Antidepressant link to rare newborn disorder is tenuous, study shows

The link between antidepressant use by pregnant mothers and the development of a serious respiratory condition in newborn babies is far more tenuous than researchers originally thought, according to a study published Tuesday.

Researchers reviewing the impact of drugs such as Prozac on the rare condition PPHN (persistent pulmonary hypertension of the newborn) found that any elevation of risk, if present, is far below the six-fold increase once thought.

The new analysis could offer encouragement to expectant mothers who struggle with severe depression and may be agonizing over whether to continue taking the drugs. Doctors say the decision whether to wean off antidepressants while pregnant remains up to each individual mother and does have its own set of risks, but the study shows that at least one major fear of taking one class of antidepressants appears to be largely unfounded.

In a study of nearly 3.8 million pregnant women enrolled in Medicaid, researchers from Harvard Medical School and Brigham and Women’s Hospital in Boston looked at whether the women who took SSRI antidepressants — short for selective serotonin reuptake inhibitors like Prozac, Zoloft or Paxil — during the final trimester of their pregnancies are at higher risk of giving birth to babies who have PPHN.

When a newborn has PPHN, fetal blood flow doesn’t redirect toward the lungs after the baby is born and begins breathing air. Instead, high blood pressure forces blood away from the lungs, and the baby’s supply of oxygen is compromised. Between 10 and 20 percent of babies born with the condition don’t survive, and on a longer-term basis, PPHN can cause seizures and chronic lung disease.

In 2006, the U.S. Food and Drug Administration issued a warning against SSRI antidepressant use in pregnant women after a study of nearly 400 women showed a six-fold increase in risk that their babies were born with PPHN.

But several more studies done after that initial one offered conflicting results, and the FDA updated its warning in 2011 to back off from urging women not to take their SSRIs, saying more research needed to be done to figure out what causes PPHN. Some of the research, for example, has pointed to delivery by caesarian section as a contributing factor, and others have shown that PPHN is associated more with mothers who are obese, have diabetes or are African-American.

The current study, which is published in the Journal of the American Medical Association, points out that the research that does show a link to the respiratory condition was done with small sample sizes.

The researchers sought to find a large sample of women to examine. They examined nearly 3.8 million pregnant women who were enrolled in Medicaid for insurance coverage in 48 states and the District of Columbia between 2000 and 2010. Among them, 128,950 of them, or 3.4 percent, took antidepressants during the 90 days before delivery, the time period that is believed to be most crucial to developing PPHN. Breaking it down further, 102,179 or 2.7 percent took an SSRI, and 0.7 percent took a non-SSRI antidepressant.

When the researchers crunched the numbers, they found that the risk of developing PPHN was 20.8 per 10,000 infants among the women who didn’t take SSRIs, while it was 31 per 10,000 infants among the women who did. The women who took SSRIs versus non-SSRIs both had the higher risk, at 31.5 per 10,000 infants and 29.1 per 10,000 infants, respectively.

While that did represent a slightly elevated risk, when the researchers adjusted their sample to account for other factors that have also been linked to mothers developing PPHN — including obesity, diabetes and being African-American — the risk of developing the condition was not statistically significant.

“What I believe our study does is actually reassure women that when they’re making that decision [about whether to take antidepressants], concern about the increased risk of PPHN should not really factor in to their decision,” said Krista Huybrechts, an epidemiologist at Brigham and Women’s and a professor of Harvard Medical School, and lead author of the study. “It was, in essence, a null result.”

Huybrechts and her team emphasized that the results only apply to this particular respiratory condition, not to other problems that have been linked to pregnant mothers taking SSRIs.

For example, some research has linked SSRI use among pregnant women to babies with higher rates of ADHD, impaired language abilities and autism spectrum disorders, though some scientists dispute those findings.

Dr. Adam Urato, a professor at Tufts University School of Medicine who has spoken out against what he calls the “epidemic of antidepressant drug exposure during pregnancy,” wrote in a 2012 blog post that a body of research “clearly demonstrates risks” when pregnant women take anti-depressants, pointing to miscarriages, premature birth and neonatal complications.

But research also shows that mothers who are depressed during their pregnancies are more likely to avoid proper neonatal care and to use drugs, alcohol or nicotine during that time than pregnant women who aren’t depressed.

Untreated depression can also lead to miscarriage and low birth rate — the very conditions the mothers fear they may cause by taking antidepressants — and can cause new mothers to be less attentive to their babies, according to the American College of Obstetricians and Gynecologists.

Even if pregnant, doctors don't recommend just stopping antidepressants altogether. Instead, it's important to slowly taper off the drugs under the supervision of the doctor who prescribed them in order to avoid uncomfortable withdrawal symptoms like dizziness and nausea that arise when levels of neurotransmitters in the brain change too fast.

The ACOG says that depression is common during pregnancy, affecting between 14 and 23 percent of women. The association estimates that around 13 percent of pregnant women took an antidepressant during pregnancy, and in 2009 it recommended that pregnant women and their doctors carefully weigh the decision about whether to take antidepressants during pregnancy based on what is best for each particular mother.

Huybrechts says this is sound advice. “It is really an individual decision for every woman with her physician, and the severity of the depression factors strongly into that decision,” she said. “I think the context is very important.”