| ObjectiveWe aimed to explore the effects of vitamin D supplementation during pregnancy on maternal glucose homeostasis,and determine whether the effects of vitamin D supplementation are influenced by their baseline vitamin D status,gestational diabetes mellitus and vitamin D receptor polymorphism.Moreover,to observe the effects of vitamin D treatment on fetal growth,as well as infant’s growth and neurodevelopment through a regular follow-up for newborns.MethodsThis study was a large,multicenter,randomized,controlled trial of vitamin D3supplementation（Registration number:Chi CTR1900023923）.3 158 pregnant women were recruited from pregnancies consulted at three antenatal clinics in Hefei（32°N latitude）,China（The First People’s Hospital,Anhui Women and Child Health Care Hospital and the First Affiliated Hospital of Anhui Medical University）.1 857eligible participants were randomized to receive vitamin D3（1 200 IU/d）or no intervention at 16-23 weeks’gestation for 8 weeks.Before the allocation,they all have been employed a oral glucose tolerance test（OGTT）.Pregnant women in the control group were advised to take 400 IU/d vitamin D3 according to the recommendation of NAM.All randomized participants were required to do a interview at gestational 24-28 weeks and 32-36 weeks,their data of demographics,lifestyle,health status and diet habits were collected by a questionnaire.Their ultrasound data was collected from medical records,and their venous blood were sampled to examine maternal 25-hydroxyvitamin D[25（OH）D],fasting plasma glucose（FPG）levels and VDR gene polymorphism including Apa I（rs7975232）,Bsm I（rs1544410）,Taq I（rs731236）and Fok I gene（rs2228570）.At delivery,maternal and neonatal outcomes were collected,included pregnancy and birth outcomes,neonatal birth size.The umbilical cord blood was collected for the examination of 25（OH）D,C reactivity protein,and lipid profiles.And the offspring’s antrophometric data were recorded before 36 months,as well as their neurodevelopmental outcomes was evaluated by ASQ-3 at 12 months.All randomized 1 857 participants were included primary analysis based on the intention-to-treat principle.Maternal demographics,health status,life habits and baseline 25（OH）D,FPG levels were compared by Student’s t test or Mann–Whitney U tests for continuous data andχ~2tests for categorical data as appropriate.We used linear mixed models to summarize changes in serum 25（OH）D and FPG over time and to test whether these changes differed by treatment assignment.In addition to,the difference in neonatal birth outcomes,antrophometric indexes and neurodevelopmental outcomes between vitamin D group and control group were compared by Student’s t test or Mann–Whitney U tests for continuous data andχ~2tests for categorical data as appropriate.ResultsIn all randomized 1 857 pregnant women,there was no difference in maternal baseline 25（OH）D concentrations（37.02[12.11]nmol/L vs.36.78[13.05]nmol/L,P=0.678）and FPG levels（4.64[0.42]vs.4.61[0.41],P=0.093）.At gestational 32-36weeks,maternal FPG levels were not significantly changed,compared with the control group.Before delivery,maternal FPG levels of the vitamin D group were not changed（0.01 mmol/L）,but a significant increase was found in the control group（0.18 mmol/L）,and the changes in FPG level of the control were significantly higher than that of the vitamin D group（-0.16 mmol/L,95%CI,-0.26,-0.06,P=0.001）.After intervention,maternal 25（OH）D concentrations were significantly increased,and the mean of changes was higher than that of the control.In terms of maternal basal 25（OH）D concentrations,the changes in maternal FPG levels of the control were significantly higher than that of the vitamin D group in participants with serum 25（OH）D concentrations≥25 nmol/L,,but did not found in the pregnant women with 25（OH）D concentrations<25 nmol/L.In our study,17.3%（321/1857）pregnant women were diagnosed with gestational diabetes mellitus,of whom 169 participants were assigned to vitamin D group,and152 participants to the control group.Further analysis showed that there were comparable between the treatments groups in maternal 25（OH）D（37.65±11.73nmol/L vs.38.54±13.53 nmol/L,P=0.839）and FPG levels（5.16±0.42 vs.5.16±0.46,P=0.065）at baseline,.Regardless of the significant decrease was found in the vitamin D and control group,the between-group difference in maternal FPG was not significant.But before delivery,maternal FPG levels significantly decreased by-0.39 mmol/L（95%CI,-0.54,-0.25,P（27）0.001）,which was greater than that of the control group（0.12 mmol/L;between-group changes,-0.27 mmol/L,95%CI,-0.51to-0.04,P=0.035）,but the significant change was only observed in pregnant women with GDM and their baseline 25（OH）D ranging from 50 nmol/L to 75 nmol/L.Moreover,among pregnant women with GDM,the effects of vitamin D supplementation on decreasing FPG levels were only found in pregnant women with Apa I（rs7975232）CC genotype,Bsm I（rs1544410）CC genotype,Taq I（rs731236）CC genotype,Fok I（rs2228570）AA genotype and GA genotype.Among 1 536pregnant women without GDM,maternal FPG did not significant change in the vitamin D group,but the mean of changes in maternal FPG was lower than that of the control at delivery,and this finding was observed in participants with basal25（OH）D higher than 50 nmol/L.Among 1 793 newborns,cord blood CRP levels（0.13[0.06]mg/L vs.0.19[0.24]mg/L,P=0.045）,the risk of preterm（3.0%vs.7.9%,P=0.017）and macrosomia（7.4%vs.15.8%,P=0.020）were lower than that of the control group.And neonatal birthweight（3349.23[364.69]g vs.3524.52[396.90]g,P<0.001）,length（49.98[1.43]cm vs.50.54[1.58]cm,P=0.002）and ponderal index（26.72[1.86]kg/m~3vs.27.22[2.01]kg/m~3,P=0.029）in the vitamin D group were lower than that of the control group.As for neonatal neurodevelopment,newborns whose mothers with GDM of the vitamin D group had higher scores in the gross motor,compared with the control group（47.65[12.1]vs.41.17[15.62],P=0.047）,but the above significant effects were not found in the pregnant women without GDM.All newborn were followed-up to 36 months,their age of BMI peak with prenatal vitamin D supplementation was later than that of the control in boys（10.44[7.42]vs.8.53[6.25],P=0.017）,and the finding was founded both in pregnant women with GDM and without GDM.ConclusionVitamin D supplementation during pregnancy not only contributes to protecting maternal glucose homeostasis for pregnant women,but also are beneficial to decreasing the risk of hyperglycemia,preterm and macrosomia,especially in pregnant women with GDM.The response to vitamin D supplementation of pregnant women was not consistent,which might be affected by their basal vitamin D concentrations and VDR gene polymorphism.In addition,prenatal vitamin D supplementation had significant effects on preventing infants’overgrowth and improving their neurodevelopment. |
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