Mark T. Kilbane

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.

Summary 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.

We describe a unique case of hyperphosphatemia associated with a very high bone turnover rate in a 51-year-old postmenopausal woman with undiagnosed anorexia nervosa (AN) who presented with a low-trauma hip fracture. In view of her severely malnourished state, she was not fit for surgery. She was treated according to a refeeding protocol that mandated bed rest. Contrary to expectation, she developed sustained hyperphosphatemia and borderline hypercalcemia. Bone remodelling markers, both resorption and formation, were markedly elevated. Parathyroid hormone (PTH) was low-normal at 1.7 pmol/L, C-terminal fibroblast growth factor 23 (FGF23) was high at 293 RU/ml, but tubular maximum reabsorption of phosphate (TmPO4/GFR) was elevated at 1.93 mmol/L. Denosumab 60 mg was administered that was followed by: rapid normalisation of serum phosphate; normalisation of resorption markers, transient hypocalcaemia with secondary hyperparathyroidism, and normalisation of both TmPO4/GFR and C-terminal FGF23. We speculate that prolonged immobilization as part of AN management led to a high remodelling state followed by hyperphosphatemia and high-normal calcium with appropriate suppression of PTH and that marked hyperphosphatemia and high TmP/GFR despite high FGF23 indicates the necessity of PTH adequacy for excess FGF23 to lower TmP/GFR.

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.

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.

Background Vitamin D status may play a role in the development of atopic diseases due to its action on lung development and immune system development and function. Aims Our objective was to assess whether 25-hydroxyvitamin D (25OHD) levels in maternal blood in pregnancy were associated with atopy in children. Methods We analysed 279 mother-child pairs from the ROLO study conducted in Dublin, Ireland. Serum 25OHD was measured at 13 and 28 weeks of pregnancy. Development of childhood atopy was self-reported by mothers at follow-up appointments at 6 months, 2 years or 5 years. Logistic regression analysis was used to evaluate associations between maternal 25OHD status and development of atopy. Results The mean (SD) 25OHD levels in early and late pregnancy were 41.9 (19.2) nmol/L and 40.2 (21.6) nmol/L, respectively. Maternal 25OHD status in early pregnancy, but not in late pregnancy, was associated with a reduced risk of atopy at 2 years (OR 0.972, CI 0.946–0.999). In early pregnancy, those with serum 25OHD levels < 30 nmol/L compared with those with 25OHD > 50 nmol/L had significantly greater risk of developing atopy at 2 years (OR 4.76, CI 1.38–16.47). Conclusions The development of childhood atopy may be associated with maternal vitamin D deficiency in early pregnancy among a cohort of women at risk of vitamin D deficiency. Further research is required to explore the relationship between vitamin D and atopy, particularly among women with poor vitamin D status, and whether supplementation should be prioritised in early pregnancy to reduce childhood atopy.

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.