Importantly, in a metaanalysis by Huang and coworkers (2014), women using antidepressants during pregnancy have higher rates of preterm birth and low-birthweight neonates. Nevertheless, in their review, Ray and Stowe (2014) concluded that the relative reproductive safety data are reassuring and that antidepressants remain a viable treatment option. Furthermore, recurrence sometime after medication is discontinued develops in 50 to 85 percent of women with an initial postpartum depressive episode. Women with a history of more than one depressive episode carry greater risk (American Psychiatric Association, 2000). Surveillance includes monitoring for thoughts of suicide or infanticide, emergence of psychosis, and response to therapy. For some women, the course of illness is severe enough to warrant hospitalization.
Fetal and Neonatal Efects of Therapy. Some known and possible fetal and neonatal efects of treatment are listed in Table 61-3. Some studies suggest that SSRIs pose an elevated teratogenic risk for fetal cardiac defects, and these have mainly focused on paroxetine (Paxil). Associations were most consistent for ventricular septal defects. The estimated risk is no greater than 1 in 200 exposed newborns (Koren, 2012). Nevertheless, the American College of Obstetricians and Gynecologists (20 16b) recommends that paroxetine be avoided in women who are either pregnant or planning pregnancy. In women exposed to paroxetine in the irst trimester, fetal echocardiography is considered. Jimenez-Solem and coworkers (2013) in their analysis of SSRIs found no association between exposure to SSRIs during pregnancy and perinatal mortality. Andersen and associates (2014) found that women discontinuing SSRI treatment in early pregnancy had a small increased risk of miscarriage, but that this was similar to the risk in women discontinuing SSRI treatment months before pregnancy. Taken together, these investigators concluded that treatment with SSRIs during pregnancy should not be discontinued for fear of miscarriage.
Of other potential efects, the risk of persistent pulmonary hypertension of the newborn rose sixfold in neonates exposed to SSRIs after 20 weeks' gestation (Chambers, 2006). his translates to an overall risk of pulmonary hypertension that would be less than 1 in 100 exposed newborns (Koren, 2012). In contrast, a population-based cohort study of 1.6 million pregnancies identiied a twofold greater rate in exposed neonates. his yields an estimated attributable risk of 2 cases per 1000 births (Kieler, 2012). In a study of more than 120,000 gravidas prescribed antidepressants, Huybrechts and coworkers (2015) found an attributed risk of 1 case per 1000 births.
In sum, the maternal risk associated with discontinuing or tapering SSRI use during pregnancy must be weighed against marginally increased neonatal risks (Ornoy, 2017). Women who abruptly discontinue either serotonin-or norepinephrinereuptake inhibitor therapy typically experience some form of withdrawal.
Not surprisingly, up to 30 percent of exposed neonates may also exhibit withdrawal symptoms. Symptoms are similar to opioid withdrawal, but typically are less severe. Neonatal SSRI withdrawal is usually self-limited, and the newborn rarely remains in the nursery more than 5 days (Koren, 2009). Currently, convincing evidence of long-term neurobehavioral efects of fetal exposure to these medications is lacking (Koren, 2012). Grzeskowiak and coworkers (2016) found no increased risk of behavioral problems in 7 -year-old children exposed to antidepressants prior to their birth.