Maternal 25-hydroxyvitamin Research Articles

Maternal excess adiposity and serum 25-hydroxyvitamin D\u2009

BackgroundVitamin 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.MethodsHealthy 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.ResultsAt 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.ConclusionsMaternal 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.

Maternal serum vitamin D level in patients complicated by preeclampsia

ObjectivesTo evaluate the relationship between maternal serum vitamin D level and severity of preeclampsia.BackgroundPregnant women with preeclampsia are susceptible to pulmonary edema, coagulation defects, and renal failure. Vitamin D is thought to play a significant role in preeclampsia as an immune modulator. It may help in producing an appropriate maternal immune response to the placenta preventing the release of antiangiogenic factors into the bloodstream and modulating hypertension.Patients and methodsA case–control study was conducted at Department of the Obstetrics and Gynecology, Menoufia General Hospital and Menoufia University Hospital from June 2019 till October 2020. The study was approved by the Ethics Committee, Faculty of Medicine, Menoufia University. This study included 100 pregnant nulliparae divided into two groups: group A included 50 pregnant women with preeclampsia either mild or severe; their blood samples were drawn at the time of delivery to check maternal serum 25-hydroxyvitamin D levels. Group B included 50 women with normal pregnancy; their blood samples were drawn at the time of delivery to check maternal serum 25-hydroxyvitamin D levels. Full history taking, general examination, vital signs, obstetrical examination, ultrasonography, lab investigations, and maternal serum vitamin D level were done for all studied women.ResultsVitamin D level was significantly decreased among the preeclampsia group (10.40–31.00 ng/ml) than the control group (15.50–32.00 ng/ml). There were significant positive correlations between vitamin D deficiency level with systolic blood pressure (r = 0.420) and diastolic blood pressure (r = 0.492).ConclusionVitamin D deficiency has a significant role in the development of preeclampsia. Larger studies including a large sample size are needed to confirm our results about vitamin D deficiency and its relation to preeclampsia.

Relationship between maternal and infants' serum 25-hydroxyvitamin d, calcium, and phosphates in an exclusively breastfeeding population

Relationship between maternal and infants' serum 25-hydroxyvitamin d, calcium, and phosphates in an exclusively breastfeeding population

Upregulation of Irisin and Vitamin D-Binding Protein Concentrations by Increasing Maternal 25-Hydrovitamin D Concentrations in Combination with Specific Genotypes of Vitamin D-Binding Protein Polymorphisms.

Dyshomeostasis of vitamin D-binding protein (VDBP) has been implicated in the pathogenesis of various pregnancy complications, including preeclampsia, preterm birth, gestational diabetes, and adverse metabolic profiles in the offspring. VDBP polymorphisms have been consistently reported to contribute to this intriguing interplay. Until recently, the effects of VDBP polymorphism heterogeneity on maternal and neonatal adipomyokine profiles have not been investigated, specifically after incorporating the different maternal and neonatal 25-hydroxyvitamin D concentration cut-offs at birth. We aimed to investigate the potential effects of maternal and neonatal VDBP polymorphisms on adiponectin, irisin, and VDBP concentrations at birth, according to different cut-offs of vitamin D status, in maternal–neonatal dyads recruited from the sunny region of Northern Greece. We obtained blood samples from 66 mother–child pairs at birth. Results indicated that (i) Neonatal serum biomarkers were not affected by any included neonatal VDBP polymorphism according to different cut-offs of neonatal vitamin D status at birth, (ii) neonatal VDBP concentration was elevated in neonates with maternal rs7041 GG genotype, (iii) maternal 25(OH)D at ≤75 nmol/L resulted in increased concentrations of maternal VBDP and irisin concentrations in women with CC genotype for rs2298850 and rs4588,whereas this effect was also evident for this cut-off for neonatal VDBP concentrations at birth for GC genotype for rs 7041, and (iv) no significant effect of neonatal VDBP polymorphisms was observed on neonatal VDBP, adiponectin, or irisin levels when stratified according to maternal 25(OH)D cut-offs. In conclusion, these findings confirm that among women with the combination of CC genotype for rs2298850 and rs4588, a specific high cut-off of maternal 25(OH)D results in increasing maternal VBDP concentrations, hence providing a mechanistic rationale for aiming for specific cut-offs of vitamin D after supplementation during pregnancy, in daily clinical practice.

Maternal Vitamin D Status and Gestational Weight Gain as Correlates of Neonatal Bone Mass in Healthy Term Breastfed Young Infants from Montreal, Canada.

The implications of maternal gestational weight gain (GWG) and vitamin D status to neonatal bone health are unclear. We tested whether maternal 25-hydroxyvitamin D (25(OH)D) and GWG relate to neonatal bone mineral content (BMC) and bone mineral density (BMD). Healthy term appropriate for gestational age breastfed neonates (n = 142) and their mothers were recruited 24–36 h after delivery and followed at 1.0 ± 0.5 month. At birth, obstetric data were collected and newborn serum 25(OH)D was measured. At 1 month, neonatal whole-body (WB) BMC, WB BMC relative to body weight (WB BMC/kg), lumbar spine BMC and BMD, maternal and neonatal 25(OH)D concentrations, and anthropometry were measured. Infant BMC and BMD between maternal 25(OH)D (<50, ≥50 nmol/L) and GWG (insufficient, adequate, and excessive) categories were compared. Maternal 25(OH)D was not related to infant whole-body BMC, BMC/kg, lumbar spine BMC, and BMD. Infants in the excessive maternal GWG category had greater (p = 0.0003) whole-body BMC and BMC/kg and lumbar spine BMC and BMD than inadequate GWG, and greater (p = 0.0063) whole-body BMC/kg and lumbar spine BMC and BMD than adequate GWG. These results suggest that maternal GWG, but not vitamin D status, modestly relates to bone mass in neonates.

Basal Vitamin D Status and Supplement Dose Are Primary Contributors to Maternal 25-Hydroxyvitamin D Response to Prenatal and Postpartum Cholecalciferol Supplementation

BackgroundVariability in the 25-hydroxyvitamin D [25(OH)D] response to prenatal and postpartum vitamin D supplementation is an important consideration for establishing vitamin D deficiency prevention regimens. ObjectivesWe aimed to examine interindividual variation in maternal and infant 25(OH)D following maternal vitamin D supplementation. MethodsIn a randomized trial of maternal vitamin D supplementation (Maternal Vitamin D for Infant Growth Trial), healthy pregnant women (n = 1300) received a prenatal cholecalciferol (vitamin D-3) dose of 0, 4200, 16,800, or 28,000 IU/wk from 17 to 24 wk of gestation followed by placebo to 6 mo postpartum. A fifth group received 28,000 IU cholecalciferol/wk both prenatally and postpartum. In a subset of participants, associations of 25(OH)D with hypothesized explanatory factors were estimated in women at delivery (n = 655) and 6 mo postpartum (n = 566), and in their infants at birth (n = 502) and 6 mo of age (n = 215). Base models included initial 25(OH)D and supplemental vitamin D dose. Multivariable models were extended to include other individual characteristics and specimen-related factors. The model coefficient of determination (R2) was used to express the percentage of total variance explained. ResultsSupplemental vitamin D intake and initial 25(OH)D accounted for the majority of variance in maternal 25(OH)D at delivery and postpartum (R2 = 70% and 79%, respectively). Additional characteristics, including BMI, contributed negligibly to remaining variance (<5% increase in R2). Variance in neonatal 25(OH)D was explained mostly by maternal delivery 25(OH)D and prenatal vitamin D intake (R2 = 82%). Variance in 25(OH)D in later infancy could only partly be explained by numerous biological, sociodemographic, and laboratory-related characteristics, including feeding practices (R2 = 43%). ConclusionsPresupplementation 25(OH)D and vitamin D supplemental dose are the major determinants of the response to maternal prenatal vitamin D intake. Vitamin D dosing regimens to prevent maternal and infant vitamin D deficiency should take into consideration the mean 25(OH)D concentration of the target population.

Maternal vitamin D and offspring fracture risk: the Vitamin D in Pregnancy study.

Maternal 25-hydroxyvitamin D (25(OH)D) in pregnancy has been shown to be associated with offspring bone measures in some studies, but few have examined fracture risk. We aimed to determine associations between maternal vitamin D status and offspring fracture risk. In total, 475 mother-child pairs participating in the Vitamin D in Pregnancy study in southeastern Australia were recruited. Maternal serum samples were taken at recruitment (< 16weeks gestation) and/or 28-32weeks gestation and analysed for 25(OH)D. Incident fractures in children were ascertained from date of birth (2002-2004) until December 31, 2012. Cox proportional hazard models included maternal age at recruitment, offspring sex, birth weight, gestation length and season of vitamin D sample. Complete follow-up data were available for 400 children (median age = 9.5years). There were 68 (17.0%) children who sustained at least one fracture. Higher maternal 25(OH)D (per 10nmol/L) in early gestation was weakly associated with a decreased fracture risk in boys (HR 0.82; 95% CI 0.68, 0.99; p = 0.048) but not girls (HR 1.10; 95% CI 0.98, 1.25; p = 0.11). At late gestation, higher maternal 25(OH)D was associated with increased fracture risk in girls (HR 1.11; 95% CI 1.01, 1.23; p = 0.038) but not boys (HR 0.94; 95% CI 0.80, 1.10; p = 0.42). No statistically significant relationships were detected in analyses investigating 25(OH)D as a categorical variable. There is some evidence that higher maternal 25(OH)D at recruitment was associated with lower fracture risk in boys, while higher maternal 25(OH)D at 28-32weeks gestation was associated with an increased fracture risk in girls.

Association between maternal serum 25-hydroxyvitamin D concentrations and the risk of pre-eclampsia in central Sudan: a case-control study.

There are few published data on the role of vitamin D concentrations during pregnancy in sub-Saharan Africa. Thus, the aim of the current study was to investigate the association between 25-hydroxyvitamin D (25[OH)]D) levels and pre-eclampsia. A case-control study, with 60 women in each arm, was conducted in Medani Hospital in Sudan. The cases were women with pre-eclampsia and healthy pregnant women as controls. The medical and obstetric history was obtained using a questionnaire. The serum 25(OH)D concentrations were measured using ELISA. The median (IQR) of 25(OH)D concentration was significantly lower in women with pre-eclampsia than in the controls (10.0 [6.5] vs 18.3 [22.1] ng/mL). Fifty-three cases with pre-eclampsia (88%) and 36 cases in the control group (60%) had vitamin D deficiency (25(OH)D level≤20 ng/mL). Multivariate logistic regression showed that the 25(OH)D levels were negatively associated with pre-eclampsia (adjusted OR [AOR]=0.87, 95% CI 0.81 to 0.92). Vitamin D-deficient women were at a higher risk of pre-eclampsia (AOR=4.51, 95% CI 1.70 to 11.94). Low 25(OH)D levels were reported in women with pre-eclampsia and were an independent risk factor for pre-eclampsia.

Investigating the Role of Functional Polymorphism of Maternal and Neonatal Vitamin D Binding Protein in the Context of 25-Hydroxyvitamin D Cutoffs as Determinants of Maternal-Neonatal Vitamin D Status Profiles in a Sunny Mediterranean Region.

Recent results indicate that dysregulation of vitamin D-binding protein (VDBP) could be involved in the development of hypovitaminosis D, and it comprises a risk factor for adverse fetal, maternal and neonatal outcomes. Until recently, there was a paucity of results regarding the effect of maternal and neonatal VDBP polymorphisms on vitamin D status during pregnancy in the Mediterranean region, with a high prevalence of hypovitaminosis D. We aimed to evaluate the combined effect of maternal and neonatal VDBP polymorphisms and different maternal and neonatal 25-hydroxyvitamin D (25(OH)D) cut-offs on maternal and neonatal vitamin D profile. Blood samples were obtained from a cohort of 66 mother–child pairs at birth. Our results revealed that: (i) Maternal VDBP polymorphisms do not affect neonatal vitamin D status at birth, in any given internationally adopted maternal or neonatal cut-off for 25(OH)D concentrations; (ii) neonatal VDBP polymorphisms are not implicated in the regulation of neonatal vitamin D status at birth; (iii) comparing the distributions of maternal VDBP polymorphisms and maternal 25(OH)D concentrations, with cut-offs at birth, revealed that mothers with a CC genotype for rs2298850 and a CC genotype for rs4588 tended to demonstrate higher 25(OH)D (≥75 nmol/L) during delivery (p = 0.05 and p = 0.04, respectively), after adjustments for biofactors that affect vitamin D equilibrium, including UVB, BMI and weeks of gestation. In conclusion, this study from Southern Europe indicates that maternal and neonatal VDBP polymorphisms do not affect neonatal vitamin D status at birth, whereas mothers with CC genotype for rs2298850 and CC genotype for rs4588 demonstrate higher 25(OH)D concentrations. Future larger studies are required to establish a causative effect of these specific polymorphisms in the attainment of an adequate (≥75 nmol/L) maternal vitamin D status during pregnancy.

Maternal Vitamin D Levels During Pregnancy and Offspring Autism Spectrum Disorder

BackgroundFindings from previous studies on maternal 25-hydroxyvitamin D [25(OH)D] levels during pregnancy and autism spectrum disorder (ASD) in offspring are inconsistent. MethodsThe association between maternal 25(OH)D levels during pregnancy and offspring ASD was examined using data from a nationwide population-based register with a nested case-control study design. The ASD cases (n = 1558) were born between 1987 and 2004 and received a diagnosis of ASD by 2015; cases were matched with an equal number of controls. Maternal 25(OH)D levels during pregnancy were measured using quantitative immunoassay from maternal sera collected during the first and early second trimesters and archived in the national biobank of the Finnish Maternity Cohort. Conditional logistic regression examined the association between maternal 25(OH)D levels and offspring ASD. ResultsIn the adjusted model, there was a significant association between increasing log-transformed maternal 25(OH)D levels and decreasing risk of offspring ASD (adjusted odds ratio [aOR] 0.75, 95% confidence interval [CI] 0.62–0.92, p = .005). Analyses by quintiles of maternal 25(OH)D levels revealed increased odds for ASD in the 2 lowest quintiles, <20 (aOR 1.36, 95% CI 1.03–1.79, p = .02) and 20–39 (aOR 1.31, 95% CI 1.01–1.70, p = .04), compared with the highest quintile. The increased risk of ASD was observed in association with deficient (<30 nmol/L) (aOR 1.44, 95% CI 1.15–1.81, p = .001) and insufficient (30–49.9 nmol/L) maternal 25(OH)D levels (aOR 1.26, 95% CI 1.04–1.52, p = .01) compared with sufficient levels. ConclusionsThis finding has implications for understanding the role of maternal vitamin D during fetal brain development and increased risk of ASD.

Large retrospective cohort study of the association between maternal 25-hydroxyvitamin D status and birth weight of neonate

Background The effect of maternal vitamin D levels on the birth weight of the offspring remains controversial, as the results are inconsistent between different populations. This large retrospective cohort study aimed to assess the relationship between maternal vitamin D levels and birth weight of neonates in southern China. Methods Serum samples were collected from 10,586 Chinese women at 13–27 weeks of pregnancy, and the 25-hydroxyvitamin D (25(OH)D) level of the participants was assessed. Using the INTERGROWTH-21st standards, the offspring were classified into three groups based on their gestational age and birth weight, which were small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). The differences in vitamin D levels among the different groups were compared, and their correlation with newborn birth weight was analyzed. Results The average maternal vitamin D concentration was 61.1 nmol/L. The 25(OH)D concentrations were 50–75 nmol/L, 25–50 nmol/L and below 25 nmol/L in 45.5%, 29.5%, and 1.6% of the participants, respectively. No significant differences were observed in the vitamin D levels between the three groups. With the increase in 25(OH)D levels, the risk of SGA and LGA tended to increase and decrease, respectively. AGA was not affected by the 25(OH)D levels. The results of the curve fitting and threshold effect analyses did not support the correlation between vitamin D levels and SGA or LGA. Based on the univariate prediction model and the model adjusted for risk factors, the area under the curve was extremely small. Thus, 25(OH)D levels are not an effective predictor of SGA and LGA. Conclusions Low maternal vitamin D levels were not associated with SGA or LGA.

Vitamin D Levels in Mother-Baby Pairs: A Cross-Sectional Prospective Study in a Rwandan Tertiary Hospital.

Exposure to the sunlight contributes largely to the production of vitamin D. However, vitamin D deficiency is a reality in tropical countries, despite enjoying enough sunlight, especially bearing women in their last trimester whose foetuses exclusively depend on their reserves. This work aimed at demonstrating the state of vitamin D in mother-baby pairs and associated factors in one of the University Hospitals in Rwanda. This cross-sectional prospective study was performed on mother-baby pairs at Kigali University Hospital. Mother's serum 25-hydroxyvitamin D levels were considered as outcomes compared with demographic, clinical and biological markers. Correlation analysis was conducted in order to assess the association between serum 25-hydroxyvitamin D levels for the couple mothers-babies. Approximately 38% of women and 65% of neonates had deficiency in 25-hydroxyvitamin D (<20 ng/ml). The use of a vitamin D rich diet within 24 h recall (p < 0.01) or 1 week recall (p < 0.001) before delivery was associated with appropriate vitamin D levels in mothers. Interestingly, a strong positive correlation was found between maternal and neonatal serum 25-hydroxyvitamin D levels (r = 0.760). There was a high rate of vitamin D deficiency in mothers and their babies. Babies born from women with deficiency were likely to develop low levels of vitamin D. This stresses on the need to strengthen the interventions for preventing vitamin D deficiency in the couple mothers-babies such as supplement in vitamin D before and after delivery, improving the quality of meals and regular contact with sunlight.

Longitudinal Vitamin D Deficiency Among Malaysian Pregnant Women and Its Correlation With Neonatal Serum 25-Hydroxyvitamin D Levels.

Objective: This study aimed to investigate the longitudinal relationship between maternal vitamin D concentrations during pregnancy and neonatal vitamin D concentrations at birth.Materials and Methods: A prospective cohort of 236 healthy pregnant women from various ethnicity in early pregnancy (≤20 weeks of pregnancy) was followed at late pregnancy (28–40 weeks of pregnancy) and birth. Maternal serum 25-hydroxyvitamin D (25(OH)D) was assessed at early pregnancy (baseline) and late pregnancy, while neonatal cord serum 25(OH)D at birth. General estimating equations (GEE) were used to analyze the longitudinal association of maternal serum 25(OH)D levels during pregnancy and neonatal cord serum 25(OH)D levels at birth with adjusting for the time exposure, maternal weight gain, ethnicity, and skin type.Results: The results showed that the prevalence of vitamin D deficiency (25(OH)D <50 nmol/L) was at 89.9, 92.2, and 96.1% in early, late pregnancy and in neonatal cord serum, respectively. The GEE analysis showed a trend that longitudinal vitamin D deficiency during pregnancy leads to lower vitamin D concentrations in neonatal cord blood (RR = 1.17; 95% CI (1.05–1.36); p = 0.04).Conclusion: Longitudinal vitamin D deficiency during pregnancy leads to vitamin D deficiency in neonates at birth. A further trial is needed to affirm this association.

Maternal Vitamin D and Newborn Telomere Length.

Nutrition is important during pregnancy for offspring health. Gestational vitamin D intake may prevent several adverse outcomes and might have an influence on offspring telomere length (TL). In this study, we want to assess the association between maternal vitamin D intake during pregnancy and newborn TL, as reflected by cord blood TL. We studied mother–child pairs enrolled in the Maternal Nutrition and Offspring’s Epigenome (MANOE) cohort, Leuven, Belgium. To calculate the dietary vitamin D intake, 108 women were asked to keep track of their diet using the seven-day estimated diet record (EDR) method. TL was assessed in 108 cord blood using a quantitative real-time PCR method. In each trimester of pregnancy, maternal serum 25-hydroxyvitamin D (25-OHD) concentration was measured. We observed a positive association (β = 0.009, p-value = 0.036) between newborn average relative TL and maternal vitamin D intake (diet + supplement) during the first trimester. In contrast, we found no association between average relative TL of the newborn and mean maternal serum 25-OHD concentrations during pregnancy. To conclude, vitamin D intake (diet + supplements), specifically during the first trimester of pregnancy, is an important factor associated with TL at birth.

A prospective study of maternal 25-hydroxyvitamin D (25OHD) in the first trimester of pregnancy and second trimester heavy metal levels

BackgroundVitamin D facilitates the absorption of calcium but may also increase absorption of other metals; the literature is conflicting. ObjectiveTo examine whether 25OHD in the first trimester of pregnancy was associated with subsequent metals levels in the late second trimester of pregnancy. MethodsWe used data from a sample of women in the LIFECODES pregnancy cohort (N = 381). 25-hydroxyvitamin D (25OHD) was measured with a chemiluminescence immunoassay in plasma samples drawn at 10 weeks of gestation. A panel of 17 metals and elements was measured in urine collected at 26 weeks of gestation. We used linear or logistic regression to estimate associations between 25OHD (dichotomous, linear, and in tertiles) and either urinary metal concentrations or the proportion of samples below the limit of detection, respectively. Multivariable models included urinary specific gravity, age, race/ethnicity, education, body mass index, insurance type, gestational age, and season. ResultsAfter multivariable adjustment, low 25OHD was associated with a 47% increase in lead level, a 60% increase in tin level, and 1.58 times the odds of detectable tungsten. A 10 ng/ml increase in 25OHD was associated with a 12% decrease in tin and an 8% increase in molybdenum. While we had a small sample size, we found some evidence of effect modification by race. Women who reported their race as Black or were classified in the other race category, who also had low 25OHD, had 40% higher thallium than women with higher 25OHD and were more likely to have detectable beryllium and tungsten. These metals were not associated with low 25OHD in women who reported their race as White. Tin and lead were higher in women with low 25OHD in all race groups. DiscussionIn total, further research is warranted to determine if vitamin D levels alter metal levels, and to elucidate the shape of the association for each metal across a range of corresponding 25OHD levels, and longitudinally, across pregnancy. This is especially true for pregnant people as exposure to metals during pregnancy has health consequences for the fetus.

Antenatal iron supplementation, FGF23, and bone metabolism in Kenyan women and their offspring: secondary analysis of a randomized controlled trial

ABSTRACTBackgroundFibroblast growth factor-23 (FGF23) regulates body phosphate homeostasis primarily by increasing phosphaturia. It also acts as a vitamin D-regulating hormone. Maternal iron deficiency is associated with perturbed expression and/or regulation of FGF23 and hence might be implicated in the pathogenesis of hypophosphatemia-driven rickets in their offspring.ObjectivesWe aimed to determine the effect of antenatal oral iron supplementation on FGF23 concentration and maternal and infant markers of bone-mineral regulation.MethodsWe performed a secondary analysis of a trial in which 470 rural Kenyan women with singleton pregnancies and hemoglobin concentrations ≥ 90 g/L were randomly allocated to daily, supervised supplementation with 60 mg elemental iron as ferrous fumarate or placebo from 13–23 weeks of gestation until 1 mo postpartum. As previously reported, iron supplementation improved iron status in mothers and neonates. For the present study, we reanalyzed all available plasma samples collected in mothers and neonates at birth, with primary outcomes being concentrations of FGF23, measured by 2 assays: 1 that detects intact hormone and C-terminal cleavage products (total-FGF23) and another that detects the intact hormone only (intact-FGF23).ResultsAnalysis was performed on 433 women (n = 216, iron group; n = 217, placebo group) and 414 neonates (n = 207, iron group; n = 207, placebo group). Antenatal iron supplementation reduced geometric mean total-FGF23 concentrations in mothers and neonates by 62.6% (95% CI: 53.0%, 70.3%) and 15.2% (95% CI: −0.3%, 28.4%, P = 0.06), respectively. In addition, it increased geometric mean neonatal intact-FGF23 concentrations by 21.6% (95% CI: 1.2%, 46.1%), increased geometric mean maternal hepcidin concentrations by 136.4% (95% CI: 86.1%, 200.3%), and decreased mean maternal 25-hydroxyvitamin D concentrations by 6.1 nmol/L (95% CI: −11.0, −1.2 nmol/L).ConclusionsAnalysis of this randomized trial confirms that iron supplementation can reverse elevated FGF23 production caused by iron deficiency in iron-deficient mothers and their neonates. Further investigations are warranted to assess to what extent iron supplementation can prevent FGF23-mediated hypophosphatemic rickets or osteomalacia.

Maternal and Cord Blood 25-Hydroxyvitamin D3 Are Associated with Increased Cord Blood and Naive and Activated Regulatory T Cells: The Barwon Infant Study.

Vitamin D has shown immune-modulatory effects but mostly in in vitro and animal studies. Regulatory T cells (Treg) are important for a balanced immune system. The relationship between vitamin D on the number of circulating neonatal Treg is unclear. We sought to investigate the association between maternal and neonatal vitamin D metabolites and cord blood (CB) Treg subsets. In a cohort of Australian infants (n = 1074), recruited using an unselected antenatal sampling frame, 158 mother-infant pairs had data on the following: 1) 25-hydroxyvitamin D3 (25(OH)D3) measures in both maternal peripheral blood (28- to 32-wk gestation) and infant CB; 2) proportions (percentage of CD4+ T cells) of CB Treg subsets (CD4+CD45RA+ FOXP3low naive Treg, and CD4+CD45RA- FOXP3high activated Treg [aTreg]); and 3) possible confounders, including maternal personal UV radiation. Multiple regression analyses were used. The median 25(OH)D3 was 85.4 and 50.7 nmol/l for maternal and CB samples, respectively. Higher maternal 25(OH)D3 levels were associated with increased CB naive Treg (relative adjusted mean difference [AMD] per 25 nmol/l increase: 5%; 95% confidence interval [CI]: 1-9%), and aTreg (AMD per 25 nmol/l increase: 17%; 95% CI: 6-28%). Furthermore, a positive association between CB 25(OH)D3 levels and CB aTreg (AMD per 25 nmol/l increase: 29%; 95% CI: 13-48%) was also evident. These results persisted after adjustment for other factors such as maternal personal UV radiation and season of birth. 25(OH)D3, may play a role in the adaptive neonatal immune system via induction of FOXP3+ Tregs. Further studies of immune priming actions of antenatal 25(OH)D3 are warranted.

145 To determine if Vitamin D prophylaxis decreases the incidence of maternal and neonatal infection

To determine if Vitamin D prophylaxis decreases the incidence of maternal and neonatal infection. A secondary analysis assessing maternal and neonatal infection was performed on a RCT in which pregnant women received Vitamin D3 3000 IU daily or no supplement. Women with a confirmed intrauterine pregnancy 12-16 weeks without a history of Vitamin D use or malabsorption disorder were included. Maternal 25-hydroxyvitamin D (25(OH)D) levels were assessed at the time of enrollment and admission for delivery. Neonatal 25(OH)D level was assessed via cord blood. Outcomes collected included clinical chorioamnionitis (temperature > 38.0°C + maternal leukocytosis, purulent cervical discharge, or fetal tachycardia), endometritis (temperature > 38.0°C + uterine tenderness on exam), neonatal infection (as documented by NICU staff), neonatal sepsis (+ blood culture) and histologic chorioamnionitis (polymorphonucleocytes in the placental amnion and chorion). Parametric and nonparametric statistics were used to compare groups. A P value of <0.05 was statistically significant. Of the 412 women enrolled, 392 (95.1%) had completed pregnancies for analysis. Demographic characteristics, including baseline 25(OH)D levels, were similar between groups. Table 1. Compared to women who did not receive Vitamin D prophylaxis, those who did had a significantly higher 25(OH)D delivery (29.18 +/- 11.87 ng/mL vs. 23.79 +/- 9.29 ng/mL; P<0.001) and cord blood levels (33.73 +/- 13.68 ng/mL vs. 26.06 +/- 9.72 ng/mL; P<0.001). Vitamin D prophylaxis did not decrease the incidence of clinical chorioamnionitis, endometritis, neonatal infection, and neonatal sepsis. Table 2. Stratification by Vitamin D deficiency status revealed a higher incidence of clinical chorioamnionitis in those who did not receive intervention and remained Vitamin D deficient at delivery (9.7% vs. 1.6%; RR 5.9 95% CI 1.3-21.7; P=0.010). Vitamin D prophylaxis does not decrease the incidence of maternal or neonatal infection. Persistent Vitamin D deficiency in pregnancy may be associated with a risk for clinical chorioamnionitis.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

143 Does vitamin d prophylaxis prevent adverse neonatal outcomes?

To determine if Vitamin D prophylaxis prevents adverse neonatal outcomes. A secondary analysis assessing neonatal outcomes was performed on a randomized control trial in which pregnant women received Vitamin D3 3000 IU daily or no supplement. Maternal 25-hydroxyvitamin D (25(OH)D) levels were assessed at the time of enrollment and admission for delivery. Neonatal 25(OH)D) level was assessed via cord blood. Neonatal outcomes collected included gestational age at delivery, birthweight, need for NICU admission, respiratory distress, neonatal infection/sepsis, and pregnancy loss. Parametric and nonparametric statistics were used to compare groups. A P value of <0.05 was statistically significant. Enrollment occurred between October 2016 and September 2019. Of the 412 women enrolled, 392 (95.1%) had completed pregnancies for analysis. Demographic characteristics including baseline maternal 25-hydroxyvitamin D (25(OH)D) levels were similar between groups. Table 1. Compared to women who did not receive Vitamin D prophylaxis, those who did had a significantly higher 25(OH)D delivery serum level (29.18 ± 11.87 ng/mL vs. 23.79 ± 9.29 ng/mL; P<0.001) and cord blood level (33.73 ± 13.68 ng/mL vs. 26.06 ± 9.72 ng/mL; P<0.001). While vitamin D prophylaxis was not associated with a decreased incidence of preterm birth, low birth weight, NICU admission, respiratory distress and neonatal infection/sepsis, use was associated with a decreased incidence of pregnancy loss (0.5 vs. 4.1%; RR 0.1 (0.01-0.9); P=0.01) and a low 5 minute Apgar score at the time of birth (1.0 vs. 5.2%; RR 0.2 (0.1-0.8); P=0.02). Table 2. Vitamin D prophylaxis not only increases baseline maternal and neonatal 25(OH)D) levels, but is also associated with a lower incidence of pregnancy loss and higher Apgar scores.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

31 Does Vitamin D Prophylaxis decrease the incidence of hypertensive disorders of pregnancy?

To determine if Vitamin D prophylaxis decreases the incidence of hypertensive disorders of pregnancy. A single center, parallel, open label, randomized control trial was performed in which pregnant women received Vitamin D3 3000 IU daily or no supplement. The primary outcome was the incidence of hypertensive disorders of pregnancy. Based on a power analysis set at 80%, a sample size of 206 women in each group (n=412) was planned for comparison. Maternal serum and cord blood were collected for 25-hydroxyvitamin D assessment. Patients were called to assess compliance with the study protocol. Maternal demographics and pregnancy outcomes were collected from the electronic medical record. Statistical analyses were performed using SPSS V24. Student’s t tests and ANOVA analyses were performed for continuous variables that were normally distributed. Chi-Square or Fisher’s exact tests were performed for categorical variables. Binary logistic regression for the primary outcome was performed adjusting for confounders. The analysis was conducted with an intent to treat model with omission of missing variables. A P value of <0.05 was statistically significant. Enrollment occurred between October 2016 and September 2019. Of the 412 women enrolled, 392 (95.1%) had completed pregnancies for analysis. Demographic characteristics including baseline maternal 25-hydroxyvitamin D (25(OH)D) levels were similar between groups. Compared to women who did not receive Vitamin D prophylaxis, those who did had a significantly higher 25(OH)D delivery serum level (29.18 +/- 11.87 ng/mL vs. 23.79 +/- 9.29 ng/mL; P<0.001) and cord blood level (33.73 +/- 13.68 ng/mL vs. 26.06 +/- 9.72 ng/mL; P<0.001). The incidence of hypertensive disorders of pregnancy was 10.5% (41/392). Vitamin D prophylaxis did not decrease the incidence of hypertensive disorders of pregnancy when compared to controls (13.1% vs. 7.7%; RR 1.7, 95% CI 0.9-2.9; P=0.10). Vitamin D prophylaxis does not prevent hypertensive disorders of pregnancy, but does increase maternal and cord blood Vitamin D levels.View Large Image Figure ViewerDownload Hi-res image Download (PPT)