Cord 25OHD Research Articles

Questioning the adequacy of standardized vitamin D supplementation protocol in very low birth weight infants: a prospective cohort study.

Preterm infants are at increased risk for vitamin D deficiency (VDD). We aimed to assess the adequacy of standardized vitamin D supplementation protocol in very low birth weight (VLBW) infants. Additionally, vitamin D status of mother/infant couples and the associations between vitamin D status at birth and morbidities of the infants were investigated. In this single-center, prospective cohort study blood samples were collected from 55 mothers just before delivery and from their infants at birth and on the 30th day of life (DOL) for 25 hydroxy vitamin D (25OHD) measurements. Vitamin D was initiated in dose of 160IU/kg by parenteral nutrition on the first DOL and oral vitamin D supplementation (400IU/day) was administered when enteral feedings reached 50% of total intake or on the 15thDOL. The median 25OHD levels of the infants were 16.12 (9.14-20.50) in cord blood and 36.32 (31.10-44.44) in venous blood on the 30th DOL (p<0.01). In 98% of the VLBW infants 25OHD reached sufficient levels on the 30th DOL. None of the mothers had sufficient vitamin D levels (25OHD >30ng/mL). Maternal 25OHD levels were correlated with the25OHD levels of the infants in cord blood (r=0.665, p<0.001). There was a significant difference in mean cord 25OHD levels between winter (13.65±5.69ng/mL) and summer seasons (19.58±11.67ng/mL) (p=0.021). No association was found between neonatal morbidity and vitamin D status. The results clearly show that by utilizing the current supplementation protocol, the majority of VLBW infants with deficient/insufficient serum 25OHD levels reached sufficient levels on the 30th DOL. Furthermore, vitamin D levels in mother/infant couples were found to be highly correlated.

SUN-632 The Impact of Vitamin D Deficiency on Pregnancy in Type 1 Diabetes

Vitamin D deficiency during pregnancy may not only impair maternal skeletal preservation and fetal skeletal formation but also influence fetal “imprinting” that may affect chronic disease susceptibility soon after birth as well as later in life.Vitamin D deficiency has been linked to multiple adverse perinatal outcomes in pregnancy including; pre-eclampsia, gestational diabetes, low birth weight, bacterial vaginosis, pre-term delivery and caesarean section. Aim: to assess 25-hydroxy vitamin D (25OHD) concentrations in women with type 1 diabetes (T1DM) during pregnancy, post-delivery and also foetal (cord blood) 25OHD concentrations and to examine relationships between these. The second aim of the study to examine potential relationships between maternal 25OHD and glycosylated haemoglobin (HbA1c) throughout pregnancy. Materials and methods: This was an observational study of 42 pregnant controls without diabetes and 39 pregnant women with T1DM. Maternal serum 25OHD was measured serially throughout the pregnancy and post-delivery. Cord blood 25OHD was measured at delivery. 25OHD was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). HbA1c was measured serially throughout the pregnancy. Control and T1DM groups were not significantly different in age or number of previous miscarriages. As expected, the T1DM group exhibited significantly higher HbA1c levels, and also had significantly increased incidence of preeclampsia (2 of 42 cases (4,8%) in control group and 5 of 39 cases in T1DM group (12,8%)) (p= 0,03). Delivery gestational age was significantly lower for babies born to mothers with T1DM (39,6±1,4 weeks in control group and 37,6±2,1 in T1DM group (p= 0,001).Vitamin D deficiency, defined as 25OHD levels,25 nmol/L, was apparent in both the control and the T1DM groups across the entire pregnancy. Greater than 90% of pregnant women were classified as insufficient at each time-point, regardless of whether they had T1DM or not. This meant that 10% of this pregnant population were at a sufficient level at some point throughout pregnancy. Similar to maternal vitamin D levels, the neonates had a high incidence of 25OHD deficiency at birth. Also were shown correlations between cord blood and maternal vitamin D. Maternal 25OHD correlated positively with cord 25OHD at all 3 trimesters in the T1DM group. Conclusions: in T1DM pregnancy, low vitamin D levels persist throughout gestation and post-delivery; maternal vitamin D levels exhibit a significant negative relationship with HbA1c levels, supporting a potential role for this vitamin in maintaining glycaemic control; larger studies investigating whether low vitamin D levels are a risk factor for preterm delivery and preeclampsia in women with diabetes are needed.

Cord serum vitamin D in a South China birth cohort.

Vitamin D deficiency during pregnancy has been associated with many adverse pregnancy and birth outcomes. Low serum 25-hydroxyvitamin D (25OHD) levels (<30 nmol/L) increases the risk of nutritional rickets. This study aimed to investigate the concentration of cord serum 25OHD in a birth cohort in Guangzhou, China and determine whether maternal lifestyle factors had any effect on these levels. A total of 854 pregnant women giving birth between Dec 2016 and Dec 2017 were recruited to this study. Basic information was obtained from the clinical database. A voluntary retrospective pregnancy lifestyle questionnaire was completed by 388 participants. The concentration of serum 25OHD, calcium, phosphorus, and alkaline phosphatase (ALP) were measured in umbilical cord blood. The mean (SD) of cord serum 25OHD was 44.7 (16.7) nmol/L. The prevalence of cord 25OHD <30 nmol/L was 22.2% and 70.4% had levels <50 nmol/L. The prevalence of vitamin D deficiency is higher in infants born in winter months (31% <30 nmol/L and 76% <50 nmol/L), compared to those born in the summer (12% <30 nmol/L and 64% <50 nmol/L). Infants born to women taking a vitamin D containing supplement had approximately 10 nmol/L higher levels of 25OHD than those who did not supplement their diets. Summer born infants have higher serum 25OHD levels at birth, but there are still infants being born with vitamin D deficiency. Vitamin D containing supplement use during pregnancy was effective in raising cord serum vitamin D levels.

46. The association of umbilical cord blood vitamin D level with children’s arterial stiffness at 7 years of age – HAPO follow up study

We recently reported the effect in utero exposure to maternal hyperglycaemia on children’s risk of abnormal glucose tolerance, obesity and higher blood pressure (BP) at 7 years of age among 962 offspring from the Hyperglycemia and Adverse Pregnancy Outcome study (HAPO) study. To investigate the association of maternal and umbilical cord vitamin D deficiency with children’s cardiometabolic risk at 7 years of age. Mothers who had joined the HAPO study, along with their children were assessed 7 years post-delivery for cardio-metabolic risk, which included carotid-femoral pulse wave velocity (cf-PWV). We performed interim analysis after 566 maternal serum at mid-gestation and 673 umbilical cord serum were analyzed for total vitamin D (25-OHD) levels using a liquid chromatography tandem mass spectrometry method which separates the biological inactive 3-epi-25(OH) D3 from 25(OH) D3, an isomer commonly present in infants. The mean maternal and umbilical cord 25-OHD levels were 58.52 ± 20.68 nmol/L and 41.06 ± 15.04 nmol/L respectively; 38.3% mothers had level below 50 nmol/l (vitamin D deficient). Maternal and umbilical cord 25-OHD significantly varied with the seasons. Umbilical cord, but not maternal, vitamin D level was negatively associated with children’s cf-PWV (unstandardized coefficients = −0.005, p = 0.003), independent of maternal glucose level at pregnancy, maternal hypertensive status at follow-up and other confounders, such as children’s age, sex & height. The association remained significant even adjusting for children’s BP (unstandardized coefficients = −0.004, p = 0.006). The result suggests that in utero vitamin D deficiency may be an independent factor for children’s future vascular risk. Further study is required to explore the association with the children’s Vitamin D status and the underlying mechanism.

A novel inverse association between cord 25-hydroxyvitamin D and leg length in boys up to three years. An Odense Child Cohort study.

Background and aimLong standing vitamin D deficiency in children causes rickets with growth impairment. We investigated whether sub-ischial leg length (SLL) is shorter, and cephalo-caudal length:length (CCL:L) ratio and sitting height:height (SH:H) ratio larger, with lower cord s-25-hydroxyvitamin D (25OHD) in the population-based prospective Odense Child Cohort, Denmark.MethodsWe included healthy singletons born to term with available measures of cord 25OHD and anthropometrics up to three years’ age. Linear regression was stratified by sex a priori and adjusted for maternal ethnicity, pre-pregnancy body mass index and smoking during pregnancy, season of blood sampling and child age.ResultsMedian (IQR) cord 25OHD was 48.0 (34.0–62.4) nmol/L. At mean age 19.1 months, n = 504, mean (SD) SLL was 31.7 (1.7) cm; CCL:L-ratio 0.62 (0.01). At 36.3 months, n = 956, mean SLL was 42.9 (2.0) cm; SH:H-ratio 0.56 (0.01). No participants had rickets. In adjusted analyses, 19-months-old boys had 0.1 cm shorter SLL (p = 0.009) and 0.1% higher CCL:L-ratio (p = 0.04) with every 10 nmol/L increase in cord 25OHD. Similar findings were seen for late pregnancy 25OHD. In the highest cord 25OHD quartile (>60.7 nmol/L), SLL was 0.8 cm shorter (95% C.I.: 1.36;-0.29, linear trend, p = 0.004), and CCL:L-ratio 0.8% higher (95% C.I. 8.0x10-05;0.01, linear trend, p = 0.01), compared to lowest quartile (<30.7 nmol/L). Similar associations with cord 25OHD were observed in 3-year-old boys. No consistent associations between 25OHD and anthropometrics were seen in girls at either age.ConclusionNo leg shortening was found with decreasing cord s-25OHD in a healthy population of infants. A small, yet significant inverse association between cord 25OHD and SLL in boys 1½-3 years warrants further investigations.

A Longitudinal Study of 25-Hydroxy Vitamin D and Parathyroid Hormone Status throughout Pregnancy and Exclusive Lactation in New Zealand Mothers and Their Infants at 45° S.

Vitamin D status and associated metabolism during pregnancy and lactation have been assessed in only a limited number of longitudinal studies, all from the northern hemisphere, with no infant data concurrently reported. Therefore, we aimed to describe longitudinal maternal and infant 25-hydroxy vitamin D (25OHD) and parathyroid hormone (PTH) status during pregnancy and up to 5 months postnatal age, in New Zealand women and their infants living at 45° S latitude. Between September 2011 and June 2013, 126 pregnant women intending to exclusively breastfeed for at least 20 weeks were recruited. Longitudinal data were collected at three time-points spanning pregnancy, and following birth and at 20 weeks postpartum. Vitamin D deficiency (25OHD < 50 nmol/L) was common, found at one or more time-points in 65% and 76% of mothers and their infants, respectively. Mean cord 25OHD was 41 nmol/L, and three infants exhibited secondary hyperparathyroidism by postnatal week 20. Maternal late pregnancy 25OHD (gestation 32–38 weeks) was closely correlated with infant cord 25OHD, r2 = 0.87 (95% CI (Confidence interval) 0.8–0.91), while no correlation was seen between early pregnancy (<20 weeks gestation) maternal and cord 25OHD, r2 = 0.06 (95% CI −0.16–0.28). Among other variables, pregnancy 25OHD status, and therefore infant status at birth, were influenced by season of conception. In conclusion, vitamin D deficiency in women and their infants is very common during pregnancy and lactation in New Zealand at 45° S. These data raise questions regarding the applicability of current pregnancy and lactation policy at this latitude, particularly recommendations relating to first trimester maternal vitamin D screening and targeted supplementation for those “at risk”.

Fetal and Maternal Genetic Variants Influencing Neonatal Vitamin D Status.

Several genetic polymorphisms determine vitamin D status. We aimed to estimate the strength of association of established 25-hydroyxvitamin D (25OHD)-associated variants in the mother and in the fetus, with 25OHD concentration in newborn umbilical cord plasma. We randomly selected 578 mother and child dyads from the prospective Norwegian Mother and Child Cohort study. 25OHD was assayed in maternal samples taken shortly after delivery and in cord samples. We genotyped the mother and child for single nucleotide polymorphisms in or near GC, DHCR7, CYP2R1, and CYP24A1, previously confirmed to be associated with 25OHD, and computed genetic risk score (GRS). The genetic associations were replicated in an independent sample of 594 subjects. Although both fetal and maternal GRS were associated with cord 25OHD, only fetal GRS remained significantly associated with cord 25OHD in a regression model with maternal and fetal GRS simultaneously (1.6 nmol/L per fetal 25OHD-increasing allele; 95% confidence interval, 0.6 to 2.5, P = 0.0001). Two fetal single nucleotide polymorphisms in the GC gene (rs2282679 and rs222040) were the strongest genetic predictors of cord 25OHD [4.0 (2.1 to 5.9) and 3.0 (1.3 to 4.8) nmol/L per fetal allele, P < 0.001], followed by rs12785878 in DHCR7 [2.0 (0.1 to 3.8) nmol/L, P = 0.037]. The independent replication sample gave similar results. With fetal genotype included in a regression model with environmental factors, R2 for cord 25OHD was 0.28. We show that fetal 25OHD-modifying genotype was a stronger predictor of cord 25OHD than corresponding maternal genotype. This raises interesting questions about fetal acquisition and placental transfer of 25OHD.

Pregnancy and cord vitamin D status and symptoms of autism spectrum disorders in toddlers: An Odense child cohort study

IntroductionVitamin D deficiency is widespread globally in pregnant women and is suggested to contribute to offspring risk of symptoms of autism spectrum disorders (ASD), but findings are inconsistent.ObjectivesTo investigate whether low prenatal 25OHD exposure and 25OHD status in early life increase risk of early symptoms of ASD.AimsTo investigate early signs of ASD.MethodsFrom the prospective birth cohort, Odense child cohort (n = 2.549), Denmark, we included singletons with their mothers with available serum concentrations of 25OHD at early pregnancy (n = 1.231), late pregnancy (n = 1.361), and birth (n = 2.082). ASD symptoms were rated by parents on the pervasive developmental problem (PDP) scale of the Child behavior checklist for ages 1½-5 (CBCL 1½-5). Associations between 25OHD and PDP score were analyzed by multiple linear and logistic regression models. A priori included covariates were gestational age, child gender, birth weight, season of birth, parity, parental psychiatric diagnoses, maternal age, smoking habits, alcohol consumption, education level, vitamin D supplementation, and pre-gestational BMI.ResultsMeans (SD) of 25OHD for early pregnancy, late pregnancy, and cord were 65.5 (21.5), 78.7 (27.0), and 47.0 (21.7) nmol/L, respectively. PDP data were obtained at a mean (SD) of 2.7 (0.6) years of age. Data from the regression analyses are pending.ConclusionsIn this well-off cohort with relatively high levels of cord 25OHD, power calculations allows us to detect a true change of 0.02 PDP scores per 10 nmol/L change in 25OHD. Further studies will clarify whether early PDP scores track later ASD diagnosis.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Inverse association between maternal 25OHD level and cord GLP-1/GIP concentrations.

Because vitamin D may have beneficial effects on glucose metabolism in pregnant women with gestational diabetes mellitus, we explored whether maternal 25-hydroxyvitamin D (25OHD) levels in normal pregnancy have association with diabetes-related hormone levels and glycated albumin (GA). A prospective cohort study was performed to collect serum samples from 612 pairs of pregnant women and cord blood of their offspring. Levels of 25OHD and GA in maternal and cord blood were measured by radioimmunoassay and enzyme assay, respectively. Using cord serum, 12 diabetes-related hormones were assayed. Spearman's rank correlation coefficient was used to quantify the strength of association between biomarkers. A prominent association between maternal and cord 25OHD levels (r = 0.76, 95% confidence intervals (CIs): 0.73-0.79, P < 0.0001) and weak association between maternal and cord GA (r = 0.22, 95% CIs: 0.14-0.30, P < 0.0001) were shown. Among the 12 diabetes-related hormones, both maternal and cord 25OHD levels showed prominent negative associations with glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These results suggest that decreased maternal 25OHD may be associated with decreased cord 25OHD and increased cord GLP-1 and GIP levels, which may be involved with the transfer of maternal glucose to the fetus.

Maternal vitamin D status in Type 1 diabetic pregnancy: Impact on neonatal vitamin D status and association with maternal glycaemic control.

1. To examine relationships between 25-hydroxy vitamin D (25OHD) in women with type 1 diabetes (T1DM) during pregnancy, post-delivery and in cord blood. 2. To investigate interactions between maternal body mass index (BMI) and foetal vitamin D status. 3. To examine relationships between maternal 25OHD and glycosylated haemoglobin (HbA1c). An observational study of 52 pregnant controls without diabetes and 65 pregnant women with T1DM in a university teaching hospital. 25OHD was measured by liquid chromatography tandem mass spectrometry. Vitamin D deficiency (25OHD <25nmol/L) was apparent in control and T1DM women in all 3 trimesters. All cord blood 25OHD were <50nmol/L. Maternal 25OHD correlated positively with cord 25OHD at all 3 trimesters in the T1DM group (p=0.02; p<0.001; p<0.001). Cord 25OHD was significantly lower for T1D women classified as obese vs. normal weight at booking [normal weight BMI <25kg/m(2) vs. obese BMI〉30kg/m(2) (nmol/L±SD); 19.93±11.15 vs. 13.73±4.74, p=0.026]. In the T1DM group, HbA1c at booking was significantly negatively correlated with maternal 25OHD at all 3 trimesters (p=0.004; p=0.001; p=0.05). In T1DM pregnancy, low vitamin D levels persist throughout gestation and post-delivery. Cord blood vitamin D levels correlate with those of the mother, and are significantly lower in obese vs normal weight women. Maternal vitamin D levels exhibit a significant negative relationship with HbA1c, supporting a potential role for this vitamin in maintaining glycaemic control.

Vitamin D supplementation and the effects on glucose metabolism during pregnancy: a randomized controlled trial.

Vitamin D deficiency in pregnancy is associated with an increased risk of gestational diabetes mellitus (GDM) and neonatal vitamin D deficiency. We conducted a double-blind, randomized controlled trial of low-dose (LD) versus high-dose (HD) vitamin D supplementation to investigate the effects of vitamin D supplementation on glucose metabolism during pregnancy. Women with plasma 25-hydroxyvitamin D (25OHD) levels <32 ng/mL before 20 weeks' gestation were randomized to oral vitamin D3 at 5,000 IU daily (HD) (n = 89) or the recommended pregnancy dose of 400 IU daily (LD) (n = 90) until delivery. The primary end point was maternal glucose levels on oral glucose tolerance test (OGTT) at 26-28 weeks' gestation. Secondary end points included neonatal 25OHD, obstetric and other neonatal outcomes, and maternal homeostasis model assessment of insulin resistance. Analysis was by intention to treat. There was no difference in maternal glucose levels on OGTT. Twelve LD women (13%) developed GDM versus seven (8%) HD women (P = 0.25). Neonatal cord 25OHD was higher in HD offspring (46 ± 11 vs. 29 ± 12 ng/mL, P < 0.001), and deficiency was more common in LD offspring (24 vs. 10%, P = 0.06). Post hoc analysis in LD women showed an inverse relationship between pretreatment 25OHD and both fasting and 2-h blood glucose level on OGTT (both P < 0.001). Baseline 25OHD remained an independent predictor after multiple regression analysis. HD vitamin D supplementation commencing at a mean of 14 weeks' gestation does not improve glucose levels in pregnancy. However, in women with baseline levels <32 ng/mL, 5,000 IU per day was well tolerated and highly effective at preventing neonatal vitamin D deficiency.

Maternal Vitamin D Status in Type 1 Diabetic Pregnancy: Impact on Neonatal Vitamin D Status and Association with Maternal Glycaemic Control

ObjectiveThe first aim of this study was to assess 25-hydroxy vitamin D (25OHD) concentrations in women with type 1 diabetes (T1DM) during pregnancy, post-delivery and also foetal (cord blood) 25OHD concentrations and to examine relationships between these. The second aim of the study was to investigate potential interactions between maternal body mass index (BMI) and foetal vitamin D status. A further study aim was to examine potential relationships between maternal 25OHD and glycosylated haemoglobin (HbA1c) throughout pregnancy.Research Design and MethodsThis was an observational study of 52 pregnant controls without diabetes and 65 pregnant women with T1DM in a university teaching hospital. Maternal serum 25OHD was measured serially throughout the pregnancy and post-delivery. Cord blood 25OHD was measured at delivery. 25OHD was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS).ResultsVitamin D deficiency (25OHD <25 nmol/L) was apparent in both the T1DM subjects and controls at all 3 pregnancy trimesters. Vitamin D levels in all cord blood were <50 nmol/L. Maternal 25OHD correlated positively with cord 25OHD at all 3 trimesters in the T1DM group (p = 0.02; p<0.001; p<0.001). 25OHD levels within cord blood were significantly lower for women with diabetes classified as obese vs. normal weight at booking [normal weight BMI <25 kg/m2 vs. obese BMI >30 kg/m2 (nmol/L±SD); 19.93±11.15 vs. 13.73±4.74, p = 0.026]. In the T1DM group, HbA1c at booking was significantly negatively correlated with maternal 25OHD at all 3 trimesters (p = 0.004; p = 0.001; p = 0.05).ConclusionIn T1DM pregnancy, low vitamin D levels persist throughout gestation and post-delivery. Cord blood vitamin D levels correlate with those of the mother, and are significantly lower in obese women than in their normal weight counterparts. Maternal vitamin D levels exhibit a significant negative relationship with HbA1c levels, supporting a potential role for this vitamin in maintaining glycaemic control.

Vitamin D supplementation during pregnancy: Effect on neonatal calcium homeostasis

We assessed whether modification of vitamin D nutritional status during the last trimester of pregnancy affects maternal and neonatal calcium homeostasis. At the end of the first trimester, 40 pregnant women were randomly assigned to either of two groups, and blood taken to assess the basal values of Ca, Pi, Mg, iPTH, 25-OHD, and 1,25(OH)2D. From the sixth month on, group 1 (+D) received 1000 IU vitamin D3 daily; group 2 (-D) served as control. At the time of delivery, maternal serum 25-OHD was higher in the +D group (P less than 0.0005). Ca, Pi, iPTH, and 1,25(OH)2D were not affected. At term, venous cord 25-OHD levels were also higher in the +D group (P less than 0.0005), and 1,25(OH)2D levels slightly lower (P less than 0.05), but neither Ca, Pi, nor iPTH differed between the two groups. Serum CaT dropped significantly (P less than 0.002) at 4 days of age in the infants from both groups, although to a lesser extent in these from the +D group (P less than 0.05). Circulating iPTH increased in both groups. Serum 25-OHD remained low in the -D group, and dropped slightly in the +D group; 1,25(OH)2D remained stable during the first 4 days of life in the -D group, and increased in the +D group (P less than 0.001). Our data demonstrate the importance of providing adequate maternal vitamin D stores to ensure better perinatal handling of calcium. This is of particular importance for populations at risk for hypovitaminosis D.