Newborns Affected by Moms’ SSRIs, But Symptoms Short-Lived

Finnish researchers have found that infants born to mothers who take SSRIs during the last trimester of their pregnancy may exhibit “serotonergic central nervous system adverse effects” during the first days of life. These adverse effects, however, are short-lived.

In the report, which appeared in the July issue of Archives of General Psychiatry, researchers from the departments of pharmacology and obstetrics and gynecology at the University of Turku in Finland prospectively followed 20 pregnant women taking either citalopram (Forest’s Celexa) or fluoxetine (Lilly’s Prozac and generics) for major depression or panic disorder and compared their infants with those of 20 women who had not taken any psychotropic medications during pregnancy.

Infants born to women taking SSRIs were found to have a fourfold higher incidence of serotonergic symptoms—most notably restlessness, tremor, and rigidity—in the first four days following birth, compared with babies born to mothers who had not taken SSRIs. In all the infants exposed to SSRIs, symptoms had markedly decreased by two weeks of age and had all but disappeared at two months of age. Notably, serotonergic symptoms were not completely absent in those infants of mothers not exposed to SSRIs.

“The study represents a novel approach to determine whether SSRIs in pregnancy have any effects on the fetus and or neonate,” said Zachary Stowe, M.D., an assistant professor of psychiatry at Emory University School of medicine and a noted American expert on the effects of SSRI use during pregnancy.

Stowe emphasized that the study focused on the two SSRIs—citalopram and fluoxetine—that have the highest rate of crossing the placenta into fetal circulation. These babies “typically receive about three quarters of the mom’s dose. In contrast, medications like paroxetine and sertraline cross the placenta significantly less,” Stowe told Psychiatric News.

At birth, all infants underwent standard clinical exams under blinded conditions. On each of the first four days of life and then at two weeks and two months, each infant underwent a neurologic status exam by pediatricians “trained to perform examinations using a specific scale for symptoms seen in a state of serotonergic overstimulation.” The exam included vital signs and observation for serotonergic symptoms including myoclonus, restlessness, tremor, shivering, hyper-reflexia, incoordination (assessed by general movements), and rigidity. In addition, each infant in the SSRI group underwent brain ultrasound and magnetic resonance imaging perinatally (at about 38 weeks) and at two months old. In each infant in the SSRI group, blood work was done to monitor levels of the active medications and their metabolites and prolactin levels. Identical laboratory studies were performed on the infants in the control group.

No differences were found between the two groups of infants in duration of pregnancy, mode of delivery, infant sex, weight at birth, weight at two months, or body temperature at birth.

Infants whose mothers were treated with SSRIs had an expectedly significant reduction (69 percent) in blood serotonin concentration, indicating more serotonin remaining active in the central nervous system rather than being metabolized. Importantly, a significant inverse relationship was seen between the serotonergic symptom score and the blood concentrations in SSRI-exposed infants, indicating serotonin symptoms were the worst for those infants exposed to the highest levels of SSRI. As medication levels dropped in the blood of the exposed infants, symptoms quickly disappeared, indicating that the symptoms were due to serotonin overstimulation, rather than an SSRI discontinuation syndrome (which would be expected to produce the opposite result—increasing symptoms with dropping blood medication levels.)

The authors of the report, led by Kari Laine, M.D., Ph.D., an assistant professor of pharmacology and clinical pharmacology at Turku University, concluded that “the clinical relevance of the present results is [to increase the] awareness of the psychiatrists who prescribe SSRIs during pregnancy and the pediatricians who treat the serotonin-related neurologic symptoms of the newborns during the first days of life. Although these effects seem to subside quickly, they may expose the infants to more serious neonatal complications such as convulsions.”

“I actually find the article to represent a positive statement about SSRIs in pregnancy,” Stowe commented. “The fact that the changes are only significant at four days postpartum, when the babies still have antidepressant in their blood, but that they are gone by two weeks postpartum in the majority of infants is evidence that [these medications] are not producing lasting effects [in the infants].”

Stowe also noted that the serotonergic effects observed by the Finnish researchers also disappeared, even in infants whose mothers were breastfeeding.

“This suggests that not only does pregnancy exposure not produce lasting effects, but also that breast feeding exposure does not affect such indices.”

An abstract of the study is posted on the Web at http://archpsyc.ama-assn.org/cgi/content/abstract/60/7/720. ▪

Arch Gen Psychiatry 2003 60 720