preliminary data on antidepressant use during pregnancy and miscarriage risk were reported from a nested case-control study in Quebec.(37) Cases (n = 5,124) were defined as pregnant women with a diagnosis or procedure related to a miscarriage, and controls (n = 51,240) were selected from the cohort and matched to each case according to the index date (date of diagnosis or procedure). Preliminary analyses indicated that use of any antidepressant was associated with an increased risk of miscarriage (OR 1.68; 95% CI 1.38-2.06).

Paroxetine (OR 1.75; 95% CI 1.31-2.34) and venlafaxine (OR 2.10; 95% CI 1.34-3.30) users had a higher risk of miscarriage than other antidepressants. This study and the study by Diav-Citrin et al, summarized earlier, (23), were among 15 studies included in a systematic review of 15 studies published1975-2009, evaluating the risk of spontaneous abortion after gestational exposure to antidepressants.(38) In adjusted analyses, paroxetine (OR1.7; 95% CI 1.3-2.3) and venlafaxine (OR 2.1; 95% CI 1.3-3.3) were significantly associated with the risk of spontaneous abortion. Casper et al compared the structural growth and developmental outcome of 31 children exposed to SSRIs in utero (26% exposed to paroxetine) with 13 children not exposed.(39)

There were no differences observed between groups for gestational age, premature births, birth weight and/or length; however, drug-exposed infants had lower APGAR scores at 1 (P=0.05) and 5 minutes (P=0.00). There were no significant differences in the Mental Development Index (MDI) between groups; however, exposed children were rated significantly lower in the Psychomotor Development Index (PDI) (P=0.03) and the Behavioral Rating Scale (BRS) (P=0.04). Evaluation of the BRS factor scales showed lower scores for motor quality in SSRI-exposed infants (P=0.01), with noticeable differences for tremulousness and fine motor movements.

Misri et al assessed the internalizing behaviors in children 4-5 years of age after previous prenatal exposure to psychotropic medications including SSRIs or SSRIs plus clonazepam (n=14 exposed to paroxetine).(40) There were no significant differences between the exposed and nonexposed groups based on parent and teacher/caregiver ratings. Based on clinician coding of the children's positivity, withdrawal, and irritability during a structured laboratory interaction, there were no significant differences observed between the two groups.

Oberlander et al compared attentional and activity behaviors in 22 four-year-olds following SSRI exposure (including paroxetine) in utero with 14 children without prenatal exposure.(41) Child externalizing behaviors (attention, aggression, attention deficit/hyperactivity, and oppositional or defiant behaviors) rated by parent or teacher were not statistically different between groups. On direct observation, persistence was significantly lower in the exposed group (P=0.03), while individual measures and composite behavioral scores of movement (activity), aggressiveness, attention, and emotion were not significantly different between the two groups.

 Pedersen et al conducted a study assessing whether prenatal antidepressant exposure was associated with time needed to achieve developmental milestones early in life compared to unexposed infants.(42) The study population consisted of 81,946 women from the Danish National Birth Cohort, of which 415 used an antidepressant during pregnancy (n = 76 paroxetine alone). At 6 months of age, fewer children exposed to antidepressants during the second or third trimester achieved all milestones (adjusted OR 2.6; 95% CI 1.2-5.8) and some motor function milestones compared to children of mothers with untreated depression (adjusted OR for sits without support" 2.1; 95% CI 1.2-.6 and adjusted OR for "all motor activity" 2.2; 95% CI 1.2-.8). At 19 months, none of the differences between exposed children and children of women with untreated depression was statistically significant except for an association between second or third trimester exposure and the inability to occupy themselves for >15 minutes (adjusted OR 2.1; 95% CI 1.09-.02).

Children exposed to SSRIs at any point during pregnancy sat without support and walked without support 8.7 and 15.2 days later (adjusted differences), respectively, than children of mothers with untreated depression, and this difference increased to 16.6 and 28.9 days in children exposed to SSRIs during the second or third trimester. The sample size did not allow stratification according to individual SSRI.