title: Maternal and Fetal Folate, Vitamin B12, and Homocysteine Concentrations and Childhood Kidney Outcomes.
abstract: 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.
  
  
  METHODS
  Population-based prospective cohort study from fetal life onward.
  
  
  METHODS
  This study was performed among 4,226 pregnant women and their children.
  
  
  METHODS
  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).
  
  
  METHODS
  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 B12concentrations 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 eGFRcyswas 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Kozeta
authors.initials: K
authors.lastname: Miliku
authors.affiliation: The Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Anne
authors.initials: A
authors.lastname: Mesu
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Eric A P
authors.initials: EAP
authors.lastname: Steegers
authors.affiliation: The Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus University Medical Center, Rotterdam, the Netherlands. Electronic address: v.jaddoe@erasmusmc.nl.
authors.forename: Vincent W V
authors.initials: VWV
authors.lastname: Jaddoe
mesh_terms: D000419:Albuminuria / Q000097:blood / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005492:Folic Acid / Q000097:blood*; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007677:Kidney Function Tests; D008297:Male; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011446:Prospective Studies; D014805:Vitamin B 12 / Q000097:blood*
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12
keywords: Folate; epidemiology; estimated glomerular filtration rate (eGFR); fetal nutritional exposure; gestation; homocysteine; kidney development; kidney function; kidney volume; maternal nutrition; methyl donors; modifiable risk factor; nephrogenesis; pediatrics; pregnancy; vitamin B(12)