Abstract
BackgroundAntipsychotic medications are increasingly used during pregnancy. Nevertheless, fetal risks are still not fully studied. It is currently unclear whether the antipsychotic treatment might induce a higher risk of fetal death. We aimed to determine if use of antipsychotic medication during pregnancy is associated with an increased risk of spontaneous abortion or stillbirth.MethodsIn a historical cohort study, we identified all clinically recognized pregnancies registered in the nationwide Danish registries from 1997 to 2008 (N = 1,005,319). Exposure was defined as any prescription of antipsychotic medications redeemed by the pregnant women during the exposure window, and recorded in the Danish National Prescription Register. Outcome was defined as any spontaneous abortion or stillbirth recorded in the Danish National Hospital Register and the Danish Medical Birth Register respectively.ResultsWomen exposed to antipsychotic medications during pregnancy had a 34% higher risk of spontaneous abortion (adjusted relative risk = 1.34; 95% confidence interval = 1.22; 1.46) compared to unexposed women, but a similar risk compared to women exposed prior to (but not during) pregnancy (adjusted relative risk = 1.04; 95% confidence interval = 0.93; 1.17). The risk of spontaneous abortion was not increased in exposed pregnancies when compared to unexposed pregnancies in the same women (adjusted hazard ratio = 1.11; 95% CI = 0.94; 1.31). A twofold higher risk of stillbirth was found in women exposed to antipsychotic medications compared with unexposed women (relative risk = 2.27; 95% confidence interval = 1.45; 3.55) and compared with women exposed only prior to pregnancy (relative risk = 2.06; 95% confidence interval = 1.01; 4.19).ConclusionsThe increased risk of spontaneous abortion found in women treated with antipsychotic medications during pregnancy is most likely due to confounding factors. The risk of stillbirth was twofold higher in pregnancies exposed to antipsychotic medication during pregnancy. Treatment with antipsychotic medications during pregnancy requires careful consideration.
Highlights
Women exposed to antipsychotic medications during pregnancy had a 34% higher risk of spontaneous abortion compared to unexposed women, but a similar risk compared to women exposed prior to pregnancy
The risk of spontaneous abortion was not increased in exposed pregnancies when compared to unexposed pregnancies in the same women
The increased risk of spontaneous abortion found in women treated with antipsychotic medications during pregnancy is most likely due to confounding factors
Summary
Women with severe psychiatric disorders, including schizophrenia, are at increased risk of pregnancy-related complications such as premature delivery, low birth weight, stillbirth [1,2,3] and induced abortion. [4] the underlying reasons are poorly understood.Treatment of pregnant women with antipsychotic medication presents an important clinical challenge. [5,6,7] As antipsychotic medications may pass the placenta barrier, [8] fetotoxic effects are possible, but the potential impact is not well described. [9] Preterm birth, [10, 11] birth complications, congenital malformations [12,13,14] and impaired motor functioning in the newborn child [15, 16] have been reported, but information about spontaneous abortion (SA) and stillbirth is sparse. In a large cohort study, Habermann et al found no significantly increased risk of SA in 561 pregnancies exposed to second-generation antipsychotics (SGA) compared with 284 pregnancies exposed to first-generation antipsychotics (FGA) and 1122 pregnancies unexposed to medication with potential teratogenic effects. Other papers reporting on risk of SA or stillbirth after prenatal exposure to antipsychotic medications are mainly based on surveillance studies; none of these include comparison groups [19,20,21,22] and most are based on only few pregnancies. We conducted a large population-based retrospective cohort study to estimate associations between maternal use of antipsychotic medications during pregnancy and SA or stillbirth while adjusting for potential confounders including prenatal maternal psychiatric disorder. We aimed to determine if use of antipsychotic medication during pregnancy is associated with an increased risk of spontaneous abortion or stillbirth
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