Blood pressure in 3-year-old girls associates inversely with umbilical cord serum 25-hydroxyvitamin D: an Odense Child Cohort study

Background: Low foetal vitamin D status may be associated with higher blood pressure (BP) in later life. Objective: To examine whether serum 25-hydroxyvitamin D2+3 (s-25OHD) in cord and pregnancy associates with systolic and diastolic BP (SBP; DBP) in children up to 3 years of age. Design: Prospective, population-based cohort study. Methods: We included 1594 singletons from the Odense Child Cohort with available cord s-25OHD and BP data at median age 3.7 months (48% girls), 18.9 months (44% girls) or 3 years (48% girls). Maternal s-25OHD was also assessed at gestational ages 12 and 29 weeks. Multiple regression models were stratified by sex a priori and adjusted for maternal educational level, season of birth and child height, weight and age. Results: In 3-year-old girls, SBP decreased with −0.7 mmHg (95% CI −1.1; −0.3, P = 0.001) and DBP with −0.4 mmHg (95% CI −0.7; −0.1, P = 0.016) for every 10 nmol/L increase in cord s-25OHD in adjusted analyses. Moreover, the adjusted odds of having SBP >90th percentile were reduced by 30% for every 10 nmol/L increase in cord s-25OHD (P = 0.004) and by 64% for cord s-25OHD above the median 45.1 nmol/L (P = 0.02). Similar findings were observed between pregnancy s-25OHD and 3-year SBP, cord s-25OHD and SBP at 18.9 months, and cord s-25OHD and DBP at 3 years. No consistent associations were observed between s-25OHD and BP in boys. Conclusion: Cord s-25OHD was inversely associated with SBP and DBP in young girls, but not in boys. Higher vitamin D status in foetal life may modulate BP in young girls. The sex difference remains unexplained

Tissue variations of mosaic genome-wide paternal uniparental disomy and phenotype of multi-syndromal congenital hyperinsulinism

Mosaic genome-wide paternal uniparental disomy (GW-pUPD) is a rarely recognised disorder. The phenotypic manifestations of multilocus imprinting defects (MLIDs) remain unclear. We report of an apparently non-syndromic infant with severe congenital hyperinsulinism (CHI) and diffuse pancreatic labelling by 18F*-DOPA-PET/CT leading to near-total pancreatectomy. The histology was atypical with pronounced proliferation of endocrine cells comprising >70% of the pancreatic tissue and a small pancreatoblastoma. Routine genetic analysis for CHI was normal in the blood and resected pancreatic tissue. At two years’ age, Beckwith-Wiedemann Syndrome (BWS) stigmata emerged, and at five years a liver tumour with focal nodular hyperplasia and an adrenal tumour were resected. pUPD was detected in 11p15 and next in the entire chromosome 11 with microsatellite markers. Quantitative fluorescent PCR with amplification of chromosome-specific DNA sequences for chromosomes 13, 18, 21 and X indicated GW-pUPD. A next generation sequencing panel with 303 SNPs on 21 chromosomes showed pUPD in both blood and pancreatic tissue. The mosaic distribution of GW-pUPD ranged from 31 to 35% in blood and buccal swap to 74% in the resected pancreas, 80% in a non-tumour liver biopsy, and 100% in the liver focal nodular hyperplasia and adrenal tumour. MLID features included transient conjugated hyperbilirubinaemia and lack of macrosomia from BWS (pUPD6); and behavioural and psychomotor manifestations of Angelman Syndrome (pUPD15) on follow-up. In conclusion, atypical pancreatic histology in apparently non-syndromic severe CHI patients may be the first clue to BWS and multi-syndromal CHI from GW-pUPD. Variations in the degree of mosaicism between tissues explained the phenotype

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

<div><p>Background and aim</p><p>Long 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.</p><p>Methods</p><p>We 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 <i>a priori</i> and adjusted for maternal ethnicity, pre-pregnancy body mass index and smoking during pregnancy, season of blood sampling and child age.</p><p>Results</p><p>Median (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.</p><p>Conclusion</p><p>No 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.</p></div

Adjusted associations between cord S-25-hydroxyvitamin D and leg length at 19 months and three years for girls and boys.

<p>The linear regression was adjusted for maternal pre-gestational BMI, smoking in pregnancy, maternal ethnicity, season of birth and exact child age at examination. Stratified by sex <i>a priori</i>.</p

Adjusted associations between S-25-hydroxyvitamin D at different time points and leg length at 19 months of age by child sex.

<p>This is a coefficient plot of linear regression showing beta-coefficients and their 95% confidence interval. The three separate regressions illustrated model the association between S-25-hydroxyvitamin D in early pregnancy, <20 weeks gestation (triangles), in late pregnancy, >20 weeks gestation (hollow squares) and in cord serum (diamonds) and leg length of 19-months-old girls and boys. No association between early pregnancy S-25-hydroxyvitamin D and leg length seen in either sex. Late pregnancy S-25-hydroxyvitamin D shows dose-response-like quality in the relationship to leg length in boys although only Q4 reaches significance, no such pattern in girls. In boys, cord S-25-hydroxyvitamin D also shows dose-response relationship to leg length, Q3 and Q4 reaching significance, but no such pattern in girls. Abbreviations: 25OHD: S-25-hydroxyvitamin D. w: weeks. GA: gestational age.</p

Adjusted associations between S-25-hydroxyvitamin D measured in early pregnancy (<20 weeks gestation), in late pregnancy (>20 weeks gestation) and in cord serum and leg length at 19 months and three years of age and cephalo-caudal length:length ratio at 19 months of age and sitting height:height ratio at three years of age.

<p>The regression models were adjusted for maternal pre-gestational BMI, smoking in pregnancy, maternal ethnicity, season of birth and exact child age at examination. Stratified by sex <i>a priori</i>.</p