Maternal Use of Antipsychotics in Early Pregnancy and Delivery Outcome

Abstract

The effect of various antipsychotics during pregnancy has repeatedly been studied, but for most atypical antipsychotics, only little information is available. We identified from the Swedish Medical Birth Register 2908 women who had reported the use of any antipsychotic or lithium in early pregnancy and studied malformation rates with data also from the Register of Congenital Malformations and the Hospital Discharge Register. Comparisons were made with all births (n = 958,729) after adjustment for some confounders. Risks were expressed as odds ratios (ORs). Most women had used dixyrazine or prochlorperazine mainly because of nausea and vomiting in early pregnancy. Seventy-nine women had used lithium, and these outcomes are reported separately. Hence, the main analysis was restricted to 570 women (576 infants) using other antipsychotics. There was a statistically significant increase in the risk for a congenital malformation-after exclusion of some common and minor conditions, the OR was 1.52 (95% confidence interval, 1.05-2.19). Exclusion of infants exposed to anticonvulsants reduced the OR only slightly. Most of the increased risk was caused by cardiovascular defects, mainly atrium or ventricular septum defect. No certain drug specificity was found. Except for an increased risk for congenital malformations, a nearly doubling of the risk for gestational diabetes and a 40% increased risk for cesarean delivery was noted. Because there seems to be little drug specificity, it is possible that underlying pathology or unidentified confounding explains the excess risk.

Deletion of GSK-3β in mice leads to hypertrophic cardiomyopathy secondary to cardiomyoblast hyperproliferation

“…The issue of whether lithium, and by extension GSK-3 inhibition, causes congenital heart defects has been debated in the literature for more than 20 years because early retrospective analyses that reported high rates of congenital heart defects in the setting of lithium treatment were flawed (30). A more recent report confirmed a marginally increased risk for a cardiac defect after maternal use of lithium (55), and administration of lithium to animal models at very early gestational stages produces heart defects (56). However, it has been difficult to determine whether the heart defects observed in these lithium studies can be extrapolated to newer, more potent GSK-3 inhibitors for several reasons.…”

British Association for Psychopharmacology consensus guidance on the use of psychotropic medication preconception, in pregnancy and postpartum 2017

“…Studies comparing women on antipsychotics with healthy controls find a nearly two-fold increased risk of GDM (approximately 4% vs 2%) (Boden et al, 2012a;Reis and Kallen, 2008), but studies which employ a disease matched control group of psychiatrically ill unexposed women find no significant risk increase in GDM or gestational hypertension (Petersen et al, 2016;Vigod et al, 2015). The risk of GDM appears similar for olanzapine or clozapine versus other antipsychotics (Boden et al, 2012b;Vigod et al, 2015).…”

“…In general, studies that compare women exposed to antipsychotics in pregnancy to healthy unexposed women report moderately increased risks for several adverse maternal and infant outcomes (including congenital malformations, pre-term birth, fetal growth abnormalities and poor neonatal adaptation) (Boden et al, 2012b;Habermann et al, 2013;Reis and Kallen, 2008;Sadowski et al, 2013). By contrast, the few studies that used a comparison group of women with psychiatric illness but unexposed to antipsychotics (Boden et al, 2012a;Lin et al, 2010; National Institute for Health and Care Excellence, 2015a; Petersen et al, 2016), or studies that adequately controlled for confounding (Vigod et al, 2015), report few associations between antipsychotics and adverse maternal or infant outcomes.…”

Perinatal Generalized Anxiety Disorder: Assessment and Treatment

“…91 In one study, atypical antipsychotic usage has been linked to an increased risk of congenital malformation, gestational diabetes, and caesarean section delivery. 92 No long-term studies track the effects of atypical antipsychotics on infant neurodevelopment. 93 …”