Maternal and Fetal Folate, Vitamin B 12 , and Homocysteine Concentrations and Childhood Kidney Outcomes

Abstract

BackgroundFolate, 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 designPopulation-based prospective cohort study from fetal life onwards.Settings & participantsThis study was performed among 4,226 pregnant women and their children.PredictorsFolate, vitamin B12 and homocysteine blood concentrations measured in early pregnancy (median gestational age 13.2 weeks (25th to 75th percentiles 12.2, 14.8) and at birth (cord blood).Outcomes & measurementsAt the median age of 6.0 years (25th to 75th percentiles 5.9, 6.3) we measured combined kidney volume with ultrasound, estimated glomerular filtration rate based on creatinine (eGFRcreat) and cystatin C (eGFRcystC) concentrations and microalbuminuria.ResultsWe 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 eGFRcystC (p-values <0.05). These associations were independent of homocysteine concentrations. Higher maternal homocysteine concentrations were associated with smaller combined kidney volume and lower childhood eGFRcystC (p-values <0.05). The association of maternal homocysteine concentrations with childhood eGFRcystC was largely explained by combined kidney volume. Higher cord blood homocysteine concentrations were associated with larger combined kidney volume and lower eGFRcystC (p-values <0.05). Folate, vitamin B12 or homocysteine concentrations were not associated microalbuminuria.LimitationsObservational study, so causality cannot be established.ConclusionOur findings suggest that folate, vitamin B12 and homocysteine concentrations during fetal life are associated with offspring kidney development. However, the effect sizes are small. Further studies are needed to replicate these findings and assess the causality and consequences for kidney health in later life.

The Relationship between Maternal Nutrition during Pregnancy and Offspring Kidney Structure and Function in Humans: A Systematic Review

“…Included studies ( n = 10) were published between 2005 and 2017 and were conducted in six countries including Bangladesh ( n = 1) [ 24 ], Nepal ( n = 2) [ 25 , 26 ], China ( n = 1) [ 27 ], Netherlands ( n = 4) [ 28 , 29 , 30 , 31 ], Canada ( n = 1) [ 32 ] and Egypt ( n = 1) [ 33 ]. The common measures of kidney structure were kidney volume, while kidney function measures were microalbuminuria, glomerular filtration rate (GFR), and albuminuria.…”

“…Table 2 describes the characteristics of the observational studies included in this review. Seven observational studies evaluated the relationship between maternal nutrition during pregnancy and offspring kidney structure and function, of which two were retrospective cohort studies [ 27 , 28 ] and five were prospective cohort studies [ 29 , 30 , 31 , 32 , 33 ]. Factors that prevented meta-analysis from being performed included the heterogeneity of outcome measures used to measure kidney structure and function, the large variation in the age at follow-up of offspring, and the diverse components of maternal diets that were assessed.…”

“…In total, seven studies were classified as of high methodological quality, of which three were RCTs [ 24 , 25 , 26 ] and four were observational [ 28 , 29 , 30 , 31 ]. All three RCTs randomly allocated participants to study groups using appropriate methods, however, none described the randomisation procedure in sufficient detail [ 24 , 25 , 26 ] and all failed to sufficiently describe the allocation concealment procedure for the randomization process.…”

“…All three RCTs randomly allocated participants to study groups using appropriate methods, however, none described the randomisation procedure in sufficient detail [ 24 , 25 , 26 ] and all failed to sufficiently describe the allocation concealment procedure for the randomization process. Inclusion/exclusion criteria and demographics of subjects were clearly described in the four observational studies [ 28 , 29 , 30 , 31 ]. The remaining three studies [ 27 , 32 , 33 ] were rated as of neutral quality.…”

Antenatal Vitamin D Preserves Placental Vascular and Fetal Growth in Experimental Chorioamnionitis Due to Intra-amniotic Endotoxin Exposure

“…17,20,24,28,46 Adverse fetal outcomes from maternal Vit D insufficiency include increased risk of low birth weight and small size for gestational age at birth. 22,47 Birth weight for gestational age has been shown to be an important predictor of PH in preterm infants with moderate to severe BPD. 48 Early injury of the developing lung impairs angiogenesis and alveolarization, resulting in simplification of the distal lung airspace and clinical manifestations of BPD.…”