Maternal 25-hydroxyvitamin Research Articles

Association of maternal serum vitamin D level with fetal pulmonary artery Doppler indices and neonatal respiratory distress syndrome.

Respiratory distress syndrome (RDS) is potentially fatal in infants. The present study investigated the association of maternal serum vitamin D level with fetal pulmonary artery Doppler indices and neonatal RDS. This cross-sectional-analytical study was conducted on 260 mothers admitted for delivery. The maternal serum 25-hydroxyvitamin D level was measured and fetal main pulmonary artery Doppler indices were evaluated. The neonate's weight, apgar score, RDS, Umbilical cord arterial pH and neonatal intensive care unit admission were recorded. There was a significant relationship between RDS and the low level of vitamin D in the mother's serum. Mothers with low vitamin D had higher fetal pulmonary artery pulsatility index (PI) and peak systolic velocity (PSV) and lower acceleration time (AT) to ejection time (ET) ratio. Also, in neonates with RDS, pulmonary artery PI was higher, and PSV and the ratio of AT to ET were significantly lower than neonates without RDS. Neonates with lower one and 5-min apgar scores were born from mothers with lower vitamin D levels. Serum levels of vitamin D in pregnant mothers as well as fetal pulmonary artery Doppler indices are correlated to RDS. There is a significant relationship between the serum level of vitamin D in pregnant mothers and fetal pulmonary artery Doppler indices.

Genetic variants and non-genetic factors associated with a high prevalence of vitamin D deficiency in full-term neonates in Malaysia

A high prevalence of vitamin D deficiency has been reported in Malaysian pregnant women, indicating that neonates at birth are at increased risk of vitamin D deficiency. Factors including low dietary vitamin D intake and single nucleotide polymorphisms in the vitamin D metabolism genes have been associated with this deficiency in the population. However, there was limited data available regarding the prevalence of neonatal vitamin D deficiency and the factors associated with it among neonates in Malaysia. Therefore, this study aimed to determine the prevalence of vitamin D deficiency and explore the associations between maternal and neonatal gene polymorphisms, as well as non-genetic factors and neonatal vitamin D deficiency. A total of 217 mother-neonate dyads were recruited for this study. Data on skin type, maternal sun exposure, dietary intake, as well as maternal and neonatal 25-hydroxyvitamin D (25OHD) concentrations were collected. Maternal and neonatal vitamin D Receptor (VDR) SNP (rs2228570) and Group-specific component (GC) SNPs (rs4588 and rs7041) genotypes were determined using high-resolution melting (HRM) and restriction fragment length polymorphism, respectively. The results showed that 60.4%, 71.4% and 95.4% of neonates had cord blood 25OHD levels below 25 nmol/L, 30 nmol/L and 50 nmol/L, respectively. After adjusting for the maternal vitamin D status, the maternal VDR rs2228570 GG genotype was significantly associated with neonatal vitamin D deficiency (25OHD<30 nmol/L) (aOR = 2.63, 95% CI: 1.18–5.87, p = 0.018). Maternal vitamin D supplement intake was found to be a protective factor. However, maternal and neonatal vitamin D binding protein (VDBP) SNPs were not associated with neonatal vitamin D deficiency. The high prevalence of neonatal vitamin D deficiency reported in this study indicates the urgent need for the development and implementation of strategies to improve neonatal vitamin D status. The findings suggest that maternal supplementation may be an effective approach to enhance the vitamin D status of neonates.

Correlation analysis of maternal serum folate and 25(OH)D levels with the incidence of fetal growth restriction in patients with preeclampsia

Background The purpose of this study was to investigate the effect of folic acid (FA) and vitamin D supplementation on increasing maternal serum folate and 25-hydroxyvitamin D [25(OH)D] concentrations during pregnancy and further reveal its role in reducing the risk of fetal growth restriction (FGR) in patients with preeclampsia (PE). Methods A total of 300 preeclamptic patients (treatment group 204 and control group 96) who had undergone routine obstetric examinations were retrospectively analyzed in this study. Data that include maternal serum levels of folate and 25(OH)D detected during early, middle, and late gestational periods from the medical records were analyzed. Multifactorial logistic regression analysis was performed to investigate the correlation of serum folate and 25(OH)D concentrations with the incidence of FGR. Results Serum folate and 25(OH)D concentrations were similar between the treatment group and control group in the early gestation. During the middle and late gestation, the serum folate and 25(OH)D levels were both continuously increased in the treatment group, but persistently decreased in the control group, leading to significant differences between the two groups (p < .001). In addition, the incidence of FGR was significantly lower in the treatment group than in the control group (p < .001). Logistic regression analysis showed significant correlations of increased serum folate and 25(OH)D levels with lower risk of FGR. Conclusions FA and vitamin D supplementations facilitated to lower the risk of FGR in preeclamptic patients. These results would be the solid foundation for the further investigation of approaches to improve adverse outcomes of pregnancy, and have potential guiding implications for clinical practice.

Fatty acids profile in pregnancies affected by neural tube defects

Abstract This study aimed to determine if maternal fatty acids (FA) levels during pregnancy are associated with the occurrence of neural tube defects (NTDs) and to explore the correlation between FA and maternal vitamin D, homocysteine, vitamin B12, and folate in cases. Plasma FA composition was assessed using capillary gas chromatography. Comparisons between cases and controls were performed by independent samples t-test for continuous variables. Cases had significantly higher levels of heptadecanoic acid, linolelaidic acid, and arachidonic acid (ARA):(eicosapentaenoic acid+docosahexaenoic acid) ratio than controls (p &lt; 0.05). Nervonic acid, ARA, adrenic acid, eicosapentaenoic acid, docosahexaenoic acid, and omega-3 polyunsaturated fatty acids (n-3 PUFA) levels were significantly lower in cases (p &lt; 0.05). Maternal 25-hydroxyvitamin D (25(OH)D) levels were positively correlated with maternal polyunsaturated fatty acids and omega-6 polyunsaturated fatty acids. RBC folate levels were negatively correlated with n-3 PUFA. Further research is required to clarify the association of FA metabolism with NTDs.

The Association of Prenatal Vitamin D Status With Pregnancy and Neonatal Outcomes.

Vitamin D inadequacy is globally prevalent among pregnant women; however, its impact on pregnancy remains inconclusive. This study aims to explore the associations of maternal and umbilical cord serum 25-hydroxyvitamin D (25(OH)D) levels with pregnancy and neonatal outcomes. We used archived serum samples from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study participants in the Hong Kong center and assayed maternal 25(OH)D levels at midgestation and umbilical cord 25(OH)D at birth using liquid chromatography-tandem mass spectroscopy. Data regarding pregnancy and perinatal outcomes were extracted from the HAPO study dataset and the hospital computerized medical system. Only 247 (16.4%) mothers and 66 (5.0%) neonates met the criteria for vitamin D sufficiency (ie, 25(OH)D ≥ 75 nmol/L). The ratio of umbilical cord to maternal vitamin D levels was positively associated with maternal age and ambient solar radiation at the month of delivery, while negatively associated with maternal serum total 25(OH)D at midgestation (all P < .001). Umbilical cord serum 25(OH)D was independently associated with a lower primary cesarean section rate (OR 0.990, 95% CI 0.982-0.999; P = .032). There were no associations of maternal and umbilical cord 25(OH)D levels with other adverse pregnancy and neonatal outcomes. Placental vitamin D transfer was found to be higher with a lower maternal vitamin D level, older maternal age, and higher ambient solar radiation at the time of the delivery. The protective effect of sufficient vitamin D in a cesarean section will require further studies.

Maternal vitamin D status and risk of childhood overweight at 5 years of age in two Nordic cohort studies.

Maternal vitamin D status during pregnancy has been suggested to have a role in childhood adiposity development, but results are conflicting. Our aims were to investigate [1] the relationships between maternal 25-hydroxyvitamin D (25OHD) during pregnancy and the child's body mass index (BMI) and risk of overweight at 5 years of age, and [2] maternal pre-pregnancy BMI as effect modifier for these associations. Data sources included a subsample from the Norwegian Mother, Father and Child Cohort Study (MoBa sub-cohort; N = 2,744) and the Swedish GraviD cohort study (N = 891). Maternal 25OHD was analyzed in gestational week 18 in the MoBa sub-cohort and week 10 in the GraviD cohort. In the MoBa sub-cohort, parents reported their child's documented measures of weight and length or height from the health card at routine check-up. In the GraviD cohort, this information was collected directly from medical records. Childhood overweight (including obesity) was identified using the International Obesity Task Force cut-offs. Linear and logistic regression models were used to investigate the association between maternal 25OHD and child's BMI and risk of overweight at 5 years of age in each cohort separately, and in a pooled dataset. In the pooled analysis, maternal 25OHD <30 nmol/L was associated with lower BMI in children at 5 years of age, but not with risk of overweight. Interaction analysis showed that the association was predominant among children of mothers with pre-pregnancy BMI ≥25 kg/m2. Low maternal vitamin D status, particularly in mothers with overweight or obesity, predicted lower BMI in their five-year-old children. However, there was no evidence of an effect on overweight in these children.

The estimated effect of season and vitamin D in the first trimester on pubertal timing in girls and boys: a cohort study and an instrumental variable analysis.

Season of birth has been associated with age at menarche. Maternal vitamin D levels in pregnancy may explain this effect. We investigated whether the season of first trimester or maternal 25-hydroxyvitamin D3 [25(OH)D3] levels were associated with pubertal timing in children. We conducted a follow-up study of 15 819 children born in 2000-03 from the Puberty Cohort, nested in the Danish National Birth Cohort (DNBC). Mean differences in attaining numerous pubertal markers, including a combined estimate for the average age at attaining all pubertal markers, were estimated for low (November-April) relative to high (May-October) sunshine exposure season in the first trimester using multivariable interval-censored regression models. Moreover, we conducted a two-sample instrumental variable analysis using season as an instrument for maternal first-trimester 25(OH)D3 plasma levels obtained from a non-overlapping subset (n = 827) in the DNBC. For the combined estimate, girls and boys of mothers who had their first trimester during November-April had earlier pubertal timing than girls and boys of mothers whose first trimester occurred during May-October: -1.0 months (95% CI: -1.7 to -0.3) and -0.7 months (95% CI: -1.4 to -0.1), respectively. In the instrumental variable analysis, girls and boys also had earlier pubertal timing: respectively, -1.3 months (95% CI: -2.1 to -0.4) and -1.0 months (95% CI: -1.8 to -0.2) per SD (22 nmol/L) decrease in 25(OH)D3. Both first pregnancy trimester during November-April and lower 25(OH)D3 were associated with earlier pubertal timing in girls and boys.

Analysis of single nucleotide polymorphisms associated with the vitamin D pathway in the placentas of women with gestational diabetes mellitus: a laboratory study.

The aim of this study was to analyze the single nucleotide polymorphisms (SNPs) of genes known to be involved in vitamin D metabolism in the placenta using the placental tissue of mothers diagnosed with gestational diabetes mellitus (GDM) to determine whether the SNPs and occurrence of GDM are related. We enrolled 80 women of the same gestational age, 40 with and 40 without GDM. The placenta was obtained from each woman after delivery and SNP genotyping was performed on seven SNPs in the CYP27B1 (rs10877012), CYP24A1 (rs2248359, rs6013897, and rs2209314), and GC (rs2282679, rs16847024, and rs3733359) genes. Maternal serum 25-hydroxyvitamin D levels were measured during the first trimester of pregnancy and before delivery. At the time of delivery, vitamin D levels were lower (21.05±12.05 mg/dL vs. 31.31±20.72 mg/dL, p=0.012) and the frequency of vitamin D deficiency was higher (60.7% vs. 32.5%, p=0.040) in the GDM group. In women with GDM, the G allele of rs10877012 was more common (86.3% vs. 65.0%, p=0.002). The rs10877012 GG genotype was more common in the GDM group (72.5% vs. 42.5%, p=0.007) and the rs10877012 TT genotype was more common in the control group (12.5% vs. 0%, p=0.007). Mothers with GDM have lower serum concentrations of vitamin D before delivery than healthy controls and vitamin D deficiency is common. A polymorphism in CYP27B1 (rs10877012), is considered to be a cause of GDM pathogenesis.

The Impact of Baseline 25-Hydroxyvitamin D Level and Gestational Age on Prenatal Vitamin D Supplementation to Prevent Offspring Asthma or Recurrent Wheezing

BackgroundPrenatal vitamin D deficiency is associated with asthma or recurrent wheezing in offspring. However, evidence from randomized trials on the efficacy of vitamin D supplementation is inconclusive. ObjectivesWe aimed to examine the differential efficacy of prenatal vitamin D supplementation based on the maternal baseline vitamin D status and the starting time of supplementation to prevent early life asthma or recurrent wheezing. MethodsWe conducted a secondary analysis of the Vitamin D Antenatal Asthma Reduction Trial (VDAART), a randomized double-blind trial of prenatal vitamin D supplementation initiated at 10–18 weeks (wks) of gestation (4400 IU of intervention/day compared with 400 IU of placebo/day) to prevent offspring asthma or recurrent wheezing by the age of 6 years. We assessed the effect of modification of supplementation by maternal baseline vitamin D status at enrollment and the timing of initiation of supplementation. ResultsAn inverse relationship was observed between maternal 25-hydroxyvitamin D (25(OH)D) levels at trial entry and 25(OH)D levels during late pregnancy (32–38 wks of gestation) in both supplementation arms (P < 0.001). Overall, supplementation efficacy was not dependent on the maternal baseline 25(OH)D status. However, a trend toward the reduction of asthma or recurrent wheezing was observed across the baseline groups in the intervention arm (P = 0.01), with the greatest reduction observed in the most severely vitamin D–deficient women (25(OH)D < 12 ng/mL; adjusted odds ratio [aOR] = 0.48; confidence interval [CI]: 0.17, 1.34). Gestational age at trial enrollment modified supplementation efficacy, showing a greater reduction of offspring asthma or recurrent wheezing with earlier intervention during pregnancy (aOR = 0.85; CI = 0.76, 0.95), particularly in women who were 9–12 wk pregnant (aOR = 0.45; CI = 0.24, 0.82). ConclusionsPregnant women with severe vitamin D deficiency show the greatest 25(OH)D improvement because of supplementation. In these women, a vitamin D dose of 4400 IU might have a preventive role in the development of early life offspring asthma or recurrent wheezing. Gestational age is suggested to modify the efficacy of prenatal vitamin D supplementation, showing the highest beneficial effect if supplementation is started during the first trimester of pregnancy.This study is an ancillary analysis from the VDAART, which is registered in ClinicalTrials.gov as NCT00902621.

Insights into Prevention of Health Complications in Small for Gestational Age (SGA) Births in Relation to Maternal Characteristics: A Narrative Review.

Small for gestational age (SGA) births are a significant clinical and public health issue. The objective of this review was to summarize maternal biological and socio-demographic factors and preventive strategies used to reduce the risk of SGA births. A literature search encompassing data from the last 15 years was conducted using electronic databases MEDLINE/PubMed, Google Scholar and Scopus to review risk factors and preventive strategies for SGA. Current evidence shows that primiparity, previous stillbirths, maternal age ≤24 and ≥35 years, single motherhood, low socio-economic status, smoking and cannabis use during pregnancy confer a significant risk of SGA births. Studies on alcohol consumption during pregnancy and SGA birth weight are inconclusive. Beneficial and preventive factors include the "Mediterranean diet" and dietary intake of vegetables. Periconceptional folic acid supplementation, maternal 25-hydroxyvitamin D, zinc and iron levels are partly associated with birth weight. No significant associations between COVID-19 vaccinations and birthweight are reported. A midwifery-led model based on early and extensive prenatal care reduces the risk of SGA births in women with low socio-economic status. Major preventive measures relate to the awareness of modifiable and non-modifiable risk factors of SGA, leading to changes in parents' lifestyles. These data support that education, monitoring during pregnancy, and implementing preventive strategies are as important as biological determinants in risk reduction of SGA births.

Vitamin D and preeclampsia: A systematic review and meta-analysis.

Preeclampsia is one of the most frequent pregnancy disorders, with a global incidence of 2%-8%. Serum 25-hydroxyvitamin D is an essential mineral for human health; some studies suggest link between 25-hydroxyvitamin D deficiency and preeclampsia, while others offer contradictory findings. Thus, the goal of this study is to evaluate the relationships between maternal 25- hydroxyvitamin D concentrations and the risk of preeclampsia. In addition to this, our study also evaluates the effects of 25- hydroxyvitamin D supplementation on the incidence of preeclampsia. Therefore, assessing 25- hydroxyvitamin D's potential as a possible intervention to lower the risk of preeclampsia. The Medline database was queried from inception until July 2021 for randomized controlled trials and observational studies without any restrictions. The studies assessing the association between 25-hydroxyvitamin D deficiency and preeclampsia and the impact of 25-hydroxyvitamin D supplementation on the incidence of preeclampsia were incorporated. The results were reported using a random-effects meta-analysis and the Mantel-Haenszel odds ratio. A p-value of <0.05 was considered significant for the analysis. This analysis includes 34 papers, including 10 randomized controlled trials and 24 observational studies. According to our pooled analysis, 25-hydroxyvitamin D supplementation was significantly associated with a lower risk of preeclampsia in pregnant women (OR: 0.50; 95% CI: 0.40-0.63; p = 0.00001), while 25-hydroxyvitamin D deficiency was significantly associated with an increased risk of preeclampsia (OR: 4.30; 95 % CI: 2.57-7.18; p < 0.00001, OR: 1.71; 95 % Cl: 1.27-2.32; p = 0.0005, OR 1.61; 95 % Cl: 1.21-2.16; p = 0.001). Results suggest that 25-hydroxyvitamin D has a significant relationship with preeclampsia as confirmed by the findings that low maternal 25-hydroxyvitamin D concentrations cause increased risk of preeclampsia while 25-hydroxyvitamin D supplementation reduces the incidence of preeclampsia. Our findings indicate that 25-hydroxyvitamin D supplementation can be used as a possible intervention strategy in preventing one of the most common causes of maternal mortality around the world, preeclampsia.

Maternal vitamin D during pregnancy and offspring autism and autism-associated traits: a prospective cohort study

BackgroundThere has been a growing interest in the association between maternal levels of vitamin D during pregnancy and offspring autism. However, whether any associations reflect causal effects is still inconclusive.MethodsWe used data from a UK-based pregnancy cohort study (Avon Longitudinal Study of Parents and Children) comprising 7689 births between 1991 and 1992 with maternal blood vitamin D levels recorded during pregnancy and at least one recorded outcome measure, including autism diagnosis and autism-associated traits. The association between each outcome with seasonal and gestational age-adjusted maternal serum 25-hydroxyvitamin D during pregnancy was estimated using confounder-adjusted regression models. Multiple imputation was used to account for missing data, and restricted cubic splines were used to investigate nonlinear associations. Mendelian randomization was used to strengthen causal inference.ResultsNo strong evidence of an association between maternal serum 25-hydroxyvitamin D during pregnancy and any offspring autism-associated outcome was found using multivariable regression analysis (autism diagnosis: adjusted OR = 0.98, 95% CI = 0.90–1.06), including with multiple imputation (autism diagnosis: adjusted OR = 0.99, 95% CI = 0.93–1.06), and no evidence of a causal effect was suggested by Mendelian randomization (autism diagnosis: causal OR = 1.08, 95% CI = 0.46–2.55). Some evidence of increased odds of autism-associated traits at lower levels of maternal serum 25-hydroxyvitamin D was found using spline analysis.LimitationsOur study was potentially limited by low power, particularly for diagnosed autism cases as an outcome. The cohort may not have captured the extreme lows of the distribution of serum 25-hydroxyvitamin D, and our analyses may have been biased by residual confounding and missing data.ConclusionsThe present study found no strong evidence of a causal link between maternal vitamin D levels in pregnancy and offspring diagnosis or traits of autism.

Maternal Android Adiposity and Vitamin D Status in Lactation Are Positive Predictors of Child Adiposity and Vitamin D Status at 2 Years of Age: A Follow-Up Study From Montréal

Abstract Objectives Recent evidence suggests that fetal exposure to both maternal excess adiposity and low maternal vitamin D status is associated with body composition of the children. The objective was to explore whether maternal android adiposity and maternal serum 25-hydroxyvitamin D (25(OH)D) during early lactation relate to child adiposity and vitamin D status at 2 years of age. Methods The present study is a follow-up of a sub-group who completed a double-blinded randomized parallel group-controlled trial of vitamin D supplementation (400 or 1000 IU/d) across infancy (NCT02563015). In this follow-up, 68 (49%) children (37 males, 31 females) returned at 24 months of age; the study was closed at the onset of the COVID-19 pandemic precluding follow-up in the remainder. Body composition (dual-energy X-ray absorptiometry) and serum 25(OH)D (immunoassay) were measured at baseline (0.2–1.5 mo postpartum) in mothers and at 24 months of age in children. Data were analyzed using a linear fixed effects model with covariates (sex, skin tone, child age, maternal 25(OH)D concentrations, parental age, and maternal android fat mass) followed by Tukey post hoc tests adjusted for multiple comparisons. Results At baseline, mothers were 31.6 (range: 19.9, 41.4) years with mean serum 25(OH)D 66.0 ± 25.3 nmol/L, percentage fat mass was 33.8 ± 5.4% and android fat mass 217.9 ± 79.7 g. In children at 24-months, mean serum 25(OH)D was above the cut-point for sufficiency of 50 nmol/L and not different between males and females (males: 82.0 ± 17.6 and females: 76.5 ± 14.0 nmol/L, P = 0.16). Postpartum maternal serum 25(OH)D was a positive predictor of children's 25(OH)D concentrations (β = 0.25 ± 0.08 nmol/L, P = 0.0031) at 24 months. Similarly, postpartum maternal android fat mass was a positive correlate of children's android fat mass (β = 0.03 ± 0.01 g, P = 0.0201). Maternal gynoid fat mass was not related to children's gynoid fat mass (P = 0.76). Overall, female children had higher android and gynoid fat mass compared to male counterparts (P = 0.0348). Conclusions Maternal android adiposity and maternal serum 25-hydroxyvitamin D are separate important modifiable correlates of children adiposity and vitamin D status at 2 years of age. These findings reinforce the importance of maternal programming of body composition and vitamin D status in children. Funding Sources The Canadian Institutes of Health Research.

Vitamin D Status and Gestational Diabetes in Russian Pregnant Women in the Period between 2012 and 2021: A Nested Case-Control Study.

Several meta-analyses found an association between low maternal serum 25-hydroxyvitamin D (25(OH)D) level and gestational diabetes mellitus (GDM). However, some of them reported significant heterogeneity. We examined the association of serum 25(OH)D concentration measured in the first and in the second halves of pregnancy with the development of GDM in Russian women surveyed in the periods of 2012–2014 and 2018–2021. We conducted a case–control study (including 318 pregnant women) nested on two previous studies. In 2012–2014, a total of 214 women (83 GDM and 131 controls) were enrolled before 15 weeks of gestation and maternal serum 25(OH)D concentrations were measured twice: at 8th–14th week of gestation and simultaneously with two-hour 75 g oral glucose tolerance test (OGTT) at 24th–32nd week of gestation. In the period of 2018–2021, 104 women (56 GDM and 48 controls) were included after OGTT and 25(OH)D concentrations were measured at 24th–32nd week of gestation. Median 25(OH)D levels were 20.0 [15.1–25.7] vs. 20.5 [14.5–27.5] ng/mL (p = 0.565) in GDM and control group in the first half of pregnancy and 25.3 [19.8–33.0] vs. 26.7 [20.8–36.8] ng/mL (p = 0.471) in the second half of pregnancy, respectively. The prevalence rates for vitamin D deficiency (25(OH)D levels < 20 ng/mL) were 49.4% and 45.8% (p = 0.608) in the first half of pregnancy and 26.2% vs. 22.1% (p = 0.516) in the second half of pregnancy in women who developed GDM and in women without GDM, respectively. The frequency of vitamin D supplements intake during pregnancy increased in 2018–2021 compared to 2012–2014 (p = 0.001). However, the third trimester 25(OH)D levels and prevalence of vitamin D deficiency (25.5 vs. 23.1, p = 0.744) did not differ in women examined in the periods of 2012–2014 and 2018–2021. To conclude, there was no association between gestational diabetes risk and maternal 25(OH)D measured both in the first and in the second halves of pregnancy. The increased prevalence of vitamin D supplements intake during pregnancy by 2018–2021 did not lead to higher levels of 25(OH)D.

Maternal vitamin D status in pregnancy and molar incisor hypomineralisation and hypomineralised second primary molars in the offspring at 7–9 years of age: a longitudinal study

PurposeThe study aimed to investigate associations between maternal vitamin D status during pregnancy and molar incisor hypomineralisation (MIH) and hypomineralised second primary molars (HSPM) among children.MethodsThe study had a longitudinal design using prospectively collected data from 176 mother and child pairs. Mothers were initially recruited in a randomised controlled trial to assess a pregnancy exercise programme. Along with the 7-year follow-up, we invited the children to a dental examination. The exposure variable was maternal serum 25-hydroxyvitamin D in gestational weeks 18–22 and 32–36, categorised as insufficient (< 50 nmol/l) and sufficient (≥ 50 nmol/l). Negative binomial hurdle models were used to analyse potential associations between the exposure variables and MIH or HSPM. The models were adjusted for potential confounders.ResultsAmong the children (7–9 years old), 32% and 22% had at least one tooth with MIH or HSPM, respectively. A significant association was found between insufficient maternal vitamin D measured in gestational weeks 18–22 and the number of affected teeth among those with MIH at 7–9 years (adjusted RR = 1.82, 95% CI 1.13–2.93).ConclusionConsidering any limitations of the present study, it has been shown that insufficient maternal serum vitamin D at mid-pregnancy was associated with a higher number of affected teeth among the offspring with MIH at 7–9 years of age. Further prospective studies are needed to investigate whether this finding is replicable and to clarify the role of maternal vitamin D status during pregnancy and MIH, as well as HSPM, in children.

Vitamin D3 supplementation during pregnancy and lactation for women living with HIV in Tanzania: A randomized controlled trial.

BackgroundObservational studies suggest that vitamin D deficiency among people living with HIV is associated with a greater risk of disease progression and death. Low levels of vitamin D in pregnancy are also associated with poor fetal and infant growth. Therefore, vitamin D supplementation may improve clinical outcomes for pregnant women living with HIV and improve fetal and postnatal growth for their infants.Methods and findingsWe conducted a randomized, triple-blind, placebo-controlled trial of vitamin D3 supplementation among pregnant and lactating women living with HIV in Dar es Salaam, Tanzania (ClinicalTrials.gov NCT02305927). Participants were randomized with 1:1 allocation stratified by study clinic to receive either daily 3,000 IU vitamin D3 supplements or matching placebo supplements from the second trimester of pregnancy (12–27 weeks) until 1 year postpartum. The primary outcomes were (i) maternal HIV progression or death, (ii) small-for-gestational-age (SGA) live births (<10th percentile), and (iii) infant stunting at 1 year of age (length-for-age z-score < −2). We also examined the effect of vitamin D3 supplementation on secondary maternal and infant health outcomes, maternal and infant serum 25-hydroxyvitamin D (25[OH]D) concentrations, and maternal hypercalcemia. An intent-to-treat analysis was used as the primary analytic approach. We enrolled 2,300 pregnant women between June 15, 2015, and April 17, 2018, and follow-up of mothers and infants was completed on October 20, 2019. There were 1,148 pregnant women randomly assigned to the vitamin D3 group, and 1,152 to the placebo group. The proportion of mothers lost to follow-up at 1 year postpartum was 6.6% in the vitamin D3 group (83 of 1,148) and 6.6% in the placebo group (76 of 1,152). The proportion of children lost to follow-up at 1 year of age was 5.5% in the vitamin D3 group (59 of 1,074 live births) and 5.2% in the placebo group (57 of 1,093 live births). There was no difference in the risk of maternal HIV progression or death, with 166 events during 1,461 person-years of follow-up in the vitamin D3 group and 141 events during 1,469 person-years of follow-up in the placebo group (hazard ratio 1.21, 95% CI 0.97 to 1.52, p = 0.09). There was no difference in the risk of SGA birth between the vitamin D3 (229 SGA births among 1,070 live births) and placebo groups (236 SGA births among 1,091 live births) (relative risk 1.03, 95% CI 0.87 to 1.22, p = 0.70). There was also no difference in the risk of infant stunting at 1 year of age between the vitamin D3 (407 events among 867 infants) and placebo groups (413 events among 873 infants) (relative risk 1.00, 95% CI 0.92 to 1.10, p = 0.95). In terms of adverse events, no cases of maternal hypercalcemia were identified. One hypersensitivity reaction to the trial supplements occurred for a pregnant woman in the placebo group. A limitation of our study is that our findings may not be generalizable to HIV-negative pregnant women or contexts where severe vitamin D deficiency is prevalent.ConclusionsThe trial findings do not support routine vitamin D supplementation for pregnant and lactating women living with HIV in Tanzania.Trial registrationClinicalTrials.gov Identifier: NCT02305927.

Effect of maternal vitamin D status on risk of adverse birth outcomes: a systematic review and dose-response meta-analysis of observational studies.

Accumulating evidence suggests that vitamin D deficiency increases the risk of adverse perinatal outcomes. However, the dose-response relationship between maternal vitamin D status and adverse birth outcomes remains unclear. Focusing on prospective observational studies, we aimed to explore the dose-response relationship of vitamin D status with the risk of low birth weight (LBW), macrosomia (MA), preterm birth (PTB), small for gestational age (SGA), and intrauterine growth restriction (IUGR). Databases including PubMed, Embase, Scopus, and Web of Science were used up to 19 January 2021 to search for observational studies that fulfilled criteria as follows: cohort studies, case-cohort studies, or nested case-control studies. Random-effects models were used to pool relative risks (RRs) and 95% confidence intervals (CIs) in the observational studies. A total of 72 publications were included in this systematic review and 71 in the meta-analysis. Maternal 25-hydroxyvitamin D (25(OH)D) concentrations were inversely associated with the risk of LBW (RR: 0.65; 95% CI 0.48-0.86), PTB (RR: 0.67; 95% CI 0.57-0.79), and SGA (RR: 0.61; 95% CI 0.49-0.76) in the highest versus lowest meta-analysis, but not associated with MA and IUGR. Linear dose-response analysis showed that each 25nmol/L increase in 25(OH)D was associated with a 6% and 10% reduction in the risk of PTB (RR: 0.94; 95% CI 0.90-0.98) and SGA (RR: 0.90; 95% CI 0.84-0.97), respectively. Our study suggests that a sufficient vitamin D status during pregnancy is protective against the risk of LBW, PTB, and SGA.

Low Maternal Serum 25-Hydroxyvitamin D Concentration Is Associated With Postpartum Hemorrhage: A Retrospective Observational Study.

ObjectiveThe primary aim of this study is to investigate the relationship between vitamin D serum level and the incidence of postpartum hemorrhage (PPH). The secondary objective is to determine the relative risk of low vitamin D associated with PPH.MethodsThis was a retrospective observational study. A total of 600 women who had delivered their babies in a single tertiary teaching hospital were enrolled. Serum blood test for 25(OH)D was performed at 35 + 0 to 36 + 6 weeks of pregnancy to measure vitamin D. A 25(OH)D level < 20 ng/mL was defined as vitamin D deficient, and a level 21–29 ng/mL as insufficient.ResultsVitamin D levels were deficient in 145 (24.1%) and insufficient in 254 (42.3%) of the women tested. Women with deficient and insufficient vitamin D levels were significantly younger than those with sufficient vitamin D levels (p < 0.001). The overall rates of PPH in the deficient and insufficient groups were 6.9% (10/145) and 6.7% (17/254), respectively, and were significantly higher than the rate of the normal vitamin D group (1.5%, p = 0.009). Women with sufficient vitamin D levels had significantly higher hemoglobin levels than those with low vitamin D levels. Higher vitamin D levels were associated with a significantly low risk of PPH (AOR: 0.93, CI: 0.89–0.98, p = 0.006).ConclusionOur results suggest that a low vitamin D level is a risk factor for PPH. Low vitamin D also related to high risk of low hemoglobin before delivery. Thus, antepartum care should include vitamin D supplements for all women if possible.

Association between Maternal Serum 25-Hydroxyvitamin D Concentrations and the Risk of Preterm Birth in Central Sudan: A Case-Control Study.

There are few published studies on the association between vitamin D concentrations and preterm birth (PB) in sub-Saharan Africa. The current study aimed to assess the association between 25-hydroxyvitamin D (25[OH)] D) levels and PB. A matched case–control study (60 women in each arm) was conducted in Medani maternity hospital in central Sudan. The cases were women with spontaneous PB, and healthy women with term deliveries were the controls. The clinical/medical and obstetric history was gathered using a questionnaire. The enzyme-linked immunosorbent assay was used to measure the serum 25(OH)D levels. Women with PB had significantly lower median (interquartile range) 25(OH)D concentrations compared with the controls (18.4 (7.3) ng/mL vs. 20.2 (16.5) ng/mL, p = 0.001). Forty-two (70.0%) women with PB and 29 (48.3%) women in the control group had vitamin D deficiency (25(OH)D level ≤ 20 ng/mL). The results of the multivariable logistic regression showed that the 25(OH)D concentrations were negatively associated with PB (adjusted odds ratio (aOR) = 0.92, 95% confidence interval (CI) = 0.87–0.97). Vitamin D-deficient pregnant women were at a higher risk of PB (aOR = 2.69, 95% CI = 1.17–6.23). Low 25(OH)D concentrations were found at the time the variable was determined in women with spontaneous PB and were an independent risk factor for PB.

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.