First Trimester Exposure to Quetiapine Appears to Be Safe

Use of the antipsychotic quetiapine during pregnancy does not appear to increase the risk of major malformations in offspring, according to a report published August 16 in AJP in Advance.

A comparison of offspring born to a small sample of women who were using the antipsychotic in the first trimester of pregnancy with those of women unexposed to quetiapine indicated no increased risk of major malformations.

“Given the considerable use of quetiapine among women of reproductive age across multiple indications, it is critical to have better information regarding the potential risks of fetal exposure to this medication so that women can make informed treatment decisions consistent with their personal wishes and the severity of their underlying psychiatric disorder,” wrote Lee Cohen, M.D., of Harvard Medical School and colleagues. “The study results suggest that quetiapine is not a major teratogen.”

Cohen is the director of the Center for Women’s Mental Health at Massachusetts General Hospital and the Edmund and Carroll Carpenter Chair in Psychiatry in Women’s Mental Health at Harvard Medical School.

The team analyzed data from the National Pregnancy Registry for Atypical Antipsychotics (NPRAA) to quantify the relative risk of major malformations associated with first-trimester exposure to quetiapine compared with women with psychiatric disorders not taking second-generation antipsychotics.

As part of participation in the registry, pregnant women aged 18 to 45 with a history of psychiatric illness were interviewed across pregnancy and the early postpartum period by telephone. Obstetric, labor, and delivery medical records and medical records from the first six months of life were screened for evidence of major malformations.

Of 152 women exposed to quetiapine during the first trimester, three gave birth to twins, resulting in 155 exposed live births. Among the 205 control women with available data, five sets of twins were born, resulting in 210 live births.

The primary outcome was the presence of a major malformation identified within six months of birth. A major malformation was defined as a structural abnormality with surgical, medical, or cosmetic importance.

Two major malformations were reported among infants with exposure to quetiapine: one infant with transposition of the great arteries and one infant with pulmonary stenosis due to dysplastic pulmonary valve. In the control group, three major malformations were reported: one infant with midshaft hypospadias requiring surgical repair, one infant with isolated cleft lip and palate, and one infant with a thickened pulmonary valve associated with mild pulmonary stenosis.

“The data from this analysis are consistent with the existing literature, which does not suggest a strong association between fetal exposure to second-generation antipsychotics and an increase in the rates of major malformations,” Cohen and colleagues wrote.

The NPRAA at Massachusetts General Hospital was established in 2008 to increase the availability of systematically gathered reproductive safety data for second-generation antipsychotics. The primary aim of the NPRAA is to delineate the risk of major malformations following in utero exposure to second-generation antipsychotics compared with a control group of women with psychiatric disorders who did not use agents in this drug class during pregnancy.

Analysis of reproductive safety data is timely given recent changes in Food and Drug Administration (FDA) regulations governing product labeling incorporated as part of the Pregnancy and Lactation Labeling Rule. That rule, which went into effect in 2015, requires narrative explanations of pregnancy risks associated with a medication with supportive data. (The previous labeling involved a grading system that was regarded as simplistic and misleading.) The regulations apply to new medications as well as approved products as new information becomes available.

“These findings represent preliminary yet important data with profound clinical implications for pregnant women and women of reproductive potential,” Cohen and colleagues wrote. “It is imperative that research efforts continue to focus on the reproductive safety of psychiatric medications that are commonly used by women during their childbearing years.” ■