Maternal and fetal folate, vitamin B12 and homocysteine concentrations and childhood kidney outcomes

BACKGROUND Folate, vitamin B12, and homocysteine concentrations during pregnancy are important factors for early development and may persistently influence kidney function in the offspring. We examined the associations of folate, vitamin B12, and homocysteine concentrations during pregnancy with kidney outcomes in school-aged children. STUDY DESIGN Population-based prospective cohort study from fetal life onward. SETTINGS & PARTICIPANTS This study was performed among 4,226 pregnant women and their children. PREDICTORS Folate, vitamin B12, and homocysteine blood concentrations measured in early pregnancy (median gestational age, 13.2 [IQR, 12.2-14.8] weeks) and at birth (cord blood). OUTCOMES & MEASUREMENTS At the median age of 6.0 (IQR, 5.9-6.3) years, we measured combined kidney volume with ultrasound, estimated glomerular filtration rate based on creatinine (eGFRcr) and cystatin C (eGFRcys) concentrations, and microalbuminuria. RESULTS We observed that higher maternal folate concentrations were associated with larger childhood combined kidney volume, whereas higher maternal vitamin B12 concentrations were associated with higher childhood eGFRcys (P for both <0.05). These associations were independent of homocysteine concentrations. Higher maternal homocysteine concentrations were associated with smaller combined kidney volume and lower childhood eGFRcys (P for both < 0.05). The association of maternal homocysteine concentrations with childhood eGFRcys was largely explained by combined kidney volume. Higher cord blood homocysteine concentrations were associated with larger combined kidney volume and lower eGFRcys (P for both < 0.05). Folate, vitamin B12, or homocysteine concentrations were not associated with microalbuminuria. LIMITATIONS Observational study, so causality cannot be established. CONCLUSIONS Our findings suggest that folate, vitamin B12, and homocysteine concentrations during fetal life are associated with offspring kidney development. However, effect sizes are small. Further studies to replicate these findings and assess the causality and consequences for kidney health in later life are needed.