In This article

• Available evidence is reassuring: Quetiapine use during pregnancy has not been associated with a meaningful increase in the risk of major congenital malformations.
• First-trimester exposure: Studies evaluating first-trimester quetiapine exposure have not found an increased adjusted risk of major congenital malformations.
• Perinatal outcomes: Overall, quetiapine has not been associated with a significant increase in adverse perinatal outcomes compared with control groups.
• Gestational diabetes: Quetiapine may increase the risk of gestational diabetes, with evidence suggesting that metabolic risk may be greater at higher doses.
• Monitoring is important: Women taking quetiapine during pregnancy should receive appropriate monitoring of weight and metabolic risk factors, while treatment decisions should balance medication-related risks with the risks of untreated psychiatric illness.

The newer atypical, or second-generation, antipsychotic medications are widely used to treat a spectrum of psychiatric disorders, including schizophrenia and other psychotic disorders, bipolar disorder, major depression, and severe anxiety disorders. Quetiapine (Seroquel) is one of the most commonly used atypical antipsychotics during pregnancy. As the use of these medications has increased, our understanding of their reproductive safety has also grown.

A new systematic review and meta-analysis provides a comprehensive assessment of pregnancy outcomes following exposure to quetiapine. 

No Increased Risk of Major Malformations

Alem and colleagues reviewed 33 studies published through February 2025, including cohort studies, case-control studies, registry-based studies, and smaller case series. The studies varied substantially in size and methodology, but together provide a large body of data on pregnancy outcomes following quetiapine exposure.

The primary outcome was the risk of major congenital malformations. Among 13,090 pregnancies exposed to quetiapine for which data on congenital malformations were available, the rate of major congenital malformations was 4.1%. This rate is within the range expected in the general population. In eight studies specifically evaluating first-trimester exposure, the pooled malformation rate was approximately 3.9%, and the available adjusted analyses did not suggest an increased risk associated with quetiapine.

Overall, the available evidence suggests that quetiapine does not appear to substantially increase the risk of major congenital malformations.

Other Pregnancy and Neonatal Outcomes

The 2026 systematic review also examined other outcomes, including risk of spontaneous abortion, preterm birth, low birth weight, neonatal outcomes—including NICU admission, Apgar scores, and perinatal mortality—and maternal outcomes, including gestational diabetes, preeclampsia, hypertensive disorders, and pregnancy weight gain.

Overall, quetiapine exposure was not associated with a significant increase in adverse perinatal outcomes compared with control groups.

However, several high-quality studies included in the meta-analysis suggest that quetiapine is associated with an increased relative risk of gestational diabetes (adjusted RR range: 1.28-2.69), even after controlling for baseline confounders. Several studies suggest that the metabolic risk may be particularly important at higher doses (400 mg or higher).

Thus, clinicians should be attentive to maternal weight gain, glucose intolerance, and gestational diabetes, particularly in women receiving higher doses or who have other risk factors for diabetes.  Importantly, the potential metabolic risk is not in itself a reason to discontinue an effective antipsychotic during pregnancy. Rather, it supports individualized treatment decisions and appropriate metabolic monitoring.

What Does This Meta-Analysis Add?

This systematic review and meta-analysis is one of the most comprehensive assessments to date of the reproductive and perinatal safety of quetiapine. The authors synthesized data from 33 observational studies and included more than 13,000 pregnancies with information on major congenital malformations.

The overall findings are reassuring:

• Quetiapine was not associated with an increased risk of major congenital malformations.
• The major malformation rate among 13,090 quetiapine-exposed pregnancies was 4.1%.
• First-trimester exposure was not associated with an increased adjusted risk of major malformations.
• Overall, quetiapine was not associated with a significant increase in adverse perinatal outcomes compared with control groups.
• However, several studies suggest that quetiapine may increase the risk of gestational diabetes, particularly at higher doses.
• These findings support metabolic monitoring during pregnancy, while also emphasizing the importance of maintaining effective treatment for women with serious psychiatric illness.

Meta-Analysis Versus Large Registry Studies

Traditionally, meta-analyses have been particularly useful when individual studies are small and have limited power to detect uncommon outcomes. Combining data across studies can increase the number of exposed pregnancies and improve the ability to identify potential safety signals.

However, large population-based registry studies have become more common and  offer important advantages of their own. They may include large numbers of exposed pregnancies, as well as large comparison groups, allowing researchers to examine risk for specific congenital malformations and other relatively uncommon outcomes. They also provide extensive information about maternal characteristics and comorbidities that may be confounding factors.

One of the most informative studies examining the reproductive safety of antipsychotic medications was conducted by Huybrechts and colleagues and published in 2023. The investigators combined data from five Nordic countries with data from the US Medicaid Analytic eXtract to examine the risk of congenital malformations following antipsychotic exposure.  By combining data from five Nordic countries and US Medicaid, the investigators were able to examine more than 26,000 antipsychotic-exposed pregnancies, as well as more than 6.4 million unexposed pregnancies, using a common design. The study included 11,065 quetiapine-exposed pregnancies, providing considerably more information than many individual studies.

The investigators found that the prevalence of major congenital malformations was higher before adjustment among women exposed to antipsychotics than among unexposed women. This is not surprising: women receiving antipsychotic treatment had substantially greater medical and psychiatric comorbidity than unexposed women.

After adjustment for potential confounding factors, however, there were no consistent safety signals suggesting that atypical antipsychotics are major teratogens. The authors concluded that their findings did not support a major increase in the risk of congenital malformations with antipsychotic exposure.

This study illustrates an important issue in studies investigating the reproductive safety of medications: the unadjusted comparison may be misleading. Women taking antipsychotic medications are more likely to have psychiatric illness, medical comorbidities, substance use, smoking, and other factors that may influence pregnancy outcomes. Large registry studies allow researchers to account for many of these factors and provide more reliable estimates of medication-associated risk.

Large registry studies offer several methodological strengths, including prospectively or routinely collected information on medication dispensing and pregnancy outcomes, large control populations, and reduced potential for recall bias.

At the same time, registry studies are not without limitations. Prescription or dispensing records do not necessarily indicate whether a woman actually took the medication, and residual confounding is always possible. Thus, prospective pregnancy registries and large population-based studies provide complementary information, and confidence in reproductive safety increases when findings from different study designs converge.

The National Pregnancy Registry for Atypical Antipsychotics

Prospective pregnancy registries are an important source of information about medication safety during pregnancy. One advantage of a prospective registry is that women are enrolled during pregnancy and information about medication exposure is collected before the pregnancy outcome is known. This reduces the potential for recall bias and allows researchers to systematically document pregnancy outcomes and review medical records to confirm the presence or absence of major congenital malformations.

The National Pregnancy Registry for Atypical Antipsychotics, based at the MGH Center for Women’s Mental Health, was established to evaluate the reproductive safety of atypical antipsychotic medications. The registry enrolls pregnant women with a history of psychiatric illness and collects detailed information about medication exposure and pregnancy outcomes. The registry is ongoing and continues to recruit participants.

Data from the registry have contributed to our understanding of the reproductive safety of several atypical antipsychotics, including aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel), and lurasidone (Latuda).

The National Pregnancy Registry for Atypical Antipsychotics continues to recruit pregnant women who have taken atypical antipsychotic medications. Pregnant women age 45 or younger with a history of psychiatric illness may be eligible to participate. Participation is confidential and involves telephone interviews and review of medical records.

To learn more or participate, call 1-866-961-2388 or visit the National Pregnancy Registry for Atypical Antipsychotics.

The Take-Home Message

For women who require treatment with quetiapine during pregnancy, the available reproductive safety data are generally reassuring. The largest body of evidence does not suggest that quetiapine is associated with a meaningful increase in the risk of major congenital malformations, and the 2026 systematic review and meta-analysis found no significant increase in adverse perinatal outcomes.

The principal concern is metabolic. Quetiapine may increase the risk of gestational diabetes, and several studies suggest that this risk may be greater with higher doses. For women taking quetiapine during pregnancy, clinicians should therefore consider baseline and ongoing assessment of weight and metabolic risk factors and ensure appropriate screening for gestational diabetes.

Treatment decisions, however, must balance potential medication-related risks against the substantial risks associated with undertreated or untreated psychiatric illness during pregnancy. For many women, continuing an effective medication may be the safest option for both mother and baby.

—Ruta Nonacs, MD PhD