Sunlight, dietary habits, genetic polymorphisms and vitamin D deficiency in urban and rural infants of Bangladesh.

We conducted an observational study to assess the prevalence and risk factors of vitamin D deficiency in 12-24 months old children living in urban and rural Bangladesh. Serum 25-hydroxyvitamin D (free 25(OH)D) level, socio-demographic status, anthropometric status, dietary intake, exposure to sunlight and single nucleotide polymorphisms in vitamin-D pathway genes were measured in 208 children. Vitamin D deficiency (free 25(OH)D < 50 nmol/l) was reported in 47% of the children. Multivariable logistic regression model identified duration to sunlight exposure (regression coefficient, ß = - 0.01; 95% CI 0.00, - 0.02; p-value < 0.05), UV index (ß = - 0.36; 95% CI 0.00, - 0.02; p-value < 0.05) and breast-feeding (ß = - 1.15; 95% CI - 0.43, - 1.86; p-value < 0.05) to be negatively associated with vitamin D deficiency. We measured the role of single nucleotide polymorphisms in pathway genes (GC-rs7041 T > G, rs4588 C > A, CYP2R1-rs206793 A > G, CYP27B1-rs10877012 A > C and DHCR7-rs12785878 G > T) and found statistically significant differences in serum vitamin D levels between various genotypes. SNPs for CYP27B1 (CA & CC genotype) had statistically significant positive association (ß = 1.61; 95% CI 2.79, 0.42; p-value < 0.05) and TT genotype of GC-rs7041 had negative association (ß = - 1.33; 95% CI - 0.02, - 2.64; p-value < 0.05) with vitamin-D deficiency in the surveyed children.

Effects of Maternal Vitamin D Supplementation During Pregnancy and Lactation on Infant Acute Respiratory Infections: Follow-up of a Randomized Trial in Bangladesh.

BACKGROUND: We examined the effect of maternal vitamin D supplementation during pregnancy and lactation on risk of acute respiratory infection (ARI) in infants up to 6 months of age in Bangladesh. METHODS: This study was nested in a randomized, double-blind, placebo-controlled, 5-arm dose-ranging trial of prenatal and postpartum vitamin D supplementation. One group of women received 0 IU vitamin D per week during pregnancy and for 26 weeks post delivery ("placebo" group), one group received high-dose prenatal vitamin D supplementation of 28 000 IU per week and 26 weeks post delivery, and there were 3 additional dose-ranging groups receiving vitamin D supplementation during pregnancy only (4200, 16 800, and 28 000 IU per week, respectively). Episodes of ARI were identified by active and passive surveillance. The primary outcome was microbiologically confirmed ARI, and the primary analysis compared the high-dose prenatal plus postpartum vitamin D vs placebo groups. RESULTS: In total, 1174 mother-infant pairs were included. Among infants born to mothers in the placebo group, 98% had a venous umbilical cord 25(OH)D level below 30 nmol/L compared with none in the high-dose prenatal plus postdelivery vitamin D group. Incidence of microbiologically confirmed ARI in the high-dose prenatal plus postpartum vitamin D (1.21 episodes per 6 person-months; N = 235) and placebo groups (1.07 episodes per 6 person-months; N = 234) was not significantly different (hazard ratio of 1.12 [95% confidence intervals: 0.90-1.40]). There were no differences in the incidence of microbiologically confirmed or clinical ARI, upper, lower, or hospitalized lower respiratory tract infection between high-dose prenatal plus postpartum vitamin D and placebo groups. CONCLUSIONS: Despite a high prevalence of maternal baseline vitamin D deficiency and significant effects of maternal vitamin D supplementation on infant vitamin D status, the intervention did not reduce the risk of microbiologically confirmed ARI in infants up to 6 months of age.

Antimicrobial Prescribing during Infant Hospital Admissions in a Birth Cohort in Dhaka, Bangladesh.

Empirical antimicrobial use is common in hospitalized infants and may contribute to antimicrobial resistance in low- and middle-income countries. In this observational birth cohort study nested in a randomized controlled trial in Dhaka, Bangladesh, inpatient antimicrobial prescription data were extracted from serious adverse event forms completed for hospitalizations of infants (0-12 months of age). The primary outcome was the proportion of inpatient admissions where systemic antimicrobials were prescribed. Infant and hospitalization-related factors associated with antimicrobial prescriptions were determined. Among 1254 infants, there were 448 admissions to 32 facilities from 2014 to 2016. Antimicrobials were prescribed in 73% of admissions with a mean antimicrobial exposure rate of 0.25 antimicrobials per day of admission [95% confidence intervals (95% CIs): 0.24-0.27]. The most common antibiotics were aminoglycosides (29%), penicillins (26%) and third-generation cephalosporins (25%). In all, 58% of antibiotics were classified as 'access', 38% 'watch' and 1% 'reserve' using the World Health Organization (WHO) Essential Medicines List classification. WHO-recommended antimicrobial regimens were used in 68% of neonatal sepsis and 9% of lower respiratory tract infection (LRTI) admissions. 'Watch' antimicrobials were used in 26% of neonatal sepsis and 76% of LRTI admissions. Compared with private facilities, antimicrobial prescription rates were lower at government [rate ratio (RR) 0.71; 95% CI: 0.61-0.83] and charitable facilities (RR 0.39; 95% CI: 0.28-0.53), after adjustment for household wealth index and parental education. Younger infant age, older maternal age and longer admission were associated with higher prescription rates. These findings highlight the need for paediatric antimicrobial stewardship programs in Bangladesh.

Increased (Pro)renin Receptor Expression in the Hypertensive Human Brain.

Overactivation of the renin-angiotensin system (RAS) - a central physiological pathway involved in controlling blood pressure (BP) - leads to hypertension. It is now well-recognized that the central nervous system (CNS) has its own local RAS, and the majority of its components are known to be expressed in the brain. In physiological and pathological states, the (pro)renin receptor (PRR), a novel component of the brain RAS, plays a key role in the formation of angiotensin II (Ang II) and also mediates Ang II-independent PRR signaling. A recent study reported that neuronal PRR activation is a novel mechanism for cardiovascular and metabolic regulation in obesity and diabetes. Expression of the PRR is increased in cardiovascular regulatory nuclei in hypertensive (HTN) animal models and plays an important role in BP regulation in the CNS. To determine the clinical significance of the brain PRR in human hypertension, we investigated whether the PRR is expressed and regulated in the paraventricular nucleus of the hypothalamus (PVN) and rostral ventrolateral medulla (RVLM) - two key cardiovascular regulatory nuclei - in postmortem brain samples of normotensive (NTN) and HTN humans. Here, we report that the PRR is expressed in neurons, but not astrocytes, of the human PVN and RVLM. Notably, PRR immunoreactivity was significantly increased in both the PVN and RVLM of HTN subjects. In addition, PVN-PRR immunoreactivity was positively correlated with systolic BP (sBP) and showed a tendency toward correlation with age but not body mass index (BMI). Collectively, our data provide clinical evidence that the PRR in the PVN and RVLM may be a key molecular player in the neural regulation of BP and cardiovascular and metabolic function in humans.

Vitamin D Supplementation in Pregnancy and Lactation and Infant Growth.

BACKGROUND: It is unclear whether maternal vitamin D supplementation during pregnancy and lactation improves fetal and infant growth in regions where vitamin D deficiency is common. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in Bangladesh to assess the effects of weekly prenatal vitamin D supplementation (from 17 to 24 weeks of gestation until birth) and postpartum vitamin D supplementation on the primary outcome of infants' length-for-age z scores at 1 year according to World Health Organization (WHO) child growth standards. One group received neither prenatal nor postpartum vitamin D (placebo group). Three groups received prenatal supplementation only, in doses of 4200 IU (prenatal 4200 group), 16,800 IU (prenatal 16,800 group), and 28,000 IU (prenatal 28,000 group). The fifth group received prenatal supplementation as well as 26 weeks of postpartum supplementation in the amount of 28,000 IU (prenatal and postpartum 28,000 group). RESULTS: Among 1164 infants assessed at 1 year of age (89.5% of 1300 pregnancies), there were no significant differences across groups in the mean (±SD) length-for-age z scores. Scores were as follows: placebo, -0.93±1.05; prenatal 4200, -1.11±1.12; prenatal 16,800, -0.97±0.97; prenatal 28,000, -1.06±1.07; and prenatal and postpartum 28,000, -0.94±1.00 (P=0.23 for a global test of differences across groups). Other anthropometric measures, birth outcomes, and morbidity did not differ significantly across groups. Vitamin D supplementation had expected effects on maternal and infant serum 25-hydroxyvitamin D and calcium concentrations, maternal urinary calcium excretion, and maternal parathyroid hormone concentrations. There were no significant differences in the frequencies of adverse events across groups, with the exception of a higher rate of possible hypercalciuria among the women receiving the highest dose. CONCLUSIONS: In a population with widespread prenatal vitamin D deficiency and fetal and infant growth restriction, maternal vitamin D supplementation from midpregnancy until birth or until 6 months post partum did not improve fetal or infant growth. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT01924013 .).