Oct. 5, 2009 — New research provides further evidence that links antidepressant use among pregnant mothers to problems for their newborns at birth.

The study showed that exposure to selective serotonin reuptake inhibitors (SSRIs) is associated with babies born an average of five days earlier and with twice the rate of premature births as infants whose mothers had no history of psychiatric illness.

Premature birth — also known as preterm birth — is commonly defined as happening before the baby has reached 37 weeks and happens in about 12% of all pregnancies. Cognitive problems, breathing problems, cerebral palsy, and digestive problems are all associated with preemie births.

Newborns whose mothers took SSRIs while expecting were also more than twice as likely to be admitted to the neonatal intensive care unit (NICU) and to have a lower 5-minute Apgar score than babies whose mothers did not take the drugs during pregnancy, according to the study. The Apgar score is a shorthand method of rating a newborn’s health status immediately after birth.

“Based on these results, we can say that there is an effect of SSRIs taken during pregnancy,” says lead researcher Najaaraq Lund, MD. “But whether or not this should be a reason for avoiding SSRIs? We still don’t have a final answer,” says Lund, who was a medical student researcher at the University of Aarhus in Denmark at the time the study was conducted.

SSRIs are the most common class of antidepressants taken by pregnant women in the U.S. The American College of Obstetricians and Gynecologists (ACOG) estimates that between 14%-23% of all pregnant women experience some form of depression during pregnancy.

In the study, Lund’s team used health records of more than 56,000 women who received prenatal care from the University of Aarhus Hospital between 1989 and 2006. The vast majority of these women had no psychiatric illness, but about 300 of them had received SSRIs during their pregnancy and nearly 5,000 of the study participants had a history of psychiatric problems but did not take any SSRIs while being treated for their pregnancy.

The study did not find significant differences between birth weight or head circumference between infants in any of the three groups.

Charles Lockwood, MD, chairman of the department of obstetrics, gynecology and reproductive sciences at Yale University, says that because women who are taking antidepressants are more likely to be sicker than those who do not — and thus more likely to deliver prematurely as a result of the stress of their mental illness — it’s possible the results were slightly confounded by this phenomenon.

“It’s sort of like the chicken and egg problem,” says Lockwood, who co-authored guidelines on the treatment for depression during pregnancy published jointly this August by ACOG and the American Psychiatric Association. “But the study still adds further weight to the possibility that the SSRIs themselves may be related to prematurity,” he says. Lockwood was not involved in the current study.

Treating Depression During Pregnancy an Ongoing Issue

The current study adds to the growing body of research devoted to helping decide whether pregnant women should take antidepressants during their pregnancy.

Previous studies have shown that the drugs lead to higher rates of NICU admissions because of withdrawal symptoms in newborns, and to higher rates of pulmonary hypertension — high blood pressure in the arteries that serve the lungs. Last month, another Danish study showed that women taking Celexa and Zoloft early in pregnancy gave birth to babies with a slightly higher rate of a certain heart defect.

Despite such problems, Lockwood warns of the dire potential outcomes of avoiding medications in some women who suffer from depression. “We must always be focused on the mother’s health because the greatest risk of under-treating a depressed mother is suicide — and that’s a really bad risk for any fetus to have,” he says.

Past studies have also shown higher rates of low birth weight and premature delivery as additional risks of being depressed while pregnant.

Although the exact mechanism is unclear, some animal studies have suggested that SSRIs might interfere with adequate blood flow to the uterus, thereby causing problems.

Pregnancy itself could cause onset of new depression or an exacerbation of pre-existing depression, says Lockwood. “Being pregnant can bring on a lot of different stresses for a woman — financial worries, physical distress from feeling nauseous and exhausted — it makes sense that there’s something about pregnancy in its essence that can trigger depression,” he says. Some theories suggest that fluctuations in certain hormone levels including progesterone and corticotropin-releasing hormone could also be part of the problem.

Strong Caution Against Discontinuing SSRI Use Among Severely Depressed Pregnant Women

“The number one thing is not to stop taking these meds if they work and if you will be depressed if you go off of them, especially if you will be severely depressed without them,” Lockwood says.

Pregnant women who are taking SSRIs should work closely with their obstetrician and psychiatrist to develop an optimal treatment plan that works for them on a case-by-case basis.

Treatment guidelines recommend that pregnant women experiencing psychotic episodes or bipolar disorder, or those who are suicidal or have been in the past should not be taken off antidepressants. Those with mild cases of depression or only a few symptoms for six months or longer can consider gradual reduction of doses or stopping drug treatment altogether, but only under close supervision of a doctor.

Behavioral therapy is another option that might work for some depressed women.

Lockwood says that women dealing with depression and mental health issues who are considering pregnancy should first attempt to get appropriate treatment, even if it requires going on antidepressant therapy.