Association of folate and vitamin B12 imbalance with adverse pregnancy outcomes among 11,549 pregnant women: An observational cohort study

Abstract

Objective: This study aimed to evaluate maternal serum levels of folate, vitamin B12, and their ratio on admission for labor and determine whether an imbalance between folate and vitamin B12, represented by a higher or lower serum folate to vitamin B12 ratio (SFVB12R), was associated with adverse pregnancy outcomes.

Methods: A retrospective cohort study of 11,549 pregnant women attending a district specialized hospital and who had serum folate (SF) and serum vitamin B12 (SVB12) levels measured at delivery was performed. The levels of SF, SVB12, and SFVB12R were defined as high (>95th percentile), normal (5-95th percentile), and low (<5th percentile). Information on pregnancy outcomes was retrieved from medical records. Linear regression was performed to examine the association of abnormal SF, SVB12, and SFVB12R levels with fetal growth indicators. Logistic regression was applied to estimate the association between abnormal SF, SVB12, and SFVB12R levels and pregnancy outcomes.

Results: Lower SF levels were associated with higher risks of intrahepatic cholestasis of pregnancy (ICP, OR 1.58; 95% CI 1.15-2.17), pre-eclampsia (PE, OR 1.89; 95% CI 1.28-2.81), and a lower risk of gestational diabetes mellitus (GDM, OR 0.40; 95% CI 0.23-0.70), whereas higher SVB12 levels were associated with a higher risk of ICP (OR 2.22; 95% CI 1.67-2.96), PE (OR 1.69; 95% CI 1.04-2.74), and GDM (OR 1.62; 95% CI 1.24-2.11). A higher SFVB12R increased birthweight (β 60.99; 95% CI 29.52-92.45) and was associated with a higher risk of large-for-gestational-age (LGA) newborns (OR 3.08; 95% CI 1.63-5.83); a lower SFVB12R decreased birthweight (β -43.81; 95% CI -75.62, -12.00) and was associated with a lower risk of LGA newborns (OR 0.75; 95% CI 0.56-1.00), and with higher risks of ICP (OR 2.03; 95% CI 1.54-2.67) and pregnancy-induced hypertension (PIH, OR 1.81; 95% CI 1.09-3.00).

Conclusion: An imbalance between folate and vitamin B12, represented by a higher or lower SFVB12R before delivery, was significantly associated with adverse pregnancy outcomes (ICP/PIH/LGA).

Keywords: birth outcome; birth weight; folate; large-for-gestational age; pregnancy complications; vitamin B12.

Figure 1

Study flow diagram.

Figure 2

Smooth curve fitting analysis of SF, SVB12, and SFVB12R with the risk of pregnancy complications. For SFVB12R vs. pregnancy complications, adjusting for maternal age, BMI, gravidity, parity; for SF vs. pregnancy complications, additionally adjusting for SVB12; for SVB12 vs. pregnancy complications, additionally adjusting for SF. SFVB12R, serum folate to vitamin B12 ratio; SF, serum folate, SVB12, serum vitamin B12; GDM, gestational diabetes mellitus; ICP, intrahepatic cholestasis of pregnancy; PE, pre-eclampsia; PIH, pregnancy induced hypertension.

Figure 3

Smooth curve fitting analysis of SF, SVB12, and SFVB12R with the risk of adverse birth outcomes. For SFVB12R vs. PTB, adjusting for maternal age, BMI, gravidity, parity, blood pressure, GDM, ICP, PE, PIH, and fetal sex; for SFVB12R vs. SGA/LGA, additionally adjusting for gestational age; for SF vs. PTB, additionally adjusting for SVB12; for SF vs. SGA/LGA, additionally adjusting for SVB12; for SVB12 vs. PTB, additionally adjusting for SF; for SVB12 vs. SGA/LGA, additionally adjusting for SF. SF, serum folate; SVB12, serum vitamin B12; SFVB12R, serum folate to vitamin B12 ratio; GDM, gestational diabetes mellitus; ICP, intrahepatic cholestasis of pregnancy; PE, pre-eclampsia; PIH, pregnancy-induced hypertension; PTB, pre-term birth; SGA/LGA, small/large for gestational age.