2G-01 - Antipsychotic Use During Pregnancy and Risk of Pregnancy and Delivery Complications: A Danish Nationwide Register-Based Cohort Study

Background: Prescriptions of antipsychotics to pregnant women have increased worldwide, but evidence on pregnancy complications and birth outcomes remains limited due to small sample sizes and mixed findings.

Objectives: To evaluate the associations between continued treatment with first-generation antipsychotics (FGs) or second-generation antipsychotics (SGs) during pregnancy and the risk of pregnancy complications and adverse birth outcomes.

Methods: We conducted a population-based cohort study using Danish registers, including all pregnancies resulting in liveborn singletons between 2004 and 2022, where the woman filled an antipsychotic prescription from one year to 30 days prior to conception. Pregnant women were classified as continuers if they filled prescriptions exclusively for either FGs or SGs from 30 days before pregnancy to 20 gestational weeks (for pregnancy complications) or throughout pregnancy (for adverse birth outcomes). Women who did not fill any prescriptions for antipsychotics during pregnancy (discontinuers) served as the comparison. SGs were further classified into high (olanzapine, quetiapine, clozapine) and low (risperidone, aripiprazole, and ziprasidone) metabolic risk groups. We estimated adjusted odds ratios (OR) using generalized estimating equations, adjusting for confounders, including pre-pregnancy BMI and psychiatric history.

Results: Among 9,583 liveborn singleton pregnancies, 453 (4.7%) were exclusively exposed to FGs and 2,219 (23.2%) to SGs. There was no difference in risk of gestational diabetes between continuers and discontinuers for either antipsychotic class (FGs: OR = 0.91 [0.56–1.47]; SGs: OR = 1.19 [0.96–1.48]), nor for gestational hypertensive disorders (FGs: OR = 1.00 [0.60–1.71]; SGs: OR = 1.20 [0.97–1.48]). A marginally increased risk was observed for high–metabolic-risk SGs (gestational diabetes: OR = 1.26 [0.98–1.62]; gestational hypertensive disorders: OR = 1.26 [0.99–1.59]). Preterm birth was less common among children of SG continuers compared to discontinuers (OR = 0.77 [0.64–0.93]), with similar findings for high-metabolic-risk SGs; no difference was seen for FGs (OR = 1.13 [0.80–1.60]). Neonatal intensive care unit admission was more frequent among children of FG continuers (OR = 1.28 [1.01–1.62]), but not for SGs (OR = 0.87 [0.73–1.03]). Birth weight was higher among children of SG continuers compared to those of discontinuers (mean difference: 40 g [5.74–73.94]); no difference was found for FGs (–50.7 g [–118.63–17.27]).

Conclusions: Continued exposure to FGs was linked to an increased risk of neonatal intensive care admission. Continued prenatal exposure to SG was associated with higher birth weight alongside a marginally reduced risk of preterm birth. No significant association with gestational diabetes and hypertension was observed for either FG or SG after adjustments.