Folic acid is positively associated with uteroplacental vascular resistance: The Generation R Study

Background and aims: Periconception folic acid supplementation may influence early placentation processes and thereby the occurrence of hypertensive pregnancy disorders. For this reason we examined the associations between periconception folic acid supplementation and uteroplacental vascular resistance, blood pressure, and the risks of gestational hypertension and preeclampsia, in 5993 pregnant women, participating in a population-based cohort study. Methods and results: Folic acid supplementation was assessed by questionnaire. Mean pulsatility index (PI) and resistance index (RI) of the uterine (UtA) and umbilical arteries (UmA) were measured by Doppler ultrasound in mid- and late pregnancy. Systolic and diastolic blood pressures (SBP, DBP) were measured in early, mid- and late pregnancy. Compared to women who did not use folic acid, preconception folic acid users had a slightly lower UtA-RI in mid-pregnancy [β -0.02, 95% confidence interval (CI) -0.03, -0.01] and late pregnancy [β -0.02, 95% CI -0.03, -0.001], a lower UtA-PI in mid-pregnancy [β -0.06, 95% CI -0.1, -0.03] and late pregnancy [β -0.03, 95% CI -0.05, -0.01], as well as tendencies towards a lower UmA-PI in mid-pregnancy [β -0.02, 95% CI -0.04, -0.001] and late pregnancy [β -0.01, 95% CI -0.02, 0.01]. Additionally, these women had slightly higher SBP and DBP throughout pregnancy. Neither the patterns of blood-pressure change during pregnancy, nor the risk of gestational hypertension and preeclampsia differed between the folic acid categories. Conclusion: Periconception folic acid supplementation is associated with lower uteroplacental vascular resistance and higher blood pressures during pregnancy. The effects are small and within physiologic ranges and seem not associated with the risk of hypertensive pregnancy disorders.

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