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

Vitamin D depletion aggravates hypertension and target-organ damage

BACKGROUND: We tested the controversial hypothesis that vitamin D depletion aggravates hypertension and target-organ damage by influencing renin. METHODS AND RESULTS: Four-week-old double-transgenic rats (dTGR) with excess angiotensin (Ang) II production due to overexpression of the human renin (hREN) and angiotensinogen (hAGT) genes received vitamin D-depleted (n=18) or standard chow (n=15) for 3 weeks. The depleted group had very low serum 25-hydroxyvitamin D levels (mean+/-SEM; 3.8+/-0.29 versus 40.6+/-1.19 nmol/L) and had higher mean systolic BP at week 5 (158+/-3.5 versus 134.6+/-3.7 mm Hg, P<0.001), week 6 (176.6+/-3.3 versus 162.3+/-3.8 mm Hg, P<0.01), and week 7 (171.6+/-5.1 versus 155.9+/-4.3 mm Hg, P<0.05). Vitamin D depletion led to increased relative heart weights and increased serum creatinine concentrations. Furthermore, the mRNAs of natriuretic peptides, neutrophil gelatinase-associated lipocalin, hREN, and rRen were increased by vitamin D depletion. Regulatory T cells in the spleen and in the circulation were not affected. Ang metabolites, including Ang II and the counter-regulatory breakdown product Ang 1 to 7, were significantly up-regulated in the vitamin D-depleted groups, while ACE-1 and ACE-2 activities were not affected. CONCLUSIONS: Short-term severe vitamin D depletion aggravated hypertension and target-organ damage in dTGR. Our data suggest that even short-term severe vitamin D deficiency may directly promote hypertension and impacts on renin-angiotensin system components that could contribute to target-organ damage. The findings add to the evidence that vitamin D deficiency could also affect human hypertension

Association between Perfluorinated Compound Exposure and Miscarriage in Danish Pregnant Women

Perfluorinated alkylated substances (PFAS) have been extensively used in consumer products and humans are widely exposed to these persistent compounds. A recent study found no association between exposure to perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) and miscarriage, but no studies have examined adverse effect of the more recently introduced PFASs. We therefore conducted a case-control study within a population-based, prospective cohort during 2010-2012. Newly pregnant women residing in the Municipality of Odense, Denmark were invited to enroll in the Odense Child Cohort at their first antenatal visit before pregnancy week 12. Among a total of 2,874 participating women, 88 suffered a miscarriage and 59 had stored serum samples, of which 56 occurred before gestational week 12. They were compared to a random sample (N=336) of delivering women, who had also donated serum samples before week 12. Using a case-control design, 51 of the women suffering a miscarriage were matched on parity and gestational day of serum sampling with 204 delivering women. In a multiple logistic regression with adjustment for age, BMI, parity and gestational age at serum sampling, women with the highest tertile of exposure to perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) in pregnancy had odds ratios for miscarriage of 16.5 (95% CI 7.4-36.6-36.5) and 2.67 (1.31-5.44), respectively, as compared to the lowest tertile. In the matched data set, the OR were 37.9 (9.9-145.2) and 3.71 (1.60-8.60), respectively. The association with perfluorohexane sulfonic acid (PFHxS) was in the same direction, but not statistically significant, while no association was found with PFOA and PFOS. Our findings require confirmation due to the possible public health importance, given that all pregnant women are exposed to these widely used compounds

Association between perfluorinated compound exposure and miscarriage in Danish pregnant women.

Perfluorinated alkylated substances (PFAS) have been extensively used in consumer products and humans are widely exposed to these persistent compounds. A recent study found no association between exposure to perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) and miscarriage, but no studies have examined adverse effect of the more recently introduced PFASs. We therefore conducted a case-control study within a population-based, prospective cohort during 2010-2012. Newly pregnant women residing in the Municipality of Odense, Denmark were invited to enroll in the Odense Child Cohort at their first antenatal visit before pregnancy week 12. Among a total of 2,874 participating women, 88 suffered a miscarriage and 59 had stored serum samples, of which 56 occurred before gestational week 12. They were compared to a random sample (N=336) of delivering women, who had also donated serum samples before week 12. Using a case-control design, 51 of the women suffering a miscarriage were matched on parity and gestational day of serum sampling with 204 delivering women. In a multiple logistic regression with adjustment for age, BMI, parity and gestational age at serum sampling, women with the highest tertile of exposure to perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) in pregnancy had odds ratios for miscarriage of 16.5 (95% CI 7.4-36.6-36.5) and 2.67 (1.31-5.44), respectively, as compared to the lowest tertile. In the matched data set, the OR were 37.9 (9.9-145.2) and 3.71 (1.60-8.60), respectively. The association with perfluorohexane sulfonic acid (PFHxS) was in the same direction, but not statistically significant, while no association was found with PFOA and PFOS. Our findings require confirmation due to the possible public health importance, given that all pregnant women are exposed to these widely used compounds

Prediction of preeclampsia with angiogenic biomarkers:Results from the prospective Odense Child Cohort

<p><i>Objective</i>: We aimed to investigate how maternal serum soluble Fms-like kinase 1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio prospectively associate to preeclampsia (PE) and clinical subtypes. <i>Methods</i>: In an unselected cohort of 1909 pregnant women, sFlt-1 and PlGF were measured with KRYPTOR assays in gestational weeks (GW) 8–14 and 20–34. Associations to PE were assessed by receiver operating characteristics and logistic regression. <i>Results</i>: Concentrations of sFlt-1, PlGF, and sFlt-1/PlGF in GW20-34 were predictive of PE development, but not in GW8-14. PlGF outperformed sFlt-1/PlGF ratio with an area under curve (AUC) of 0.755 vs. 0.704, <i>p</i> = 0.002. The highest AUC values for PlGF and sFlt-1/PlGF ratio were seen for severe early-onset PE (0.901 and 0.883). Negative predictive values were high for all PE types, but positive predictive values were low. <i>Conclusion</i>: PlGF and sFlt-1/PlGF had good predictive value for PE at GW20-34 in a population-based unselected cohort, however with low positive predictive value.</p

Diagnosis of preeclampsia with soluble Fms-like tyrosine kinase 1/placental growth factor ratio:an inter-assay comparison

The angiogenic factor ratio soluble Fms-kinase 1 (sFlt-1)/placental growth factor (PlGF) is a novel diagnostic tool for preeclampsia. We compared the efficacy of the KRYPTOR (BRAHMS) automated assays for sFlt-1 and PlGF with the Elecsys (Roche) assays in a routine clinical setting. Preeclamptic women (n = 39) were included shortly after the time of diagnosis. Normotensive control pregnancies were matched by gestational age (n = 76). The KRYPTOR assays performed comparably or superior to Elecsys (sFlt-1/PlGF area under the curve 0.746 versus 0.735; P = .09; for non-obese 0.820 versus 0.805, P = .047). For early-onset preeclampsia, KRYPTOR area under the curve increased to 0.929 with a 100% specificity for preeclampsia at cut-off 85 and an 88.9% sensitivity for preeclampsia at cut-off 33. For women with preeclampsia and preterm delivery or Hemolysis, Elevated Liver enzymes, Low Platelet count (HELLP) syndrome, the KRYPTOR sFlt-1/PlGF ratio was manifold increased (P < .01). The sFlt-1/PlGF ratio proved especially useful in early-onset preeclampsia, preeclampsia with preterm delivery or HELLP, and among non-obese women

Recruitment and sampling strategy in the Odense Child Cohort.

<p>Recruitment and sampling strategy in the Odense Child Cohort.</p