QTc Interval Changes in Preeclampsia vs. Normal Pregnancy: A Systematic Review and Meta-Analysis

Abstract

Pregnancy induces significant adaptations in the cardio-autonomic nervous system, with additional cardiac stress in preeclampsia potentially impacting ventricular repolarization. Despite the widespread use of QT-prolonging drugs during pregnancy, the extent of heart rate (HR)-corrected QT (QTc) interval changes during normal pregnancy and preeclampsia remains unclear. This study aimed to quantify changes in QTc interval across different trimesters of normal pregnancy and third-trimester preeclampsia. Eight databases were systematically searched from their inception to January 13, 2025. Any type of study design, except case reports/series, reporting QT interval and HR or RR interval, and/or QTc interval for at least one trimester were included. Those reporting at least two trimesters or one trimester with nonpregnant controls were pooled in meta-analyses using random-effect models to calculate pooled mean differences (MD) across trimesters. Data from 57 studies (6,686 participants) were included with 33 studies (5,153 participants) pooled in meta-analyses. Compared with nonpregnant individuals, QTc intervals increased across trimesters of normal pregnancy and in third-trimester preeclampsia. Meta-analyses revealed significant increases in QTc interval during first (MD = 10.0 msec), second (MD = 20.2 msec), and third trimesters (MD = 23.0 msec) compared with nonpregnant individuals. Furthermore, preeclampsia increased the QTc interval by 21.7 msec during the third trimester compared to normal pregnancy. No publication bias was detected, and the overall quality scores of most studies were fair (n = 23) or poor (n = 33). A significant QTc interval lengthening throughout normal pregnancy was identified, and to a greater extent during preeclampsia. The arrhythmogenicity in third-trimester preeclampsia with a known risk for QTc interval prolongation, especially with using QT-prolonging drugs, warrants further investigation.

Figure 1

PRISMA flow diagram of study selection and screening.

Figure 2

Changes of QTc interval between different trimesters of normal pregnancy and preeclampsia. Box plots show mean QTc intervals (msec) across trimesters of normal pregnancy and preeclampsia using (a) all combined methods of QT interval rate correction and (b) Bazett‐corrected QT intervals.

Figure 3

Meta‐analyses on the changes of QTc interval between different trimesters of normal pregnancy and preeclampsia. Forest plots show QTc interval changes (msec) between (a) normal first trimester vs. nonpregnant individuals, (b) normal second trimester vs. nonpregnant individuals, (c) normal third trimester vs. nonpregnant individuals, and (d) preeclampsia third trimester vs. normal third‐trimester individuals. For each study, the blue square and horizontal lines represent the respective point estimate and accompanying 95% CI. The vertical solid line on the forest plot represents the point estimate of the MD of 0. The blue diamonds represent the 95% CI summary of pooled MD. CI, confidence interval; MD, mean difference; msec, millisecond.