Maternal vitamin D concentrations during pregnancy, fetal growth patterns, and risks of adverse birth outcomes.
Maternal vitamin D deficiency during pregnancy may affect fetal outcomes.



The objective of this study was to examine whether maternal 25-hydroxyvitamin D [25(OH)D] concentrations in pregnancy affect fetal growth patterns and birth outcomes.



This was a population-based prospective cohort in Rotterdam, Netherlands in 7098 mothers and their offspring. We measured 25(OH)D concentrations at a median gestational age of 20.3 wk (range: 18.5-23.3 wk). Vitamin D concentrations were analyzed continuously and in quartiles. Fetal head circumference and body length and weight were estimated by repeated ultrasounds, and preterm birth (gestational age <37 wk) and small size for gestational age (less than the fifth percentile) were determined.



Adjusted multivariate regression analyses showed that, compared with mothers with second-trimester 25(OH)D concentrations in the highest quartile, those with 25(OH)D concentrations in the lower quartiles had offspring with third-trimester fetal growth restriction, leading to a smaller head circumference, shorter body length, and lower body weight at birth (all P < 0.05). Mothers who had 25(OH)D concentrations in the lowest quartile had an increased risk of preterm delivery (OR: 1.72; 95% CI: 1.14, 2.60) and children who were small for gestational age (OR: 2.07; 95% CI: 1.33, 3.22). The estimated population attributable risk of 25(OH)D concentrations <50 nmol/L for preterm birth or small size for gestational age were 17.3% and 22.6%, respectively. The observed associations were not based on extreme 25(OH)D deficiency, but presented within the common ranges.



Low maternal 25(OH)D concentrations are associated with proportional fetal growth restriction and with an increased risk of preterm birth and small size for gestational age at birth. Further studies are needed to investigate the causality of these associations and the potential for public health interventions.
Generation R Study Group, Department of Epidemiology, Department of Paediatrics.
Kozeta
0000-0002-9614-7191
K
Miliku
Queensland Brain Institute, The University of Queensland, Brisbane, Australia; and Queensland Centre for Mental Health Research, Park Centre for Mental Health, Wacol, Australia.
Anna
A
Vinkhuyzen
Generation R Study Group, Department of Child and Adolescent Psychiatry, and.
Laura Me
LM
Blanken
Queensland Brain Institute, The University of Queensland, Brisbane, Australia; and Queensland Centre for Mental Health Research, Park Centre for Mental Health, Wacol, Australia.
John J
JJ
McGrath
Queensland Brain Institute, The University of Queensland, Brisbane, Australia; and Queensland Centre for Mental Health Research, Park Centre for Mental Health, Wacol, Australia.
Darryl W
DW
Eyles
Queensland Brain Institute, The University of Queensland, Brisbane, Australia; and Queensland Centre for Mental Health Research, Park Centre for Mental Health, Wacol, Australia.
Thomas H
TH
Burne
Department of Epidemiology.
Albert
0000-0002-9865-121X
A
Hofman
Department of Epidemiology, Department of Child and Adolescent Psychiatry, and.
Henning
H
Tiemeier
Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Rotterdam, Netherlands;
Eric Ap
EA
Steegers
Generation R Study Group, Department of Epidemiology, Department of Paediatrics.
Romy
R
Gaillard
Generation R Study Group, Department of Epidemiology, Department of Paediatrics, v.jaddoe@erasmusmc.nl.
Vincent Wv
0000-0003-2939-0041
VW
Jaddoe
D000328:Adult; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D047109:Fetal Development / Q000502:physiology*; D005317:Fetal Growth Retardation / Q000097:blood / Q000453:epidemiology; D020567:Fetal Weight; D005333:Fetus / Q000033:anatomy & histology; D005865:Gestational Age; D006801:Humans; D007236:Infant, Small for Gestational Age; D009426:Netherlands / Q000453:epidemiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood*; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000453:epidemiology; D011446:Prospective Studies; D012307:Risk Factors; D016216:Ultrasonography, Prenatal; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000150:complications* / Q000453:epidemiology
D014807:Vitamin D; C104450:25-hydroxyvitamin D
25(OH)D; birth weight; fetal growth; pediatrics; pregnancy; preterm birth; small-size for gestational age; vitamin D