Interactive Effects of Maternal Vitamin D Status and Socio-Economic Status on the Risk of Spontaneous Abortion: Evidence from Henan Province, China

Background: Maternal vitamin D deficiency might generate adverse reproductive outcomes, and socio-economic inequalities in micronutrient-related diseases have often been found. This study aimed to explore the interactive effects of maternal vitamin D status and socio-economic status (SES) on risk of spontaneous abortion. Methods: A population-based case–control study was conducted including 293 women with spontaneous abortion and 498 control women in December 2009 and January, 2010 in Henan Province, China. Information on pregnancy outcomes, maternal demographic, lifestyle and exposure factors and blood samples were collected at the same time. Vitamin D deficiency was defined as 25(OH)D < 20 ng/mL. SES index was constructed with principal component analysis by aggregating women’s and their husbands’ education level and occupation, and household income and expenditure. Interactive effects were assessed on a multiplicative scale with ratio of the odds ratio (ROR). Results: Compared to those with high SES and vitamin D sufficiency, women with vitamin D deficiency and low SES index had an increased risk of spontaneous abortion (aOR: 1.99; 95% CI: 1.23–3.23). The ROR was 2.06 (95% CI: 1.04–4.10), indicating a significant positive multiplicative interaction. Conclusions: Maternal low SES may strengthen the effect of vitamin D deficiency exposure on spontaneous abortion risk in this Chinese population.

The Effect of Maternal Vitamin D Status on Fetal Growth and Stunting: A Systematic Review

Background and Objective: Impaired fetal growth and stunting remain immense public health problems involving maternal nutrition during pregnancy, as linear growth failure in children is the most common form of undernutrition across the world. Although both are preventable through adequate prenatal care and nutrition, impaired fetal growth and stunting continue to be implicated in multiple child health morbidities, physical, and psychological functioning. Recent knowledge and requirements for normal fetal and neonatal development are lacking. This systematic review investigates the effects of maternal vitamin D status on fetal growth and stunting. Methods: We reviewed three widely-used publications databases: the National Institutes of Health’s PubMed, Clarivate Analytics’ Web of Science, and Google Scholar using pre-established inclusion and exclusion criteria and keyword search strategy. Studies from 2010 to 2020 were included if they reported vitamin D levels on pregnant women, indicated growth outcomes and used quantitative measurements. We excluded non-English language studies, studies with ambiguous outcomes, studies that did not specify vitamin D intake, and studies that involved other maternal health complications. The search was implemented using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: Out of a total of 2,481 studies reviewed, we identified 8 studies on vitamin D and fetal growth and stunting. Published literature addressing maternal vitamin D status on fetal growth and stunting remains ambiguous. Five studies demonstrated improvements in fetal and humerus z-scores, which are known proxies for fetal growth, in groups with higher vitamin D status. Three studies found no statistical significance between vitamin D levels and fetal growth. Vitamin D status and ethnicity were correlated; vitamin D interacts with calcium levels in pregnant mothers to improve bone mineralization and fetal growth. Conclusion and Implications for Translation: Further studies are needed to understand the relationship between maternal vitamin D, ethnicity, and fetal growth and the long-term effects of maternal vitamin D levels on neonatal, early childhood, and adolescent growth. Copyright © 2021 Karmali et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY 4.0.

Interrelationships Among Vitamin D Status and Body Composition in Mother-Infant Dyads

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 hour) 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 mixed model ANOVA were used while adjusting for covariates.Results: At birth, infant serum 25(OH)D mean concentrations were below the cut-point for sufficiency of 50 nmol/L 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 inversely associated 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) with magnitude of difference of 220.4 g or ~28% difference (adjusting for covariates). Conclusions: Maternal vitamin D status is positively correlated with neonatal vitamin D. 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.

Association between Maternal and Neonatal Vitamin D status and the Development of Congenital Anomalies

Background Vitamin D (VD) is a remarkable problem during pregnancy. VD plays a crucial role in cellular growth and differentiation during embryogenesis. VD deficiency in pregnancy is associated with various maternal and neonatal comorbidities. In this study, we aimed to evaluate the potential association between maternal and neonatal vitamin D status and the subsequent development of congenital anomalies. Patients and methods A case-control study involving 30 mothers and their neonates born with gross structural congenital anomalies as cases and 30 mothers and their healthy neonates as controls recruited from Ain Shams University Children Hospital. Maternal and Neonatal blood samples were obtained to determine serum 25hydroxyvitamin D. The 25-hydroxyvitamin D concentration was stratified into a severe deficient&lt;10ng/ml, deficient &lt;20ng/ml, insufficient 20-29ng/ml and sufficient &gt;30ng/ml. Status above 150ng/ml presents high risk of toxicity. Results There were statistically significant differences between the two groups regarding maternal and neonatal vitamin D serum level within 29 days postpartum. Mean maternal vitamin D level in cases was 23.8ng/ml versus 42.13ng/ml in controls (P = 0,000). Mean neonatal vitamin D level in cases was 15.97ng/ml versus 28.9ng/ml in controls (P = 0,000).There was significant positive correlation between both maternal and neonatal vitamin D level with birth weight. Conclusion A compromised maternal vitamin D status is associated with an increased prevalence of congenital anomalies in offspring. Therefore, improvement of the periconceptional maternal vitamin D status is recommended.

Association of vitamin D levels with preeclampsia

Objectives: This study was aimed to assess maternal vitamin D status during pregnancy and determine the association between maternal 25(OH) D levels with risk of preeclampsia (PE). Methods: A cross-sectional study was conducted with 172 pregnant women recruited from JPMC between January and December 2017 who were divided as normotensive (n=80) and pre-eclamptic (n=92) groups. Blood pressure was recorded at 20 and 32 weeks of gestation. Five ml of blood sample was collected at 20 weeks of gestation to assess the vitamin D levels by commercially available ELISA assay. Results: PE group had a significantly higher systolic (p<0.001) and diastolic (p<0.001) blood pressure at 20 weeks of gestation. Vitamin D levels were reported to be significantly lower (p<0.001) in the PE group (17.97±9.38 ng/ml) as compared to normotensive group (42.18±25.17 ng/ml). A strong negative correlation of Vitamin D levels with systolic blood pressure (r=-0.428; p<0.001) and diastolic blood pressure (r= -0.375; p<0.001) was found. Conclusion: This study found a strong relationship between low vitamin D levels and pre-eclamptic manifestation. Keywords: Vitamin D; Pre-eclampsia; Pregnancy; Hypertension. Continuous....

Vitamin D Deficiency in Mexican Pregnant Women: Is Supplementation with ≤400 IU/day Enough?

Controversy remains surrounding vitamin D routine supplementation in healthy pregnancy, and the doses are unclear. The aim of this study was to describe maternal vitamin D status throughout pregnancy in a group of Mexican women and evaluate the effect of frequently prescribed doses of vitamin D3 on longitudinal 25-OH-D concentrations, adjusting for obesity, season, and other factors. We conducted a cohort study (Instituto Nacional de Perinatología-INPer) (2017–2020)) of healthy pregnant women without complications. Pregestational overweight/obesity (body mass index ≥ 25), vitamin D3 supplementation (prescribed by physician; 0–250, 250–400, and >400 IU/day), and serum 25-OH-D concentrations (ELISA) were evaluated in each trimester of pregnancy. Vitamin D deficiency or insufficiency was computed (<20 and <30 ng/mL, respectively). We studied 141 adult women; 58.5% had pregestational obesity or overweight. In the first trimester, 45.8% of the women were supplemented with vitamin D3; 51.4% had vitamin D insufficiency and 37.3%, deficiency. In the third trimester, 75.4% of the women were supplemented, and 20% of them still had deficiency. The final general mixed linear model showed that 25-OH-D significantly increased throughout pregnancy (p < 0.001); the highest increase was observed in the third trimester in women with doses >400 IU/day of vitamin D3 (+4 ng/mL, 95% CI: 1.72–8.11 ng/mL). In winter/autumn, 25-OH-D concentrations were also lower (p ≤ 0.05). In this group of pregnant Mexican women, the prevalence of vitamin D deficiency and insufficiency was high. A higher increase in 25-OH-D concentrations during pregnancy was observed when the women were supplemented with >400 IU/day. Common supplementation doses of 250–400 IU/day were insufficient for achieving an adequate maternal vitamin D status.

Maternal Vitamin D Status Affects Hepatitis B Vaccine Response in Breastfeeding Infants

Objectives Vitamin D (VitD) affects immune function across the lifespan, which includes pregnancy and lactation. We hypothesized that the response of fully breastfeeding (BrF) infants to HBV would differ as a function of maternal and/or infant's vitD status as measured by circulating 25-hydroxyD (25-D) concentration. Methods Plasma 25-D concentration and HBV titers were measured in a subset of mothers and exclusively BrF infants (n = 56 pairs) participating in a lactation vitD supplementation clinical trial. Mothers were randomized to receive either 400 vs. 6400 IU vitD3/day and infants 400 IU/day or placebo (if mother was in 6400 IU group). An additional 14 infants were exclusively formula-fed (FF). 25-D concentration (RIA) and infant anti-HBV IgG titers (ELISA) after 3 vaccinations (7 months of age) were measured. The associations between maternal vitD treatment group, circulating 25-D, and HBV IgG titers were explored using t-tests, ANOVA and linear correlations. Results After 3 vaccinations, all infants in this study were considered to be highly immune to HBV (plasma anti-HBV surface IgG titer &gt;100 IU/mL). However, we found that mean anti-HBV IgG titers in exclusively BrF infants were significantly lower if mother was vitD sufficient (2200 vs 4500 IU/ml; P = 0.017), with inverse correlation between infant IgG titers and maternal vitD status (r = −0.31; P = 0.02). We also found that these infant anti-HBV titers were not significantly correlated with their own vitD status (P = 0.18). Results also showed that mean titers in exclusively FF infants were not correlated with vitD status and were nearly identical to those of BrF infants of vitD-insufficient mothers. Conclusions Though still considered immune after 3 vaccinations, HBV IgG titers of BrF infants differed at 7 months of age by maternal vitD treatment and not on the basis of infant vitD status. These findings suggest that effects of vitD on breastmilk composition results in regulation of an infant's immune response perhaps by induction of immunotolerance, whether through blunting of a massive immune response to HBV antigens or affecting a more rapid switch from active plasma cells to memory B cells. A currently ongoing lactation pilot study continues to collect samples to confirm and expand these findings. Funding Sources NIH/NCATS, SC Translational Research Institute, MUSC Pediatrics.