David Baxter PhD
Late Founder
Antenatal SSRI antidepressant exposure poses only small risk to babies
June 28, 2007
The risk of birth defects following antenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants is controversial. Early studies indicated that SSRIs didn't increase the risks of birth defects when such defects were studied as a group. However, birth defects are not a single entity and individual defects have distinct causes. More recent studies reported elevated risks for some birth defects.
In response to those studies a committee of the American College of Obstetricians and Gynecologists issued a recommendation to its members last November that SSRIs be discontinued when a patients becomes pregnant.
Now two large new studies published in the New England Journal of Medicine have found that the birth defect risk from taking SSRIs is very low. One study found only a small increase in some rare defects and the other was unable to find any link in most cases.
In the first study, researchers from Boston University's Slone Epidemiology Center report that individual SSRIs may increase the risk for some specific defects, but these are rare and the absolute risks are small.
Using data from the Slone Epidemiology Center's Birth Defects Study, an ongoing program of case-control surveillance of medication use in relation to birth defects, the researchers considered relationships between first trimester SSRI use and the risk of various birth defects among mothers of 9,849 infants with birth defects and 5,860 infants without defects.
The researchers analyzed defects previously linked to SSRI use and found overall SSRI use was not associated with significantly increased risks of craniosynostosis (where connections between skull bones close prematurely), omphalocele (intestines or other abdominal organs protrude from the navel) or of congenital and overall heart defects.
The lack of an association with congential heart defects is at odds with FDA and drug company warnings of such a link. The authors of both new studies suggest that previous findings of a strong link may have resulted from chance associations being magnified by multiple comparisons of the data.
Analysis of individual SSRIs and specific defects showed significant associations between sertraline (Zoloft?) and omphalocele and septal defects (defects in the walls that separate the chambers of the heart) and between paroxetine (Paxil?) and certain heart defects that interfere with blood flow to the lungs. This last association was also reported in the second paper, from the U.S. Centers for Disease Control and Prevention's (CDC) National Birth Defects Prevention Study. However, the Boston University researchers stress that even if a specific SSRI increased rates four-fold, as was observed for some of these associations, the risk of having an affected child would be less than one percent.
"Our analyses did not confirm previously reported associations between overall use of SSRIs and a number of birth defects," said lead author Carol Louik, ScD, an assistant professor at the Slone Epidemiology Center at Boston University. "Rather our study suggests that risks are limited to specific SSRIs in relation to specific birth defects. Still, it is important to keep in perspective that the baseline risks for these rare defects are small, so even if the modest increased risks we observed are correct, the chances of having a child with such a defect are quite small," she added.
"This is a valuable contribution," said Dr. Jon Shaw, director of child and adolescent psychiatry at the University of Miami's Miller School of Medicine commentating on the study. "It substantiates the need to always be prudent in prescribing antidepressants."
Funding for this study was provided by GlaxoSmithKline, the manufacturer of Paxil, the National Institute of Child Health and Human Development, the National Heart, Lung and Blood Institute, Aventis and Sanofi-Pasteur.
In the CDC study, researchers from the University of British Columbia at Vancouver and the CDC's National Center on Birth Defects and Developmental Disabilities assessed the risks of first trimester SSRI exposure using data from the CDC-funded National Birth Defects Prevention Study of 9622 infants with major birth defects and 4092 control infants (selected randomly from the same geographic areas) born from 1997 through 2002. SSRI exposure was defined as treatment with any SSRI from 1 month before to 3 months after conception. Birth defects were assigned to 26 categories and sub categories.
The study looked at the four most commonly prescribed SSRIs, fluoxetine (Prozac?), sertraline (Zoloft?), paroxetine (Paxil?), and citalopram (Celexa?).
They found some associations between SSRI use and anencephaly (a brain defect), craniosynostosis and omphalocele, however, the number of cases of each was too small to be conclusive. For example, while there was a 2.4 times greater risk of an child being born with anencephaly, only 9 of the 214 babies born with this defect had been exposed to SSRIs. There was a 2.5 times greater risk for craniosynostosis (24 exposed from 432 cases) and 2.8 times increased risk of omphalocele (11 of 181 cases). For each defect the absolute risk was small and within the 3 percent risk of major birth defect that applies to all pregnancies.
None of these defects had been associated with SSRI use in previous studies and the researchers suggest the results require confirmation by other studies. "CDC plans to continue to study the association to clarify whether a true risk exists," the CDC said in a statement on the study.
"Overall, our results are generally reassuring with respect to the use of antidepressants during pregnancy," said CDC epidemiologist Jennita Reefhuis, one of the authors of the study. "We know that both the mother and baby benefit when a pregnant woman with a serious depressive illness is able to stay on some sort of treatment. The risks may vary for different SSRIs and groups of women. It's important that women talk with their doctor about the risks and benefits of taking SSRIs during pregnancy."
Louik C, Lin AE, Werler MM, Hern?ndez-D?az S, Mitchell AA. First-Trimester Use of Selective Serotonin-Reuptake Inhibitors and the Risk of Birth Defects. NEJM 200 Jun 28;356:2675-2683 [Abstract]
Alwan S, Reefhuis J, Rasmussen JA, Olney RS, Friedman JM. Use of Selective Serotonin-Reuptake Inhibitors in Pregnancy and the Risk of Birth Defects. NEJM 2007 Jun 28;356:2684-2692 [Abstract]
June 28, 2007
The risk of birth defects following antenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants is controversial. Early studies indicated that SSRIs didn't increase the risks of birth defects when such defects were studied as a group. However, birth defects are not a single entity and individual defects have distinct causes. More recent studies reported elevated risks for some birth defects.
In response to those studies a committee of the American College of Obstetricians and Gynecologists issued a recommendation to its members last November that SSRIs be discontinued when a patients becomes pregnant.
Now two large new studies published in the New England Journal of Medicine have found that the birth defect risk from taking SSRIs is very low. One study found only a small increase in some rare defects and the other was unable to find any link in most cases.
In the first study, researchers from Boston University's Slone Epidemiology Center report that individual SSRIs may increase the risk for some specific defects, but these are rare and the absolute risks are small.
Using data from the Slone Epidemiology Center's Birth Defects Study, an ongoing program of case-control surveillance of medication use in relation to birth defects, the researchers considered relationships between first trimester SSRI use and the risk of various birth defects among mothers of 9,849 infants with birth defects and 5,860 infants without defects.
The researchers analyzed defects previously linked to SSRI use and found overall SSRI use was not associated with significantly increased risks of craniosynostosis (where connections between skull bones close prematurely), omphalocele (intestines or other abdominal organs protrude from the navel) or of congenital and overall heart defects.
The lack of an association with congential heart defects is at odds with FDA and drug company warnings of such a link. The authors of both new studies suggest that previous findings of a strong link may have resulted from chance associations being magnified by multiple comparisons of the data.
Analysis of individual SSRIs and specific defects showed significant associations between sertraline (Zoloft?) and omphalocele and septal defects (defects in the walls that separate the chambers of the heart) and between paroxetine (Paxil?) and certain heart defects that interfere with blood flow to the lungs. This last association was also reported in the second paper, from the U.S. Centers for Disease Control and Prevention's (CDC) National Birth Defects Prevention Study. However, the Boston University researchers stress that even if a specific SSRI increased rates four-fold, as was observed for some of these associations, the risk of having an affected child would be less than one percent.
"Our analyses did not confirm previously reported associations between overall use of SSRIs and a number of birth defects," said lead author Carol Louik, ScD, an assistant professor at the Slone Epidemiology Center at Boston University. "Rather our study suggests that risks are limited to specific SSRIs in relation to specific birth defects. Still, it is important to keep in perspective that the baseline risks for these rare defects are small, so even if the modest increased risks we observed are correct, the chances of having a child with such a defect are quite small," she added.
"This is a valuable contribution," said Dr. Jon Shaw, director of child and adolescent psychiatry at the University of Miami's Miller School of Medicine commentating on the study. "It substantiates the need to always be prudent in prescribing antidepressants."
Funding for this study was provided by GlaxoSmithKline, the manufacturer of Paxil, the National Institute of Child Health and Human Development, the National Heart, Lung and Blood Institute, Aventis and Sanofi-Pasteur.
In the CDC study, researchers from the University of British Columbia at Vancouver and the CDC's National Center on Birth Defects and Developmental Disabilities assessed the risks of first trimester SSRI exposure using data from the CDC-funded National Birth Defects Prevention Study of 9622 infants with major birth defects and 4092 control infants (selected randomly from the same geographic areas) born from 1997 through 2002. SSRI exposure was defined as treatment with any SSRI from 1 month before to 3 months after conception. Birth defects were assigned to 26 categories and sub categories.
The study looked at the four most commonly prescribed SSRIs, fluoxetine (Prozac?), sertraline (Zoloft?), paroxetine (Paxil?), and citalopram (Celexa?).
They found some associations between SSRI use and anencephaly (a brain defect), craniosynostosis and omphalocele, however, the number of cases of each was too small to be conclusive. For example, while there was a 2.4 times greater risk of an child being born with anencephaly, only 9 of the 214 babies born with this defect had been exposed to SSRIs. There was a 2.5 times greater risk for craniosynostosis (24 exposed from 432 cases) and 2.8 times increased risk of omphalocele (11 of 181 cases). For each defect the absolute risk was small and within the 3 percent risk of major birth defect that applies to all pregnancies.
None of these defects had been associated with SSRI use in previous studies and the researchers suggest the results require confirmation by other studies. "CDC plans to continue to study the association to clarify whether a true risk exists," the CDC said in a statement on the study.
"Overall, our results are generally reassuring with respect to the use of antidepressants during pregnancy," said CDC epidemiologist Jennita Reefhuis, one of the authors of the study. "We know that both the mother and baby benefit when a pregnant woman with a serious depressive illness is able to stay on some sort of treatment. The risks may vary for different SSRIs and groups of women. It's important that women talk with their doctor about the risks and benefits of taking SSRIs during pregnancy."
Louik C, Lin AE, Werler MM, Hern?ndez-D?az S, Mitchell AA. First-Trimester Use of Selective Serotonin-Reuptake Inhibitors and the Risk of Birth Defects. NEJM 200 Jun 28;356:2675-2683 [Abstract]
Alwan S, Reefhuis J, Rasmussen JA, Olney RS, Friedman JM. Use of Selective Serotonin-Reuptake Inhibitors in Pregnancy and the Risk of Birth Defects. NEJM 2007 Jun 28;356:2684-2692 [Abstract]
