Moms' SSRI Use Linked to Pulmonary Hypertension in Newborns

Deborah Brauser

January 16, 2014

Maternal antidepressant use has been linked to a low but statistically significant increased risk for persistent pulmonary hypertension (PPH) in newborns exposed to the drugs in late pregnancy, new research shows.

A meta-analysis of 7 studies showed a significant association between PPH and infants of expectant mothers who used selective serotonin reuptake inhibitors (SSRIs) during their last trimester, even after several moderator variables were examined.

However, the absolute risk was low, report the investigators.

"The risk difference, which is something we wanted to look at for clinicians, was about 3 per 1000 infants," lead author Sophie Grigoriadis, MD, PhD, head of the women's mood and anxiety clinic at Sunnybrook Health Sciences Center in Toronto, Canada, and associate professor of psychiatry at the University of Toronto, told Medscape Medical News.

There was no association found between newborn PPH and SSRI exposure during early pregnancy.

Still, the researchers add that "it is imperative" that the mother's health, as well as the fetus', be weighed heavily in all treatment decisions.

"She and her family must be counselled on both the risks of exposing the fetus to antidepressant drugs and the risks of severe depressive illness," they write.

The study was published online January 14 in BMJ.

Rare Condition

According to the investigators, PPH of the newborn is relatively rare, with an estimated prevalence of 1.9 per 1000 live births. Symptoms of this condition can include respiratory distress or even hypoxia.

Although the US Food and Drug Administration and Health Canada issued clinician advisories in 2006 about the potential association between maternal use of SSRs and PPH of the newborn, the US advisory was revised in 2011.

At that time, it stated that "given the conflicting results from different studies, it is premature to reach any conclusion" about this possible link.

"To date no meta-analysis has been published to summarise the data and potentially help resolve these conflicting findings for the clinician," write the investigators.

Dr. Sophie Grigoriadis

Dr. Grigoriadis reported that the investigators have been engaged in a large research program to understand the risk of various treatments so that they can develop a reference guide to help clinicians and their patients make more informed treatment decisions. Examining the risk for PPH after prenatal exposure to SSRIs was just one of the studies included as part of this research.

The investigators reviewed 3077 abstracts before choosing 7 English language studies that met all of their inclusion criteria. All infants were of at least 33 or 34 weeks' gestation. No preterm births were included.

Results showed a significantly increased risk for PPH in newborns who were exposed to SSRIs in late pregnancy (odds ratio [OR], 2.50; 95% confidence interval [CI], 1.32 - 4.73; P = .005) but not for those exposed during early pregnancy (OR, 1.23).

The absolute risk difference for newborns developing PPH after late pregnancy exposure to SSRIs was 2.85 to 3.5 per 1000 infants; the number needed to treat to harm was 286 to 351 women.

In other words, 268 to 351 women would need to be treated with an SSRI in late pregnancy to result in an average of 1 additional case of newborn PPH.

On the other hand, 2288 women would need to be treated with an SSRI in early pregnancy to see 1 additional case of PPH.

Education, Discussion Needed

"Our moderator analyses did not find study design, congenital malformations, or meconium aspiration to be significant effect modifiers," report the investigators, adding that maternal obesity and cesarean delivery could not be examined as possible moderating effects.

Overall, the researchers note that depression during pregnancy should not be left untreated ― and antidepressants may be necessary, especially for severe depressive episodes.

"Although the odds for [PPH] of the newborn seem to be greater with the use of SSRIs later in pregnancy, despite the limitations of the original studies, the risk is still low," they note.

"Results…still concur with earlier statements that fewer than 1 infant in 100 will develop this condition after antenatal exposure to SSRIs," they add.

Still, the investigators write that pregnant women who are considering the use of these medications should be educated about PPH "and that it can typically be managed successfully if it does occur."

In addition, they stress that neonatologists should be made aware of any exposure to SSRIs.

No Clear Answers

"This study makes an important contribution because the investigators quantify the effects across a number of studies instead of just summarizing them," Katrina C. Johnson, PhD, assistant professor in the Department of Psychiatry and Behavioral Sciences at Emory University in Atlanta, Georgia, told Medscape Medical News.

However, "because the overall association was small but statistically significant, it does not provide patients and physicians with clear answers when trying to make treatment decisions," she added.

Dr. Johnson, who was not involved in the research, noted that the small number of studies included in the review was "concerning."

"This was particularly surprising given the amount of attention this topic has received in the media and in general reviews of antidepressant exposure during pregnancy," she said.

She added that she was also disappointed that the authors were not able to test statistically how other risk factors, such as maternal body mass index or premature birth, might interact with prenatal SSRI exposure.

"This would be an important future direction for other studies. Might mothers with multiple risk factors weigh their treatment options differently than mothers with no other risk factors?"

Overall, Dr. Johnson said that the key take-home message is that women need to take an active role in their own mental health care, before, during, and after pregnancy.

"They should ask questions and partner with their physician to assess the risks and benefits of treating with medication. They should [also] feel free to ask for a second opinion if they don't feel their concerns are being fully addressed," she said.

Recently, Dr. Johnson and colleagues published a small study in the Archives of General Psychiatry showing that infants with prenatal exposure to antipsychotics had lower neuromotor performance scores than those who were not exposed to the drugs.

However, then as now, she noted that maternal mental illness can be harmful for a baby's development, and women should never just stop taking their medication.

"Going off all medications suddenly following a positive pregnancy test is dangerous. Likewise, a physician who dismisses a woman's concerns about the potential effects of taking antidepressants during pregnancy is undesirable."

Several of the study authors have reported possible conflicts, which are fully listed in the original article. Dr. Johnson reports no relevant financial relationships.

BMJ. Published online January 14, 2014. Full article

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