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Abstract 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

Abstract 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.

Tumor-induced osteomalacia (TIO) is an ultrarare disorder that is caused by renal phosphate wasting due to uncontrolled tumoral production of fibroblast growth factor 23 (FGF23) from phosphaturic mesenchymal tumors. Surgical removal of the tumor is curative. There is limited information on the biochemical changes in mineral metabolism and bone remodeling activity after surgery, but it is reported that surgery is followed by a hungry bone syndrome (HBS) with hypocalcemia and secondary hyperparathyroidism. We report the biochemical response to surgery in two patients, who presented with severe TIO, as manifested by proximal myopathy, multiple stress fractures, high FGF23, low serum phosphate, low maximum renal phosphate reabsorption threshold (TmP/GFR), and low 1,25-dihydroxy-vitamin D (1,25(OH)2D). Prior to surgery, both patients developed secondary hyperparathyroidism and one case had progressed to tertiary hyperparathyroidism. After surgery there was normalization of FGF23, TmP/GFR, and phosphate. High 1,25(OH)2D was recorded. One patient had hypocalcaemia and worsening secondary hyperparathyroidism consistent with HBS; the other patient did not have hypocalcemia but had worsening tertiary hyperparathyroidism that only resolved with cinacalcet. There was a marked increase in bone remodeling markers, both resorption and formation, consistent with a high bone turnover state. There was a different pattern of change in bone specific alkaline phosphatase, reflecting healing of osteomalacia. Biochemical monitoring in the post-surgical management of TIO is warranted for guiding adjustments in medical intervention, both short-term and long-term. Future use of burosumab prior to surgery for TIO may ameliorate the immediate post-surgery effects.

Abstract Background Vitamin D status and season are intrinsically linked, and both have been proposed to be associated with glucose homeostasis in pregnancy, with conflicting results. We aimed to determine if exposure to winter and low maternal 25 hydroxyvitamin D (25OHD) in early pregnancy were associated with maternal glucose metabolism. Methods This is a secondary data analysis of 334 pregnant women enrolled in the ROLO study, Dublin. Serum 25OHD, fasting glucose, insulin and insulin resistance (HOMA-IR) were measured in early (12 weeks’ gestation) and late pregnancy (28 weeks’ gestation). Season of first antenatal visit was categorised as extended winter (November–April) or extended summer (May–October). Multiple linear regression models, adjusted for confounders, were used for analysis. Results Those who attended their first antenatal visit in extended winter had lower 25OHD compared to extended summer (32.9 nmol/L vs. 44.1 nmol/L, P

Abstract Background Vitamin D status in pregnancy and offspring bone health effects are well established, yet limited knowledge exists on the effect of maternal vitamin D status on offspring size/adiposity. This study examines the association of early (13 weeks), late (28 weeks) pregnancy and neonatal (umbilical) 25-hydroxyvitamin D (25OHD) on offspring size/adiposity. Methods This analysis included mother-infant pairs from the ROLO study at birth (n = 292), 6–9 months (n = 160) and 2–2.5 years (n = 287) postpartum. Results Using Institute of Medicine 2011 Report criteria, 30% of women in early pregnancy and 38% in late pregnancy were at risk of vitamin D deficiency (25OHD

Abstract Endometriosis is a chronic systemic disease, which results in endometrial-type tissue growing outside the uterus, and affects approximately 10% of reproductive-aged women worldwide. Its aetiology is poorly understood, and there is currently no long-term cure. Development and persistence of the disease depend on several coexisting factors including the vaginal microbiome. However, the role played by this important entity in endometriosis and its systemic involvement is not fully understood. Here, we investigated the vaginal microbiota, the serum and urine glycome, and antibody glycosylation in endometriosis patients. We reveal an endometriosis-specific vaginal microbiota in patients, being distinct from that present in a control group. Endometriosis patients were typified by a loss of the dominant Lactobacillus species, i.e. Lactobacillus iners, increased bacterial diversity and the presence of species such as Anaerococcus senegalensis, Prevotella jejuni, Porphyromonas bennonis and Anaerococcus octavius. The presence of trigalactosylated and triantennary serum glycans and urine core fucosylated mono-antennary glycans from IgG correlated with the vaginal presence of the bacterium A. senegalensis in endometriosis patients. Urine glycans did not differ in endometriosis, but urine IgG identified four novel sulfated glycans differing from serum IgG indicating functional relevance. Our findings contribute to understanding the relationships between the vaginal microbiota and the serum and urine glycome on the one hand, and endometriosis on the other. Further functional studies are warranted.

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

ABSTRACT 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.