To quantify the association between maternal uric acid levels and pre-eclampsia risk in a large collection of primigravid women. A case–control study (1365 cases of pre-eclampsia and 1886 normotensive controls) was conducted. Pre-eclampsia was defined as blood pressure ≥ 140/90 mmHg and proteinuria ≥ 300 mg/24 h. Sub-outcome analysis included early, intermediate, and late pre-eclampsia. Multivariable analysis for pre-eclampsia and its sub-outcomes was conducted using binary and multinomial logistic regression, respectively. Additionally, a systematic review and meta-analysis of cohort studies measuring uric acid levels < 20 weeks of gestation was performed to rule out reverse causation. There was a positive linear association between increasing uric acid levels and presence of pre-eclampsia. Adjusted odds ratio of pre-eclampsia was 1.21 (95%CI 1.11–1.33) for every one standard deviation increase in uric acid levels. No differences in the magnitude of association were observed between early and late pre-eclampsia. Three studies with uric acid measured < 20 weeks’ gestation were identified, with a pooled OR for pre-eclampsia of 1.46 (95%CI 1.22–1.75) for a top vs. bottom quartile comparison. Maternal uric acid levels are associated with risk of pre-eclampsia. Mendelian randomisation studies would be helpful to further explore the causal role of uric acid in pre-eclampsia.

(1) Background: Fibroblast growth factor 21 (FGF-21) is an endocrine factor involved in glucose and lipid metabolism that exerts pleiotropic effects. The aim of this study was to investigate the serum FGF-21 profile in healthy and mild preeclamptic pregnant women at each trimester of pregnancy; (2) Methods: Serum FGF-21 levels were determined by ELISA in a nested case-control study within a longitudinal cohort study that included healthy (n = 54) and mild preeclamptic (n = 20) pregnant women, women at three months after delivery (n = 20) and eumenorrheic women during the menstrual cycle (n = 20); (3) Results: FGF-21 levels were significantly lower in the mid-luteal phase compared to the early follicular phase of the menstrual cycle in eumenorrheic women (p < 0.01). Maternal levels of FGF-21 were significantly lower in the first and second trimesters and peaked during the third trimester in healthy pregnant women (p < 0.01). Serum levels of FGF-21 in healthy pregnant were significantly lower in the first and second trimester of pregnancy compared with the follicular phase of the menstrual cycle and postpartum (p < 0.01). Serum FGF-21 levels were significantly higher in preeclamptic compared to healthy pregnant women during pregnancy (p < 0.01); (4) Conclusions: These results suggest that a peak of FGF-21 towards the end of pregnancy in healthy pregnancy and higher levels in preeclamptic women might play a critical role that contributes to protecting against the negatives effects of high concentrations of non-esterified fatty acids (NEFA) and hypertensive disorder. Furthermore, FGF-21 might play an important role in reproductive function in healthy eumenorrheic women during the menstrual cycle.