PII-007 - CHANGES IN QTC ACROSS DIFFERENT TRIMESTERS OF PREGNANCY AND PRE-ECLAMPSIA: A SYSTEMATIC REVIEW AND META-ANALYSIS

O. Aboshady¹, J. Raffa¹, S. Quinney², J. Tisdale¹, B. Overholser¹; ¹College of Pharmacy, Purdue University, Indianapolis, IN, USA, ²School of Medicine, Indiana University, Indianapolis, IN, USA.

Background: Pregnancy induces adaptations in the cardio-autonomic nervous system, including increased heart rate, cardiac hypertrophy, and escalated sympathetic activity. Preeclampsia causes additional cardiac stress due to increased cardiac workload, leading to ventricular remodeling which affects cardiac repolarization. Nevertheless, the extent of the heart rate-corrected QT (QTc) interval changes, an important biomarker for drug safety, throughout pregnancy remains uncertain. This study aims to quantify the changes in QTc across pregnancy trimesters, with and without preeclampsia.

Methods: Seven databases (PubMed, Embase, Scopus, Web of Science, CINAHL, PsychINFO, and Cochrane) were searched using predetermined keywords from their inception to November 2022. Manual and backward citation analyses were also performed. Included studies reported QT and heart rate/RR, and/or QTc for at least one trimester during pregnancy with or without preeclampsia. For included studies that reported at least two trimesters or one trimester and non-pregnant controls, a meta-analysis using a random-effects model with RevMan 5.4 was performed to determine the mean difference between trimesters. NIH Quality Assessment Tools were used. The study protocol was registered in PROSPERO (CRD42023427889).

Results: After screening 7,248 studies, 53 (6,685 patients; 37 cross-sectional, 8 cohort, 8 control arms) were included, with 29 (4,703 patients; 24 cross-sectional, 4 cohort, 1 control arm) pooled for meta-analysis. During pregnancy, QTc increased compared to non-pregnant women (Figure 1). Meta-analysis showed that QTc significantly increased by 10.0 ms (95% CI: 6.8 to 13.2; I2= 0%) during the first trimester, 20.1 ms (95% CI: 14.1 to 26.0; I2 = 84%) during the second trimester, and 22.5 ms (95% CI: 15.0 to 30.1; I2 = 98%) during the third trimester, compared to non-pregnant women. Similarly, pre-eclampsia increased QTc by 21.9 ms (95% CI: 8.9 to 35.0; I2= 93%) during the third trimester compared with healthy pregnant women. There was no publication bias, and the overall quality scores of studies were fair (n = 21) or poor (n= 31).

Conclusion: A significant trend for increasing QTc throughout pregnancy was identified, especially in preeclampsia. The overall quality and heterogeneity of studies warrant well-designed prospective studies to confirm these results.