Prenatal Vitamin D Supplementation and Child Respiratory Health: A Randomised Controlled Trial Vitamin D During Pregnancy and Infancy and Infant Serum 25-Hydroxyvitamin D Concentration The Vitamin D Antenatal Asthma Reduction Trial (VDAART): rationale, design, and methods of a randomized, controlled trial of vitamin D supplementation in pregnancy for the primary prevention of asthma and allergies in children. Evaluation of Vitamin D Supplementation Doses during Pregnancy in a Population at High Risk for Deficiency A Simplified Regimen Compared with WHO Guidelines Decreases Antenatal Calcium Supplement Intake for Prevention of Preeclampsia in a Cluster-Randomized Noninferiority Trial in Rural Kenya. Vitamin D3 Supplementation During Pregnancy and Lactation Improves Vitamin D Status of the Mother–Infant Dyad Early pregnancy vitamin D status and risk of preeclampsia. Rationale and Design of Khuzestan Vitamin D Deficiency Screening Program in Pregnancy: A Stratified Randomized Vitamin D Supplementation Controlled Trial Effect of vitamin D3 supplementation in pregnancy on risk of pre-eclampsia - Randomized controlled trial. Maternal vitamin D sufficiency and reduced placental gene expression in angiogenic biomarkers related to comorbidities of pregnancy Maternal vitamin D supplementation during pregnancy and lactation to prevent acute respiratory infections in infancy in Dhaka, Bangladesh (MDARI trial): protocol for a prospective cohort study nested within a randomized controlled trial Maternal vitamin D supplementation in pregnancy and offspring outcomes: a double-blind randomized placebo-controlled trial Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. Efficacy and safety of Vitamin D supplementation during pregnancy: A randomized trial of two different levels of dosing on maternal and neonatal Vitamin D outcome The effects of vitamin D supplementation on maternal and neonatal outcome: A randomized clinical trial Analyzing Adherence to Prenatal Supplement: Does Pill Count Measure Up? The Role of Vitamin D in the Transcriptional Program of Human Pregnancy Maternal vitamin D supplementation during pregnancy and lactation to promote infant growth in Dhaka, Bangladesh (MDIG trial): study protocol for a randomized controlled trial Effect of various doses of vitamin D supplementation on pregnant women with gestational diabetes mellitus: A randomized controlled trial. Vitamin D supplementation during pregnancy: Effect on the neonatal immune system in a randomized controlled trial Effect of vitamin D replacement on maternal and neonatal outcomes: a randomised controlled trial in pregnant women with hypovitaminosis D. A protocol Pharmacokinetics of High-Dose Weekly Oral Vitamin D3 Supplementation during the Third Trimester of Pregnancy in Dhaka, Bangladesh Vitamin D supplementation in pregnancy, prenatal 25(OH)D levels, race, and subsequent asthma or recurrent wheeze in offspring: Secondary analyses from the Vitamin D Antenatal Asthma Reduction Trial High-Dose Monthly Maternal Cholecalciferol Supplementation during Breastfeeding Affects Maternal and Infant Vitamin D Status at 5 Months Postpartum: A Randomized Controlled Trial. Effect of vitamin D supplementation during pregnancy on neonatal mineral homeostasis and anthropometry of the newborn and infant. Vitamin D activity of breast milk in women randomly assigned to vitamin D3 supplementation during pregnancy. Effect of Vitamin D3 Supplementation During Pregnancy on Risk of Persistent Wheeze in the Offspring: A Randomized Clinical Trial. The effect of different doses of vitamin D supplementation on insulin resistance during pregnancy Daily Cholecalciferol Supplementation during Pregnancy Alters Markers of Regulatory Immunity, Inflammation, and Clinical Outcomes in a Randomized Controlled Trial. Vitamin D requirement in pregnancy to prevent deficiency in neonates: a randomised trial. Vitamin D supplementation during pregnancy and infancy reduces aeroallergen sensitization: a randomized controlled trial Comparison of sun exposure versus vitamin D supplementation for pregnant women with vitamin D deficiency Effects of Maternal Vitamin D Supplementation on the Maternal and Infant Epigenome. Vitamin D Supplementation in Pregnancy: A Controlled Trial of Two Methods The effects of vitamin D and omega-3 fatty acid co-supplementation on glycemic control and lipid concentrations in patients with gestational diabetes. Randomized controlled trial (RCT) of vitamin D supplementation in pregnancy in a population with endemic vitamin D deficiency. Gestational Age and Maternal Serum 25-hydroxyvitamin D Concentration Interact to Affect the 24,25-dihydroxyvitamin D Concentration in Pregnant Adolescents. A randomized trial of vitamin D supplementation in 2 community health center networks in South Carolina. Effectiveness of Prenatal Vitamin D Deficiency Screening and Treatment Program: A Stratified Randomized Field Trial Estimation of the maternal vitamin D intake that maintains circulating 25-hydroxyvitamin D in late gestation at a concentration sufficient to keep umbilical cord sera ≥25–30 nmol/L: a dose-response, double-blind, randomized placebo-controlled trial in pregnant women at northern latitude Vitamin D supplementation in pregnancy and lactation to promote infant growth Effect of Prenatal Supplementation With Vitamin D on Asthma or Recurrent Wheezing in Offspring by Age 3 Years: The VDAART Randomized Clinical Trial. Factors influencing the infant gut microbiome at age 3‐6 months: Findings from the ethnically diverse Vitamin D Antenatal Asthma Reduction Trial (VDAART) Tracking of 25-hydroxyvitamin D status during pregnancy: the importance of vitamin D supplementation. Bone mineral density during pregnancy in women participating in a randomized controlled trial of vitamin D supplementation. Effect of treatment of vitamin D deficiency and insufficiency during pregnancy on fetal growth indices and maternal weight gain: a randomized clinical trial. Maternal vitamin D₃ supplementation at 50 μg/d protects against low serum 25-hydroxyvitamin D in infants at 8 wk of age: a randomized controlled trial of 3 doses of vitamin D beginning in gestation and continued in lactation.
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 OBJECTIVE : To determine the vitamin D dose necessary to achieve serum 25-hydroxyvitamin D ( 25(OH)D ) concentration ≥20 ng/mL during infancy . METHODS : A r and omized , double-blind , placebo-controlled trial in New Zeal and . Pregnant mothers , from 27 weeks ’ gestation to birth , and then their infants , from birth to age 6 months , were r and omly assigned to 1 of 3 mother/infant groups : placebo/placebo , vitamin D3 1000/400 IU , or vitamin D3 2000/800 IU . Serum 25(OH)D and calcium concentrations were measured at enrollment , 36 weeks ’ gestation , in cord blood , and in infants at 2 , 4 , and 6 months of age . RESULTS : Two-hundred- and -sixty pregnant women were r and omized . At enrollment , the proportions with serum 25(OH)D ≥20 ng/mL for placebo , lower-dose , and higher-dose groups were 54 % , 64 % , and 55 % , respectively . The proportion with 25(OH)D ≥20 ng/mL was larger in both intervention groups at 36 weeks ’ gestation ( 50 % , 91 % , 89 % , P < .001 ) . In comparison with placebo , the proportion of infants with 25(OH)D ≥20 ng/mL was larger in both intervention groups to age 4 months : cord blood ( 22 % , 72 % , 71 % , P < .001 ) , 2 months ( 50 % , 82 % , 92 % , P < .001 ) , and 4 months ( 66 % , 87 % , 87 % , P = .004 ) , but only in the higher-dose group at age 6 months ( 74 % , 82 % , 89 % , P = .07 ; higher dose versus placebo P = .03 , lower dose versus placebo P = .21 ) . CONCLUSIONS : Daily vitamin D supplementation during pregnancy and then infancy with 1000/400 IU or 2000/800 IU increases the proportion of infants with 25(OH)D ≥20 ng/mL , with the higher dose sustaining this increase for longer There is intense interest in the role of vitamin D in the development of asthma and allergies . However , studies differ on whether a higher vitamin D intake or status in pregnancy or at birth is protective against asthma and allergies . To address this uncertainty , the Vitamin D Antenatal Asthma Reduction Trial ( VDAART ) was developed . VDAART is a r and omized , double-blind , placebo-controlled trial of vitamin D supplementation  in pregnant women to determine whether prenatal supplementation can prevent the development of  asthma and allergies in women 's offspring . A secondary aim is to determine whether vitamin D supplementation can prevent the development of pregnancy complications , such as preeclampsia , preterm birth , and gestational diabetes .  Women were r and omized to the treatment arm of 4000IU/day of vitamin D3 plus a daily multivitamin that contained 400IU of vitamin D3 or the placebo arm of placebo plus a multivitamin that contained 400IU daily of vitamin D3 . Women who were between the gestational ages of 10 and 18 weeks were r and omized from three clinical centers across the United States - Boston Medical Center , Washington University in St. Louis , and Kaiser Permanente Southern California Region ( San Diego , CA ) . Supplementation took place throughout pregnancy . Monthly monitoring of urinary calcium to creatinine ratio was performed in addition to medical record review for adverse events . Offspring are being evaluated quarterly through question naires and yearly during in-person visits until the 3rd birthday of the child . Ancillary studies will investigate neonatal T-regulatory cell function , maternal vaginal flora , and maternal and child intestinal flora Aim / Background : Vitamin D supplementation during pregnancy is a well-accepted recommendation worldwide ; however , the debate about the correct dose is ongoing . We aim ed to compare daily doses of 600 , 1,200 , and 2,000 IU in this r and omized , controlled study . Methods : The study group consisted of 91 pregnant women aged 16 - 42 years admitted to Kocaeli Maternity and Children Hospital between April 2011 and April 2012 . The participants were r and omly divided into 3 groups . 600 , 1,200 , and 2,000 IU/day of vitamin D was supplemented to group 1 ( control group , n = 31 ) , group 2 ( n = 31 ) , and group 3 ( n = 32 ) , respectively . Serum calcium , 25-hydroxyvitamin D ( 25OHD ) , and the calcium/creatinine ratio in spot urine sample s were measured in the follow-up period . The serum calcium and 25OHD levels of the mothers ' infants were measured as well . Results : The frequency of vitamin D sufficiency after supplementation was 80 % in group 3 and it was significantly higher than in groups 1 ( 42 % ) and 2 ( 39 % ) ( p = 0.03 ) . The frequency of vitamin D sufficiency in the infants of the participants was 91 % in group 3 and it was significantly higher than in groups 1 ( 36 % ) and 2 ( 52 % ) ( p = 0.006 ) . Conclusions : At least 2,000 IU/day of vitamin D is needed to ensure adequate vitamin D status in pregnancy and early infancy Background : To prevent preeclampsia , the WHO recommends antenatal calcium supplementation in population s with inadequate habitual intake . The WHO recommends 1500 - 2000 mg Ca/d with iron-folic acid ( IFA ) taken separately , a complex pill-taking regimen . Objective : The objective of this study was to test the hypothesis that simpler regimens with lower daily dosages would lead to higher adherence and similar supplement intake . Methods : In the Micronutrient Initiative Calcium Supplementation study , we compared the mean daily supplement intake associated with 2 dosing regimens with the use of a parallel , cluster-r and omized noninferiority trial implemented in 16 primary health care facilities in rural Kenya . The st and ard regimen was 3 × 500 mg Ca/d in 3 pill-taking events , and the low-dose regimen was 2 × 500 mg Ca/d in 2 pill-taking events ; both regimens included a 200 IU cholecalciferol and calcium pill and a separate IFA pill . We enrolled 990 pregnant women between 16 and 30 wk of gestation . The primary outcome was supplemental calcium intake measured by pill counts 4 and 8 wk after recruitment . We carried out intention-to-treat analyses with the use of mixed-effect models , with regimen as the fixed effect and health care facilities as a r and om effect , by using a noninferiority margin of 125 mg Ca/d . Results : Women in facilities assigned to the st and ard regimen consumed a mean of 1198 mg Ca/d , whereas those assigned to the low-dose regimen consumed 810 mg Ca/d . The difference in intake was 388 mg Ca/d ( 95 % CI = 341 , 434 mg Ca/d ) , exceeding the prespecified margin of 125 mg Ca/d . The overall adherence rate was 80 % and did not differ between study arms . Conclusions : Contrary to our expectation , a simpler , lower-dose regimen led to significantly lower supplement intake than the regimen recommended by the WHO . Further studies are needed to precisely characterize the dose-response relation of calcium supplementation and preeclampsia risk and to examine cost effectiveness of lower and simpler regimens in program setting s. This trial was registered at clinical trials.gov as NCT02238704 Objective To identify the combined effect of prenatal and postnatal vitamin D3 supplementation on the vitamin D status of pregnant and lactating women and their exclusively breastfed infants . Design Double‐blind , r and omized controlled trial . Setting Upper Midwestern U.S. , hospital‐based obstetric practice . Participants Pregnant women ( N = 13 ) planning to exclusively breastfeed were r and omized at 24 to 28 weeks gestation to receive vitamin D3 at a dosage of 400 IU ( control group , n = 6 ) or 3,800 IU ( intervention group , n = 7 ) daily through 4 to 6 weeks postpartum . Vitamin D status was determined at enrollment and in mother – infant dyads at 24 to 72 hours after birth and 4 to 6 weeks postpartum . Methods Serum 25‐hydroxyvitamin D levels were measured to determine the effect of vitamin D3 supplementation on the vitamin D status of mothers and infants . Analysis of covariance was used to compare differences in 25‐hydroxyvitamin D levels between the control and intervention groups . Results The mothers ’ vitamin D levels were significantly higher in the intervention group than in the control group at birth ( p = .044 ) and at 4 to 6 weeks postpartum ( p = .002 ) . Infants in the intervention group had significantly higher vitamin D levels at birth ( p = .021 ) and nonsignificant , clinical ly relevant increases at 4 to 6 weeks of age ( p = .256 ) . No differences were found between maternal groups in serum calcium or parathyroid hormone levels . Conclusion Prenatal to postpartum vitamin D3 supplementation is an effective intervention to increase a mother ’s vitamin D status and to promote optimal vitamin D status in newborns and exclusively breastfed infants BACKGROUND Low vitamin D status in pregnancy was proposed as a risk factor of  preeclampsia  . METHODS We assessed the effect of vitamin D supplementation ( 4,400 vs. 400 IU/day ) , initiated early in pregnancy ( 10 - 18 weeks ) , on the development of preeclampsia . The effects of serum vitamin D ( 25-hydroxyvitamin D [ 25OHD ] ) levels on preeclampsia incidence at trial entry and in the third trimester ( 32 - 38 weeks ) were studied . We also conducted a nested case-control study of 157 women to investigate peripheral blood vitamin D-associated gene expression profiles at 10 to 18 weeks in 47 participants who developed preeclampsia . RESULTS Of 881 women r and omized , outcome data were available for 816 , with 67 ( 8.2 % ) developing preeclampsia . There was no significant difference between treatment ( N = 408 ) or control ( N = 408 ) groups in the incidence of preeclampsia ( 8.08 % vs. 8.33 % , respectively ; relative risk : 0.97 ; 95 % CI , 0.61 - 1.53 ) . However , in a cohort analysis and after adjustment for confounders , a significant effect of sufficient vitamin D status ( 25OHD ≥30 ng/ml ) was observed in both early and late pregnancy compared with insufficient levels ( 25OHD < 30 ng/ml ) ( adjusted odds ratio , 0.28 ; 95 % CI , 0.10 - 0.96 ) . Differential expression of 348 vitamin D-associated genes ( 158 upregulated ) was found in peripheral blood of women who developed preeclampsia ( FDR < 0.05 in the Vitamin D Antenatal Asthma Reduction Trial [ VDAART ] ; P < 0.05 in a replication cohort ) . Functional enrichment and network analyses of this vitamin D-associated gene set suggests several highly functional modules related to systematic inflammatory and immune responses , including some nodes with a high degree of connectivity . CONCLUSIONS Vitamin D supplementation initiated in weeks 10 - 18 of pregnancy did not reduce preeclampsia incidence in the intention-to-treat paradigm . However , vitamin D levels of 30 ng/ml or higher at trial entry and in late pregnancy were associated with a lower risk of preeclampsia . Differentially expressed vitamin D-associated transcriptomes implicated the emergence of an early pregnancy , distinctive immune response in women who went on to develop preeclampsia . TRIAL REGISTRATION Clinical Trials.gov NCT00920621 . FUNDING Quebec Breast Cancer Foundation and Genome Canada Innovation Network . This trial was funded by the National Heart , Lung , and Blood Institute . For details see Acknowledgments Background Although there have been marked improvements in our underst and ing of vitamin D functions in different diseases , gaps on its role during pregnancy remain . Due to the lack of consensus on the most accurate marker of vitamin D deficiency during pregnancy and the optimal level of 25-hydroxyvitamin D , 25(OH)D , for its definition , vitamin D deficiency assessment during pregnancy is a complicated process . Besides , the optimal protocol for treatment of hypovitaminosis D and its effect on maternal and neonatal outcomes are still unclear . Objective The aim of our study was to estimate the prevalence of vitamin D deficiency in the first trimester of pregnancy and to compare vitamin D screening strategy with no screening . Also , we intended to compare the effectiveness of various treatment regimens on maternal and neonatal outcomes in Masjed-Soleyman and Shushtar cities of Khuzestan province , Iran . Methods This was a two-phase study . First , a population -based cross-sectional study was conducted ; recruiting 1600 and 900 first trimester pregnant women from health centers of Masjed-Soleyman and Shushtar , respectively , using stratified multistage cluster sampling with probability proportional to size ( PPS ) method . Second , to assess the effect of screening strategy on maternal and neonatal outcomes , Masjed-Soleyman participants were assigned to a screening program versus Shushtar participants who became the nonscreening arm . Within the framework of the screening regimen , an 8-arm blind r and omized clinical trial was undertaken to compare the effects of various treatment protocol s. A total of 800 pregnant women with vitamin D deficiency were selected using simple r and om sampling from the 1600 individuals of Masjed-Soleyman as interventional groups . Serum concentrations of 25(OH)D were classified as : ( 1 ) severe deficient ( < 10ng/ml ) , ( 2 ) moderate deficient ( 10 - 20ng/ml ) , and ( 3 ) normal status ( > 20ng/ml ) . Those with severe and moderate deficiency were r and omly divided into 4 subgroups and received vitamin D3 based on protocol and were followed until delivery . Data was analyzed according to the intention-to-treat principle . Results Recruitment commenced in July , 2014 , and as estimated , nearly 3.5 years is needed to complete the study . Results of this study will ( 1 ) provide reliable information regarding the prevalence of vitamin D deficiency during pregnancy using universal vitamin D screening approach and ( 2 ) determine the beneficial effects of universal screening and compare the various treatment protocol s in terms of pregnancy outcomes . Conclusions Since vitamin D deficiency is a prevalent disorder in pregnancy among Iranian population , this study will ensure creation of reliable evidence -based findings and will enable clinicians to better evaluate and treat vitamin D deficient pregnant women . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 2014102519660N1 ; http://www.i rct .ir/ search result .php?keyword=&id=19660&number=1&prt=7805&total=10&m=1 ( Archived by WebCite at http://www.webcitation.org/6p3lkqFdV BACKGROUND Vitamin D plays pivotal role in decidualization and implantation of the placenta . Recent research es have shown that low level of vitamin D3 " 25-hydroxyvitamin D ( 25[OH]D ) " in serum is a risk factor for pre-eclampsia . Latest evidence supports role of vitamin D3 deficiency treatment in reducing the risk of pre-eclampsia . The aim of this study is to determine the effect of antenatal supplementation of vitamin D3 on the risk of pre-eclampsia and to explore the dose effect in attaining the vitamin D3 normal level . METHOD An open labelled r and omized controlled study was conducted on 179 pregnant women presenting in King Fahad Medical City antenatal clinic from Oct 2012-Oct 2015 . Patients with age less than 20 years or more than 40 years , pregnancy with fetal anomalies , history of hypertension , pre-eclampsia , recurrent miscarriage , chronic renal or hepatic disease and malignancy were excluded from the study .  Serum 25[OH]D was analysed during the first trimester ( between 6 and 12 weeks of pregnancy ) . Patients with vitamin D3 deficiency ( serum levels < 25 nmol/L ) were included in the study and r and omized for vitamin D3 supplementation 400 IU ( Group 1 ) versus 4000 IU ( Group 2 ) . Both groups were compared for the prevalence of pre-eclampsia and dose effect on vitamin D level . RESULTS Of 179 gravidae enrolled , 164 completed the trial .  Mean maternal 25[OH]D was significantly increased in group 2 from 16.3 ± 5 nmol/mL to 72.3 ± 30.9 nmol/mL compared with group 1 from 17.5 ± 6.7 nmol/mL to 35.3 ± 20.7 nmol/mL ( p > 0.0001 ) . The relative risk reduction ( RRR ) for attaining ≥75 nmol/L before delivery was significantly higher ( RRR 93.2 [ CI 79 - 98 ] when treated with 4000 IU . The total incidence of pre-eclampsia in the study population was 4.3 % . In comparison to group 1 , the group 2 reported fewer pre-eclampsia events during the study period ( 8.6 % versus 1.2 % ; p < 0.05 ) . The total number of IUGRs was lesser in the group 2 ( 9.6 % ) versus group 1 ( 22.2 % ) ; p = 0.027 . However , other obstetric outcomes were comparable between both groups . CONCLUSION Vitamin D supplementation in the deficient group reduces the risk of pre-eclampsia and IUGR in a dose dependant manner . However larger clinical trials are essential to investigate optimum dosage of vitamin D3 in this group INTRODUCTION Maternal circulating 25-hydroxyvitamin D [ 25(OH)D ] has been shown to optimize production of 1,25-dihydroxyvitamin D [ 1,25(OH)2D ] during pregnancy at approximately 100nmoles/L , which has pronounced effects on fetal health outcomes . Additionally , associations are noted between low maternal 25(OH)D concentrations and vascular pregnancy complications , such as preeclampsia . To further eluci date the effects of vitamin D activity in pregnancy , we investigated the role of maternal 25(OH)D , the nutritional indicator of vitamin D status , in relation to placental maintenance and , specifically , expression of placental gene targets related to angiogenesis and vitamin D metabolism . METHODS A focused analysis of placental mRNA expression related to angiogenesis , pregnancy maintenance , and vitamin D metabolism was conducted in placentas from 43 subjects enrolled in a r and omized controlled trial supplementing 400IU or 4400IU of vitamin D3 per day during pregnancy . Placental mRNA was isolated from biopsies within one hour of delivery , followed by quantitative PCR . We classified pregnant women with circulating concentrations of < 100nmoles/L as deficient and those with ≥100nmoles/L as sufficient . The value of each gene 's change in the PCR cycle threshold ( ΔCT ) , which is a relative measure of target concentration , was compared with maternal 25(OH)D concentrations < 100nmoles/L and ≥100nmoles/L based on a two- sample Wilcoxon test . RESULTS Soluble FMS-like tyrosine kinase 1 ( sFlt-1 ) and vascular endothelial growth factor ( VEGF ) gene expression was significantly downregulated in the maternal subgroup with circulating 25(OH)D ≥100ng/mL compared to the subgroup < 100ng/mL. DISCUSSION Here , we report a significant association between maternal vitamin D status and the expression of sFlt-1 and VEGF at the mRNA level . Achieving maternal circulating 25(OH)D ≥100nmoles/L suggests the impact of maternal vitamin D3 supplementation on gene transcription in the placenta , thereby potentially decreasing antiangiogenic factors that may contribute to vascular pregnancy complications Background Early infancy is a high-risk period for severe acute respiratory infection ( ARI ) , particularly in low-income countries with re source -limited health systems . Lower respiratory tract infection ( LRTI ) is commonly preceded by upper respiratory infection ( URTI ) , and often caused by respiratory syncytial virus ( RSV ) , influenza and other common community-acquired viral pathogens . Vitamin D status is a c and i date modifiable early-life determinant of the host antiviral immune response and thus may influence the risk of ARI-associated morbidity in high-risk population s. Methods / Design In the Maternal Vitamin D for Infant Growth ( MDIG ) study in Dhaka , Bangladesh ( NCT01924013 ) , 1300 pregnant women are r and omized to one of five groups : placebo , 4200 IU/week , 16,800 IU/week , or 28,000 IU/week from 2nd trimester to delivery plus placebo from 0–6 months postpartum ; or , 28,000 IU/week prenatal and until 6-months postpartum . In the Maternal Vitamin D for ARI in Infancy ( MDARI ) sub- study nested within the MDIG trial , trained personnel conduct weekly postnatal home visits to inquire about ARI symptoms and conduct a st and ardized clinical assessment . Supplementary home visits between surveillance visits are conducted when caregivers make phone notifications of new infant symptoms . Mid-turbinate nasal swab sample s are obtained from infants who meet st and ardized clinical ARI criteria . Specimens are tested by polymerase chain reaction ( PCR ) for 8 viruses ( influenza A/B , parainfluenza 1/2/3 , RSV , adenovirus , and human metapneumovirus ) , and nasal carriage density of Streptococcus pneumoniae . The primary outcome is the incidence rate of microbiologically-positive viral ARI , using incidence rate ratios to estimate between-group differences . We hypothesize that among infants 0–6 months of age , the incidence of microbiologically-confirmed viral ARI will be significantly lower in infants whose mothers received high-dose prenatal/postpartum vitamin D supplements versus placebo . Secondary outcomes include incidence of ARI associated with specific pathogens ( influenza A or B , RSV ) , clinical ARI , and density of pneumococcal carriage . Discussion If shown to reduce the risk of viral ARI in infancy , integration of maternal prenatal/postpartum vitamin D supplementation into antenatal care programs in South Asia may be a feasible primary preventive strategy to reduce the burden of ARI-associated morbidity and mortality in young infants . Trial registration NCT02388516 , registered March 9 , 2015 We studied bone mineral content ( BMC ) , bone mineral density ( BMD ) , and body composition in offspring of women supplemented with vitamin D during pregnancy . Pregnant women were r and omized to receive oral cholecalciferol 60,000 units 4 weekly ( group 1 ) , 8 weekly ( group 2 ) , or placebo ( group 3 ) . All received 1 g calcium daily ( groups 1 and 2 without , and group 3 with 400 units vitamin D ) . Offspring at 12–16 months underwent dual-energy X-ray absorptiometry .  Maternal hypovitaminosis D  at recruitment was common ( serum 25OHD < 50 nmol/L in 88 % ) and severe ( 25OHD < 25 nmol/L in 46 % ) . Groups 1 and 2 ( n = 23 and 13 , median age 14 months ) had higher cord blood 25OHD ( 47.8 ± 13.8 and 31.0 ± 14.0 nmol/L ) versus group 3 ( n = 16 , median age 16 months , 17.8 ± 13.5 nmol/L , p < 0.001 ) . Babies in group 3 had higher whole-body BMC ( 250.8 ± 42.5 gm ) and BMD ( 0.335 ± 0.033 gm/cm2 ) compared to group 1 ( 213.1 ± 46.2 gm and 0.295 ± 0.041 gm/cm2 ) and group 2 ( 202.9 ± 29.9 gm and 0.287 ± 0.023 gm/cm2 ) ( p = 0.006 and 0.001 , respectively ) . In multivariate analysis , age , weight z score , and lean body mass remained significant contributors to BMC . Parameters of body composition were comparable among the groups . Vitamin D supplementation to pregnant women with severe deficiency in doses that improved cord blood 25OHD did not result in improved bone health or body composition in offspring at 12–16 months , compared to a dose too small to improve 25OHD levels 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 Introduction : Pregnant women represent a typical group susceptible to dietary and mineral deficiencies . This study was sought to assess the efficacy and safety of various doses of 25-hydroxyvitamin D ( 25[OH]D ) supplementation during pregnancy and ratify the inadequacy of the recommended daily allowance for Vitamin D in vulnerable groups . Material s and Methods : A total of 100 pregnant women were included in this open-label , parallel group , prospect i ve , r and omized , and controlled trial . Study subjects were assigned to four treatment groups : Group 1 ( n = 26 ) , 1000 IU of Vitamin D daily ; Group 2 ( n = 21 ) , 30,000 IU of Vitamin D monthly ; Group 3 ( n = 27 ) , 2000 IU of Vitamin D daily ; and Group 4 ( n = 26 ) , 60,000 IU Vitamin D monthly . Group 1 and 2 were further analyzed together as Group 1 K ( 1000 IU daily and 30,000 IU monthly ) , and Group 3 and 4 as Group 2 K ( 2000 IU daily and 60,000 IU monthly ) . The analysis was done on an intention to treat basis . Results : A total of 87 patients completed the study ; 21 in Group 1 , 25 in Group 2 , 18 in Group 3 , and 23 in Group 4 . The levels of 25(OH)D at baseline ranged from 1.3 to 58.0 with a mean of 24.2 ± 15.1 ng/ml . Postsupplementation , 25(OH)D levels ranged from 11.5 to 70.3 with a mean of 40.2 ± 12.2 ng/ml . The postsupplementation levels of 25(OH)D were higher in Group 2 K ( 42.86 ± 12.83 ) than in Group 1 K ( 36.96 ± 10.56 ) with P value of 0.023 . Conclusion : We concluded that Vitamin D supplementation with 2000 IU/day or 60,000 IU/month is very effective and safe in achieving Vitamin D sufficiency in pregnant women Background : Vitamin D supplementation during pregnancy has been supposed to defend against adverse gestational outcomes . Objective : This r and omized clinical trial study was conducted to assess the effects of 50,000 IU of vitamin D every two weeks supplementation on the incidence of  gestational diabetes ( GDM ) , gestational hypertension , preeclampsia and preterm labor , vitamin D status at term and neonatal outcomes contrasted with pregnant women that received 400 IU vitamin D daily . Material s and Methods : 500 women with gestational age 12 - 16 weeks and serum 25 hydroxy vitamin D ( 25 ( OH ) D ) less than 30 ng/ml r and omly categorized in two groups . Group A received 400 IU vitamin D daily and group B 50,000 IU vitamin D every 2 weeks orally until delivery . Maternal and Neonatal outcomes were assessed in two groups . Results : The incidence of GDM in group B was significantly lower than group A ( 6.7 % versus 13.4 % ) and odds ratio ( 95 % Confidence interval ) was 0.46 ( 0.24 - 0.87 ) ( P=0.01 ) . The mean ± SD level of 25 ( OH ) D at the time of delivery in mothers in group B was significantly higher than A ( 37.9 ± 19.8 versus 27.2 ± 18.8 ng/ml , respectively ) ( P=0.001 ) . There were no differences in the incidence of preeclampsia , gestational hypertension , preterm labor , and low birth weight between two groups . The mean level of 25 ( OH ) D in cord blood of group B was significantly higher than group A ( 37.9 ± 18 versus 29.7 ± 19ng/ml , respectively ) . Anthropometric measures between neonates were not significantly different . Conclusion : Our study showed 50,000 IU vitamin D every 2 weeks decreased the incidence of GDM Objective . To determine if adherence as measured by pill count would show a significant association with serum-based measures of adherence . Methods . Data were obtained from a prenatal vitamin D supplementation trial where subjects were stratified by race and r and omized into three dosing groups : 400 ( control ) , 2000 , or 4000 IU vitamin D3/day . One measurement of adherence was obtained via pill counts remaining compared to a novel definition for adherence using serum 25-hydroxy-vitamin D ( 25-OH-D ) levels ( absolute change in 25(OH)D over the study period and the subject 's steady-state variation in their 25(OH)D levels ) . A multivariate logistic regression model examined whether mean percent adherence by pill count was significantly associated with the adherence measure by serum metabolite levels . Results . Subjects ' mean percentage of adherence by pill count was not a significant predictor of adherence by serum metabolite levels . This finding was robust across a series of sensitivity analyses . Conclusions . Based on our novel definition of adherence , pill count was not a reliable predictor of adherence to protocol , and calls into question how adherence is measured in clinical research . Our findings have implication s regarding the determination of efficacy of medications under study and offer an alternative approach to measuring adherence of long half-life supplements/medications Background Patterns of gene expression of human pregnancy are poorly understood . In a trial of vitamin D supplementation in pregnant women , peripheral blood transcriptomes were measured longitudinally on 30 women and used to characterize gene co-expression networks . Objective Studies suggest that increased maternal Vitamin D levels may reduce the risk of asthma in early life , yet the underlying mechanisms have not been examined . In this study , we used a network-based approach to examine changes in gene expression profiles during the course of normal pregnancy and evaluated their association with maternal Vitamin D levels . Design The VDAART study is a r and omized clinical trial of vitamin D supplementation in pregnancy for reduction of pediatric asthma risk . The trial enrolled 881 women at 10–18 weeks of gestation . Longitudinal gene expression measures were obtained on thirty pregnant women , using RNA isolated from peripheral blood sample s obtained in the first and third trimesters . Differentially expressed genes were identified using significance of analysis of microarrays ( SAM ) , and clustered using a weighted gene co-expression network analysis ( WGCNA ) . Gene-set enrichment was performed to identify major biological pathways . Results Comparison of transcriptional profiles between first and third trimesters of pregnancy identified 5839 significantly differentially expressed genes ( FDR<0.05 ) . Weighted gene co-expression network analysis clustered these transcripts into 14 co-expression modules of which two showed significant correlation with maternal vitamin D levels . Pathway analysis of these two modules revealed genes enriched in immune defense pathways and extracellular matrix reorganization as well as genes enriched in notch signaling and transcription factor networks . Conclusion Our data show that gene expression profiles of healthy pregnant women change during the course of pregnancy and suggest that maternal Vitamin D levels influence transcriptional profiles . These alterations of the maternal transcriptome may contribute to fetal immune imprinting and reduce allergic sensitization in early life . Trial Registration clinical trials.gov Background Vitamin D regulates bone mineral metabolism and skeletal development . Some observational studies have suggested that prenatal vitamin D deficiency increases the risk of adverse pregnancy and /or birth outcomes ; however , there is scant evidence from controlled trials , leading the World Health Organization to advise against routine vitamin D supplementation in pregnancy . Importantly , little is known about the effect of maternal vitamin D status on infant linear growth in communities in South Asia where stunting is highly prevalent and maternal-infant vitamin D status is commonly suboptimal . Methods / Design The Maternal Vitamin D for Infant Growth study is a r and omized , placebo-controlled , dose-ranging trial of  maternal vitamin D supplementation during pregnancy and lactation in Dhaka , Bangladesh . The primary aims are to estimate ( 1 ) the effect of maternal prenatal oral vitamin D3 supplementation ( 4200 IU/wk , 16,800 IU/wk , or 28,000 IU/wk , administered as weekly doses ) versus placebo on infant length at 1 year of age and ( 2 ) the effect of maternal postpartum oral vitamin D3 supplementation ( 28,000 IU/wk ) versus placebo on length at 1 year of age among infants born to women who received vitamin D 28,000 IU/wk during pregnancy . Generally healthy pregnant women ( n = 1300 ) in the second trimester ( 17–24 weeks of gestation ) are r and omized to one of five parallel arms : placebo 4200 IU/wk , 16,800 IU/wk , or 28,000 IU/wk in the prenatal period and placebo in the postpartum period or 28,000 IU/wk in the prenatal period and 28,000 IU/wk in the postpartum period . Household- and clinic-based follow-up of mother-infant pairs is conducted weekly by trained personnel until 26 weeks postpartum and every 3 months thereafter . The primary trial outcome measure is length for age z-score at 1 year of age . Anthropometric measurements , clinical information , and biological specimens collected at scheduled intervals will enable the assessment of a range of maternal , perinatal , and infant outcomes . Discussion The role of vitamin D in maternal and infant health remains unresolved . This trial is expected to contribute unique insights into the effects of improving maternal-infant vitamin D status in a low-income setting where stunting and adverse perinatal outcomes represent significant public health burdens . Trial registration Clinical Trials.gov identifier : NCT01924013 . Registered on 13 August It has previously been reported that the influence of vitamin D on the metabolism of calcium and phosphorus is associated with diabetes , cardiovascular disease , Alzheimer 's disease , cancer and other systemic diseases , and is considered an important indicator of general health . The present study was conducted to determine the effect of various doses of vitamin D supplementation on glucose metabolism , lipid concentrations , inflammation and the levels of oxidative stress of pregnant women with gestational diabetes mellitus ( GDM ) . The present r and omized , double-blind placebo-controlled clinical trial was conducted on 133 pregnant women with GDM during weeks 24 - 28 of pregnancy . The patients were r and omly divided into four groups . The control group ( n=20 ) received a placebo ( sucrose ; one granule/day ) , the low dosage group ( n=38 ) received the daily recommended intake of 200 IU vitamin D ( calciferol ) daily , the medium dosage group ( n=38 ) received 50,000 IU monthly ( 2,000 IU daily for 25 days ) and the high dosage group ( n=37 ) received 50,000 IU every 2 weeks ( 4,000 IU daily for 12.5 days ) . The general characteristics and dietary intakes of the patients with GDM were similar between each group . Using ELISA kits , it was determined that insulin , homeostatic model assessment -insulin resistance and total cholesterol were significantly reduced by high dosage vitamin D supplementation ( P<0.05 ) . Total antioxidant capacity and total glutathione levels were significantly elevated as a result of high dosage vitamin D supplementation ( P<0.01 ) . In conclusion , high-dose vitamin D supplementation ( 50,000 IU every 2 weeks ) significantly improved insulin resistance in pregnant women with GDM & NA ; Figure . No caption available . Background : Programming of the immune system during fetal development can influence asthma‐related risk factors and outcomes in later life . Vitamin D is a well‐recognized immune modulator , and deficiency of this nutrient during pregnancy is hypothesized to influence disease development in offspring . Objective : We sought to investigate the effect on neonatal immunity of maternal supplementation with 4400 IU/d vitamin D3 during the second and third trimesters of pregnancy by using a subset of cord blood sample s from a r and omized , double‐blind , placebo‐controlled clinical trial ( the Vitamin D Antenatal Asthma Reduction Trial ) . Methods : Cord blood sample s from neonates born to mothers supplemented with 4400 IU/d ( n = 26 ) or 400 IU/d ( n = 25 ) of vitamin D3  were analyzed for immune cell composition by flow cytometry , Toll‐like receptor ( TLR ) expression by quantitative PCR , and cytokine secretion after stimulation with mitogenic , TLR , and T‐cell stimuli by cytometric bead array . Responsiveness to the glucocorticoid dexamethasone was determined . Results : Supplementation of mothers with 4400 IU of vitamin D3 result ed in an enhanced broad‐spectrum proinflammatory cytokine response of cord blood mononuclear cells to innate and mitogenic stimuli ( P = .0009 ) , with an average 1.7‐ to 2.1‐fold increase in levels of several proinflammatory cytokines ( GM‐CSF , IFN‐&ggr ; , IL‐1&bgr ; , IL‐6 , and IL‐8 ) across stimuli , a higher gene expression level of TLR2 ( P = .02 ) and TLR9 ( P = .02 ) , a greater than 4‐fold increase in IL‐17A ( P = .03 ) production after polyclonal T‐cell stimulation , and an enhanced IL‐10 response of cord blood mononuclear cells to dexamethasone treatment in culture ( P = .018 ) . Conclusion : Vitamin D exposure during fetal development influences the immune system of the neonate , which can contribute to protection from asthma‐related , including infectious , outcomes in early life Introduction The vitamin D recommended doses during pregnancy differ between societies . The WHO guidelines do not recommend routine prenatal supplementation , but they underscore the fact that women with the lowest levels may benefit most . The effects of routine supplementation during pregnancy on maternal and neonatal clinical outcomes have not been investigated in the Middle East , where hypovitaminosis D is prevalent . Our hypothesis is that in Middle Eastern pregnant women , a vitamin D dose of 3000 IU/day is required to reach a desirable maternal 25-hydroxyvitamin D [ 25(OH)D ] level , and to positively impact infant bone mineral content ( BMC ) . Methods and analysis This is a multicentre blinded r and omised controlled trial . Pregnant women presenting to the Obstetrics and Gynaecology clinics will be approached . Eligible women will be r and omised to daily equivalent doses of cholecalciferol , 600 IU or 3000 IU , from 15 to 18 weeks gestation until delivery . Maternal 25(OH)D and chemistries will be assessed at study entry , during the third trimester and at delivery . Neonatal anthropometric variables and 25(OH)D level will be measured at birth , and bone and fat mass assessment by dual-energy X-ray absorptiometry scan at 1 month . A sample size of 280 pregnant women is needed to demonstrate a statistically significant difference in the proportion of women reaching a 25(OH)D level ≥50 nmol/L at delivery , and a difference in infant BMC of 6 (10)g , for a 90 % power and a 2.5 % level of significance . The proportions of women achieving a target 25(OH)D level will be compared between the two arms , using χ2 . An independent t test will be used to compare mean infant BMC between the two arms . The primary analysis is an intention-to-treat analysis of unadjusted results . Ethics and dissemination The protocol has been approved by the Institutional Review Board at the American University of Beirut-Lebanon ( IM.GEHF.22 ) . The trial results will be published in peer- review ed medical journals and presented at scientific conferences . Trial registration number NCT02434380 A pharmacokinetic study was conducted to assess the biochemical dose-response and tolerability of high-dose prenatal vitamin D3 supplementation  in Dhaka , Bangladesh ( 23 ° N ) . Pregnant women at 27–30 weeks gestation ( n = 28 ) were r and omized to 70,000 IU once + 35,000 IU/week vitamin D3 ( group PH : pregnant , higher dose ) or 14,000 IU/week vitamin D3 ( PL : pregnant , lower dose ) until delivery . A group of non-pregnant women ( n = 16 ) was similarly administered 70,000 IU once + 35,000 IU/week for 10 weeks ( NH : non-pregnant , higher-dose ) . Rise ( ∆ ) in serum 25-hydroxyvitamin D concentration ( [ 25(OH)D ] ) above baseline was the primary pharmacokinetic outcome . Baseline mean [ 25(OH)D ] were similar in PH and PL ( 35 nmol/L vs. 31 nmol/L , p = 0.34 ) . A dose-response effect was observed : ∆[25(OH)D ] at modeled steady-state was 19 nmol/L ( 95 % CI , 1 to 37 ) higher in PH vs. PL ( p = 0.044 ) . ∆[25(OH)D ] at modeled steady-state was lower in PH versus NH but the difference was not significant ( −15 nmol/L , 95 % CI −34 to 5 ; p = 0.13 ) . In PH , 100 % attained [ 25(OH)D ] ≥ 50 nmol/L and 90 % attained [ 25(OH)D ] ≥ 80 nmol/L ; in PL , 89 % attained [ 25(OH)D ] ≥ 50 nmol/L but 56 % attained [ 25(OH)D ] ≥ 80 nmol/L. Cord [ 25(OH)D ] ( n = 23 ) was slightly higher in PH versus PL ( 117 nmol/L vs. 98 nmol/L ; p = 0.07 ) . Vitamin D3  was well tolerated ; there were no supplement-related serious adverse clinical events or hypercalcemia . In summary , a regimen of an initial dose of 70,000 IU and 35,000 IU/week vitamin D3 in the third trimester of pregnancy was non-hypercalcemic and attained [ 25(OH)D ] ≥ 80 nmol/L in virtually all mothers and newborns . Further research is required to establish the safety of high-dose vitamin D3 in pregnancy and to determine if supplement-induced [ 25(OH)D ] elevations lead to maternal-infant health benefits Background Nutrient trials differ from drug trials because participants have varying circulating levels at entry into the trial . Objective We sought to study the effect of a vitamin D intervention in pregnancy between subjects of different races and the association between 25‐hydroxyvitamin D3 ( 25[OH]D ) levels in pregnancy and the risk of asthma/recurrent wheeze in offspring . Methods The Vitamin D Antenatal Asthma Reduction Trial is a r and omized trial of pregnant women at risk of having children with asthma r and omized to 4400 international units/d vitamin D or placebo plus 400 international units/d vitamin D. Asthma and  recurrent wheezing until age 3 years were recorded . Results African American ( AA ) women ( n = 312 ) had lower initial levels of 25(OH)D ( mean [ SD ] , 17.6 ng/mL [ 8.3 ng/mL ] ) compared with non‐AA women ( n = 400 ; 27.1 ng/mL [ 9.7 ng/mL ] , P < .001 ) . No racial difference was found from vitamin D supplementation in pregnancy on asthma/recurrent wheezing in offspring ( P for interaction = .77 ) . Having an initial level of greater than 30 ng/mL and being r and omized to the intervention group was associated with the lowest risk for asthma/recurrent wheeze by age 3 years compared with having an initial level of less than 20 ng/mL and receiving placebo ( adjusted odds ratio , 0.42 ; 95 % CI , 0.19‐0.91 ) . Conclusions We did not find differences between AA and non‐AA mothers in the effect of maternal vitamin D supplementation and asthma/recurrent wheeze in offspring at 3 years . Maternal supplementation of vitamin D , particularly in mothers with initial 25(OH)D levels of greater than 30 ng/mL , reduced asthma/recurrent wheeze in the offspring through age 3 years , suggesting that higher vitamin D status beginning in early pregnancy is necessary for asthma/recurrent wheeze prevention in early life . Graphical abstract Figure . No Caption available BACKGROUND Many countries recommend daily infant vitamin D supplementation during breastfeeding , but compliance is often poor . A monthly , high-dose maternal regimen may offer an alternative strategy , but its efficacy is unknown . OBJECTIVE The objective of the study was to determine the effect of 2 different monthly maternal doses of cholecalciferol on maternal and infant 25-hydroxyvitamin D [ 25(OH)D ] status during the first 5 mo of breastfeeding . METHODS With the use of a r and omized , double-blind , placebo-controlled design , women who were planning to exclusively breastfeed for 6 mo ( n = 90 ; mean age : 32.1 y ; 71 % exclusively breastfeeding at week 20 ) were r and omly assigned to receive either cholecalciferol ( 50,000 or 100,000 IU ) or a placebo monthly from week 4 to week 20 postpartum . The treatment effects relative to placebo were estimated as changes in maternal and infant serum 25(OH)D from baseline to week 20 postpartum by using a linear fixed-effects regression model . Additional secondary analyses , adjusted for potential confounders such as season of birth , vitamin D-fortified formula intake , and infant or maternal skin color , were also conducted . RESULTS After 16 wk of supplementation , changes in maternal serum 25(OH)D were significantly higher in the 50,000-IU/mo ( 12.8 nmol/L ; 95 % CI : 0.4 , 25.2 nmol/L ) and 100,000-IU/mo ( 21.5 nmol/L ; 95 % CI : 9.2 , 33.8 nmol/L ) groups than in the placebo group ( P = 0.43 and P < 0.001 , respectively ) . For infants , the unadjusted mean changes in serum 25(OH)D were 4.5 nmol/L ( 95 % CI : -16.2 , 25.0 nmol/L ) for the 50,000-IU/mo group and 15.8 nmol/L ( 95 % CI : -4.7 , 36.4 nmol/L ) for the 100,000-IU/mo group , but the changes did not differ from the placebo reference group . However , after adjustment for season of birth , vitamin D-fortified formula intake , and infant skin color , the mean change effect size for the 100,000-IU/mo group was 19.1 nmol/L ( 95 % CI : 2.5 , 35.6 nmol/L ; P = 0.025 ) higher than that in the placebo group . CONCLUSIONS Maternal cholecalciferol supplementation at a dose of 100,000 IU/mo during the first 5 mo of breastfeeding potentially benefits infant vitamin D status . Further studies are required to determine optimum dose and dosing frequency . This trial was registered at www.anzctr.org.au as ACTRN12611000108910 Hypovitaminosis D is common in India . In the present prospect i ve partially r and omised study of vitamin D ( D₃ ) supplementation during pregnancy , subjects were r and omised in the second trimester to receive either one oral dose of 1500 μg vitamin D₃  ( group 1 , n 48 ) or two doses of 3000 μg vitamin D₃ each in the second and third trimesters ( group 2 , n 49 ) . Maternal 25-hydroxyvitamin D ( 25(OH)D ) at term , cord blood ( CB ) alkaline phosphatase ( ALP ) , neonatal serum Ca and anthropometry were measured in these subjects and in forty-three non-supplemented mother-infant pairs ( usual care ) . Median maternal 25(OH)D at term was higher in group 2 ( 58·7 , interquartile range ( IQR ) 38·4 - 89·4 nmol/l ) v. group 1 ( 26·2 , IQR 17·7 - 57·7 nmol/l ) and usual-care group ( 39·2 , IQR 21·2 - 73·4 nmol/l ) ( P = 0·000 ) . CB ALP was increased ( > 8.02 μkat/l or > 480 IU/l ) in 66·7 % of the usual-care group v. 41·9 % of group 1 and 38·9 % of group 2 ( P = 0·03 ) . Neonatal Ca and CB 25(OH)D did not differ significantly in the three groups . Birth weight , length and head circumference were greater and the anterior fontanelle was smaller in groups 1 and 2 ( 3·08 and 3·03 kg , 50·3 and 50·1 cm , 34·5 and 34·4 cm , 2·6 and 2·5 cm , respectively ) v. usual care ( 2·77 kg , 49·4 , 33·6 , 3·3 cm ; P = 0·000 for length , head circumference and fontanelle and P = 0·003 for weight ) . These differences were still evident at 9 months . We conclude that both 1500 μg and two doses of  3000  μg vitamin  D₃ had a beneficial effect on infant anthropometry , the larger dose also improving CB ALP and maternal BACKGROUND Human milk is typically low in vitamin D activity ( VDA ) . Whether the vitamin D content of breast milk at birth can be increased by supplementing the mother during pregnancy has not been reported to the best of our knowledge . OBJECTIVE We examined the effect of vitamin D supplementation during pregnancy on breast-milk VDA in the first 2 mo of lactation . DESIGN Breast-milk sample s were obtained from women who were enrolled in a r and omized , double-blinded , placebo-controlled trial of vitamin D supplementation during pregnancy . Pregnant women were enrolled at 27 wk of gestation and r and omly assigned to the following 3 groups : a placebo group , a group who received one dosage of daily oral vitamin D3 ( 1000 IU ) , or a group who received 2 dosages of daily oral vitamin D3 ( 2000 IU ) . Serum 25-hydroxyvitamin D [ 25(OH)D ] was measured at enrollment , at 36 wk of gestation , and in cord blood at birth . Study participants who were breastfeeding were invited to provide breast-milk sample s for VDA measurement [ concentration of vitamin D2 , vitamin D3 , 25(OH)D2 , and 25(OH)D3 ] at 2 wk and 2 mo postpartum . A linear mixed model was used to compare breast-milk VDA between the 3 study groups . RESULTS A total of 75 women provided breast-milk sample s ( 44 women provided breast-milk sample s at both 2 wk and 2 mo postpartum ) . The mean ( 95 % CI ) VDA at age 2 wk was 52 IU/L ( 12 , 217 IU/L ) in the placebo group , 51 IU/L ( 17 , 151 IU/L ) in the 1000-IU group , and 74 IU/L ( 25 , 221 IU/L ) in the 2000-IU group ; and at age 2 mo , the mean ( 95 % CI ) VDA was 45 IU/L ( 16 , 124 IU/L ) , 43 IU/L ( 18 , 103 IU/L ) , and 58 IU/L ( 15 , 224 IU/L ) , respectively . There was no significant interaction in VDA between the sample - collection time and treatment ( P = 0.61 ) , but there was a difference between lower- and higher-dosage treatment groups ( P = 0.04 ) . CONCLUSION Maternal vitamin D supplementation during pregnancy of 2000 IU/d ( compared with 1000 IU/d and with a placebo ) results in a higher VDA of breast milk ≥2 mo postpartum . This trial was registered at the Australian New Zeal and Clinical Trials Registry as ACTRN12610000483055 IMPORTANCE Observational studies have suggested that increased dietary vitamin D intake during pregnancy may protect against wheezing in the offspring , but the preventive effect of vitamin D supplementation to pregnant women is unknown . OBJECTIVE To determine whether supplementation of vitamin D3 during the third trimester of pregnancy reduces the risk of persistent wheeze in the offspring . DESIGN , SETTING , AND PARTICIPANTS A double-blind , single-center , r and omized clinical trial conducted within the Copenhagen Prospect i ve Studies on Asthma in Childhood 2010 cohort . Enrollment began March 2009 with a goal of 708 participants , but due to delayed ethical approval , only 623 women were recruited at 24 weeks of pregnancy . Follow-up of the children ( N = 581 ) was completed when the youngest child reached age 3 years in March 2014 . INTERVENTIONS Vitamin D3 ( 2400 IU/d ; n = 315 ) or matching placebo tablets ( n = 308 ) from pregnancy week 24 to 1 week postpartum . All women received 400 IU/d of vitamin D3 as part of usual pregnancy care . MAIN OUTCOMES AND MEASURES Age at onset of persistent wheeze in the first 3 years of life . Secondary outcomes included number of episodes of troublesome lung symptoms , asthma , respiratory tract infections , and neonatal airway immunology . Adverse events were assessed . RESULTS Of the 581 children ,  persistent wheeze  was diagnosed during the first 3 years of life in 47 children ( 16 % ) in the  vitamin D3 group and 57 children ( 20 % ) in the  control group .  Vitamin D3 supplementation was not associated with the risk of persistent wheeze , but the number of episodes of troublesome lung symptoms was reduced , and the airway immune profile was up-regulated ( principal component analysis , P = .04 ) . There was no effect on additional end points . Intrauterine death was observed in 1 fetus ( < 1 % ) in the vitamin D3 group vs 3 fetuses ( 1 % ) in the control group and congenital malformations in 17 neonates ( 5 % ) in the vitamin D3 group vs 23 neonates ( 8 % ) in the control group . [ table : see text ] . CONCLUSIONS AND RELEVANCE The use of 2800 IU/d of vitamin D3 during the third trimester of pregnancy compared with 400 IU/d did not result in a statistically significant reduced risk of persistent wheeze in the offspring through age 3 years . However , interpretation of the study is limited by a wide CI that includes a clinical ly important protective effect . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00856947 Abstract Low serum vitamin D levels are correlated with insulin resistance during pregnancy . We have assessed the effects of different doses of vitamin D on insulin resistance during pregnancy . A r and omized clinical trial was done on 120 women with a gestational age of less than 12 weeks . The women were divided into three groups r and omly . Group A received 200 IU vitamin D daily , group B 50 000 IU vitamin D monthly and group C 50 000 IU vitamin D every 2 weeks from 12 weeks of pregnancy until delivery . The serum levels of fasting blood sugar ( FBS ) , insulin , calcium and 25-hydroxyvitamin D were measured before and after intervention . We used the homeostatic model assessment of insulin resistance ( HOMA-IR ) as a surrogate measure of insulin resistance . The mean ± st and ard deviation of serum 25-hydroxyvitamin D increased in group C from 7.3 ± 5.9 to 34.1 ± 11.5 ng/ml and in group B it increased from 7.3 ± 5.3 to 27.23 ± 10.7 ng/ml , but the level of vitamin D in group A increased from 8.3 ± 7.8 to 17.7 ± 9.3 ng/ml ( p < 0.001 ) . The mean differences of insulin and HOMA-IR before and after intervention in groups A and C were significant ( p = 0.01 , p = 0.02 ) . This study has shown that supplementation of pregnant women with 50 000 IU vitamin D every 2 weeks improved insulin resistance significantly BACKGROUND Vitamin D deficiency is widespread in pregnancy and has been associated with adverse health conditions in mothers and infants .  Vitamin D supplementation in pregnancy may support the maintenance of pregnancy by its effects on innate and adaptive immunity . OBJECTIVE We assessed the effects of vitamin D supplementation during pregnancy on vitamin D status and markers of immune function associated with adverse pregnancy outcomes . METHODS We conducted a r and omized , controlled , double-blind intervention of 2 doses of cholecalciferol ( 400 and 2000 IU/d ) from < 20 wk to delivery in 57 pregnant women .  Vitamin D status , regulatory and inflammatory T cells , markers of innate immunity and systemic inflammation , and clinical outcomes including maternal blood pressure and birth weight were assessed at 26 and 36 wk of pregnancy . RESULTS Supplementation with 2000 IU/d vitamin D had a greater effect on the change in vitamin D status over pregnancy ( P < 0.0001 ) and the final value at 36 wk ( P < 0.0001 ) than 400 IU/d , increasing serum 25-hydroxyvitamin D from 81.1 nmol/L at baseline to 116 nmol/L at 36 wk and from 69.6 nmol/L at baseline to 85.6 nmol/L at 36 wk , respectively . The 2000-IU/d group had 36 % more interleukin-10 + regulatory CD4 + T cells at 36 wk than did the 400-IU/d group ( P < 0.007 ) . The daily intake of 2000 compared with 400 IU/d tended to dampen the pregnancy-related increase in diastolic blood pressure by 1.3-fold ( P = 0.06 ) and increase birth weight by 8.6 % ( P = 0.06 ) , but these differences were not statistically significant . CONCLUSIONS Supplementation with 2000 IU/d is more effective at increasing vitamin D status in pregnant women than 400 IU/d and is associated with increased regulatory T cell immunity that may prevent adverse outcomes caused by excess inflammation . This trial was registered at clinical trials.gov as NCT01417351 INTRODUCTION The exact amount of vitamin D required for pregnant women to adequately supply the foetus during pregnancy is still unclear . This r and omised trial attempted to determine the optimal dose of vitamin D necessary during pregnancy in order to attain a vitamin D level > 20 ng/mL in neonates . METHODS A total of 51 healthy , pregnant women in Yazd , Iran , were recruited in 2009 . Of these , 34 were r and omised to receive either 50,000 IU ( Group A ) or 100,000 IU ( Group B ) of vitamin D3 per month from the second trimester of pregnancy . The remaining 17 pregnant women , who formed the third group ( Group C ) and were found to have vitamin D deficiency , were initially treated with 200,000 IU of vitamin D3 , following which the dose was adjusted to 50,000 IU per month . 25-hydroxyvitamin D ( 25[OH]D ) in cord blood was measured by chemiluminescence immunoassay , and a serum 25(OH)D level < 20 ng/mL was defined as deficiency . RESULTS All the pregnant women had a vitamin D level < 30 ng/mL at the beginning of the second trimester . The neonates of 76 % of women from Group A had sufficient levels of 25(OH)D. All the neonates born to women in Groups B and C had 25(OH)D > 20 ng/mL. No side effects were observed in our participants during the period of vitamin D supplementation . CONCLUSION A vitamin D3dose > 50,000 IU/month is required during the second and third trimesters of pregnancy for vitamin D-deficient pregnant women in order for their neonates to achieve serum 25(OH)D levels > 20 ng/mL. Supplementation with < 50,000 IU/month is insufficient to ensure a vitamin D level > 20 ng/mL in all neonates born to vitamin D-deficient pregnant women Vitamin D has immune‐modulating effects . We determined whether vitamin D supplementation during pregnancy and infancy prevents aeroallergen sensitization and primary care respiratory illness presentations Abstract Introduction : Maternal vitamin D deficiency is widespread health problem that is more important in pregnant women , which affects fetus growth and bone development . The aim of this study was to evaluate the effect of sun exposure versus vitamin D supplementation for pregnant women with vitamin D deficiency . Material s and methods : This prospect i ve clinical trial was performed on 87 pregnant women with vitamin D deficiency . Group A was treated with vitamin D 4000 IU per day for 10 weeks , while group B was recommended for sun exposure for 30 minutes daily ( 30 % body surface area ) for 10 weeks in summer and between 10 am–4 pm in direct sunlight . After the delivery , 25-hydroxyvitamin D3 levels were measured in the same previous center . Moreover , weight , height , and head circumference of fetus were measured at delivery in both groups and compared with each other . Results : After 10-week intervention , 25-hydroxyvitamin D3 levels was significantly higher in group treated with vitamin D as compared to sun expose group ( 31.27 versus 19.79 ng/ml ) . ( p < .001 ) . However , height ( p = .118 ) , weight ( p = .245 ) , and head circumference ( p = .681 ) of infants in both groups did not show significant differences . Conclusions : Vitamin D supplementation is more effective than sun exposure in increasing 25-hydroxyvitamin D3 in pregnant women with vitamin D deficiency INTRODUCTION Mothers and infants are at high risk for inadequate vitamin D status . Mechanisms by which vitamin D may affect maternal and infant DNA methylation are poorly understood . OBJECTIVE This study quantified the effects of vitamin D3 supplementation on DNA methylation in pregnant and lactating women and their breastfed infants . MATERIAL S AND METHODS In this r and omized controlled pilot study , pregnant women received vitamin D3 400 international units ( IU ) ( n = 6 ; control ) or 3,800 IU ( n = 7 ; intervention ) daily from late second trimester through 4 - 6 weeks postpartum . Epigenome-wide DNA methylation was quantified in leukocytes collected from mothers at birth and mother-infant dyads at 4 - 6 weeks postpartum . RESULTS At birth , intervention group mothers showed DNA methylation gain and loss at 76 and 89 cytosine-guanine ( CpG ) dinucleotides , respectively , compared to controls . Postpartum , methylation gain was noted at 200 and loss at 102 CpGs . Associated gene clusters showed strongest biologic relevance for cell migration/motility and cellular membrane function at birth and cadherin signaling and immune function at postpartum . Breastfed 4 - 6-week-old infants of intervention mothers showed DNA methylation gain and loss in 217 and 213 CpGs , respectively , compared to controls . Genes showing differential methylation mapped most strongly to collagen metabolic processes and regulation of apoptosis . CONCLUSIONS Maternal vitamin D supplementation during pregnancy and lactation alters DNA methylation in mothers and breastfed infants . Additional work is needed to fully eluci date the short- and long-term biologic effects of vitamin D supplementation at varying doses , which could hold important implication s for establishing clinical recommendations for prenatal and offspring health promotion & NA ; A r and omized study was conducted to evaluate the effects of single‐dose and daily vitamin D supplementation in pregnant women during the last trimester of a winter pregnancy in the Northwest of France . The women were divided into three r and omized groups : one ( N = 21 ) was given a vitamin D2 supplement of 1000 IU/day during the last three months of pregnancy , one ( N = 27 ) was given a single oral dose of 5 mg at the seventh month of pregnancy , and one ( N = 29 ) acted as a control . Venous plasma sample s were obtained at delivery from the women and from cord blood , and levels of calcium , 25‐OHD , and 1,25(OH)2D were determined . No significant difference in plasma calcium concentration was found among the three groups , but within each group plasma calcium concentrations were higher in the cord sample s than in the respective maternal sample s. The levels of the two metabolites measured were consistently lower in the cord sample s than in the respective maternal sample s. Cord 25‐OHD concentrations correlated with those of maternal plasma . No significant modification of maternal calciuria or of the birth weight of term infants was observed . 25‐OHD concentrations were greater in maternal and cord plasma from treated mothers , but only a slight difference was observed between the supplemented groups . 1,25(OH)2D concentrations were not significantly different in the three groups . A single 5‐mg dose of vitamin D given orally at the seventh month of pregnancy provides effective prophylaxis in the authors ’ region . ( Obstet Gynecol 68:300 , 1986 OBJECTIVE This study was performed to evaluate the effects of vitamin D and omega-3 fatty acids co-supplementation on glucose metabolism and lipid concentrations in gestational diabetes ( GDM ) patients . METHODS This r and omized double-blind placebo-controlled clinical trial was done among 140 GDM patients . Participants were r and omly divided into 4 groups to receive : ( 1 ) 1000 mg omega-3 fatty acids containing 360 mg eicosapentaenoic acid and 240 mg docosahexaenoic acid ( DHA ) twice a day + vitamin D placebo ( n = 35 ) ; ( 2 ) 50,000 IU vitamin D every 2 weeks + omega-3 fatty acids placebo ( n = 35 ) ; ( 3 ) 50,000 IU vitamin D every 2 weeks + 1000 mg omega-3 fatty acids twice a day ( n = 35 ) , and ( 4 ) vitamin D placebo + omega-3 fatty acids placebo ( n = 35 ) for 6 weeks . RESULTS After 6 weeks of intervention , patients who received combined vitamin D and omega-3 fatty acids supplements compared with vitamin D , omega-3 fatty acids , and placebo had significantly decreased fasting plasma glucose ( -7.3 ± 7.8 , -6.9 ± 6.6 , -4.0 ± 2.5 , and + 1.0 ± 11.4 mg/dL , respectively , P < .001 ) , serum insulin levels ( -1.9 ± 1.9 , -1.3 ± 6.3 , -0.4 ± 6.3 , and + 2.6 ± 6.5 μIU/mL , respectively , P = .005 ) , homeostatic model of assessment for insulin resistance ( -0.7 ± 0.6 , -0.5 ± 1.4 , -0.2 ± 1.5 , and + 0.6 ± 1.5 , respectively , P < .001 ) and increased quantitative insulin sensitivity check index ( + 0.01 ± 0.01 , + 0.008 ± 0.02 , + 0.002 ± 0.02 , and -0.005 ± 0.02 , respectively , P = .001 ) . In addition , changes in serum triglycerides ( -8.2 ± 41.0 , + 7.6 ± 31.5 , + 3.6 ± 29.9 , and + 20.1 ± 29.6 mg/dL , respectively , P = .006 ) and very low-density lipoprotein cholesterol ( -1.6 ± 8.2 , + 1.5 ± 6.3 , + 0.8 ± 6.0 , and + 4.0 ± 5.9 mg/dL , respectively , P = .006 ) in the vitamin D plus omega-3 fatty acids group were significantly different from the changes in these indicators in the vitamin D , omega-3 fatty acids , and placebo groups . CONCLUSION Overall , vitamin D and omega-3 fatty acids co-supplementation for 6 weeks among GDM patients  had beneficial effects on fasting plasma glucose , serum insulin levels , homeostatic model of assessment for insulin resistance , quantitative insulin sensitivity check index , serum triglycerides , and very low-density lipoprotein cholesterol levels BACKGROUND Vitamin D ( vD ) deficiency in pregnancy is a global health problem and the amount of vD supplementation to prevent vD deficiency is controversial . OBJECTIVE The objective of the study was to determine effectiveness and safety of prenatal 2000 IU and 4000 IU/d compared with 400 IU/d vD3 supplementation in a r and omized controlled trial in population in which vD deficiency is endemic . DESIGN / METHODS Arab women were r and omized at 12 - 16 weeks of gestation to 400 , 2000 , and 4000 IU/d  vD3 , which were continued to delivery . Serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations were measured during pregnancy and at delivery . The primary outcome was the maternal and cord blood 25(OH)D , and the secondary outcomes were the achievement of sufficient serum 25(OH)D of 32 ng/mL or greater ( ≥80 nmol/L ) at delivery . SETTING The locations were primary care and tertiary perinatal care centers . RESULTS Of 192 enrolled , 162 ( 84 % ) continued to delivery . Mean serum 25(OH)D of 8.2 ng/mL ( 20.5 nmol/L ) at enrollment was low . Mean serum 25(OH)D concentrations at delivery and in cord blood were significantly higher in the 2000 and 4000 IU than the 400 IU/d group ( P < .001 ) and was highest in the 4000 IU/d group . The percent who achieved 25(OH)D greater than 32 ng/mL and greater than 20 ng/mL concentrations in mothers and infants was highest in 4000 IU/d group . Safety measurements were similar by group and no adverse event related to vD supplementation . CONCLUSIONS Vitamin D supplementation of 2000 and 4000 IU/d appeared safe in pregnancy , and 4000 IU/d was most effective in optimizing serum 25(OH)D concentrations in mothers and their infants . These findings could apply to other population s in which vD deficiency is endemic Background Interpretation of  serum vitamin D biomarkers  across pregnancy is complex due to limited underst and ing of pregnancy adaptations in vitamin D metabolism . During pregnancy , both gestational age and serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations may influence the concentrations of 1,25-dihydroxyvitamin D [ 1,25(OH)2D ] , 24,25-dihydroxyvitamin D [ 24,25(OH)2D ] , and parathyroid hormone ( PTH ) . Objective We aim ed to identify predictors of change in serum 25(OH)D across gestation in pregnant adolescents and to assess the contribution made by cholecalciferol ( vitamin D3 ) supplementation . We sought to determine whether gestational age and 25(OH)D concentration interacted to affect serum 1,25(OH)2D , 24,25(OH)2D , or PTH . Methods Pregnant adolescents ( n = 78 , 59 % African American , mean ± SD age : 17 ± 1 y ) living in Rochester , NY ( latitude 43 ° N ) were supplemented with 200 IU or 2000 IU vitamin D3/d and allowed to continue their daily prenatal supplement that contained 400 IU vitamin D3 . Serum was collected at study entry ( 18 ± 5 wk of gestation ) , halfway through study participation , and at delivery ( 40 ± 2 wk ) . Serum concentrations of the biochemical markers were modeled with linear mixed-effects regression models . Results Vitamin D3 supplement intake and season of delivery determined change in 25(OH)D across pregnancy . Fall-winter delivery was associated with a decline in 25(OH)D unless vitamin D3 supplement intake was > 872 IU/d . The interaction of gestational age and 25(OH)D affected 24,25(OH)2D concentrations . For a given 25(OH)D concentration , model-predicted serum 24,25(OH)2D increased across gestation except when 25(OH)D was < 13 ng/mL. Below this threshold , 24,25(OH)2D was predicted to decline over time . Mean serum 1,25(OH)2D was elevated ( > 100 pg/mL ) throughout the study . Conclusion Our results suggest that when maternal serum 25(OH)D was low , its catabolism into 24,25(OH)2D decreased or remained stable as pregnancy progressed in order to maintain persistently elevated serum 1,25(OH)2D . Furthermore , in adolescents living at latitude 43 ° N , st and ard prenatal supplementation did not prevent a seasonal decline in 25(OH)D during pregnancy . This study was registered at clinical trials.gov as NCT01815047 OBJECTIVE We sought to determine whether 4000 IU/d ( vs 2000 IU/d ) of vitamin D during pregnancy is safe and improves maternal/neonatal 25-hydroxyvitamin D [ 25(OH)D ] in a dose-dependent manner . STUDY DESIGN A total of 257 pregnant women 12 - 16 weeks ' gestation were enrolled . R and omization to 2000 vs 4000 IU/d followed 1-month run-in at 2000 IU/d . Participants were monitored for hypercalciuria , hypercalcemia , and 25(OH)D status . RESULTS Maternal 25(OH)D ( n = 161 ) increased from 22.7 ng/mL ( SD 9.7 ) at baseline to 36.2 ng/mL ( SD 15 ) and 37.9 ng/mL ( SD 13.5 ) in the 2000 and 4000 IU groups , respectively . While maternal 25(OH)D change from baseline did not differ between groups , 25(OH)D monthly increase differed between groups ( P < .01 ) . No supplementation-related adverse events occurred . Mean cord blood 25(OH)D was 22.1 ± 10.3 ng/mL in 2000 IU and 27.0 ± 13.3 ng/mL in 4000 IU groups ( P = .024 ) . After controlling for race and study site , preterm birth and labor were inversely associated with predelivery and mean 25(OH)D , but not baseline 25(OH)D. CONCLUSION Maternal supplementation with vitamin D 2000 and 4000 IU/d during pregnancy improved maternal/neonatal vitamin D status . Evidence of risk reduction in infection , preterm labor , and preterm birth was suggestive , requiring additional studies powered for these endpoints Context Despite evidence on the association between hypovitaminosis D and adverse pregnancy outcomes and the positive impact of vitamin D supplementation , no evidence exists supporting a universal screening program in pregnancy as part of routine prenatal care . Objective We sought to determine the effectiveness of a prenatal screening program on optimizing 25-hydroxyvitamin D [ 25(OH)D ] levels and preventing pregnancy complications . Also , to identify a safe regimen , we compared several regimens in a subgroup of vitamin D-deficient pregnant women . Design Two cities of Masjed-Soleyman and Shushtar from Khuzestan province , Iran , were selected as the screening and nonscreening arms , respectively . Within the screening arm , a r and omized controlled trial was conducted on 800 pregnant women . Setting Health centers of Masjed-Soleyman and Shushtar cities . Patients or Participants Pregnant women aged 18 to 40 years . Intervention Women with moderate [ 25(OH)D , 10 to 20 ng/mL ] and severe [ 25(OH)D , < 10 ng/mL ] deficiency were r and omly divided into four subgroups and received vitamin D3 ( D3 ) until delivery . Main Outcome Measure Maternal concentration of 25(OH)D at delivery and rate of pregnancy complications . Results After supplementation , only 2 % of the women in the nonscreening site met the sufficiency level ( > 20 ng/mL ) vs 53 % of the women in the screening site . Adverse pregnancy outcomes , including preeclampsia , gestational diabetes mellitus , and preterm delivery , were decreased by 60 % , 50 % , and 40 % , respectively , in the screening site . A D3 injection in addition to monthly 50,000 IU maintenance therapy contributed the most to achievement of sufficient levels at delivery . Conclusions A prenatal vitamin D screening and treatment program is an effective approach in detecting deficient women , improving 25(OH)D levels , and decreasing pregnancy adverse outcomes ABSTRACT Background In the absence of dose-response data , Dietary Reference Values for vitamin D in nonpregnant adults are extended to pregnancy . Objective The aim was to estimate vitamin D intake needed to maintain maternal 25-hydroxyvitamin D [ 25(OH)D ] in late gestation at a concentration sufficient to prevent newborn 25(OH)D < 25–30 nmol/L , a threshold indicative of increased risk of nutritional rickets . Design We conducted a 3-arm , dose-response , double-blind , r and omized placebo-controlled trial in Cork , Irel and ( 51.9oN ) . A total of 144 white-skinned pregnant women were assigned to receive 0 , 10 ( 400 IU ) , or 20 ( 800 IU ) µg vitamin D3/d from ≤18 wk of gestation . Vitamin D metabolites at 14 , 24 , and 36 wk of gestation and in cord sera , including 25(OH)D3 , 3-epi-25(OH)D3 , 24,25(OH)2D3 , and 25(OH)D2 were quantified by liquid chromatography – t and em mass spectrometry . A curvilinear regression model predicted the total vitamin D intake ( from diet and antenatal supplements plus treatment dose ) that maintained maternal 25(OH)D in late gestation at a concentration sufficient to maintain cord 25(OH)D at ≥25–30 nmol/L. Results Mean ± SD baseline 25(OH)D was 54.9 ± 10.7 nmol/L. Total vitamin D intakes at the study endpoint ( 36 wk of gestation ) were 12.1 ± 8.0 , 21.9 ± 5.3 , and 33.7 ± 5.1 µg/d in the placebo and 10-µg and 20-µg vitamin D3 groups , respectively ; and 25(OH)D was 24.3 ± 5.8 and 29.2 ± 5.6 nmol/L higher in the 10- and 20-µg groups , respectively , compared with placebo ( P < 0.001 ) . For maternal 25(OH)D concentrations ≥50 nmol/L , 95 % of cord sera were ≥30 nmol/L and 99 % were > 25 nmol/L. The estimated vitamin D intake required to maintain serum 25(OH)D at ≥50 nmol/L in 97.5 % of women was 28.9 µg/d . Conclusions Thirty micrograms of vitamin D per day safely maintained serum 25(OH)D concentrations at ≥50 nmol/L in almost all white-skinned women during pregnancy at a northern latitude , which kept 25(OH)D at > 25 nmol/L in 99 % and ≥30 nmol/L in 95 % of umbilical cord sera . This trial was registered at www . clinical trials.gov as NCT02506439 Background It is unclear whether maternal vitamin D supplementation during pregnancy and lactation improves fetal and infant growth in regions where vitamin D deficiency is common . Methods We conducted a r and omized , double‐blind , placebo‐controlled trial in Bangladesh to assess the effects of weekly prenatal vitamin D supplementation ( from 17 to 24 weeks of gestation until birth ) and postpartum vitamin D supplementation on the primary outcome of infants ' length‐for‐age z scores at 1 year according to World Health Organization ( WHO ) child growth st and ards . One group received neither prenatal nor postpartum vitamin D ( placebo group ) . Three groups received prenatal supplementation only , in doses of 4200 IU ( prenatal 4200 group ) , 16,800 IU ( prenatal 16,800 group ) , and 28,000 IU ( prenatal 28,000 group ) . The fifth group received prenatal supplementation as well as 26 weeks of postpartum supplementation in the amount of 28,000 IU ( prenatal and postpartum 28,000 group ) . Results Among 1164 infants assessed at 1 year of age ( 89.5 % of 1300 pregnancies ) , there were no significant differences across groups in the mean ( ±SD ) length‐for‐age z scores . Scores were as follows : placebo , ‐0.93±1.05 ; prenatal 4200 , ‐1.11±1.12 ; prenatal 16,800 , ‐0.97±0.97 ; prenatal 28,000 , ‐1.06±1.07 ; and prenatal and postpartum 28,000 , ‐0.94±1.00 ( P=0.23 for a global test of differences across groups ) . Other anthropometric measures , birth outcomes , and morbidity did not differ significantly across groups . Vitamin D supplementation had expected effects on maternal and infant serum 25‐hydroxyvitamin D and calcium concentrations , maternal urinary calcium excretion , and maternal parathyroid hormone concentrations . There were no significant differences in the frequencies of adverse events across groups , with the exception of a higher rate of possible hypercalciuria among the women receiving the highest dose . Conclusions In a population with widespread prenatal vitamin D deficiency and fetal and infant growth restriction , maternal vitamin D supplementation from midpregnancy until birth or until 6 months post partum did not improve fetal or infant growth . ( Funded by the Bill and Melinda Gates Foundation ; Clinical Trials.gov number , NCT01924013 . IMPORTANCE Asthma and wheezing begin early in life , and prenatal vitamin D deficiency has been variably associated with these disorders in offspring . OBJECTIVE To determine whether prenatal vitamin D ( cholecalciferol ) supplementation can prevent  asthma or recurrent wheeze in early childhood . DESIGN , SETTING , AND PARTICIPANTS The Vitamin D Antenatal Asthma Reduction Trial was a r and omized , double-blind , placebo-controlled trial conducted in 3 centers across the United States . Enrollment began in October 2009 and completed follow-up in January 2015 . Eight hundred eighty-one pregnant women between the ages of 18 and 39 years at high risk of having children with asthma were r and omized at 10 to 18 weeks ' gestation . Five participants were deemed ineligible shortly after r and omization and were discontinued . INTERVENTIONS Four hundred forty women were r and omized to receive daily 4000 IU vitamin D plus a prenatal vitamin containing 400 IU vitamin D , and 436 women were r and omized to receive a placebo plus a prenatal vitamin containing 400 IU vitamin D. MAIN OUTCOMES AND MEASURES Co primary outcomes of ( 1 ) parental report of physician-diagnosed asthma or recurrent wheezing through 3 years of age and ( 2 ) third trimester maternal 25-hydroxyvitamin D levels . RESULTS Eight hundred ten infants were born in the study , and 806 were included in the analyses for the 3-year outcomes . Two hundred eighteen children developed asthma or recurrent wheeze : 98 of 405 ( 24.3 % ; 95 % CI , 18.7%-28.5 % ) in the 4400-IU group vs 120 of 401 ( 30.4 % , 95 % CI , 25.7%-73.1 % ) in the 400-IU group ( hazard ratio , 0.8 ; 95 % CI , 0.6 - 1.0 ; P = .051 ) . Of the women in the 4400-IU group whose blood levels were checked , 289 ( 74.9 % ) had 25-hydroxyvitamin D levels of 30 ng/mL or higher by the third trimester of pregnancy compared with 133 of 391 ( 34.0 % ) in the 400-IU group ( difference , 40.9 % ; 95 % CI , 34.2%-47.5 % , P < .001 ) . CONCLUSIONS AND RELEVANCE In pregnant women at risk of having a child with asthma , supplementation with 4400 IU/d of vitamin D compared with 400 IU/d significantly increased vitamin D levels in the women . The incidence of asthma and recurrent wheezing in their children at age 3 years was lower by 6.1 % , but this did not meet statistical significance ; however , the study may have been underpowered . Longer follow-up of the children is ongoing to determine whether the difference is clinical ly important . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00920621 Background : The gut microbiome in infancy influences immune system maturation , and may have an important impact on allergic disease risk . Objective : We sought to determine how prenatal and early life factors impact the gut microbiome in a relatively large , ethnically diverse study population of infants at age 3 to 6 months , who were enrolled in Vitamin D Antenatal Asthma Reduction Trial , a clinical trial of vitamin D supplementation in pregnancy to prevent asthma and allergies in offspring . Methods : We performed 16S rRNA gene sequencing on 333 infants ' stool sample s. Microbial diversity was computed using the Shannon index . Factor analysis applied to the top 25 most abundant taxa revealed 4 underlying bacterial coabundance groups ; the first dominated by Firmicutes ( Lachnospiraceae/Clostridiales ) , the second by Proteobacteria ( Klebsiella/Enterobacter ) , the third by Bacteriodetes , and the fourth by Veillonella . Scores for coabundance groups were used as outcomes in regression models , with prenatal/birth and demographic characteristics as independent predictors . Multivariate analysis , using all microbial community members , was also conducted . Results : White race/ethnicity was associated with lower diversity but higher Bacteroidetes coabundance scores . C‐section birth was associated with higher diversity , but decreased Bacteroidetes coabundance scores . Firmicutes scores were higher for infants born by C‐section . Breast‐fed infants had lower proportions of Clostridiales . Cord blood vitamin D was linked to increased Lachnobacterium , but decreased Lactococcus . Conclusions : The findings presented here suggest that race , mode of delivery , breast‐feeding , and cord blood vitamin D levels are associated with infant gut microbiome composition , with possible long‐term implication s for immune system modulation and asthma/allergic disease incidence BACKGROUND The role of maternal 25-hydroxyvitamin D [ 25(OH)D ] in fetal development is uncertain , and findings of observational studies have been inconsistent . Most studies have assessed 25(OH)D only one time during pregnancy , but to our knowledge , the tracking of an individual 's 25(OH)D during pregnancy has not been assessed previously . OBJECTIVE We determined the tracking of serum 25(OH)D from early to late pregnancy and factors that influence this . DESIGN The Southampton Women 's Survey is a prospect i ve mother-offspring birth-cohort study .  Lifestyle , diet , and 25(OH)D status were assessed at 11 and 34 wk of gestation . A Fourier transformation was used to model the seasonal variation in 25(OH)D for early and late pregnancy separately , and the difference between the measured and seasonally modeled 25(OH)D was calculated to generate a season-corrected 25(OH)D. Tracking was assessed with the use of the Pearson correlation coefficient , and multivariate linear regression was used to determine factors associated with the change in season-corrected 25(OH)D. RESULTS A total of 1753 women had 25(OH)D measured in both early and late pregnancy . There was a moderate correlation between season-corrected 25(OH)D measurements at 11 and 34 wk of gestation ( r = 0.53 , P < 0.0001 ; n = 1753 ) . Vitamin D supplementation was the strongest predictor of tracking ; in comparison with women who never used supplements , the discontinuation of supplementation after 11 wk was associated with a reduction in season-corrected 25(OH)D ( β = -7.3 nmol/L ; P < 0.001 ) , whereas the commencement ( β = 12.6 nmol/L ; P < 0.001 ) or continuation ( β = 6.6 nmol/L ; P < 0.001 ) of supplementation was associated with increases in season-corrected 25(OH)D. Higher pregnancy weight gain was associated with a reduction in season-corrected 25(OH)D ( β = -0.4 nmol · L(-1 ) · kg(-1 ) ; P = 0.015 ) , whereas greater physical activity ( β = 0.4 nmol/L per h/wk ; P = 0.011 ) was associated with increases . CONCLUSIONS There is a moderate tracking of 25(OH)D status through pregnancy ; factors such as vitamin D supplementation , weight gain , and physical activity are associated with changes in season-corrected 25(OH)D from early to late gestation . These findings have implication s for study design s and analyses and approaches to intervention studies and clinical care Background : Little is known about bone mineral density ( BMD ) during pregnancy . Advances in technology with lower radiation emissions by dual-energy X-ray absorptiometry instruments now permit the safe measurement of BMD during pregnancy . Objective : We evaluated maternal BMD during pregnancy as a function of vitamin D status in women of diverse racial/ethnic background s. Design : A total of 301 women who underwent BMD measurements at 12 - 20 wk of gestation and again at 0 - 14 wk postpartum were included in this analysis . Women were a subset of subjects who were recruited for a r and omized , controlled , double-blind trial of vitamin D supplementation in pregnancy ( 400 , 2000 , or 4000 IU/d ) . Results : Treatment had no significant effect on changes in BMD that occurred between 12 - 20 wk of gestation and 0 - 14 wk postpartum . Similarly , changes in spine and femoral neck bone mineral contents ( BMC s ) were not significantly different in the treatment groups . In addition , vitamin D inadequacy ( serum 25-hydroxyvitamin D concentration , averaged across pregnancy , < 50 nmol/L ) was not associated with changes in BMD or BMC . There were significant racial/ethnic differences in spine BMD .  African Americans  lost more spine BMD than did Caucasians ( -0.04 ± 0.04 compared with -0.02 ± 0.04 g/cm2 ; P = 0.033 ) . In addition , baseline obesity was associated with a greater loss of femoral neck BMD . The means ± SDs of femoral neck BMD loss were -0.02 ± 0.05 and 0.0 ± 0.03 g/cm2 for groups with baseline body mass index ( BMI ; in kg/m2 ) ≥30 and < 30 , respectively . Conclusion : These findings do not support a dose effect of vitamin D supplementation on bone health and suggest that race/ethnicity and BMI play an important role in pregnancy bone health . This trial was registered at clinical trials.gov as NCT00292591 OBJECTIVE To determine whether treatment of low serum vitamin D in pregnant women improves fetal growth indices . STUDY DESIGN In this open-label r and omized clinical trial , 130 Iranian pregnant women ( 24 - 26 weeks of gestation ) with vitamin D deficiency or insufficiency [ 25(OH)D < 30ng/ml ] were divided at r and om into an intervention group and a control group . The control group received 200 mg calcium plus a multivitamin ( containing vitamin D3 400U ) each day , and the intervention group received 200 mg calcium plus a multivitamin ( containing vitamin D3 400U ) each day , plus vitamin D3 ( 50,000U ) each week for 8 weeks . At delivery , maternal and cord blood 25(OH)D levels , maternal weight gain , neonatal length , neonatal weight and neonatal head circumference were compared between two groups . Serum vitamin D was measured using enzyme-linked immunosorbent assay . A multivariate regression analysis was performed to examine the independent effect of maternal vitamin D level on fetal growth indices . RESULTS Mean ( ±st and ard deviation ) length ( intervention group : 49±1.6 cm ; control group : 48.2±1.7 cm ; p=0.001 ) , head circumference ( intervention group : 35.9±0.7 cm ; control group : 35.3±1.0 cm ; p=0.001 ) and weight ( intervention group : 3429±351.9 g ; control group : 3258.8±328.2 g ; p=0.01 ) were higher in the intervention group compared with the control group . Mean maternal weight gain was higher in the intervention group compared with the control group ( 13.3±2.4 kg vs 11.7±2.7 kg ; p=0.006 ) . Multivariate regression analysis for maternal weight gain , neonatal length , neonatal weight and neonatal head circumference showed an independent correlation with maternal vitamin D level . CONCLUSION Treatment of low serum vitamin D during pregnancy improves fetal growth indices and maternal weight gain BACKGROUND Vitamin D supplementation is recommended for breastfed infants .  Maternal supplementation beginning in gestation is a potential alternative , but its efficacy in maintaining infant 25-hydroxyvitamin D [ 25(OH)D ] concentration after birth is unknown . OBJECTIVES We determined the effect of 3 doses of maternal vitamin D supplementation beginning in gestation and continued in lactation on infant serum 25(OH)D and compared the prevalence of infant serum 25(OH)D cutoffs ( > 30 , > 40 , > 50 , and > 75 nmol/L ) by dose at 8 wk of age . DESIGN Pregnant women ( n = 226 ) were r and omly allocated to receive 10 , 25 , or 50 μg vitamin D₃/d from 13 to 24 wk of gestation until 8 wk postpartum , with no infant supplementation . Mother and infant blood was collected at 8 wk postpartum . RESULTS At 8 wk postpartum , mean [ nmol/L ( 95 % CI ) ] infant 25(OH)D at 8 wk was higher in the 50-μg/d [ 75 ( 67 , 83 ) ] than in the 25-μg/d [ 52 ( 45 , 58 ) ] or 10-μg/d [ 45 ( 38 , 52 ) ] vitamin D groups ( P < 0.05 ) . Fewer infants born to mothers in the 50-μg/d group had a 25(OH)D concentration < 30 nmol/L ( indicative of deficiency ) than infants in the 25- and 10-μg/d groups , respectively ( 2 % compared with 16 % and 43 % ; P < 0.05 ) . Fewer than 15 % of infants in the 10- or 25-μg/d groups achieved a 25(OH)D concentration > 75 nmol/L compared with 44 % in the 50-μg/d group ( P < 0.05 ) . Almost all infants ( ∼98 % , n = 44 ) born to mothers in the 50-μg/d group achieved a 25(OH)D concentration > 30 nmol/L. At 8 wk postpartum , mean maternal 25(OH)D concentration was higher in the 50-μg/d [ 88 ( 84 , 91 ) ] than in the 25-μg/d [ 78 ( 74 , 81 ) ] or 10-μg/d [ 69 ( 66 , 73 ) ] groups ( P < 0.05 ) . CONCLUSIONS Maternal supplementation beginning in gestation with 50 μg vitamin D₃/d protects 98 % of unsupplemented breastfed infants against 25(OH)D deficiency ( < 30 nmol/L ) to at least 8 wk , whereas 10 or 25 μg vitamin D/d protects only 57 % and 84 % of infants , respectively
BACKGROUND Vitamin D deficiency during pregnancy increases the risk of pre-eclampsia , gestational diabetes , preterm birth , and low birthweight .
In a previous Cochrane Review we found that supplementing pregnant women with vitamin D alone compared to no vitamin D supplementation may reduce the risk of pre-eclampsia , gestational diabetes , and low birthweight and may increase the risk of preterm births if it is combined with calcium .
However the effects of different vitamin D regimens are not yet clear .
OBJECTIVES To assess the effects and safety of different regimens of vitamin D supplementation alone or in combination with calcium or other vitamins , minerals or nutrients during pregnancy , specifically doses of 601 international units per day ( IU/d ) or more versus 600 IU/d or less ; and 4000 IU/d or more versus 3999 IU/d or less .