Vitamin D Status of Infants of Mothers with Gestational Diabetes: Status at Birth and a Randomized Controlled Trial of Vitamin D Supplementation across Infancy.

BACKGROUND: Vitamin D status and requirements of infants of women with gestational diabetes mellitus (GDM) are unclear. OBJECTIVES: The objectives were to assess vitamin D status in infants of mothers with GDM and compare vitamin D status in response to 400 vs. 1000 IU/d vitamin D supplementation in infants born with serum 25-hydroxyvitamin D [25(OH)D] <50 nmol/L. METHODS: Women with GDM delivering full-term infants (n = 98; March 2017-2019, Montreal, Canada) were surveyed for demographic and lifestyle factors. Pregnancy history was obtained from medical records. Newborn serum 25(OH)D was measured (immunoassay) and categorized as <30 (deficient) or ≥40 nmol/L (adequate). Breastfed neonates (n = 16) with serum 25(OH)D <50 nmol/L at birth were randomly assigned to 400 or 1000 IU/d of supplemental cholecalciferol (vitamin D3), and serum 25(OH)D was measured at baseline (≤1 mo) and 3, 6, and 12 mo of age. Groups were compared using a linear mixed-effects model and Tukey-Kramer post hoc tests. RESULTS: Mean newborn serum 25(OH)D was 46.4 (95% CI: 43.9, 49.9) nmol/L, with 15.3% (95% CI: 8.2%, 22.4%) <30 nmol/L and 61.2% (95% CI: 51.6%, 70.9%) ≥40 nmol/L. During the trial, most infants were breastfed to 3 mo (400 IU/d: 87.5%; 1000 IU/d: 75.0%). Mean (± SEM) infant serum 25(OH)D was higher in the 1000-IU/d group at 3 mo (79.9 ± 5.9 vs. 111.5 ± 15.2 nmol/L; P = 0.0263), and although not different at 6-12 mo, was maintained at >50 nmol/L. CONCLUSIONS: Most infants of women with GDM had adequate vitamin D status in this study. In those born with serum 25(OH)D <50 nmol/L, vitamin D status was corrected by 3 mo of age in response to 400 or 1000 IU/d of supplemental vitamin D. Dietary guidance should continue to recommend that all women who could become pregnant take a multivitamin supplement and that breastfed infants receive 400 IU/d of supplemental vitamin D. This study and ancillary trial were registered at clinicaltrials.gov (https://www. CLINICALTRIALS: gov/ct2/show/NCT02563015) as NCT02563015.

Maternal excess adiposity and serum 25-hydroxyvitamin D < 50 nmol/L are associated with elevated whole body fat mass in healthy breastfed neonates.

BACKGROUND: Vitamin D status of pregnant women is associated with body composition of the offspring. The objective of this study was to assess whether the association between maternal vitamin D status and neonatal adiposity is modified by maternal adiposity preconception. METHODS: Healthy mothers and their term appropriate weight for gestational age (AGA) infants (n = 142; 59% male, Greater Montreal, March 2016-2019) were studied at birth and 1 month postpartum (2-6 weeks). Newborn (24-36 h) serum was collected to measure total 25-hydroxyvitamin D [25(OH)D] (immunoassay); maternal pre-pregnancy BMI was obtained from the medical record. Anthropometry, body composition (dual-energy X-ray absorptiometry) and serum 25(OH)D were measured at 2-6 weeks postpartum in mothers and infants. Mothers were grouped into 4 categories based on their vitamin D status (sufficient 25(OH)D ≥ 50 nmol/L vs. at risk of being insufficient < 50 nmol/L) and pre-pregnancy BMI (< 25 vs. ≥25 kg/m2): insufficient-recommended weight (I-RW, n = 24); insufficient-overweight/obese (I-OW/O, n = 21); sufficient-recommended weight (S-RW, n = 69); and sufficient-overweight/obese (S-OW/O, n = 28). Partial correlation and linear fixed effects model were used while adjusting for covariates. RESULTS: At birth, infant serum 25(OH)D mean concentrations were below 50 nmol/L, the cut-point for sufficiency, for both maternal pre-pregnancy BMI categories; 47.8 [95%CI: 43.8, 51.9] nmol/L if BMI < 25 kg/m2 and 38.1 [95%CI: 33.5, 42.7] nmol/L if BMI ≥25 kg/m2. Infant serum 25(OH)D concentrations at birth (r = 0.77; P < 0.0001) and 1 month (r = 0.59, P < 0.0001) were positively correlated with maternal postpartum serum 25(OH)D concentrations. Maternal serum 25(OH)D concentration was weakly correlated with maternal percent whole body fat mass (r = - 0.26, P = 0.002). Infants of mothers in I-OW/O had higher fat mass versus those of mothers in S-OW/O (914.0 [95%CI: 766.4, 1061.6] vs. 780.7 [95%CI: 659.3, 902.0] g; effect size [Hedges' g: 0.42]; P = 0.04 adjusting for covariates) with magnitude of difference of 220.4 g or ~ 28% difference. CONCLUSIONS: Maternal and neonatal vitamin D status are positively correlated. In this study, maternal adiposity and serum 25(OH)D < 50 nmol/L are dual exposures for neonatal adiposity. These findings reinforce the importance of vitamin D supplementation early in infancy irrespective of vitamin D stores acquired in utero and maternal weight status.

Patterns of Bone Mineral Accretion and Sex Differences in Healthy Term Vitamin D Replete and Breastfed Infants From Montreal, Canada: Bone Mass Reference Data.

Infancy is a period of rapid bone growth and mineral accretion; nonetheless, reference data remain scarce for this age group. The purpose of this report is to generate reference data for bone mass in breastfed vitamin D replete infants and investigate patterns of bone mineral accretion and sex differences. This is a secondary analysis from a double-blinded randomized controlled trial (NCT00381914). Healthy term breastfed (exclusively or mixed) infants were randomized to different doses of oral vitamin D supplementation (400-1600 IU/d) and followed prospectively from 1 to 12 mo. Plasma 25-hydroxyvitamin D (LC-MS/MS), bone mineral content (BMC; whole body (WB) and lumbar spine (LS)) and bone mineral density (BMD; LS) were measured at 1, 3, 6, 9, and 12 mo by dual-energy x-ray absorptiometry (Hologic Discovery 4500A) with no effect of supplementation on bone outcomes. For the purpose of this analysis, 63 infants with adequate plasma 25-hydroxyvitamin D ≥ 50 nmol/L at baseline, were included. Differences over time and between sexes were tested using mixed model repeated measures ANOVA. Infants (31 males, 32 females) were 39.5 ± 1.1 wk gestational age at birth and appropriate for gestational age. WB BMC, LS BMC, and LS BMD increased by 143.2%, 116.8%, and 31.1% respectively across infancy. WB BMC was higher (4.2% - 9.4%; p = 0.03) in males than in females across the study. After adjusting WB BMC for weight, length or head BMC, sex differences were not evident. LS BMC and LS BMD did not vary by sex. LS BMD growth charts for both sexes combined, were generated using LMS chartmaker. WB BMC more than doubles during the first year of life confirming the importance of skeletal growth and the need for age-specific reference data in infancy. Sex differences in BMC, if any, are mostly driven by differences in body size.

Normative Data for Lean Mass and Fat Mass in Healthy Predominantly Breast-Fed Term Infants From 1 Month to 1 Year of Age.

BACKGROUND: A leaner body phenotype in infancy plays an important role in the early life prevention of obesity. However, there is a dearth of reference data for body composition in infancy. This study aimed to create a normative reference dataset for lean (LM) and fat (FM) mass and accretion rates in healthy infants. METHODS: Healthy term-born infants (35 boys; 35 girls) were studied at ≤ 1, 3, 6, 9, and 12 mo of age for growth and compared to World Health Organization standards. LM (g) and FM (g) were measured using DXA (APEX version 13.3:3, Hologic 4500A) in infant whole-body mode. Sex specific reference curves were generated using the LMS method (LMSchartmaker, Medical Research Council, UK). RESULTS: Infants were predominantly white (82.9%), breastfed (98.4% ≥ 3 mo), and grew in length and weight within World Health Organization Z-score ranges for normal growth across infancy. LM accretion was 327.4 ± 12.5 g/mo representing 95% increment in LM. Boys had more LM compared to girls at 12 mo (7807.4 ± 1114.0 vs 6817.4 ± 1016.1 g; p = 0.008). FM accretion was 114.3 ± 12.0 g/mo representing 114% increment in FM with no difference between the sexes. CONCLUSIONS: This data, which is based on a healthy sample of infants, characterizes LM and FM accretion during the first year of life and will aid in the interpretation of body composition.

Effect of Vitamin D Supplementation on Bone Mass in Infants With 25-Hydroxyvitamin D Concentrations Less Than 50 nmol/L: A Prespecified Secondary Analysis of a Randomized Clinical Trial.

Importance: The dose of supplemental vitamin D needed in infants born with serum 25-hydroxyvitamin D (25[OH]D) concentrations less than 50 nmol/L (ie, 20 ng/mL) is unclear. Objective: To determine whether a higher dose (1000 IU vs 400 IU per day) is required in infants born with 25(OH)D concentrations less than 50 nmol/L for bone mineral accretion across infancy. Design, Setting, and Participants: In this prespecified secondary analysis of a double-blinded randomized clinical trial, conducted from March 2016 to March 2019 in a single center in Greater Montreal, Quebec, Canada, a consecutive sample of 139 healthy term singletons were recruited from 866 infants screened for vitamin D status at birth. Data were analyzed from June 2021 to November 2022. Interventions: Capillary blood was collected 24 to 36 hours after birth to measure serum total 25(OH)D concentrations. Infants with 25(OH)D concentrations less than 50 nmol/L were randomized to receive either 1000 IU or 400 IU per day of oral vitamin D3 supplementation from age 1 to 12 months. Infants with 25(OH)D concentrations of 50 nmol/L or greater formed a reference group. Main Outcomes and Measures: Measures at age 1, 3, 6, and 12 months were preplanned and included whole-body bone mineral content, lumbar spine bone mineral content, and bone mineral density using dual-energy x-ray absorptiometry, and serum 25(OH)D3 using liquid chromatography tandem mass spectrometry. Results: Of 139 included infants, 81 (58.3%) were male, and the median (IQR) gestational age at birth was 39.6 (38.9-40.6) weeks. A total of 49 infants were included in the 1000 IU per day group, 49 infants in the 400 IU per day group, and 41 in the reference group. Mean (SD) whole-body bone mineral content was not different between trial groups over time (1000 IU per day, 173.09 [2.36] g; 400 IU per day, 165.94 [66.08] g). Similarly, no differences were observed in lumbar spine bone mineral content or density. Mean (SD) serum 25(OH)D3 concentrations were significantly higher in the 1000 IU per day group from age 3 to 12 months (3 months, 115.2 [35.3] nmol/L; 6 months, 121.6 [34.4] nmol/L; 12 months, 99.6 [28.8] nmol/L) compared with the 400 IU per day trial group (3 months, 77.4 [23.3] nmol/L; 6 months, 85.1 [18.6] nmol/L; 12 months, 82.3 [14.3] nmol/L). Conclusions and Relevance: In this study, a higher dose of vitamin D supplementation in infants born with 25(OH)D concentrations less than 50 nmol/L did not present advantages to bone mass in infancy. This study supports a standard dose of 400 IU per day of vitamin D supplementation for breastfed infants in Montreal. Trial Registration: ClinicalTrials.gov Identifier: NCT02563015.

Correction of neonatal vitamin D status using 1000 IU vitamin D/d increased lean body mass by 12 months of age compared with 400 IU/d: a randomized controlled trial.

BACKGROUND: Intrauterine exposure to maternal vitamin D status <50 nmol/L of serum 25-hydroxyvitamin D [25(OH)D] may adversely affect infant body composition. Whether postnatal interventions can reprogram for a leaner body phenotype is unknown. OBJECTIVES: The primary objective was to test whether 1000 IU/d of supplemental vitamin D (compared with 400 IU/d) improves lean mass in infants born with serum 25(OH)D <50 nmol/L. METHODS: Healthy, term, breastfed infants (Montréal, Canada, March 2016-2019) were assessed for serum 25(OH)D (immunoassay) 24-36 h postpartum. Infants with serum 25(OH)D <50nmol/L at 24-36 h were eligible for the trial and randomly assigned at baseline (1 mo postpartum) to 400 (29 males, 20 females) or 1000 IU/d (29 males, 20 females) of vitamin D until 12 mo. Infants (23 males, 18 females) with 25(OH)D ≥50 nmol/L (sufficient) formed a nonrandomized reference group provided 400 IU/d. Anthropometry, body composition (DXA), and serum 25(OH)D concentrations were measured at 1, 3, 6, and 12 mo. RESULTS: At baseline, mean ± SD serum 25(OH)D concentrations in infants allocated to the 400 and 1000 IU/d vitamin D groups were 45.8 ± 14.1 and 47.6 ± 13.4, respectively; for the reference group it was 69.2 ± 16.4 nmol/L. Serum 25(OH)D concentration increased on average to ≥50 nmol/L in the trial groups at 3-12 mo. Lean mass varied differently between groups over time; at 12 mo it was higher in the 1000 IU/d vitamin D group than in the 400 IU/d group (mean ± SD: 7013 ± 904.6 compared with 6690.4 ± 1121.7 g, P = 0.0428), but not the reference group (mean ± SD: 6715.1 ± 784.6 g, P = 0.19). Whole-body fat mass was not different between the groups over time. CONCLUSIONS: Vitamin D supplementation (400 or 1000 IU/d) during infancy readily corrects vitamin D status, whereas 1000 IU/d modestly increases lean mass by 12 mo. The long-term implications require further research. This trial was registered at clinicaltrials.gov as NCT02563015.

Ethnicity and Immigration Status as Risk Factors for Gestational Diabetes Mellitus, Anemia and Pregnancy Outcomes Among Food Insecure Women Attending the Montreal Diet Dispensary Program.

OBJECTIVE: The primary aim of this study was to characterize the rate of adverse pregnancy outcomes in a multicultural group of low-income women. METHODS: Data were extracted from the Montreal Diet Dispensary's database between June 2013 and December 2015. Risk was evaluated using logistic regression adjusted for covariates. RESULTS: Of the 1,387 pregnancies, the prevalence of gestational diabetes mellitus (GDM) was 17.2% (95% confidence interval [CI], 15.1% to 19.3%), maternal anemia 44.9% (95% CI, 41.9% to 47.9%) and hypertension 3.8% (95% CI, 2.8% to 4.8%). The prevalence of small-for-gestational-age infants was 5.5% (95% CI, 4.3% to 6.7%), preterm births 4.7% (95% CI, 3.6% to 5.9%), low birthweight 4.2% (95% CI, 3.1% to 5.2%) and large-for-gestational-age infants was 10.6% (95% CI, 9.0% to 12.2%). Asian women had an increased odds of gestational diabetes mellitus (adjusted odds ratio [aOR], 1.86; 95% CI, 1.17 to 2.98) and SGA infants (aOR, 2.35; 95% CI 1.21 to 4.57) compared with white women. Anemia was more likely for black women compared with white women (aOR, 1.74; 95% CI, 1.29 to 2.35). Black women were more at risk of preterm birth (aOR, 1.79; 95% CI, 1.01 to 3.19). Immigrants showed an increased risk of maternal anemia compared with Canadian-born women (aOR, 1.85; 95% CI, 1.06 to 3.21). CONCLUSIONS: As disparities in maternal and infant outcomes were present, nutritional intervention(s) need to be targeted toward prevention of adverse pregnancy outcomes, prioritization of higher-risk groups and adaptation of the program to a multiethnic low-income population.

Effects of Milk and Milk-Product Consumption on Growth among Children and Adolescents Aged 6-18 Years: A Meta-Analysis of Randomized Controlled Trials.

Although studies have suggested that milk and milk-product consumption may influence growth during childhood and puberty, results are inconsistent. This meta-analysis was performed to evaluate the available evidence of randomized controlled trials (RCTs) assessing whether milk and milk-product consumption could affect growth and body composition among children and adolescents aged 6-18 y. PubMed, EMBASE, Web of Science, and The Cochrane Library databases were systematically searched for all RCTs published up to December 2017 that investigated milk and milk-product consumption (≥12 wk) on growth and body composition among participants (aged 6-18 y) without undernourishment or diseases. Study screening and data extraction by 2 reviewers followed established PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The Cochrane Collaboration's tool was used to assess the quality of the trials. Data were pooled using a random-effects model. Seventeen trials with 2844 children and adolescents were included. Milk and milk-product interventions resulted in a greater increase in body weight (0.48 kg; 95% CI: 0.19, 0.76 kg; P  =  0.001), lean mass (0.21 kg; 95% CI: 0.01, 0.41 kg; P  = 0.04), and attenuated gain in percentage body fat (-0.27%; 95% CI: -0.45%, -0.09%; P  = 0.003) compared with control groups. However, there were no significant changes in fat mass, height, or waist circumference in the intervention groups compared with the control groups (P ≥ 0.05). In subgroup analyses, the baseline weight and age, and the duration of intervention were associated with the efficacy of milk and milk-product intake on the change in lean mass, percentage body fat, and waist circumference, respectively (test for subgroup differences: P < 0.05). Children and adolescents aged 6-18 y consuming milk and milk products are more likely to achieve a lean body phenotype. This meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42018086850.

Maternal risk factors and newborn infant vitamin D status: a scoping literature review.

Low vitamin D (VitD) status is common among newborn infants, more so in temperate latitudes with evidence that maternal VitD deficiency is a major risk factor given that the neonate relies solely on maternal-fetal transfer of VitD. This scoping review was conducted to provide an overview of the latest evidence from studies regarding the impact of maternal risk factors on infant 25-hydryoxyvitamin D [25(OH)D] concentrations with a focus on studies in Canada and the United States. Several maternal risk factors that contribute to low maternal-fetal 25(OH)D concentrations have been reported over many decades, but no clear pattern has been established for multiethnic populations. For example, darker skin pigmentation and ethnicity are common risk factors for low VitD status. Studies in predominantly white women showed that supplementation of VitD during pregnancy causes significant increases in maternal serum 25(OH)D which often improves cord serum 25(OH)D values. In addition, VitD recommendations by health care professionals and adherence to supplementation by pregnant women appear to positively influence maternal and infant 25(OH)D concentrations. Conversely, winter season, obesity, lower socioeconomic status including lifestyle factors (smoking), and use of medication pose risk for lower maternal-fetal transfer of VitD. However, there is still a dearth of pertinent data on the relationship between some of the maternal risk factors and newborn 25(OH)D concentrations, for instance, relationships between gestational diabetes and neonatal VitD status. Additional research is required to determine if the same target for 25(OH)D concentrations applies for pregnant women, neonates, and infants.

Socio-Demographic and Lifestyle Factors Predict 5-Year Changes in Adiposity among a Group of Black South African Adults.

The rising prevalence of obesity and excessive adiposity are global public health concerns. Understanding determinants of changes in adiposity over time is critical for informing effective evidence-based prevention or treatment. However, limited information is available to achieve this objective. Cultural, demographic, environmental, and behavioral factors including socio-economic status (SES) likely account for obesity development. To this end, we related these variables to anthropometric measures in 1058 black adult Tswana-speaking South Africans who were HIV negative in a prospective study over five years. Body mass index (BMI) and waist circumference increased in both sexes, whereas triceps skinfold thickness remained the same. Over the five years, women moved to higher BMI categories and more were diagnosed with central obesity. Age correlated negatively, whereas SES, physical activity, energy, and fat intake correlated positively with adiposity markers in women. In men, SES, marital status, physical activity, and being urban predicted increases in adiposity. For women, SES and urbanicity increased, whereas menopause and smoking decreased adiposity. Among men, smokers had less change in BMI than those that never smoked over five years. Our findings suggest that interventions, focusing on the urban living, the married and those with the highest SES-the high-risk groups identified herein-are of primary importance to contain morbidity and premature mortality due to obesity in black South Africans.