The Danish study also shows that the risk is greatest when moms-to-be take more than one selective serotonin reuptake inhibitor (SSRI) antidepressant or switch SSRIs early in pregnancy.
The new study shows the overall risk for congenital heart problems associated with SSRI to be quite low.
But babies born to women who had filled prescriptions for more than one SSRI had a fourfold increase in septal heart defects -- a malformation of the wall that divides the left and right sides of the heart.
Unclear if All SSRIs Carry Risk
The finding will no doubt add to the confusion surrounding the safety of specific SSRIs during pregnancy.
In 2005, based on the research at the time, the FDA singled out the drug Paxil, warning that its use was associated with an increased risk for heart defect.
It has since become common practice for doctors to switch women taking Paxil to another SSRI when they become pregnant or are considering pregnancy.
But more recent studies suggest that women who take Paxil have no greater risk for delivering babies with the heart defect than women who take other antidepressants.
In the Danish study, use of Celexa and Zoloft early in pregnancy was associated with a small increased risk for the heart defect, but no association was seen in women who took Paxil or Prozac.
The study compared the incidence of birth defects among babies born to Danish women who did and did not take SSRIs during their first trimester. The study included more than 400,000 children born between 1996 and 2003.
Septal heart defects occurred in 0.5% of children born to mothers who did not take antidepressants and 0.9% of children born to mothers who did. SSRI use was not linked to any other major birth defect.
"The bottom line is the risk associated with SSRI use appears to be very small, and this has to be balanced against the very real risk associated with having untreated depression during pregnancy," study researcher Lars H. Pedersen of Aarhus University tells WebMD.
Larger Studies Needed
Pedersen says much larger studies are needed to determine whether any one SSRI is safer or less safe than any other during pregnancy.
In an editorial published with the study Friday in BMJ Online First, birth defects researcher Christina Chambers, PhD, agrees that larger studies are needed.
Chambers is an epidemiologist and associate professor at the University of California, San Diego School of Medicine.
"If an increased risk for major congenital malformations does exist, this study and others suggest that the absolute risk for the individual pregnant woman is very low," she writes. "Furthermore, each of the more commonly used drugs in this class has been implicated in at least one study, so it is difficult to conclude that one SSRI is 'safer' than another."
Last month, two leading medical groups in the U.S. teamed up to issue guidelines for treating depression during pregnancy.
The joint statement from the American College of Obstetricians and Gynecologists (ACOG) and the American Psychiatric Association (APA) recommended that:
- Women who experience psychotic episodes, have bipolar disorder, or those who are suicidal or have a history of suicide attempts should not be taken off antidepressants.
- Women with mild depression and those who have had few symptoms for six months or longer can consider gradually reducing their drug doses or stopping drugs altogether under the close supervision of their prescribing doctor.
- Psychotherapy and other treatments may be an appropriate alternative to drugs during pregnancy for some, but not all, women with depression.
Chambers tells WebMD that the joint ACOG/APA guidelines should help women and their doctors understand their options.
"Every pregnant woman has about a 3% risk of having a baby with a birth defect," she says. "If there is a risk associated with SSRI use it is very small over and above this baseline risk."