Serum homocysteine and folate concentrations in early pregnancy and subsequent events of adverse pregnancy outcome: the Sichuan Homocysteine study

BACKGROUND: Hyperhomocysteinemia may be a risk factor for endothelial dysfunction. Folate and vitamin B12 regulate the homocysteine metabolic process. This study aimed to evaluate the associations between subsequent events of adverse pregnancy outcome and early variables of homocysteine, folate, and vitamin B12 in pregnant women. METHODS: This multicenter, retrospective, case–control study involved 563 pregnant women with adverse pregnancy outcome and 600 controls. Adverse pregnancy outcomes included one or more of the following events: preeclampsia, preterm birth, low birth weight, and stillbirth. The associations between subsequent events of adverse pregnancy outcome and early variables of homocysteine, folate, and vitamin B12; metabolic parameters; inflammatory markers; anthropometrics; and lifestyle habits at 11–12 weeks of gestation were analyzed using the logistic regression model. RESULTS: Compared to the lower quartile homocysteine concentrations, the upper quartile homocysteine concentrations were associated with preeclampsia, preterm birth and low birth weight. On the contrary, the lower quartile folate concentrations were associated with preeclampsia, preterm birth and low birth weight compared with the upper quartile folate concentrations. The incidence of adverse pregnancy outcome increased progressively from the first to fourth homocysteine quartiles but decreased progressively from the first to fourth folate quartiles. After adjusting for confounding factors, multivariate logistic regression analysis showed that besides systolic blood pressure, diastolic blood pressure, body mass index and age, homocysteine (IV vs I quartile, aOR 5.89, 95% CI 4.08–8.51, P < 0.001), folate (IV vs I quartile, aOR 0.35, 95% CI 0.25–0.50, P < 0.001), folate supplementation (yes vs no, aOR 0.55, 95% CI 0.35–0.86, P = 0.010) during early pregnancy were independently associated with subsequent events of adverse pregnancy outcome, and vitamin B12 was rejected. Of these, the homocysteine revealed the highest odds ratio in all risk variables, and folate showed the lowest odds ratio in all protective variables. CONCLUSIONS: Higher homocysteine concentration and lower folate level during early pregnancy were associated with adverse pregnancy outcome. However, no association was found between vitamin B12 and adverse pregnancy outcome. Supplementation with folate in early pregnancy may reduce adverse pregnancy outcome.