Perinatal outcomes associated with antidepressant exposure during pregnancy are described in the literature.(27,43,44,45,46,47,48,49) Dubnov-Raz et al analyzed data collected on all neonates born to mothers receiving SSRIs or venlafaxine during pregnancy in Israel between 2000 and 2005 to determine the effect of antenatal SSRI exposure on the QT interval in newborns.(50) Prolonged QTc interval was defined as >460 milliseconds (ms). Fifty-two neonates born to mothers receiving a SSRI (paroxetine, n = 25) at onset of labor (with no other concomitant chronic medications) were compared with 52 newborns of healthy mothers taking no medications before delivery, matched according to gestational age.

The mean QTc interval was significantly longer in neonates exposed to SSRIs compared with control (unexposed) neonates (409 vs 392 ms; P = 0.02). The mean uncorrected QT interval was 7.5% longer (280 vs. 261 ms, P < 0.001) and the mean JT interval was 10% longer (229 vs. 209 ms; P < 0.001) in exposed newborns. Mean QTc intervals were similar among the most commonly used SSRIs, suggesting a class effect on QT interval. Five SSRI-exposed neonates (10%) had a markedly prolonged QTc interval (>460 ms) compared to no unexposed infants (P = 0.057); 3 of these infants had been exposed to paroxetine and the remaining 2 to fluoxetine. All 5 infants had normal QTc intervals upon follow-up ECG (within 48 hours for 3 infants and at 1 year for 2 infants).

Infants exposed to SSRIs in late pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN).(51) Chambers et al enrolled 377 infants born with PPHN and 836 healthy infants in a retrospective case-control evaluation to evaluate whether PPHN is associated with exposure to SSRIs during late pregnancy. Of these infants, 14 with PPHN and 6 healthy controls were exposed to an SSRI after the 20th week of pregnancy (adjusted OR 6.1; 95% CI 2.2- 16.8). The risk for developing PPHN was approximately six-fold higher for infants exposed to SSRIs after the 20th week of gestation compared to infants who had not been exposed to antidepressants during pregnancy.

Of the 377 infants with PPHN, 4 had been exposed to paroxetine. The number of patients in each group was too small to examine the effects of dose size, specific SSRI used, or reduction of the length of exposure before delivery.

 Andrade et al completed a retrospective study using the databases of four health plans to evaluate the prevalence of PPHN among infants whose mothers were exposed to antidepressants (SSRIs, TCAs, and miscellaneous antidepressants) in the third trimester of pregnancy compared to the prevalence among infants whose mothers were not exposed.(52) Women delivering an infant in a hospital from January 1, 1996, through December 31, 2000, were included. Of the 1104 infants exposed to antidepressants in the third trimester and a matched sample of 1104 unexposed infants, five infants were classified with PPHN. The prevalence of PPHN among infants exposed to any antidepressant was 1.81 per 1000 (95% CI 0.22, 6.54), while the prevalence of PPHN among nonexposed infants was 2.72 per 1000 (95% CI 0.56, 7.93).