Objective: We aimed to study whether antipsychotic use during pregnancy is associated with gestational diabetes.
Methods: This was a Swedish national register-based cohort study on the Medical Birth Register and the Prescribed Drug Register including all 1,307,487 singleton births between July 2006 and December 2017. Antipsychotics were divided into first-generation antipsychotics (n = 728), high-risk metabolic second-generation antipsychotics including olanzapine, clozapine and quetiapine (n = 1710), and other second-generation antipsychotics (n = 541). The risks for gestational diabetes, foetal growth disturbances, pre-eclampsia, caesarean section and preterm labour were assessed. Women treated during pregnancy were compared to women not treated during pregnancy and to women who used antipsychotics before/after but not during pregnancy.
Results: The crude risk ratio for gestational diabetes for women treated with high-risk metabolic second-generation antipsychotics during pregnancy was 2.2 (95% confidence interval [CI] 1.6-2.9) compared to untreated pregnant women (n = 1,296,539) and 1.8 (95% CI 1.4-2.5) compared to women treated before/after pregnancy (n = 34,492). After adjustment for maternal factors including body mass index, the risk ratios were 1.8 (95% CI 1.3-2.4) and 1.6 (95% CI 1.2-2.1). Exposed infants had an increased risk of being large for gestational age: adjusted risk ratios 1.6 (95% CI 1.3-1.9) and 1.3 (95% CI 1.1-1.6) compared to no maternal antipsychotic use during pregnancy and maternal use before/after the pregnancy. Other antipsychotics were not associated with metabolic risks.
Conclusions: Olanzapine, clozapine and quetiapine used during pregnancy were associated with increased risks for gestational diabetes and the infant being large for gestational age. Enhanced metabolic monitoring should be considered for pregnant women using these drugs.
The use of second-generation antipsychotics amongst pregnant women is increasing. The side effects of these drugs, for example weight gain and increased blood sugar, are well described for the general population. In particular, olanzapine, quetiapine and clozapine are known to cause these effects. Studies on their effects on blood sugar control in pregnant women have however been conflicting. Pregnancy itself also imposes a risk for increased blood sugar levels and gestational diabetes. The purpose of this study was to evaluate the risk of gestational diabetes connected to the use of antipsychotics during pregnancy. The study was nationwide and register based including 1.3 million births in Sweden between July 2006 and December 2017. The rates of gestational diabetes and the infants being small for gestational age or large for gestational age amongst women treated with antipsychotics were compared to the rates in pregnant women who did not receive antipsychotics and to rates in a control group of women treated with antipsychotics before/after but not during pregnancy. Antipsychotics were divided into three groups: (i) first-generation antipsychotics, (ii) high-risk second-generation antipsychotics including olanzapine, quetiapine and clozapine, and (iii) other second-generation antipsychotics. Women treated with high-risk second-generation antipsychotics were found to have an increased risk of gestational diabetes and giving birth to an infant being large for gestational age, both when compared with untreated pregnant women and with the control group. Other antipsychotics were not connected to increased risks of these outcomes. Hence, pregnant women treated with olanzapine, quetiapine or clozapine should be monitored regarding blood sugar levels.
© 2022. The Author(s).