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Link between antidepressants and newborn disorder may not be as strong as scientists thought

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The risk for persistent pulmonary hypertension of the newborn is low

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Women often worry about taking antidepressants during a pregnancy. Depending on the drug that an expecting mother takes, a fetus's chance of being born with a birth defect can increase. But a large study now suggests that the one of the defects — persistent pulmonary hypertension of the newborn, a life-threatening condition — is probably far lower than was previously suggested. The finding could help some women, namely women who suffer from severe depression and who don’t respond to other treatments, feel more secure about their decision to take antidepressants during a pregnancy; doing so might not be nearly as risky as some studies have suggested in the past.

PPHN is life-threateningBabies who are born with persistent pulmonary hypertension of the newborn — or PPHN — have trouble transitioning from fetal blood circulation to newborn circulation, which decreases their supply of oxygen after birth. Among the general population, a child's risk of developing PPHN is low, but some studies have found that the risk increases if an expecting mother takes antidepressants during the last few months of pregnancy. As a result, the FDA issued a warning in 2006 that said that the most common type of antidepressant — SSRIs— had been linked to the ailment (the FDA revised its position in 2011, stating that the link was "unclear").

Yet about 14 percent of non-pregnant women in the US have current major or minor depression. If that depression occurs during a pregnancy, it can affect mother-infant attachment, as well as the behavior and development in infants and children. Taken together, it’s easy to see why doctors might want to make sure that the link between antidepressants and PPHN is one that warrants forgoing antidepressants.

The risk increase disappearedIn the study, researchers used Medicaid data to extract information about 3.8 million women, some of whom had filled a prescription for an antidepressant 90 days before giving birth and who had received a depression diagnosis. They found that, indeed, PPHN was diagnosed more frequently in babies of women who took an antidepressant during pregnancy compared with the babies of women who did not. But when the researchers accounted for other risk factors that could contribute to this difference — factors like drug abuse, missing prenatal visits, and smoking — the increase disappeared. "There is basically no increase after the adjustment," says Krista Huybrechts, a pharmacoepidemiologist at Harvard University and a co-author of the study published today in JAMA.

The results do not mean that antidepressant use during the last few months of a pregnancy definitely does not increase a fetus’s risk of being born with PPHN. It’s entirely possible that the drugs do contribute, but "if the risk increase is at all present, it is much more modest than previous studies have suggested," Huybrechts says.

"The study is well done," says Jennifer Payne, director of the Women's Mood Disorders Center at Johns Hopkins University. "We would all love to have a large study that was able to control for all the known risk factors, so we can determine if the association is due to the antidepressant use or the underlying characteristics of the population." The authors of this study were able to control for several risk factors, she says — something that previous studies didn’t necessarily do.

Hard to know if the women took the antidepressantsThe study has some limitations that are worth considering, however. For one thing, the researchers weren’t able to verify that the women who were filling prescriptions for antidepressants were actually taking the drugs. It’s possible that they weren’t. "Filling a prescription for an antidepressant is not equivalent to taking an antidepressant," says Nancy Byatt, a psychiatrist who specializes in perinatal health at the University of Massachusetts. But an additional analysis of women who had filled two prescriptions 90 days before delivery — an act that suggests that they were taking their drugs, Huybrechts says — didn’t change the study’s results. This suggests that using women who filled one prescription probably doesn’t weaken the results.

The study may have also missed some women who's depression was undiagnosed, Byatt says. "It is well known that depression during pregnancy is under-diagnosed and under-treated." That said, Byatt also thinks the study was well conducted.

Concerns about PPHN shouldn't factor "majorly"The finding should be reassuring for women who suffer from very severe and debilitating depression and who don’t respond to other treatments. "There is an abundance of studies that demonstrate that exposure to depression [in the womb] is associated with bad outcomes for the baby" — outcomes that include low birth weight, preterm birth, "as well as postpartum depression which is associated with slower language development and lower IQ in exposed children," Payne explains. That’s why concerns about the risk of PPHN shouldn’t factor "majorly" into the decision to take antidepressants, Huybrechts says. "Women still need to think about other potential risks, but they should also think about the benefits that using antidepressants might have for their own health."