Selective serotonin-reuptake inhibitors and persistent pulmonary hypertension of the newborn.

to the editor: Several publications have recently reported an association between maternal treatment with selective serotonin-reuptake inhibitors (SSRIs) late in pregnancy and adverse outcomes in infants. These outcomes have included persistent pulmonary hypertension of the newborn (PPHN), as reported by Chambers et al. (Feb. 9 issue),1 and the neonatal abstinence syndrome, a condition found in infants born with drug dependency.2 Also, the Food and Drug Administration recently published a public health advisory concerning increased rates of congenital defects (and, specifically, heart defects) after the use of the SSRI paroxetine early in pregnancy.3 However, little information is available on the frequency of SSRI treatment during pregnancy.4 We have obtained such data from the National Birth Defects Prevention Study, a populationbased, case–control study of congenital anomalies conducted in eight states (Arkansas, California, Georgia, Iowa, Massachusetts, New Jersey, New York, and Texas).5 Mothers of liveborn infants without birth defects (controls) were randomly selected at each site. Among 4094 control mothers who delivered their infants from October 1997 to December 2002 and completed an hour-long interview on exposures during pregnancy, 113 reported the use of SSRIs within three months before conception and through the end of pregnancy (2.8 percent), including 95 who used SSRIs during pregnancy (2.3 percent). These findings were similar to those regarding the frequency of use of SSRIs during pregnancy in the study by Chambers et al. among the matched controls (2.9 percent).1 Figure 1 shows the prevalence of the use of SSRIs (and, specifically, of fluoxetine, sertraline, and paroxetine) and the use of any prescription antidepressant within three months before conception and through the end of pregnancy. The use of the drugs decreased after the first month of pregnancy: of the 76 women who used an SSRI in the first month of pregnancy, 23 discontinued treatment by the second month (30.3 percent). Between 1997 and 2002, there was no significant change in the reported use of SSRIs during pregnancy (1.5 percent of pregnancies in 1997 and 1998, 2.8 percent in 1999 and 2000, and 2.3 percent in 2001 and 2002); the reported use of any prescription antidepressant followed a similar pattern (2.0 percent, 3.3 percent, and 2.6 percent, respectively). Of 151 specific reports of antidepressant use by 140 control mothers before and during pregnancy, most involved SSRIs (77.5 percent), with bupropion (a norepinephrineand dopamine-reuptake inhibitor) the second most