Association between iron status, preeclampsia and gestational hypertension: A bidirectional two-sample Mendelian...

Area of Science:

• Reproductive health
• Maternal-fetal medicine
• Genetic epidemiology

Background:

• Observational studies suggest a link between iron overload in pregnancy and preeclampsia (PE) and gestational hypertension (GH).
• The causal relationship between maternal iron status and these pregnancy complications remains unclear.

Purpose of the Study:

• To investigate the potential causal association between genetically determined iron status and the risk of preeclampsia (PE) and gestational hypertension (GH).
• To differentiate between observational associations and causal links using Mendelian randomization.

Main Methods:

• A two-sample Mendelian randomization (MR) study was conducted.
• Genome-wide association study (GWAS) summary statistics for iron status (serum iron, ferritin, TIBC, TSAT) and pregnancy outcomes (PE, GH) were utilized.
• Multiple MR methods, including inverse variance weighted (IVW), MR-Egger, and MR-PRESSO, were employed to assess causality and pleiotropy.

Main Results:

• Increased serum iron levels were associated with a higher risk of preeclampsia (OR = 1.24, P = 0.02).
• No significant causal associations were found between ferritin, total iron-binding capacity (TIBC), transferrin saturation (TSAT), and preeclampsia.
• No evidence supported a causal link between iron status and gestational hypertension, or a reverse causation from PE/GH to iron status.

Conclusions:

• This Mendelian randomization study provides evidence for a causal association between higher serum iron levels and an increased risk of preeclampsia.
• The findings suggest that elevated serum iron is a potential causal factor for preeclampsia, distinct from observational correlations.