Genetics May Affect Fetal Susceptibility to SSRIs' Pulmonary Effects



VANCOUVER, B.C. – The impact of selective serotonin reuptake inhibitors on fetal pulmonary vascular physiology may boil down to genetics, study results suggest.

In a study of 55 pregnant women who were near term, a variety of right pulmonary artery measures (such as flow and impedance) did not differ significantly between fetuses of women who had been taking SSRIs since conception and those of women who had not. There was also no measurable effect of acute exposure to SSRIs.

However, within the SSRI-exposed group only, fetal right pulmonary artery flow was about 40% higher for infants who experienced respiratory distress in the neonatal period than for their counterparts who did not.

"So there is something different about this particular group in terms of the fact that they developed respiratory distress," commented lead investigator Dr. Kenneth Lim. "Maybe they respond to the SSRIs differently; maybe there is a genetic polymorphism that makes them more susceptible."

Regardless, this difference can be tapped to elucidate the effects of in utero exposure, he added. "It just sort of gives us an idea that maybe we need to look at that a little bit more closely in the next phase of our studies, to try to determine whether there is something going on in the pulmonary system of these babies."

Some 4% of pregnant women in British Columbia are taking SSRIs, according to Dr. Lim of the department of obstetrics and gynecology at the University of British Columbia in Vancouver. "In a province our size, that’s about 1,500-2,000 patients a year who are exposed to SSRIs," he noted at the annual meeting of the Society of Obstetricians and Gynaecologists of Canada.

Previous studies have determined that maternal use of this class of drugs has a variety of deleterious effects on the infant, including low birth weight, prematurity, and a type of withdrawal syndrome characterized by irritability and jitteriness.

"But interestingly, there is also a link with respiratory distress, which tends to be more like a TTN [transient tachypnea of the newborn]-type respiratory distress, and also, there have been case reports of primary pulmonary hypertension," he noted.

The pathogenesis of these pulmonary abnormalities is unclear. "We do know that serotonin itself is a very powerful vasoconstrictor, but it has differential effects in different tissues," Dr. Lim explained.

Preclinically, serotonin impairs lung fluid resorption, suggesting that SSRI-exposed infants may be unable to reabsorb lung fluid after birth; one SSRI has been found to increase arterial smooth muscle cell proliferation.

Pregnant women were eligible for the study if their fetus did not have any anomalies, if they were not taking any illicit or prescription drugs (other than SSRIs), and if they did not have any serious medical conditions.

The investigators enrolled two groups. The nonexposed control group consisted of healthy women who were at low risk for complications and who had not taken SSRIs during pregnancy. The exposed group consisted of women with a mood disorder who had been taking SSRIs since the time of conception.

At a gestational age of about 36 weeks, the women underwent a morning ultrasound exam to assess fetal pulmonary vasculature. Those taking an SSRI then took their medication for the day. In the afternoon, all women had a second ultrasound.

This approach allowed assessment of the effects of both chronic SSRI exposure (by comparing exposed and nonexposed groups) and acute SSRI exposure (by comparing morning and afternoon measurements in the exposed group), Dr. Lim explained.

Results were based on 23 women taking SSRIs (predominantly fluoxetine) and 32 control women. They were 33 years old, on average. Only a single woman in each group smoked during pregnancy. Those in the SSRI group had higher scores for depression.

At delivery, the gestational age was significantly younger in the SSRI-exposed group (39.0 vs. 40.0 weeks). Additionally, the SSRI-exposed infants had a smaller head circumference (34.1 vs. 35.0 cm) and poorer Apgar scores at 1 minute (7.5 vs. 8.4).

Infants in the SSRI-exposed group also were more likely to have respiratory distress (30% vs. 3%) and jitteriness (39% vs. 3%).

"These are all things that have been previously documented, so basically, these kids are behaving the way that we expect from previous studies," commented Dr. Lim.

When it came to fetal right pulmonary artery parameters, there were no significant differences between SSRI-exposed and SSRI-nonexposed groups, or between morning and afternoon within the exposed group, in terms of pulsatility index, resistance index (a measure of blood flow impedance in the artery), peak systolic velocity, diameter, area, and flow.


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