Link between some antidepressants and birth defects is confirmed

Their analysis, published in the BMJ on Wednesday, included 17,952 mothers of children born with birth defects and 9,857 mothers of children without birth defects born between 1997 and 2009 at 10 centers. A total of 1,285 reported taking SSRIs, selective serotonin reuptake inhibitors, during one month before conception through the first trimester of pregnancy -- the period believed to be the most vulnerable for a baby in the womb.

The drug most commonly used by the study participants was Zoloft (sertraline), followed by Prozac (fluoxetine) and Paxil (paroxetine), Celexa (citalopram), and Lexapro (escitalopram).

Birth defects are alarmingly common, affecting one in every 33 babies born in the United States but scientists are still in the early stages of determining what causes most of them. Since the Food and Drug Administration issued an advisory warning of a potential association in December 2005 between paroxetine and heart defects in infants, researchers have launched numerous studies to try to figure out whether this is really an issue, but have come to conflicting conclusions.

"[T]he inconsistent reports have limited opportunities for clinicians to carefully evaluate the risk compared with benefit of specific SSRIs for given patient during pregnancy," the researchers wrote.

The new CDC study provides evidence that some SSRIs may be riskier than others.

While previous studies had shown associations between sertraline and five kinds of birth defects, the CDC study was unable to confirm any of them. Jennita Reefhuis, lead author of the study and an epidemiologist in the birth defects branch of the CDC, said in an interview that this was "reassuring" since this was the most commonly used drug among the group studied.

The researchers did find there is reason to be concerned about two other SSRIs, however. Children born to mothers who had taken paroxetine had a higher incidence of anencephaly, in which a baby is born without parts of the brain and skull, as well as defects of the heart and abdominal wall. Fluoxetine was associated with higher incidence of a heart defect and craniosyntosis, a condition that affects one or more of the joints in a baby's skull.

Reefhuis said that while the associations were clear in their study, the absolute risk to the babies appeared to be small. For instance, the risk of anencephaly for children of women who take paroxetine would increase from 2 per 10,000 to 7 per 10,000.

"It is a doubling or more in some cases, but you have to keep in mind that that a doubling of small risk is still a small risk," she said.

Reefhuis said there were a number of limitations to the study, including the fact that the researchers did not know the dose of the antidepressants taken by the women or why they were taking them. She said a new CDC-funded study is underway that will look more closely at these factors and will zero in more closely on babies born with the severest types of birth defects.

Treatment guidelines regarding depression during pregnancy published in 2009 by the American Psychiatric Association and the American College of Obstetricians and Gynecologists recommend discontinuing antidepressants if women are minimally symptomatic for a long period of time, but allow for the initiation or continuation of antidepressants if a woman is experiencing a moderate or severe episode or has a history of them.

Reefhuis said that the research team acknowledges how serious depression and other mental health issues can be and that many women may need to take medications during pregnancy but that they should be in close contact with their providers to determine whether any modifications need to be made.

"Ideally she should do this as she is starting planning, before pregnancy. It does take a while to establish whether these drugs are working and it can take weeks to taper off if they are not," she said.