Prenatal Vitamin D Supplementation and Child Respiratory Health: A Randomised Controlled Trial Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. Effect of vitamin D supplementation during pregnancy on foetal growth. Randomized placebo-controlled trial of high-dose prenatal third-trimester vitamin D3 supplementation in Bangladesh: the AViDD trial Vitamin D supplements in pregnant Asian women: effects on calcium status and fetal growth. Effect of vitamin D supplementation in the reduce risk of preeclampsia in nulliparous women International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project Effect of multiple-micronutrient supplementation on maternal nutrient status, infant birth weight and gestational age at birth in a low-income, multi-ethnic population. The Effect of Vitamin D and Calcium plus Vitamin D during Pregnancy on Pregnancy and Birth Outcomes: a Randomized Controlled Trial. Obstetric and neonatal outcomes of maternal vitamin D supplementation: results of an open-label, randomized controlled trial of antenatal vitamin D supplementation in Pakistani women.
Background Observational studies suggest high prenatal vitamin D intake may be associated with reduced childhood wheezing .  We examined the effect of prenatal vitamin D on childhood wheezing  in an interventional study . Methods We r and omised 180 pregnant women at 27 weeks gestation to either  no vitamin D , 800 IU ergocalciferol daily until delivery or single oral bolus of 200,000 IU cholecalciferol  , in an ethnically stratified , r and omised controlled trial . Supplementation improved but did not optimise vitamin D status . Research ers blind to allocation assessed offspring at 3 years . Primary outcome was any history of wheeze assessed by vali date d question naire . Secondary outcomes included atopy , respiratory infection , impulse oscillometry and exhaled nitric oxide . Primary analyses used logistic and linear regression . Results We evaluated 158 of 180 ( 88 % ) offspring at age 3 years for the primary outcome . Atopy was assessed by skin test for 95 children ( 53 % ) , serum IgE for 86 ( 48 % ) , exhaled nitric oxide for 62 ( 34 % ) and impulse oscillometry of acceptable quality for 51 ( 28 % ) . We found no difference between supplemented and control groups in risk of wheeze  [ no vitamin D : 14/50 ( 28 % ) ; any vitamin D : 26/108 ( 24 % ) ( risk ratio 0.86 ; 95 % confidence interval 0.49 , 1.50 ; P = 0.69 ) ] . There was no significant difference in atopy , eczema risk , lung function or exhaled nitric oxide between supplemented groups and controls . Conclusion Prenatal vitamin D supplementation in late pregnancy that had a modest effect on cord blood vitamin D level , was not associated with decreased wheezing in offspring at age three years . Trial Registration Controlled-Trials.com IS RCT BACKGROUND The cholecalciferol inputs required to achieve or maintain any given serum 25-hydroxycholecalciferol concentration are not known , particularly within ranges comparable to the probable physiologic supply of the vitamin . OBJECTIVES The objectives were to establish the quantitative relation between steady state cholecalciferol input and the result ing serum 25-hydroxycholecalciferol concentration and to estimate the proportion of the daily requirement during winter that is met by cholecalciferol reserves in body tissue stores . DESIGN Cholecalciferol was administered daily in controlled oral doses labeled at 0 , 25 , 125 , and 250 micro g cholecalciferol for approximately 20 wk during the winter to 67 men living in Omaha ( 41.2 degrees N latitude ) . The time course of serum 25-hydroxycholecalciferol concentration was measured at intervals over the course of treatment . RESULTS From a mean baseline value of 70.3 nmol/L , equilibrium concentrations of serum 25-hydroxycholecalciferol changed during the winter months in direct proportion to the dose , with a slope of approximately 0.70 nmol/L for each additional 1 micro g cholecalciferol input . The calculated oral input required to sustain the serum 25-hydroxycholecalciferol concentration present before the study ( ie , in the autumn ) was 12.5 micro g ( 500 IU)/d , whereas the total amount from all sources ( supplement , food , tissue stores ) needed to sustain the starting 25-hydroxycholecalciferol concentration was estimated at approximately 96 micro g ( approximately 3800 IU)/d . By difference , the tissue stores provided approximately 78 - 82 micro g/d . CONCLUSIONS Healthy men seem to use 3000 - 5000 IU cholecalciferol/d , apparently meeting > 80 % of their winter cholecalciferol need with cutaneously synthesized accumulations from solar sources during the preceding summer months . Current recommended vitamin D inputs are inadequate to maintain serum 25-hydroxycholecalciferol concentration in the absence of substantial cutaneous production of vitamin The need , safety , and effectiveness of vitamin D supplementation during pregnancy remain controversial . In this r and omized , controlled trial , women with a singleton pregnancy at 12 to 16 weeks ' gestation received 400 , 2000 , or 4000 IU of vitamin D(3 ) per day until delivery . The primary outcome was maternal/neonatal circulating 25-hydroxyvitamin D [ 25(OH)D ] concentration at delivery , with secondary outcomes of a 25(OH)D concentration of 80 nmol/L or greater achieved and the 25(OH)D concentration required to achieve maximal 1,25-dihydroxyvitamin D(3 ) [ 1,25(OH)(2)D(3 ) ] production . Of the 494 women enrolled , 350 women continued until delivery : Mean 25(OH)D concentrations by group at delivery and 1 month before delivery were significantly different ( p < 0.0001 ) , and the percent who achieved sufficiency was significantly different by group , greatest in 4000-IU group ( p < 0.0001 ) . The relative risk ( RR ) for achieving a concentration of 80 nmol/L or greater within 1 month of delivery was significantly different between the 2000- and the 400-IU groups ( RR = 1.52 , 95 % CI 1.24 - 1.86 ) , the 4000- and the 400-IU groups ( RR = 1.60 , 95 % CI 1.32 - 1.95 ) but not between the 4000- and . 2000-IU groups ( RR = 1.06 , 95 % CI 0.93 - 1.19 ) . Circulating 25(OH)D had a direct influence on circulating 1,25(OH)(2)D(3 ) concentrations throughout pregnancy ( p < 0.0001 ) , with maximal production of 1,25(OH)(2)D(3 ) in all strata in the 4000-IU group . There were no differences between groups on any safety measure . Not a single adverse event was attributed to vitamin D supplementation or circulating 25(OH)D levels . It is concluded that vitamin D supplementation of 4000 IU/d for pregnant women is safe and most effective in achieving sufficiency in all women and their neonates regardless of race , whereas the current estimated average requirement is comparatively ineffective at achieving adequate circulating 25(OH)D concentrations , especially in African Americans Chez 100 femmes enceintes , l'administration de 2 doses de 600000 UI de vitamine D du 3eme trimestre a entraine une amelioration significative des parametres biochimiques maternels et du serum du cordon , du poids de naissance et de certaines autres mesures anthropometriques du nouveau-ne comparativement a 100 femmes enceintes ne recevant pas de Background Antenatal vitamin D status may be associated with the risk of adverse pregnancy and neonatal outcomes ; however , the benefits of vitamin D supplementation during pregnancy remain unknown . Methods We conducted a double-blind placebo-controlled r and omized trial to evaluate the effect of high-dose prenatal 3rd trimester vitamin D3 supplementation on maternal and neonatal ( cord blood ) serum 25-hydroxyvitamin D ( 25(OH)D ) concentration ( primary biochemical efficacy outcome ) and maternal serum calcium concentration ( primary safety measure ) . Eligibility criteria were pregnant women aged 18 to < 35 years , at 26 to 29 weeks gestation , and residing in Dhaka , Bangladesh . 160 women were r and omized by 1:1 allocation to one of two parallel intervention groups ; placebo ( n = 80 ) or 35,000 IU/week of vitamin D3 ( n = 80 ) until delivery . All participants , study personnel and study investigators were blind to treatment allocation . Results Mean maternal 25(OH)D concentration was similar in the vitamin D and placebo groups at baseline ( 45 vs. 44 nmol/L ; p = 0.66 ) , but was significantly higher in the vitamin D group vs. placebo group among mothers at delivery ( 134 vs. 38 nmol/L ; p < 0.001 ) and newborns ( cord blood : 103 vs. 39 ; p < 0.001 ) . In the vitamin D group , 95 % of neonates and 100 % of mothers attained 25(OH)D > 50 nmol/L , versus 21 % mothers and 19 % of neonates in the placebo group . No participants met criteria for hypercalcemia , there were no known supplement-related adverse events , and major pregnancy outcomes were similar between groups . Conclusions Antenatal 3rd-trimester vitamin D3 supplementation ( 35,000 IU/week ) significantly raised maternal and cord serum 25(OH)D concentrations above 50 nmol/L in almost all participants without inducing hypercalcemia or other observed safety concerns . Doses up to 35,000 IU/week may be cautiously used in further research aim ed at establishing the clinical effects and safety of vitamin D3 supplementation in pregnancy . Trial registration This trial was registered at Clinical Trials.gov ( NCT01126528 ) In a double-blind trial of vitamin D supplements in pregnant Asian women calciferol ( ergocalciferol , 1000 IU/day ) was administered to 59 women and placebo to 67 controls during the last trimester . The two groups had similar distributions of maternal age , height , parity , number of vegetarians , countries of origin , and sex and gestation of the infants . At entry to the trial maternal serum 25-hydroxy vitamin D ( 25-OHD ) concentrations were low in both treatment and control groups and significantly lower in vegetarians than non-vegetarians . Mothers in the treatment group gained weight faster in the last trimester than those in the control group , and at term they and their infants all had adequate plasma 25-OHD concentrations , Mothers and infants in the control group , however , had low plasma concentrations of 25-OHD and calcium and raised plasma alkaline phosphatase ( bone isoenzyme ) activity . Five of these infants developed symptomatic hypocalcaemia . Almost twice as many infants in the control group were small for gestational age ( 29 % v 15 % ) , but there were no significant differences between the two groups of infants in antropometric measurements . Infants in the control group , however , had larger fontanelles , suggesting impaired ossification of the skull . Because of the benefits to mothers and infants in the treatment group and the absence of side effects , vitamin D supplements should be given to all pregnant Asian women in the United Kingdom Background : The exact role of vitamin D in the development and severity of preeclampsia is still unclear . The aim of the present study was to investigate the association between vitamin D supplement and preeclampsia in pregnant women . Material s and Methods : In this r and omized controlled trial , in 2012 , 140 nulliparous pregnant women in two groups received supplementation with 600 IU/day of vitamin D or supplementation free of vitamin D at 16 week gestation until the delivery . The main outcomes included the frequency of preeclampsia and subtypes by clinical severity and infant birth weight . Results : Mean of maternal age and gestational age at the delivery in all studied subjects were 25 ± 4.1 years and 37.4 ± 3 weeks , respectively , which were not statistically significant between the groups . Preeclampsia was observed in two subjects in case group compared to seven subjects in control group , which was not significant ( P-value = 0.09 ) . In case group , subjects with preeclampsia diagnosed as mild preeclampsia and in control group four subjects were mild , and three were severe . No significant differences were noted between the case and control groups in the frequency of preeclampsia subtypes by clinical severity . Infant birth weight in case group who was significantly higher than control group , which was statistically significant between groups ( P-value = 0.09 ) . Conclusion : In summary , our results demonstrated that vitamin D supplementation during the third trimester of pregnancy ; despite the non-significant association between vitamin D supplementation and preeclampsia , reduce the risk of preeclampsia . However , further studies needs to be done BACKGROUND In 2006 , WHO produced international growth st and ards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee . Using the same methods and conceptual approach , the Fetal Growth Longitudinal Study ( FGLS ) , part of the INTERGROWTH-21(st ) Project , aim ed to develop international growth and size st and ards for fetuses . METHODS The multicentre , population -based FGLS assessed fetal growth in geographically defined urban population s in eight countries , in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided . We used ultrasound to take fetal anthropometric measurements prospect ively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction . All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown-rump length in the first trimester . The five primary ultrasound measures of fetal growth -- head circumference , biparietal diameter , occipitofrontal diameter , abdominal circumference , and femur length -- were obtained every 5 weeks ( within 1 week either side ) from 14 weeks to 42 weeks of gestation . The best fitting curves for the five measures were selected using second-degree fractional polynomials and further modelled in a multilevel framework to account for the longitudinal design of the study . FINDINGS We screened 13,108 women commencing antenatal care at less than 14 weeks and 0 days of gestation , of whom 4607 ( 35 % ) were eligible . 4321 ( 94 % ) eligible women had pregnancies without major complications and delivered live singletons without congenital malformations ( the analysis population ) . We documented very low maternal and perinatal mortality and morbidity , confirming that the participants were at low risk of adverse outcomes . For each of the five fetal growth measures , the mean differences between the observed and smoothed centiles for the 3rd , 50th , and 97th centiles , respectively , were small : 2·25 mm ( SD 3·0 ) , 0·02 mm ( 3·0 ) , and -2·69 mm ( 3·2 ) for head circumference ; 0·83 mm ( 0·9 ) , -0·05 mm ( 0·8 ) , and -0·84 mm ( 1·0 ) for biparietal diameter ; 0·63 mm ( 1·2 ) , 0·04 mm ( 1·1 ) , and -1·05 mm ( 1·3 ) for occipitofrontal diameter ; 2·99 mm ( 3·1 ) , 0·25 mm ( 3·2 ) , and -4·22 mm ( 3·7 ) for abdominal circumference ; and 0·62 mm ( 0·8 ) , 0·03 mm ( 0·8 ) , and -0·65 mm ( 0·8 ) for femur length . We calculated the 3rd , 5th 10th , 50th , 90th , 95th and 97th centile curves according to gestational age for these ultrasound measures , representing the international st and ards for fetal growth . INTERPRETATION We recommend these international fetal growth st and ards for the clinical interpretation of routinely taken ultrasound measurements and for comparisons across population s. FUNDING Bill & Melinda Gates Foundation Poor nutrient intake during pregnancy can adversely affect both infant and maternal health . The aim was to investigate the efficacy of multiple-micronutrient supplementation during pregnancy in a socially deprived population in the developed world . We conducted a r and omised , double-blind , placebo-controlled trial of multiple-micronutrient supplementation including 20 mg Fe and 400 microg folic acid , from the first trimester of pregnancy in 402 mothers , in East London , UK .  Nutrient status was measured at recruitment , and at 26 and 34 weeks of gestation . Infants were weighed at birth . At recruitment the prevalence of anaemia was 13 % , vitamin D insufficiency 72 % , thiamin deficiency 12 % and folate deficiency 5 % , with no differences between groups . Only 39 % of women completed the study ; rates of non-compliance were similar in both groups . Intention-to-treat analysis showed that participants receiving treatment had higher mean Hb at 26 weeks of gestation ( 110 ( sd 10 ) v.108 ( sd 10 ) g/l ; P = 0.041 ) and 34 weeks of gestation ( 113 ( sd 12 ) v.109 ( sd 10 ) g/l ; P = 0.003 ) and packed cell volume concentrations at 26 weeks of gestation ( 0.330 ( sd 0.025 ) v. 0.323 ( sd 0.026 ) l/l ; P = 0.011 ) and 34 weeks of gestation ( 0.338 ( sd 0.029 ) v. 0.330 ( sd 0.028 ) l/l ; P = 0.014 ) compared with controls . Analysis of compliant women showed supplemented women had higher median concentrations of serum ferritin , erythrocyte folate and 25-hydroxyvitamin D later in gestation than controls . In the compliant subset ( n 149 ) , placebo mothers had more small-for-gestational age ( SGA ) infants ( eight SGA v. thirteen ; P = 0.042 ) than treatment mothers . Baseline micronutrient deficiencies were common ; the multiple-micronutrient supplement was well-tolerated and improved nutrient status .  Multiple-micronutrient supplements from early pregnancy may be beneficial and larger studies are required to assess impact on birth outcomes and infant development INTRODUCTION Evidence suggests a high prevalence of calcium and vitamin D deficiencies exists in both pregnant women and babies . Adequate intake of micronutrients has great importance especially during pregnancy and lactation period . Thus , the present study aim ed at assessing the effect of vitamin D and calcium-vitamin D on pregnancy and birth outcomes ( including duration of pregnancy , type of delivery and infant anthropometric indicators ) . METHODS A r and omized , controlled , clinical , triple-blind trial conducted on 126 pregnant women referring to Tabriz health centers in 2013 - 14 . Subjects were allocated into three groups using block r and omization . Interventional groups received vitamin D , calcium-vitamin D and placebo pills daily for 60 days . ANCOVA and Chi-square tests were used for data analysis . RESULTS By controlling BMI before and during pregnancy , there were no significant differences between the group in average neonatal weight , height and head circumference , duration of pregnancy , type of delivery and gestational age at the time of delivery . CONCLUSION The results show that calcium-vitamin D and vitamin D have no effect on duration of pregnancy , type of delivery and infant anthropometric indicators OBJECTIVE The objective of the study was to determine whether vitamin D ( vitD ) supplementation during pregnancy affects obstetric and neonatal outcomes . SETTING The study was conducted at a university hospital in Karachi , Pakistan . METHODS The study was a single-center , open-label , r and omized , controlled trial of routine care ( group A , 200 mg ferrous sulfate and 600 mg calcium daily ) vs vitD supplementation ( group B , 4000 IU vitamin D3 daily ) , started at 20 weeks and continued till delivery . Maternal serum sample s of 25-hydroxyvitamin D ( 25OHD ) were collected at baseline and delivery . Neonatal vitD status was assessed in cord blood or in neonatal serum sample s within 48 hours of birth . Obstetric outcomes included gestational hypertension , gestational diabetes , and preterm labor , and neonatal well-being included small for gestational age , birth weight , length , head circumference , and 1- and 5-minute Apgar scores . RESULTS Of 207 gravidae enrolled , 193 completed the trial .  Maternal age , vitD status , and gestational age at enrollment were comparable between the two groups . At delivery , maternal 25OHD was increased in group B ( 18.3 ± 11 ng/dL vs 8.82 ± 11.84 ng/dL ( P = .001 ) compared with group A ( 6.9 ± 7.0 ng/dL vs 6.32 ± 3.97 ng/dL , P = .06 ) . The obstetric outcomes were comparable between the two groups ( P > .05 ) . Neonatal 25OHD levels were significantly higher in group B compared with group A ( 19.22 ± 12.19 ng/dL vs 6.27 ± 5.2 ng/dL ) . There was positive correlation between maternal and neonatal 25OHD levels ( r = 0.83 , P = .001 ) . One- and 5-minute Apgar scores were significantly higher in group B ( 7.10 ± 0.66 vs 6.90 ± 0.50 , P = .026 , and 8.53 ± 0.68 vs 8.33 ± 0.81 , P = .051 , respectively ) . Neonatal anthropometric parameters were comparable between the two groups ( P > .05 ) . CONCLUSION Maternal vitD supplementation improved maternal and neonatal vitD status
During pregnancy , vitamin D supplementation may be a feasible strategy to help prevent  low birthweight ( LBW ) and small for gestational age ( SGA ) births .
However , evidence from r and omized controlled trials ( RCTs ) is inconclusive , probably due to heterogeneity in study design and type of intervention .