Kallen conducted an epidemiological study utilizing the Swedish Medical Birth Registry to examine neonatal outcome after maternal use of antidepressants in late pregnancy.(49) Infants born between July 1995 and December 2001 were selected for study and those whose mothers had been prescribed an antidepressant after the first antenatal care visit were identified. A total of 997 infants whose mothers received antidepressant therapy after the first antenatal visit were included in the study. Among the 987 mothers, 395 had used tricyclic drugs, 558 had used SSRIs (paroxetine, n = 106), and 63 had used other antidepressants. There were 31 women who had used 2 antidepressants during late pregnancy, of whom 19 had used a tricyclic and an SSRI and 8 had used an SSRI and an antidepressant other than a tricyclic or another SSRI. The pregnancy weeks when the drug was used were not stated in 387 cases, in 70 cases the drug was stopped before week 24, and in 561 cases, the drug was started or continued past week 23. Gestational duration, birth weight and fetal growth were examined in singleton births. The OR for preterm delivery (<37 weeks) for infants exposed to any antidepressant was 1.96 (95% CI, 1.60-2.41), and there was no significant difference between the ORs when the mother had used a tricyclic drug [2.50 (95% CI, 1.87-3.34)] and when she had used an SSRI [2.06 (95% CI, 1.58-2.69)]. For women using any antidepressant after pregnancy week 23, the OR for preterm delivery was 2.02 (95% CI, 1.54-2.63).

In view of the previous findings on paroxetine the author specifically compared neonatal outcome following paroxetine exposure with that for other SSRIs (as a group).(49) Only crude comparisons were made (without adjustment for year of birth, maternal age, etc.), because numbers were low and comparisons were made within SSRIs, where it was noted that confounding factors should be roughly equal. Paroxetine exposure gave higher ORs than exposure to other SSRIs for some conditions [preterm delivery (OR 1.28), low birth weight (OR 1.44), LGA (OR 1.77), respiratory distress (OR 1.23) and convulsions (OR 1.4)], but none reached statistical significance. Paroxetine was associated with lower ORs than other SSRIs for SGA, jaundice and hypoglycemia. On the basis of these data, the author concluded that outcomes after exposure to paroxetine were not worse than after exposure to other SSRIs.

Calderon-Margalit et al conducted a prospective cohort study of 2793 pregnant women to determine the association between psychotropic medication use during pregnancy with preterm delivery (primary outcome) and other adverse perinatal outcomes.(53) Three hundred women had used any psychotropic medication during pregnancy, and 31 women had taken paroxetine. Odds ratios were adjusted for maternal age, race/ethnicity, marital status, education, smoking during pregnancy, preeclampsia, parity, and singleton pregnancy. Maternal use of any SSRI or SNRI was associated with a nonsignificant increased risk of preterm delivery (adjusted OR, 1.34; 95% CI, 0.76-2.36); this risk was statistically significant for mothers who began taking SSRIs after the first trimester (adjusted OR, 4.79; 95% CI 1.66-13.9; P =0.004). Maternal use of paroxetine was associated with a non-statistically significant increased risk of preterm delivery (adjusted OR, 2.30; 95% CI, 0.90-5.83; P = 0.081). Maternal use of any SSRItherapy was not associated with small-for-gestational-age infant, low Apgar score, or respiratory distress syndrome. Use of any SSRI after the first trimester was associated with low birthweight (OR, 5.01;95% CI, 1.37-18.4; P = 0.015).

Sanz et al conducted a review of spontaneously reported cases of suspected SSRI-induced neonatalwithdrawal syndrome reported to the World Health Organization Collaborating Centre for International Drug Monitoring before the second quarter of 2003.(54) Of the 93 suspected cases identified, 64 were associated with paroxetine. Based on a logarithmic analysis to measure for an association of particular drugs and adverse drug reports, paroxetine, sertraline (n = 9), citalopram (n = 7), and fluoxetine (n =14) were all demonstrated to have a statistically significant association between the drug and neonatal convulsions or neonatal withdrawal syndrome.

Levinson-Castiel et al found a 30% (18/60) rate of neonatal abstinence syndrome (NAS) [45% severe and 55% mild] in a large population-based study that included infants with a reported prolonged in-utero exposure to SSRIs.(55) Of these neonates 62% (37/60) were exposed to paroxetine at a dose range of 10-40 mg.