No effect of maternal calcium intake and bone resorption during pregnancy on offspring bone mineral density at age 5 years.

Maternal nutrition during pregnancy plays a role in offspring bone health. In a prospective cohort study, offspring bone mineral density at 5 years was not associated with maternal calcium intake or maternal bone resorption during pregnancy. PURPOSE: Suboptimal bone mineral density in childhood can result in osteoporosis later in life. We reported previously that lower calcium intake during pregnancy was associated with higher maternal bone resorption during pregnancy and that lower maternal dietary calcium and higher maternal bone resorption in pregnancy were associated with lower maternal bone mineral density (BMD) 5 years later. The current study sought to investigate the effect of both maternal dietary calcium intake and maternal bone resorption during pregnancy on offspring BMD at 5 years. METHODS: Data collected as part of the ROLO longitudinal cohort study (n = 103, mother-child dyads) were used in the current analysis. ROLO started as a randomised controlled trial of a low glycemic index diet during second pregnancy in women with macrosomia in first pregnancy in order to prevent recurrence of macrosomia. Maternal dietary intakes were assessed using 3-day food diaries completed during each trimester of pregnancy. Bone resorption in early and late pregnancy was calculated through urinary excretion of cross-linked N-telopeptides (uNTX). Offspring whole-body BMD at 5 years was measured using dual-energy X-ray absorptiometry. RESULTS: Offspring BMD at 5 years correlated with offspring body mass index (r = .385; p < .001) and offspring BMD was higher in boys than girls (t = 2.91; p = .004). Offspring BMD at 5 years was not associated with either maternal calcium intake or uNTX during pregnancy, after controlling for offspring body mass index and offspring sex. CONCLUSION: Offspring BMD at 5 years is not associated with either maternal calcium intake or maternal bone resorption during pregnancy.

Interlaboratory comparison of 25-hydroxyvitamin D assays: Vitamin D Standardization Program (VDSP) Intercomparison Study 2 - Part 2 ligand binding assays - impact of 25-hydroxyvitamin D2 and 24R,25-dihydroxyvitamin D3 on assay performance.

An interlaboratory comparison study was conducted by the Vitamin D Standardization Program (VDSP) to assess the performance of ligand binding assays (Part 2) for the determination of serum total 25-hydroxyvitamin D [25(OH)D]. Fifty single-donor samples were assigned target values for concentrations of 25-hydroxyvitamin D2 [25(OH)D2], 25-hydroxyvitamin D3 [25(OH)D3], 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3], and 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] using isotope dilution liquid chromatography-tandem mass spectrometry (ID LC-MS/MS). VDSP Intercomparison Study 2 Part 2 includes results from 17 laboratories using 32 ligand binding assays. Assay performance was evaluated using mean % bias compared to the assigned target values and using linear regression analysis of the test assay mean results and the target values. Only 50% of the ligand binding assays achieved the VDSP criterion of mean % bias ≤ |± 5%|. For the 13 unique ligand binding assays evaluated in this study, only 4 assays were consistently within ± 5% mean bias and 4 assays were consistently outside ± 5% mean bias regardless of the laboratory performing the assay. Based on multivariable regression analysis using the concentrations of individual vitamin D metabolites in the 50 single-donor samples, most assays underestimate 25(OH)D2 and several assays (Abbott, bioMérieux, DiaSorin, IDS-EIA, and IDS-iSYS) may have cross-reactivity from 24R,25(OH)2D3. The results of this interlaboratory study represent the most comprehensive comparison of 25(OH)D ligand binding assays published to date and is the only study to assess the impact of 24R,25(OH)2D3 content using results from a reference measurement procedure.

Assessment of serum total 25-hydroxyvitamin D assays for Vitamin D External Quality Assessment Scheme (DEQAS) materials distributed at ambient and frozen conditions.

The Vitamin D External Quality Assessment Scheme (DEQAS) distributes human serum samples four times per year to over 1000 participants worldwide for the determination of total serum 25-hydroxyvitamin D [25(OH)D)]. These samples are stored at -40 °C prior to distribution and the participants are instructed to store the samples frozen at -20 °C or lower after receipt; however, the samples are shipped to participants at ambient conditions (i.e., no temperature control). To address the question of whether shipment at ambient conditions is sufficient for reliable performance of various 25(OH)D assays, the equivalence of DEQAS human serum samples shipped under frozen and ambient conditions was assessed. As part of a Vitamin D Standardization Program (VDSP) commutability study, two sets of the same nine DEQAS samples were shipped to participants at ambient temperature and frozen on dry ice. Twenty-eight laboratories participated in this study and provided 34 sets of results for the measurement of 25(OH)D using 20 ligand binding assays and 14 liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Equivalence of the assay response for the frozen versus ambient DEQAS samples for each assay was evaluated using multi-level modeling, paired t-tests including a false discovery rate (FDR) approach, and ordinary least squares linear regression analysis of frozen versus ambient results. Using the paired t-test and confirmed by FDR testing, differences in the results for the ambient and frozen samples were found to be statistically significant at p < 0.05 for four assays (DiaSorin, DIAsource, Siemens, and SNIBE prototype). For all 14 LC-MS/MS assays, the differences in the results for the ambient- and frozen-shipped samples were not found to be significant at p < 0.05 indicating that these analytes were stable during shipment at ambient conditions. Even though assay results have been shown to vary considerably among different 25(OH)D assays in other studies, the results of this study also indicate that sample handling/transport conditions may influence 25(OH)D assay response for several assays.

Higher Inflammation Is Associated with Cardiometabolic Phenotype and Biochemical Health in Women with Obesity.

INTRODUCTION: Metabolic or inflammatory markers may predict adverse outcomes in women with obesity. We sought to describe metabolic-obesity phenotypes of women using novel staging tools and investigate relationships with inflammation. METHODS: In a cross-sectional study, we collected fasting blood samples from sixty-four females with body mass index (BMI) ≥28 kg/m2. Participants were classified as metabolically healthy or metabolically unhealthy obesity (MUO) using the cardiometabolic disease staging system (CMDS) and Edmonton obesity staging system (EOSS). Data were analyzed using independent sample t tests, Pearson's correlations, and multiple logistic regression. RESULTS: Mean (SD) age was 40.2 (9.3) years with median (IQR) BMI 31.8 (30.3-35.7) kg/m2. The prevalence of MUO was 46.9% and 81.3% using CMDS and EOSS criteria, respectively. Women with raised CMDS scores had higher C3 (1.34 [0.20] vs. 1.18 [0.15], p = 0.001) and C-reactive protein (CRP) (2.89 [1.31-7.61] vs. 1.39 [0.74-3.60], p = 0.034). C3 correlated with insulin (r = 0.52), hemoglobin A1c (r = 0.37), and C-peptide (r = 0.58), all p < 0.05. C3 above the median (>1.23 g/L) increased odds of raised CMDS score, when controlled for age, BMI, ethnicity, and smoking (OR = 6.56, 95% CI: 1.63, 26.47, p = 0.008). CONCLUSION: The prevalence of MUO was lower using CMDS than EOSS. C3 and CRP may be useful clinical biomarkers of risk or treatment targets in women with obesity.

The effects of acute hyponatraemia on bone turnover in patients with subarachnoid haemorrhage: A preliminary report.

CONTEXT: Animal data and cross-sectional human studies have established that chronic hyponatraemia predisposes to osteoporosis; the effects of acute hyponatraemia on bone turnover have not been determined. Our objective was to test the hypothesis that acute hyponatraemia leads to dynamic effects on bone turnover. DESIGN: A prospective observational pilot study. METHODS: Bone turnover markers [C-terminal crosslinking telopeptide of type 1 collagen (CTX-1), N-propeptide of type 1 collagen (P1NP) and osteocalcin] were measured prospectively over one week in 22 eunatraemic patients with subarachnoid haemorrhage. Patients treated with glucocorticoids were excluded. RESULTS: Eight patients developed acute hyponatraemia, median nadir plasma sodium concentration 131 mmol/L (IQR 128-132), and 14 remained eunatraemic, nadir plasma sodium concentration 136 mmol/L (IQR 133-137). Significant main effects of hyponatraemia were found for P1NP (p = .02) and P1NP:CTX-1 ratio (p = .02), both fell in patients with acute hyponatraemia, with significant interaction between hyponatraemia and time from baseline for P1NP (p = .02). Significant main effects of time from baseline (p < .001) but not hyponatraemia (p = .07) were found for osteocalcin. For CTX-1, significant main effects of time from baseline (p = .001) but not hyponatraemia (p = .65) were found. There was a positive correlation between change in P1NP:CTX-1 ratio and nadir plasma sodium concentration, r = +.43, p = .04. Median serum cortisol (measured on days 1, 3 and 7) was higher in the hyponatraemia group than in those who remained eunatraemic, 545 nmol/L (IQR 373-778) versus 444 nmol/L (IQR 379-542) p = .03. CONCLUSION: These data suggest that acute mild hyponatraemia is associated with a reduction in bone formation activity.

Assessment of serum total 25-hydroxyvitamin D assay commutability of Standard Reference Materials and College of American Pathologists Accuracy-Based Vitamin D (ABVD) Scheme and Vitamin D External Quality Assessment Scheme (DEQAS) materials: Vitamin D Standardization Program (VDSP) Commutability Study 2.

An interlaboratory study was conducted through the Vitamin D Standardization Program (VDSP) to assess commutability of Standard Reference Materials® (SRMs) and proficiency testing/external quality assessment (PT/EQA) samples for determination of serum total 25-hydroxyvitamin D [25(OH)D] using ligand binding assays and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A set of 50 single-donor serum samples were assigned target values for 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] using reference measurement procedures (RMPs). SRM and PT/EQA samples evaluated included SRM 972a (four levels), SRM 2973, six College of American Pathologists (CAP) Accuracy-Based Vitamin D (ABVD) samples, and nine Vitamin D External Quality Assessment Scheme (DEQAS) samples. Results were received from 28 different laboratories using 20 ligand binding assays and 14 LC-MS/MS methods. Using the test assay results for total serum 25(OH)D (i.e., the sum of 25(OH)D2 and 25(OH)D3) determined for the single-donor samples and the RMP target values, the linear regression and 95% prediction intervals (PIs) were calculated. Using a subset of 42 samples that had concentrations of 25(OH)D2 below 30 nmol/L, one or more of the SRM and PT/EQA samples with high concentrations of 25(OH)D2 were deemed non-commutable using 5 of 11 unique ligand binding assays. SRM 972a (level 4), which has high exogenous concentration of 3-epi-25(OH)D3, was deemed non-commutable for 50% of the LC-MS/MS assays.

The impact of diet, body composition, and physical activity on child bone mineral density at five years of age-findings from the ROLO Kids Study.

Bone health is extremely important in early childhood because children with low bone mineral density (BMD) are at a greater risk of bone fractures. While physical activity and intake of both calcium and vitamin D benefit BMD in older children, there is limited research on the determinants of good bone health in early childhood. The aim of this cross-sectional study was to investigate the impact of diet, physical activity, and body composition on BMD at five years of age. Dietary intakes and physical activity levels were measured through questionnaires. Whole body BMD was measured by dual-energy X-ray absorptiometry in 102 children. Child weight, height, circumferences, skinfolds and serum 25-hydroxyvitamin D (25OHD) concentrations were assessed. There was no association between BMD and dietary calcium, dietary vitamin D, 25OHD, physical activity, or sedentary behaviour. Several measures of body composition were significantly positively associated with BMD; however, neither fat mass nor lean body mass was associated with BMD.Conclusion: Although we found no association between self-reported dietary and lifestyle factors and bone health in early years, increased body size was linked with higher BMD. These findings are important as identifying modifiable factors that can improve bone health at a young age is of utmost importance.What is Known:• Bone health is extremely important in early childhood, as children with low bone mineral density (BMD) are at greater risk of bone fractures.• Physical activity has been found to be beneficial for bone health in adolescents, and body composition has also been associated with BMD in teenage years.• Limited research on the determinants of good bone health in early childhood.What is New:• No association between self-reported lifestyle and dietary factors with bone health in early childhood.• Increased body size was associated with higher BMD at five years of age.

Blood pressure in pregnancy-A stress test for hypertension? Five-year, prospective, follow-up of the ROLO study.

OBJECTIVE: To investigate whether maternal blood pressure (BP) below the diagnostic criteria of hypertensive disorders of pregnancy (HDP) is associated with maternal BP 5 years later. DESIGN: Prospective, observational study. SETTING: Dublin, Ireland (2007-2011). SAMPLE: Three hundred twenty-nine women from the ROLO study (Randomized cOntrol trial of LOw glycaemic index diet to prevent the recurrence of macrosomia). METHODS: Maternal BP measurements were taken during pregnancy (13, 28 and 34 weeks' gestation and day 1 postpartum) and at the 5-year follow-up. Systolic BP (SBP) and diastolic BP (DBP) were categorized as normal (SBP < 120 and DBP < 80 mm Hg), elevated (SBP 120-129 and DBP < 80 mm Hg), HTN stage 1 (SBP 130-139 or DBP 80-89 mm Hg) or HTN stage 2 (SBP ≥ 140 or DBP ≥ 90 mm Hg) at each timepoint. MAIN OUTCOME MEASURES: Maternal blood pressure at the 5-year follow-up. RESULTS: Women with elevated BP at 28 and 34 weeks' gestation had 2.68 (95% CI: 1.36-5.26) and 2.45-fold (95% CI: 1.22-4.95) increased odds of HTN stage 1 respectively, at the 5-year follow-up, compared to those with normal BP in pregnancy. CONCLUSION: Elevated BP at 28 and 34 weeks' gestation was associated with an increased risk of HTN stage 1 at 5 years later. Thus, raised BP, below the diagnostic criteria of HDP, could be flagged for follow-up postpartum.

Congenital hypophosphataemia in adults: determinants of bone turnover markers and amelioration of renal phosphate wasting following total parathyroidectomy.

Congenital hypophosphataemia (CH) is a collection of disorders that cause defective bone mineralisation manifesting with rickets in childhood and osteomalacia in adulthood. Bone turnover markers (BTMs) are surrogate measures of metabolic bone disease severity. We explored the utility of BTMs in 27 adults with CH: 23 had X-linked hypophosphataemia (XLH), of whom 2 were hypoparathyroid post-total parathyroidectomy (PTx); 2 had autosomal dominant hypophosphataemic rickets (ADHR), and 2 had none of the known mutations. We measured the renal tubular maximum reabsorption rate of phosphate (TmP/GFR), C-terminal fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), ionised calcium, 1,25-dihydroxyvitamin D [1,25(OH)2D], and a panel of BTMs: serum bone-specific alkaline phosphatase (bone ALP), osteocalcin (Oc), total procollagen type I amino-terminal propeptide (PINP), and carboxy-terminal telopeptide of type I collagen (CTX); and urine amino-terminal telopeptides of type I collagen (uNTX). After excluding 2 patients with XLH and PTx, the frequency of abnormal elevation in BTMs was: bone ALP (96%); CTX (72%); PINP (52%); uNTX (48%); Oc (28%). The strongest association with bone ALP was TmP/GFR. Those patients receiving phosphate supplements and alfacalcidol had significant elevation in CTX. The 2 patients with XLH and PTx had normalisation of TmP/GFR and near normalisation of BTMs post-operatively, despite marked elevation in both C-terminal and intact FGF23. In conclusion, BTMs in our CH patients indicated that most have abnormalities consistent with osteomalacia and many have mild secondary hyperparathyroidism; and the normalisation of TmP/GFR after total PTx in 2 cases of XLH remains unexplained, but possible causes are speculated.

Calcium intake in winter pregnancy attenuates impact of vitamin D inadequacy on urine NTX, a marker of bone resorption.

PURPOSE: Pregnancy is characterised by increased bone turnover, but high bone turnover with resorption exceeding formation may lead to negative maternal bone remodelling. Recent studies are conflicting regarding the effect of calcium on skeletal health in pregnancy. The aim of this study was to examine the seasonal effect of serum 25-hydroxyvitamin D (25OHD) and dietary calcium on a marker of bone resorption. METHODS: This was prospective study of 205 pregnant women [two cohorts; early pregnancy at 13 weeks (n = 96), and late pregnancy at 28 weeks (n = 109)]. Serum 25OHD and urine cross-linked N-telopeptides of type I collagen (uNTX) were measured at both time points. Intakes of vitamin D and calcium were recorded using 3-day food diaries at each trimester. RESULTS: Compared to summer pregnancies, winter pregnancies had significantly lower 25OHD and significantly higher uNTX. Higher calcium intakes were negatively correlated with uNTX in winter, but not summer. In late pregnancy, compared to those reporting calcium intakes ≥1000 mg/day, intakes of <1000 mg/day were associated with a greater increase in uNTX in winter pregnancies than in summer (41.8 vs. 0.9%). Increasing calcium intake in winter by 200 mg/day predicted a 13.3% reduction in late pregnancy uNTX. CONCLUSIONS: In late pregnancy, during winter months when 25OHD is inadequate, intakes of dietary calcium <1000 mg/day were associated with significantly increased bone resorption (uNTX). Additional dietary calcium is associated with reduced bone resorption in late pregnancy, with greater effect observed in winter. Further research regarding optimal dietary calcium and 25OHD in pregnancy is required, particularly for women gestating through winter.

Striking difference of periarticular bone density change in early psoriatic arthritis and rheumatoid arthritis following anti-rheumatic treatment as measured by digital X-ray radiogrammetry.

OBJECTIVES: To examine changes in hand BMD as measured by digital X-ray radiogrammetry (DXR-BMD) in early PsA compared with RA patients prior to and 3 and 12 months after introducing an antirheumatic treatment. Further, to identify predictors for hand bone loss at the time of disease presentation. METHODS: Recent-onset, active, treatment-naïve patients were recruited. Clinical assessment, hand X-rays and DXR were obtained at 0, 3 and 12 months. Mean DXR-BMD for both hands and changes in DXR-BMD (mg/cm(2)/month) were compared between the two groups. We compared baseline disease characteristics of patients with normal hand DXR-BMD with those with bone loss. Logistic regression analyses were performed to identify predictors of hand BMD loss. RESULTS: A total of 64 patients were included. Hand DXR-BMD decreased in RA throughout the study (P = 0.043). Changes in periarticular bone density over 12 months differed between PsA and RA (P = 0.001). Hand bone loss at 3 months was associated with elevated BMI [odds ratio (OR) = 3.59, P = 0.041] and heavier alcohol intake (OR = 1.13, P = 0.035). Diagnosis of RA (OR = 57.48, P = 0.008), heavier alcohol intake (OR = 1.27, P = 0.012) and higher swollen joint count (SJC28) (OR = 1.5, P = 0.036) were independent predictors for hand bone loss in the first year. CONCLUSION: Following treatment, we found ongoing hand bone loss in RA and unchanged periarticular bone density in PsA, supporting the hypothesis that different pathomechanisms are involved in hand bone remodelling in PsA. Presence of RA, heavier alcohol intake and higher SJC were identified as independent predictors for hand bone loss over 1 year.

An association between abnormal bone turnover, systemic inflammation, and osteoporosis in patients with chronic pancreatitis: a case-matched study.

INTRODUCTION: Because of deteriorating exocrine function, malabsorption renders chronic pancreatitis (CP) patients at risk of osteoporosis and fracture. However, the pathogenesis of low bone mineral density (BMD) has not been characterized. We hypothesized that bone turnover is elevated in CP, and we sought to investigate an association between bone metabolism and systemic inflammation. METHODS: Twenty-nine CP patients and twenty-nine matched controls were recruited. Bone-turnover markers procollagen 1 amino-terminal propeptide (P1NP), OC (osteocalcin; bone formation markers), and carboxy-terminal telopeptide of type I collagen (CTX-I; bone resorption marker) were measured along with vitamin D (25-hydroxyvitamin D, 25OHD), parathyroid hormone (PTH), interleukin 6 (IL-6), high-sensitivity (hs) C-reactive protein (CRP), and sex/thyroid hormones. BMD was measured by dual-energy X-ray absorptiometry. Smoking status was noted. RESULTS: Of the CP patients, 31% had osteoporosis and 44.8% osteopenia (controls: 6.9 and 51.7%, respectively; P=0.019). BMD was lower for patients at the lumbar spine (P=0.014) and femoral neck (P=0.029). Patients had elevated bone formation (P1NP (P=0.0068), OC (P=0.033)) and bone resportion (CTX-I (P=0.016)) compared with controls. Patients had lower 25OHD compared with controls (P=0.0126) and higher inflammatory markers (hsCRP, P=0.0013). Sex and thyroid hormone levels were similar. Patients with lowest 25OHD levels had highest P1NP. In a multivariable model, age, PTH, and smoking were predictive of 25OHD. Patients with osteoporosis had higher P1NP, PTH, and IL-6 and lower 25OHD. Using analysis of variance, inflammation (hsCRP) was highest in those with lowest 25OHD and lowest BMD. CONCLUSIONS: For the first time, bone turnover was shown to be abnormal in CP, and importantly, an association between low 25-OHD, smoking, and systematic inflammation was identified. Moreover, those with osteoporosis had the highest systemic inflammation. Together these factors provide an avenue for potential modification of risk factors, which may ultimately reduce bone loss and avert fractures in this group.

The Association of Vitamin D Status with Acute Respiratory Morbidity in Preterm Infants.

OBJECTIVE: To assess the association between serum 25-hydroxyvitamin D (25OHD) levels and outcomes in preterm infants (<32 weeks gestation). STUDY DESIGN: Serum 25OHD was measured in mothers and their infants within 24 hours of birth, before the start of enteral vitamin D supplementation, and at discharge from the neonatal intensive care unit. We evaluated the associations between vitamin D status and various early preterm outcomes. RESULTS: Ninety-four preterm infants and their mothers were included; 92% of the infants had a 25OHD level≤50 nmol/L (20 ng/mL), and 64% had a 25OHD level<30 nmol/L (12 ng/mL). A low 25OHD level (<30 nmol/L) in preterm infants at birth was associated with increased oxygen requirement (P=.008), increased duration of intermittent positive-pressure ventilation during resuscitation at delivery (P=.032), and greater need for assisted ventilation (P=.013). CONCLUSION: We observed a high prevalence of low 25OHD (<30 nmol/L), and found an association between vitamin D status and acute respiratory morbidity in preterm infants after birth.

Inadequate vitamin D levels are associated with culture positive sepsis and poor outcomes in paediatric intensive care.

AIM: This study aimed to assess vitamin D status, and its determinants, in paediatric patients with suspected sepsis who were admitted to a paediatric intensive care unit (PICU). We also investigated the association between vitamin D status and clinical outcomes. METHODS: Serum 25-hydroxy vitamin D (25OHD) and clinical determinants were prospectively assessed in children with suspected sepsis (<12 years old) admitted to the PICU. The relationship between 25OHD and clinical outcomes was evaluated. Vitamin D status was also assessed in control children of a similar age. RESULTS: We enrolled 120 children with suspected sepsis admitted to the PICU and 30 paediatric controls. 25OHD was <50 nmol/L in 59% of the children admitted to the PICU and 25OHD was lower than in the controls (47 ± 29 vs 66 ± 26 nmol/L, p < 0.001). After adjusting for potential confounders, 25OHD was strongly associated with culture positive sepsis (p < 0.001), the paediatric index of mortality (p = 0.026) and the duration of mechanical ventilation (p = 0.008). There was a negative correlation between 25OHD and C-reactive protein (CRP): each 0.1% decrease in 25OHD increased CRP (p = 0.04). CONCLUSION: Children admitted to the PICU with suspected sepsis had lower 25OHD than controls and inadequate 25OHD status was associated with confirmed sepsis and poor outcomes.

Vitamin D nutritional status in preterm infants and response to supplementation.

Little is known about vitamin D status in preterm infants and their response to supplementation. To investigate this, we assessed serum 25-hydroxyvitamin D (25OHD) levels using RIA in a consecutive sample of stable preterm very low birth weight (VLBW) infants (born ≤ 32 weeks gestation or birth weight ≤ 1·5 kg), and we explored associated factors. Serum 25OHD level was first assessed once infants were tolerating feeds (n 274). If this first 25OHD level was below 50 nmol/l (20 ng/ml), which is the level associated with covering requirements in terms of skeletal health in the majority, then we recommended prolonged augmented vitamin D intake ( ≥ 10 µg (400 IU) daily) from a combination of fortified feeds and vitamin supplements and follow-up re-assessment at approximately 6 weeks corrected age (n 148). The first assessment, conducted at a median for chronological age of 18 (interquartile range (IQR) 11-28) d, found that 78 % had serum 25OHD levels below 50 nmol/l. Multivariable analysis demonstrated that the determinants of serum 25OHD levels were duration of vitamin D supplementation and gestational age at birth (r 2 0·215; P< 0·001). At follow-up, after a median of 104 (IQR 78-127) d, 87 % achieved levels ≥ 50 nmol/l and 8 % had levels >125 nmol/l, a level associated with potential risk of harm. We conclude that low 25OHD levels are an issue for preterm VLBW infants, warranting early nutritional intervention. In infants with serum 25OHD levels < 50 nmol/l, a vitamin D intake of ≥ 10 µg (400 IU) daily achieves target levels in the majority; however, further work is needed to determine the exact dose to safely meet target levels without overcorrection.

The impact of macrosomia on cardiometabolic health in preteens: findings from the ROLO longitudinal birth cohort study.

BACKGROUND: Macrosomia (birthweight ≥ 4 kg or ≥ 4.5 kg) is strongly associated with a predisposition to childhood obesity, which in turn is linked with adverse cardiometabolic health. Despite this, there is a lack of longitudinal investigation on the impact of high birthweight on cardiometabolic outcomes in youth. The preteen period represents an important window of opportunity to further explore this link, to potentially prevent cardiometabolic profiles worsening during puberty. METHODS: This is a secondary analysis of 9-11-year-olds (n = 405) born to mothers in the ROLO longitudinal birth cohort study, who previously delivered an infant with macrosomia. Preteens were dichotomised into those born with and without macrosomia, using two common cut-off criteria (birthweight ≥ 4 kg (n = 208) and < 4 kg; ≥ 4.5 kg (n = 65) and < 4.5 kg). Cardiometabolic health was assessed using anthropometry, dual-energy x-ray absorptiometry, blood pressure, heart rate, cardiorespiratory endurance (20-m shuttle run test), and non-fasting serum biomarkers for a subgroup (n = 213). Statistical comparisons between the two groups were explored using independent t-tests, Mann-Whitney U tests, and Chi-square tests. Crude and adjusted linear regression models investigated associations between macrosomia and preteen cardiometabolic outcomes. RESULTS: In total, 29.3% (n = 119) of preteens had overweight/obesity based on their BMI z-score. Preteens born ≥ 4 kg had lower median (IQR) C3 concentrations (1.38 (1.22, 1.52) g/L vs. 1.4 (1.26, 1.6) g/L, p = 0.043) and lower median (IQR) ICAM-1 concentrations (345.39 (290.34, 394.91) ng/mL vs. 387.44 (312.91, 441.83) ng/mL, p = 0.040), than those born < 4 kg. Those born ≥ 4.5 kg had higher mean (SD) BMI z-scores (0.71 (0.99) vs. 0.36 (1.09), p = 0.016), and higher median (IQR) lean mass (24.76 (23.28, 28.51) kg vs. 23.87 (21.9, 26.79) kg, p = 0.021), than those born < 4.5 kg. Adjusted linear regression analyses revealed birthweight ≥ 4 kg was negatively associated with C3 concentration (g/L) (B = - 0.095, 95% CI = - 0.162, - 0.029, p = 0.005) and birthweight ≥ 4.5 kg was positively associated with weight z-score (B = 0.325, 95% CI = 0.018, 0.633, p = 0.038), height z-score (B = 0.391, 95% CI = 0.079, 0.703, p = 0.014), lean mass (kg) (B = 1.353, 95% CI = 0.264, 2.442, p = 0.015) and cardiorespiratory endurance (B = 0.407, 95% CI = 0.006, 0.808, p = 0.047). CONCLUSION: This study found no strong evidence to suggest that macrosomia is associated with adverse preteen cardiometabolic health. Macrosomia alone may not be a long-term cardiometabolic risk factor. Trial registration ISRCTN54392969 registered at  www.isrctn.com .

N-glycans from serum IgG and total serum glycoproteins specific for endometriosis.

Endometriosis is a chronic inflammatory gynaecological disease characterized by the growth of endometrial tissue outside the uterine cavity. There are currently no definitive non-invasive diagnostic tools. Glycosylation is the most common posttranslational modification of proteins and altered glycosylation has been found in many diseases, including chronic inflammatory conditions and cancer. Sialylation and galactosylation on serum IgG have previously been found to be altered in endometriosis and serum sialylation changed after Zoladex (Goserelin Acetate) therapy. Using IgG and whole serum glycoproteins, we investigated N-glycosylation in two clinical cohorts of women with and without endometriosis. PNGase F-digested serum samples were fluorescently labelled and N-glycans were profiled by ultra-performance liquid chromatography. Clinical data was collected to link glycomic findings with metabolic and hormonal profiles. Total serum glycoprotein and IgG glycosylation differed in patients with endometriosis compared to control cases. The most significantly altered was glycan peak 3 from IgG, containing bisected biantennary glycans, which was decreased in the endometriosis cohorts (p = 0.0000005-0.018). In conclusion, this is the first pilot study to identify changes in N-glycans from whole serum glycoproteins associated with endometriosis. A larger validation study is now warranted and such studies should include the follow-up of surgically and pharmacologically treated patients.

COVID-19 pandemic and vitamin D: rising trends in status and in daily amounts of vitamin D provided by supplements.

OBJECTIVES: Since the onset of the COVID-19 pandemic in 2020, there have been plausible suggestions about the need to augment vitamin D intake by supplementation in order to prevent SARS-CoV2 infection and reduce mortality. Some groups have advocated supplementation for all adults, but governmental agencies have advocated targeted supplementation. We sought to explore the effect of the COVID-19 pandemic on both vitamin D status and on the dose of new-to-market vitamin D supplements. SETTING: University hospital, Dublin, Ireland. PARTICIPANTS: Laboratory-based samples of circulating 25-hydroxyvitamin D (25OHD) (n=100 505). PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes: comparing yearly average 25OHD prior to the pandemic (April 2019 to March 2020) with during the pandemic (April 2020 to March 2021) and comparing the dose of new-to-market vitamin D supplements between 2017 and 2021 (n=2689). SECONDARY OUTCOME: comparing prevalence of vitamin D deficiency and vitamin D excess during the two time periods. RESULTS: The average yearly serum 25OHD measurement increased by 2.8 nmol/L (61.4, 95% CI 61.5 to 61.7 vs 58.6, 95% CI 58.4 to 58.9, p<0.001), which was almost threefold higher than two similar trend analyses that we conducted between 1993 and 2016. There was a lower prevalence of low 25OHD and a higher prevalence of high 25OHD. The dose of new-to-market vitamin D supplements was higher in the years 2020-2021 compared with the years 2017-2019 (p<0.001). CONCLUSIONS: We showed significant increases in serum 25OHD and in the dose of new-to-market vitamin D supplements. The frequency of low vitamin D status reduced indicating benefit, but the frequency of vitamin D excess increased indicating risk of harm. Rather than a blanket recommendation about vitamin D supplementation for all adults, we recommend a targeted approach of supplementation within current governmental guidelines to at-risk groups and cautioning consumers about adverse effects of high dose supplements on the market.

Renal Phosphate Handling: Independent Effects of Circulating FGF23, PTH, and Calcium.

Excess fibroblast growth factor 23 (FGF23), excess PTH, and an increase in extracellular calcium cause hypophosphatemia by lowering the maximum renal phosphate reabsorption threshold (TmP/GFR). We recently reported two cases of X-linked hypophosphatemia (XLH) with severe tertiary hyperparathyroidism who had normalization of TmP/GFR upon being rendered hypoparathyroid following total parathyroidectomy, despite marked excess in both C-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23). We explored the effects of FGF23, PTH, and calcium on TmP/GFR in a cross-sectional study (n = 74) across a spectrum of clinical cases with abnormalities in TmP/GFR, PTH, and FGF23. This comprised three groups: FGF23-dependent hypophosphatemia (n = 27), hypoparathyroidism (HOPT; n = 17), and chronic kidney disease (n = 30). Measurements included TmP/GFR, cFGF23, PTH, ionized calcium, vitamin D metabolites, and bone turnover markers. The combined effect of cFGF23, PTH, and ionized calcium on TmP/GFR was modeled using hierarchical multiple regression and was probed by moderation analysis with PROCESS. Modeling analysis showed independent effects on TmP/GFR by cFGF23, PTH, and ionized calcium in conjunction with a weak but significant effect of the interaction term for PTH and FGF23; probing showed that the effect was most prominent during PTH deficiency. Teriparatide 20 µg daily was self-administered for 28 days by one case of X-linked hypophosphatemia with hypoparathyroidism (XLH-HOPT) to assess the response of TmP/GFR, cFGF23, iFGF23, nephrogenous cyclic adenosine monophosphate (NcAMP), vitamin D metabolites, and bone turnover markers. After 28 days, TmP/GFR was lowered from 1.10 mmol/L to 0.48 mmol/L; this was accompanied by increases in NcAMP, ionized calcium, and bone turnover markers. In conclusion, the effect of FGF23 excess on TmP/GFR is altered by PTH such that the effect is ameliorated by hypoparathyroidism and the effect is augmented by hyperparathyroidism. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

No effect of calcium and vitamin D intake on maternal blood pressure in a healthy pregnant population.

OBJECTIVES: Clinical studies have reported an inverse relationship between calcium and vitamin D intake and hypertensive disorders of pregnancy (HDP). The aim of this study was to investigate if there was an association between calcium/vitamin D intake, and vitamin D (25OHD) status, and maternal blood pressure (BP), during pregnancy and at 5-year follow-up. STUDY DESIGN: This was an observational study of 415 women who participated in the ROLO (Randomised cOntrolled trial of LOw glycaemic index diet for the prevention of recurrence of macrosomia) study. Maternal BP measurements were taken during each trimester and at 5-year follow-up. Calcium and vitamin D intake were determined at each trimester and 25OHD was measured in early and late pregnancy. RESULTS: Over two-thirds of the cohort were vitamin D sufficient (25OHD > 30 nmol/L) and had adequate calcium intake (>750 mg/day). There was no correlation between calcium intake or vitamin D intake and maternal BP in trimester 1 to 3 or at 5-year follow-up. Vitamin D status at 13 weeks' gestation negatively correlated with mean arterial pressure in trimester 1 (r = -0.152, p = 0.044). There was no correlation however between 25OHD at 28 weeks' gestation and BP at 28 or 34 weeks' gestation or 25OHD and BP at 5-year follow-up. CONCLUSIONS: In a healthy population of women with adequate calcium and vitamin D intake, no clinically significant correlation existed between calcium and vitamin D and maternal BP.