From Medscape Medical News CME
News Author: Janis Kelly
October 14, 2009 — Infants of mothers who took selective serotonin reuptake inhibitors (SSRIs) during pregnancy are at greater risk for preterm birth, a low 5-minute Apgar score, and admission to the neonatal intensive care unit (NICU), according to a report in the October issue of the Archives of Pediatrics & Adolescent Medicine.
Whether these risks outweigh the risks to the developing infant of a mother’s untreated depression during gestation is unknown, as are the long-term implications for the child’s health and development. The research team was led by Najaaraq Lund, MD, from the Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau, and Aarhus University, Denmark.
Dr. Lund told Medscape Psychiatry that his group’s most important findings were that prenatal exposure to SSRIs was associated with increased risk for preterm delivery, low 5-minute Apgar score, and increased chance of NICU admission (which was not explained by either Apgar score or gestational age). The researchers found no association between prenatal SSRI exposure and birth weight or head circumference after controlling for confounders.
The researchers compared birth outcomes including gestational age, birth weight, and Apgar score among babies born to 329 women who were treated with SSRIs, 4902 women who had a history of psychiatric illness but were not treated with SSRIs, and 51,770 women who had no history of psychiatric illness. They controlled for maternal characteristics including parity, age, body mass index, smoking, alcohol intake, coffee intake, marital status, and education.
Women who took SSRIs during pregnancy gave birth an average of 5 days earlier and had twice the risk for preterm delivery as women with no history of psychiatric illness. Infants exposed to the medications in utero were significantly more likely than infants in the 2 groups not exposed to have a 5-minute Apgar score of 7 or below or to be admitted to the NICU.
SSRIs and Pregnancy Outcomes
Outcome SSRI (n = 329) Psychiatric History, No SSRIs (n = 4902) Control (n = 51,770) Adjusted OR for SSRI vs Control
Preterm delivery (%) 8.80 5.00 4.90 2.02
5-min Apgar 5 to <8 (%) 4.90 1.00 1.20 4.44
NICU admit (%) 16.40 9.00 7.40 2.39
Mean gestational age (days) 276 279 280 —
Exposed infants admitted to the NICU experienced symptoms that could be caused by withdrawal from or adverse effects of SSRIs, including jitteriness, seizures, respiratory problems, infections, and jaundice.
"The article contributes to the total body of evidence regarding SSRIs during pregnancy. It suggests that in utero exposure to SSRI does affect the fetus and that special attention must be granted to exposed pregnancies," said Dr. Lund. "The clinical impact needs to be addressed further. All pregnant women using or considering [using] SSRIs should discuss risks and benefits of the medication with their ob-gyn and psychiatrist. Special awareness during pregnancy and around the time of delivery is warranted."
The study results support the joint statement from the American Psychiatric Association and American College of Obstetricians and Gynecologists, he added.
Increased Risk With Prenatal SSRIs, Apart From Depression Risk
Christina Chambers, PhD, MPH, told Medscape Psychiatry that this study is "consistent with many previous studies that have shown…a doubling of risk for preterm delivery and increased NICU admission, including our study first reporting these findings for fluoxetine back in 1996."
"The new information this study adds is that the increased risks remain even when compared to women with a history of psychiatric illness," Dr. Chambers said. "This has been a concern with many previous studies; that is, that the adverse outcomes could be related to the underlying illness and not the drug. It would be more convincing if the study were able to tell us that women in the psychiatric illness comparison group had the same diagnosis and same severity of disease as the women in the treated group, because you could argue that the majority of women in the psychiatric illness comparison [group] were not symptomatic and/or had mild enough illness to not need treatment."
Dr. Chambers noted that 1 major factor the Lund study was unable to address was timing of SSRI exposure. "Our study and several others have suggested that women who continue using SSRIs into the third trimester are at risk of these complications, and not women who discontinue use in the first trimester. This study was not able to differentiate among women on duration of exposure," she said.
Dr. Chambers is associate professor of pediatrics and family and preventive medicine at the University of California–San Diego, in La Jolla.
Tim F. Oberlander, MD, a coauthor of the American Psychiatric Association and American College of Obstetricians and Gynecologists joint statement, told Medscape Psychiatry that the Lund study is notable because it addresses the "holy grail" of prenatal drug exposure research: the question of how the effects of the drugs the mother is taking differ from the effects of her underlying mood disorder disease on fetal and infant development. Most earlier studies focused on the drug rather than the disease.
Dr. Oberlander is senior scholar in developmental neurosciences and child health at the Child and Family Research Institute and professor of developmental pediatrics at the University of British Columbia and at British Columbia Children’s Hospital, Vancouver, Canada. His research group recently reported an association between adverse neonatal outcomes after prenatal SSRI exposure in infants with a particular serotonin transporter promoter genotype.
"Another strength of this study is that the researchers were able to use data on many maternal characteristics related to lifestyle, such as the mother’s body mass index, alcohol intake, tobacco use, marital status, and education. That is truly remarkable for a population-based study," Dr. Oberlander said. One factor he would have liked more information about is the disease severity in the SSRI vs psychiatric non-SSRI groups.
Effects of Depression on Fetus vs Effects of Antidepressants: More Data Needed
Dr. Oberlander emphasized the importance of interpreting these data in the context of the deleterious effects of untreated maternal depression on fetal and infant health. "In considering these treatment issues, I am for stacking the deck in favor of early, positive brain growth in babies, but we also need to appreciate the profound effect that a mother’s anxiety, depression, or other mood disorder can have on the baby. That a mother’s mood could affect the baby was known even in biblical times," he said. "Clinically, anyone treating either mother or baby should follow them with close surveillance even after childbirth, including finding out what the context of the pregnancy is and what kind of support the mother has at home."
Going forward, Dr. Oberlander would like to see long-term follow-up of the babies in this study who were preterm, had low 5-minute Apgar scores, or were admitted to the NICU, to determine whether there are lasting adverse effects on the child’s development and well-being.
The study was supported by the Danish Medical Research Council. The authors have disclosed no relevant financial relationships.
Arch Pediatr Adolesc Med. 2009;163:949–954. Abstract
More information about use of antidepressants during pregnancy and infant health are available on the Mayo Clinic Web site.