Quetiapine (Seroquel) is a widely used atypical antipsychotic for conditions that include schizophrenia, bipolar disorder, major depression, and severe anxiety disorders. As use in pregnancy has risen, reproductive safety data have expanded. A 2026 systematic review and meta-analysis by Alem and colleagues pooled results from 33 observational studies—cohort, case-control, registry-based studies, and case series—published through February 2025 to assess pregnancy outcomes after quetiapine exposure.
The pooled data included more than 13,000 pregnancies with information on major congenital malformations and examined primary and secondary outcomes: major congenital malformations, spontaneous abortion, preterm birth, low birth weight, neonatal outcomes (NICU admission, Apgar scores, perinatal mortality), and maternal outcomes such as gestational diabetes, preeclampsia, hypertensive disorders, and pregnancy weight gain.
Across 13,090 quetiapine-exposed pregnancies with malformation data, the pooled rate of major congenital malformations was 4.1%, a proportion the authors note is within the expected range for the general population. In eight studies focused on first-trimester exposure, the pooled malformation rate was approximately 3.9%.
Adjusted analyses reported in the reviewed studies did not identify an increased risk of major congenital malformations associated with quetiapine exposure, including first-trimester exposures. The overall synthesis from the meta-analysis is that quetiapine does not appear to substantially increase the risk of major congenital malformations based on currently available observational data.
The review examined perinatal and neonatal outcomes and found that, in pooled analyses, quetiapine exposure was not associated with a significant increase in adverse perinatal outcomes compared with control groups. Outcomes assessed included spontaneous abortion, preterm delivery, low birth weight, NICU admission, Apgar scores, and perinatal mortality.
A recurring maternal concern in several higher-quality studies included in the meta-analysis was an increased adjusted relative risk for gestational diabetes. Reported adjusted relative risks ranged from about 1.28 to 2.69 in these studies, and multiple analyses suggested that metabolic risk may be dose-dependent, with greater risk observed at doses of 400 mg or higher. The authors emphasize monitoring of maternal weight, glucose intolerance, and gestational diabetes risk—particularly for women on higher quetiapine doses or with other diabetes risk factors.
Importantly, the presence of a metabolic risk signal is framed as a reason to individualize care and increase monitoring, not as an automatic reason to discontinue effective antipsychotic treatment during pregnancy.
Meta-analyses increase statistical power by combining smaller studies and can detect uncommon outcomes that single studies may miss. However, large population-based registry studies provide complementary advantages, including large numbers of exposed pregnancies, expansive comparison groups, prospectively collected dispensing and outcome data, and richer covariate information to address confounding.
An example highlighted in the article is the study by Huybrechts and colleagues (published 2023), which combined data from five Nordic countries and US Medicaid. That investigation included 11,065 quetiapine-exposed pregnancies and, before adjustment, found a higher prevalence of major congenital malformations among antipsychotic-exposed women. After adjustment for maternal characteristics and comorbidities, however, the study did not identify consistent safety signals indicating that atypical antipsychotics are major teratogens.
These findings illustrate a key methodological point: unadjusted comparisons can be misleading because women treated with antipsychotics frequently have greater psychiatric and medical comorbidity, substance use, and other risk factors. Registry studies mitigate some biases but have limitations too—dispensing records do not confirm medication ingestion, and residual confounding may persist. The convergence of findings across study designs strengthens confidence in safety conclusions.
Prospective pregnancy registries add important information because exposure data are collected before pregnancy outcomes are known, reducing recall bias and allowing systematic outcome confirmation through medical record review. The National Pregnancy Registry for Atypical Antipsychotics, based at the MGH Center for Women’s Mental Health, was established to evaluate reproductive safety for this drug class and continues to recruit pregnant women with psychiatric illness.
The registry collects detailed exposure information and pregnancy outcomes and has contributed data on aripiprazole, olanzapine, quetiapine, and lurasidone. Eligibility generally includes pregnant women age 45 or younger with a history of psychiatric illness. Participation is confidential and involves telephone interviews and medical record review. For those interested, the registry contact provided in the source is 1-866-961-2388 and additional information is available via the registry website.
The assembled evidence from the systematic review and from large registry studies is generally reassuring with respect to major congenital malformations: pooled rates among quetiapine-exposed pregnancies do not indicate a clear increase compared with expectations for the general population, and first-trimester adjusted analyses have not shown increased risk.
The primary clinical concern identified is metabolic: several studies report an increased risk of gestational diabetes, with higher doses of quetiapine (≥400 mg) potentially conferring greater risk. Clinicians should therefore:
The evidence underscores individualized treatment planning, appropriate metabolic monitoring during pregnancy, and the value of prospective data collection through registries to continue refining safety estimates.
References
Alem GM, Fatani S, Aldosari SA, Ahmed N, Balaha M, Balaha MF. Perinatal Safety of Quetiapine During Pregnancy: A Systematic Review, Meta-Analysis, and Evidence Gaps. J Clin Psychopharmacol. 2026 May-Jun;46(3):322-337.
Huybrechts KF, Straub L, Karlsson P, Pazzagli L, Furu K, Gissler M, Hernandez-Diaz S, Nørgaard M, Zoega H, Bateman BT, Cesta CE, Cohen JM, Leinonen MK, Reutfors J, Selmer RM, Su. (Study combining Nordic registries and US Medicaid cited in source.)