Vitamin D? Supplementation in Batswana Children and Adults with HIV: A Pilot Double Blind Randomized Controlled Trial

ObjectivesSince vitamin D insufficiency is common worldwide in people with HIV, we explored safety and efficacy of high dose cholecalciferol (D₃) in Botswana, and evaluated potential modifiers of serum 25 hydroxy vitamin D change (Δ25D).DesignProspective randomized double-blind 12-week pilot trial of subjects ages 5.0–50.9 years.MethodsSixty subjects randomized within five age groups to either 4000 or 7000IU per day of D₃ and evaluated for vitamin D, parathyroid hormone, HIV, safety and growth status. Efficacy was defined as serum 25 hydroxy vitamin D (25D) ≥32ng/mL, and safety as no simultaneous elevation of serum calcium and 25D. Also assessed were HIV plasma viral RNA viral load (VL), CD4%, anti-retroviral therapy (ART) regime, and height-adjusted (HAZ), weight-adjusted (WAZ) and Body Mass Index (BMIZ) Z scores.ResultsSubjects were 50% male, age (mean±SD) 19.5±11.8 years, CD4% 31.8±10.4, with baseline VL log₁₀ range of <1.4 to 3.8 and VL detectable (>1.4) in 22%. From baseline to 12 weeks, 25D increased from 36±9ng/ml to 56±18ng/ml (p<0.0001) and 68% and 90% had 25D ≥32ng/ml, respectively (p = 0.02). Δ25D was similar by dose. No subjects had simultaneously increased serum calcium and 25D. WAZ and BMIZ improved by 12 weeks (p<0.04). HAZ and CD4% increased and VL decreased in the 7000IU/d group (p<0.04). Younger (5–13y) and older (30–50y) subjects had greater Δ25D than those 14–29y (26±17 and 28±12 vs. 11±11ng/ml, respectively, p≤0.001). Δ25D was higher with efavirenz or nevirapine compared to protease inhibitor based treatment (22±12, 27±17, vs. 13±10, respectively, p≤0.03).ConclusionsIn a pilot study in Botswana, 12-week high dose D₃ supplementation was safe and improved vitamin D, growth and HIV status; age and ART regimen were significant effect modifiers.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02189902","term_id":"NCT02189902"}}NCT02189902     

Vitamin D Status among Young Children Aged 1–3 Years: A Cross-Sectional Study in Wuxi,China

Background

The increasingly recognized importance of vitamin D has been discussed and vitamin D status among young children has attracted widespread attention in recent years. However, study on vitamin D status in young children aged 1–3 y is limited in China.

Objective

To evaluate the nutritional vitamin D status of young children aged 1–3 y in Wuxi, southeastern China.

Methods

A large cohort of 5,571 young children aged 1–3 y were recruited in this study who visited the child health clinics at the Wuxi Maternity and Child Health Hospital (latitude 31.57°N) during January 2014 to January 2015. Wuxi was located in southeastern China at a latitude of 31.57°N. Finger-stick blood sampling was conducted in all the subjects and serum 25-Hydroxyvitamin D (25(OH)D) levels were measured to evaluate their vitamin D status.

Results

In this study, serum 25(OH)D levels of young children at the age of 1–3 years ranged from 20.6–132.9 nmol/L (Median: 71.5 nmol/L). 16.1% of the population had vitamin D deficiency (<50 nmol/L), while 38.8% of the subjects had a sufficient (50–74.9 nmol/L) vitamin D level. An optimal vitamin D status (≥75 nmol/L) was found in 45.1% of the young children. The prevalence of vitamin D deficiency was higher in autumn (19.5%) than in summer (12.1%). There was no significant difference in vitamin D status between genders. The binary logistic regression analysis revealed that child age was strongly associated with vitamin D deficiency (adjusted OR: 1.173; 95%CI: 1.053–1.308; P = 0.004).

Conclusions

The prevalence of vitamin D deficiency was 16.1% among young children aged 1–3 y in Wuxi. Season and child age were associated with their vitamin D status. It is implied that young children should receive adequate amounts of vitamin D supplementation and spend more time outdoors to prolong the sunlight exposure when they grow older.     

Immunogenicity,Impact on Carriage and Reactogenicity of 10-Valent Pneumococcal Non-Typeable Haemophilus influenzae Protein D Conjugate Vaccine in Kenyan Children Aged 1–4 Years: A Randomized Controlled Trial

Background

The impact on carriage and optimal schedule for primary vaccination of older children with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) are unknown.

Methods

600 Kenyan children aged 12–59 months were vaccinated at days 0, 60 and 180 in a double-blind randomized controlled trial according to the following vaccine sequence: Group A: PHiD-CV, PHiD-CV, diphtheria/tetanus/acellular pertussis vaccine (DTaP); Group B: PHiD-CV, DTaP, PHiD-CV; Group C: hepatitis A vaccine (HAV), DTaP, HAV. Nasopharyngeal carriage of Streptococcus pneumoniae was measured at five timepoints. In 375 subjects, serotype-specific responses were measured by 22F-inhibition ELISA and opsonophagocytic killing assays (OPA) one month after vaccination.

Results

Following one dose of PHiD-CV, >90% of recipients developed IgG≥0.35 µg/mL to serotypes 1, 4, 5, 7F, 9V and 18C and OPA≥8 to serotypes 4, 7F, 9V, 18C, 23F. After a second dose >90% of recipients had IgG≥0.35 µg/mL to all vaccine serotypes and OPA≥8 to all vaccine serotypes except 1 and 6B. At day 180, carriage of vaccine-type pneumococci was 21% in recipients of two doses of PHiD-CV (Group A) compared to 31% in controls (p = 0.04). Fever after dose 1 was reported by 41% of PHiD-CV recipients compared to 26% of HAV recipients (p<0.001). Other local and systemic adverse experiences were similar between groups.

Conclusions

Vaccination of children aged 12–59 months with two doses of PHiD-CV two to six months apart was immunogenic, reduced vaccine-type pneumococcal carriage and was well-tolerated. Administration of PHiD-CV would be expected to provide effective protection against vaccine-type disease.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01028326","term_id":"NCT01028326"}}NCT01028326     

Family-Based Cluster Randomized Controlled Trial Enhancing Physical Activity and Motor Competence in 4–7-Year-Old Children

Little is known of how to involve families in physical activity (PA) interventions for children. In this cluster randomized controlled trial, we recruited families with four- to seven-year-old children to participate in a year-long study where parents in the intervention group families (n = 46) received tailored counseling to increase children’s PA. Structured PA was not served. Control group families (n = 45) did not receive any counseling. PA in all children (n = 91; mean age 6.16 ± 1.13 years at the baseline) was measured by accelerometers at the baseline and after three, six, nine and 12 months. Motor competence (MC) (n = 89) was measured at the baseline and after six and 12 months by a KTK (KörperkoordinationsTest für Kinder) and throwing and catching a ball (TCB) protocols. The effect of parental counseling on study outcomes was analyzed by a linear mixed-effects model fit by REML and by a Mann-Whitney U test in the case of the TCB. As season was hypothesized to affect counseling effect, an interaction of season on the study outcomes was examined. The results show significant decrease of MVPA in the intervention group when compared to the control group (p < .05). The TCB showed a nearly significant improvement at six months in the intervention group compared to the controls (p = .051), but not at 12 months. The intervention group had a steadier development of the KTK when the interaction of season was taken into account. In conclusion, more knowledge of family constructs associating with the effectiveness of counseling is needed for understanding how to enhance PA in children by parents. However, a hypothesis may be put forward that family-based counseling during an inactive season rather than an active season may provide a more lasting effect on the development of KTK in children.

Trial Registration

Controlled-Trials.com ISRCTN28668090     

Acquisition of Visuomotor Abilities and Intellectual Quotient in Children Aged 4–10 Years: Relationship with Micronutrient Nutritional Status

Lethargy, poor attention, and the high rate and severity of infections in malnourished children affect their educational achievement. We therefore studied the association between visuomotor abilities and intelligence quotient (IQ) and their relationship with iron, zinc, and copper. A cross-sectional study was carried out on a sample of 89 healthy children (age range, 4-10 years). Evaluations of visuomotor ability and IQ were performed with the Developmental Test of Visual Motor Integration (VMI) and the Scale for Measurement of Intelligence for children aged 3-18 years, respectively. Nutritional status was assessed using anthropometry and biochemical assessments, which included serum ferritin, zinc and copper levels, and Hb. The sample was classified as having low or normal VMI scores: 47 children (52.8%, mean age 7 +/- 1.5 years) had low VMI, and 42 (47.2%, mean age 7 +/- 2.06 years) had normal VMI. There were no statistically significant differences in socioeconomic and cultural condition between both groups. We found significantly higher serum copper and ferritin levels in normal as compared to low VMI, but we did not find any differences with zinc. IQ was significantly higher in normal vs low VMI children. The fact that children with abnormal VMI presented low mean serum copper and ferritin concentrations could indicate that copper and iron deficiencies in this sample could be related with visuomotor abilities.     

Impact of Malaria Control on Mortality and Anemia among Tanzanian Children Less than Five Years of Age, 1999–2010

Background

Mainland Tanzania scaled up multiple malaria control interventions between 1999 and 2010. We evaluated whether, and to what extent, reductions in all-cause under-five child mortality (U5CM) tracked with malaria control intensification during this period.

Methods

Four nationally representative household surveys permitted trend analysis for malaria intervention coverage, severe anemia (hemoglobin <8 g/dL) prevalence (SAP) among children 6–59 months, and U5CM rates stratified by background characteristics, age, and malaria endemicity. Prevalence of contextual factors (e.g., vaccination, nutrition) likely to influence U5CM were also assessed. Population attributable risk percentage (PAR%) estimates for malaria interventions and contextual factors that changed over time were used to estimate magnitude of impact on U5CM.

Results

Household ownership of insecticide-treated nets (ITNs) rose from near zero in 1999 to 64% (95% CI, 61.7–65.2) in 2010. Intermittent preventive treatment of malaria in pregnancy reached 26% (95% CI, 23.6–28.0) by 2010. Sulfadoxine-pyrimethamine replaced chloroquine in 2002 and artemisinin-based combination therapy was introduced in 2007. SAP among children 6–59 months declined 50% between 2005 (11.1%; 95% CI, 10.0–12.3%) and 2010 (5.5%; 95% CI, 4.7–6.4%) and U5CM declined by 45% between baseline (1995–9) and endpoint (2005–9), from 148 to 81 deaths/1000 live births, respectively. Mortality declined 55% among children 1–23 months of age in higher malaria endemicity areas. A large reduction in U5CM was attributable to ITNs (PAR% = 11) with other malaria interventions adding further gains. Multiple contextual factors also contributed to survival gains.

Conclusion

Marked declines in U5CM occurred in Tanzania between 1999 and 2010 with high impact from ITNs and ACTs. High-risk children (1–24 months of age in high malaria endemicity) experienced the greatest declines in mortality and SAP. Malaria control should remain a policy priority to sustain and further accelerate progress in child survival.     

Evaluation of Status of Zinc, Copper, and Iron Levels in Biological Samples of Normal Children and Children with Night Blindness with Age Groups of 3–7 and 8–12 Years

The causes of night blindness in children are multifactorial, and particular consideration has been given to childhood nutritional deficiency, which is the most common problem found in underdeveloped countries. Such deficiency can result in physiological and pathological processes that in turn influence hair composition. This study was designed to compare the levels of zinc (Zn), copper (Cu), and iron (Fe) in scalp hair, blood, and urine of both genders of children with night blindness with age range of 3–7 and 8–12 years, comparing them to sex- and age-matched controls. A microwave-assisted wet acid digestion procedure was developed as a sample pretreatment, for the determination of zinc, copper, and iron in biological samples of children with night blindness. The proposed method was validated by using conventional wet digestion and certified reference samples of hair, blood, and urine. The digests of all biological samples were analyzed for Cu, Fe, and Zn by flame atomic absorption spectrometry using an air/acetylene flame. The results indicated significantly lower levels of Fe, Cu, and Zn in the biological samples (blood and scalp hair) of male and female children with night blindness, compared with control subjects of both genders. These data present guidance to clinicians and other professionals investigating the deficiency of essential trace metals in biological samples (scalp hair and blood) of children with night blindness.     

Effects of Dexamethasone and Insulin Alone or in Combination on Energy and Protein Metabolism Indicators and Milk Production in Dairy Cows in Early Lactation – A Randomized Controlled Trial

Objectives

This study investigated the effects of dexamethasone and insulin, when administered at 3^rd or 10^th day of lactation on energy and protein metabolism in dairy cows.

Materials and Methods

Two hundred Holstein cows were enrolled in a randomized controlled clinical trial. The cows were randomly assigned to receive 1 of 4 treatments at 3 or 10 days in milk: control group, 10-mL i.m. injection of sterile water, group insulin, s.c. injection of 100 units of insulin, group dexamethasone, i.m. injection of 20 mg of dexamethasone, group insulin plus dexamethasone, i.m. injection of 20 mg of dexamethasone and 100 units of insulin. The cows randomly assigned to receive the treatments on 3 or 10 days of lactation. Serum samples obtained at the time of enrollment, time of treatment and at 2, 4, 7 and 14 days after intervention. The sera were analyzed for β-hydroxybutyrate (BHBA), nonesterified fatty acids (NEFA), glucose, cholesterol, albumin, urea, and aspartate amino transferase (AST). Data were analyzed using a repeated measures mixed model that accounted for the effects of parity, body condition score, dystocia, retained placenta, metritis and the random effect of cow.

Results

There was no significant interaction of group of treatment and time of intervention (day 3 or 10 post-partum) on serum components. Cows that received insulin or dexamethasone alone or in combination, had lower BHBA 2 days after treatment compared with control cows, whereas concentrations of NEFA, were unaffected suggesting that glucocorticoids lipolytic effects do not appear to be important in healthy cows. AST activities significantly reduced in cows that received dexamethasone with or without insulin at 2 and 4 days after treatment. Albumin and urea concentrations 2 days after treatment were higher for cows that received dexamethasone only or dexamethasone plus insulin compared with control and Ins received cows. There were no treatment effects on test-day milk production, milk fat and protein percentages.

Conclusions

The results suggested that administration of glucocorticoids in early lactation resulted in short-term improvement of metabolism in postpartum dairy cows in biochemical terms.     

Effect of Vitamin D Supplementation on Cardiometabolic Risks and Health-Related Quality of Life among Urban Premenopausal Women in a Tropical Country – A Randomized Controlled Trial

Background

Many observational studies linked vitamin D to cardiometabolic risks besides its pivotal role in musculoskeletal diseases, but evidence from trials is lacking and inconsistent.

Aim

To determine whether Vitamin D supplementation in urban premenopausal women with vitamin D deficiency can improve cardiometabolic risks and health-related quality of life (HRQOL).

Design

A double-blind randomized controlled trial was conducted in Kuala Lumpur, Malaysia. A total of 192 vitamin D deficient (<50 nmol/l) premenopausal women were randomized to receive either vitamin D 50,000 IU or placebo once a week for 2 months and then monthly for 10 months. Primary outcomes were serum 25(OH)D, serum lipid profiles, blood pressure and HOMA-IR measured at baseline, 6 months and 12 months. HRQOL was assessed with SF-36 at baseline and 12 months.

Results

Ninety three and ninety-nine women were randomised into intervention and placebo groups respectively. After 12 months, there were significant differences in the serum 25(OH)D concentration (mean difference: 49.54; 95% CI: 43.94 to 55.14) nmol/l) and PTH levels (mean difference: −1.02; 95% CI: −1.67 to −0.38 pmol/l) in the intervention group compared to placebo group. There was significant difference between treatment group in both serum 25(OH)D and PTH. There was no effect of supplementation on HOMA-IR, serum lipid profiles and blood pressure (all p>0.05) between two groups. There was a small but significant improvement in HRQOL in the components of vitality (mean difference: 5.041; 95% CI: 0.709 to 9.374) and mental component score (mean difference: 2.951; 95% CI: 0.573 to 5.329) in the intervention group compared to placebo group.

Conclusion

Large and less frequent dosage vitamin D supplementation was safe and effective in the achievement of vitamin D sufficiency. However, there was no improvement in measured cardiometabolic risk factors in premenopausal women. Conversely vitamin D supplementation improves some components of HRQOL.

Trial Registration

Australian New Zealand Clinical Trial Registry ACTRN12612000452897     

Helicobacter pylori Seropositivity’s Association with Markers of Iron, 1-Carbon Metabolism,and Antioxidant Status among US Adults: A Structural Equations Modeling Approach

Objectives

We tested a model in which Helicobacter pylori seropositivity (Hp_s) predicted iron status, which in turn acted as a predictor for markers of 1-C metabolism that were then allowed to predict antioxidant status.

Methods

National Health and Nutrition Examination Surveys (NHANES 1999–2000) cross-sectional data among adults aged 20–85 y were analyzed (n = 3,055). Markers of Hp_s, iron status (serum ferritin and transferrin saturation (TS)); 1-C metabolism (serum folate (FOL_serum), B-12, total homocysteine (tHcy), methylmalonic acid (MMA)) and antioxidant status (vitamins A and E) were entered into a structural equations model (SEM).

Results

Predictors of Hp_s included older age, lower education and income, racial/ethnic groups (lowest among Non-Hispanic Whites), and lifetime cigarette smoking. SEM modeling indicated that Hp_s had a direct inverse relationship with iron status (combining serum ferritin and TS) which in turn was positively related to 1-C metabolites (higher serum folate, B-12 or lower tHcy/MMA) that were positively associated with antioxidant status (combining serum vitamins A and E). Another pathway that was found bypassed 1-C metabolites (Hps → Iron_st → Antiox). The sum of all indirect effects from Hp_s combining both pathways and the other indirect pathways in the model (Hps → Iron_st → OneCarbon; Hps →OneCarbon →Antiox) was estimated at β = -0.006±0.003, p<0.05.

Conclusions

In sum, of the total effect of H. pylori seropositivity on antioxidant status, two significant indirect pathways through Iron status and 1-Carbon metabolites were found. Randomized controlled trials should be conducted to uncover the concomitant causal effect of H. pylori eradication on improving iron status, folate, B-12 and antioxidant status among H. pylori seropositive individuals.     

Evaluation of Status of Cadmium, Lead, and Nickel Levels in Biological Samples of Normal and Night Blindness Children of Age Groups 3–7 and 8–12 Years

The causes of night blindness in children are multifactorial, and particular consideration has been given to childhood trace metals toxicity, which is the most common problem found in underdeveloped countries. This study was designed to compare the levels of cadmium (Cd), lead (Pb), and nickel (Ni) in scalp hair, blood, and urine of night blindness children age ranged 3–7 and 8–12 years of both genders, comparing them to sex- and age-matched controls. A microwave-assisted wet acid digestion procedure was developed as a sample pretreatment, for the determination of Cd, Pb, and Ni in biological samples of night blindness children. The proposed method was validated by using conventional wet digestion and certified reference samples of hair, blood, and urine. The digests of all biological samples were analyzed for Cd, Pb, and Ni by electrothermal atomic absorption spectrometry. The results indicated significantly higher levels of Cd, Pb, and Ni in the biological samples (blood, scalp hair, and urine) of male and female night blindness children, compared with control subjects of both genders. These data present guidance to clinicians and other professional investigating toxicity of trace metals in biological samples of night blindness children.     

Risk Factors for Death among Children Less than 5 Years Old Hospitalized with Diarrhea in Rural Western Kenya, 2005–2007: A Cohort Study

Background

Diarrhea is a leading cause of childhood morbidity and mortality in sub-Saharan Africa. Data on risk factors for mortality are limited. We conducted hospital-based surveillance to characterize the etiology of diarrhea and identify risk factors for death among children hospitalized with diarrhea in rural western Kenya.

Methods and Findings

We enrolled all children <5 years old, hospitalized with diarrhea (≥3 loose stools in 24 hours) at two district hospitals in Nyanza Province, western Kenya. Clinical and demographic information was collected. Stool specimens were tested for bacterial and viral pathogens. Bivariate and multivariable logistic regression analyses were carried out to identify risk factors for death. From May 23, 2005 to May 22, 2007, 1,146 children <5 years old were enrolled; 107 (9%) children died during hospitalization. Nontyphoidal Salmonella were identified in 10% (118), Campylobacter in 5% (57), and Shigella in 4% (42) of 1,137 stool samples; rotavirus was detected in 19% (196) of 1,021 stool samples. Among stools from children who died, nontyphoidal Salmonella were detected in 22%, Shigella in 11%, rotavirus in 9%, Campylobacter in 5%, and S. Typhi in <1%. In multivariable analysis, infants who died were more likely to have nontyphoidal Salmonella (adjusted odds ratio [aOR] = 6·8; 95% CI 3·1–14·9), and children <5 years to have Shigella (aOR = 5·5; 95% CI 2·2–14·0) identified than children who survived. Children who died were less likely to be infected with rotavirus (OR = 0·4; 95% CI 0·2–0·8). Further risk factors for death included being malnourished (aOR = 4·2; 95% CI 2·1–8·7); having oral thrush on physical exam (aOR = 2·3; 95% CI 1·4–3·8); having previously sought care at a hospital for the illness (aOR = 2·2; 95% CI 1·2–3·8); and being dehydrated as diagnosed at discharge/death (aOR = 2·5; 95% CI 1·5–4·1). A clinical diagnosis of malaria, and malaria parasites seen on blood smear, were not associated with increased risk of death. This study only captured in-hospital childhood deaths, and likely missed a substantial number of additional deaths that occurred at home.

Conclusion

Nontyphoidal Salmonella and Shigella are associated with mortality among rural Kenyan children with diarrhea who access a hospital. Improved prevention and treatment of diarrheal disease is necessary. Enhanced surveillance and simplified laboratory diagnostics in Africa may assist clinicians in appropriately treating potentially fatal diarrheal illness. Please see later in the article for the Editors'' Summary     

Chlorproguanil?Dapsone?Artesunate versus Artemether?Lumefantrine: A Randomized,Double-Blind Phase III Trial in African Children and Adolescents with Uncomplicated Plasmodium falciparum Malaria

Background

Chlorproguanil−dapsone−artesunate (CDA) was developed as an affordable, simple, fixed-dose artemisinin-based combination therapy for use in Africa. This trial was a randomized parallel-group, double-blind, double-dummy study to compare CDA and artemether−lumefantrine (AL) efficacy in uncomplicated Plasmodium falciparum malaria and further define the CDA safety profile, particularly its hematological safety in glucose-6-phosphate dehydrogenase (G6PD) -deficient patients.

Methods and Findings

The trial was conducted at medical centers at 11 sites in five African countries between June 2006 and August 2007. 1372 patients (≥1 to <15 years old, median age 3 years) with acute uncomplicated P. falciparum malaria were randomized (2∶1) to receive CDA 2/2.5/4 mg/kg once daily for three days (N = 914) or six-doses of AL over three days (N = 458). Non-inferiority of CDA versus AL for efficacy was evaluated in the Day 28 per-protocol (PP) population using parasitological cure (polymerase chain reaction [PCR]-corrected). Cure rates were 94.1% (703/747) for CDA and 97.4% (369/379) for AL (treatment difference –3.3%, 95%CI –5.6, −0.9). CDA was non-inferior to AL, but there was simultaneous superiority of AL (upper 95%CI limit <0). Adequate clinical and parasitological response at Day 28 (uncorrected for reinfection) was 79% (604/765) with CDA and 83% (315/381) with AL. In patients with a G6PD-deficient genotype (94/603 [16%] hemizygous males, 22/598 [4%] homozygous females), CDA had the propensity to cause severe and clinically concerning hemoglobin decreases: the mean hemoglobin nadir was 75 g/L (95%CI 71, 79) at Day 7 versus 97 g/L (95%CI 91, 102) for AL. There were three deaths, unrelated to study medication (two with CDA, one with AL).

Conclusions

Although parasitologically effective at Day 28, the hemolytic potential of CDA in G6PD-deficient patients makes it unsuitable for use in a public health setting in Africa.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00344006","term_id":"NCT00344006"}}NCT00344006     

Risk Factors for Severe Cholera among Children under Five in Rural and Urban Bangladesh, 2000–2008: A Hospital-Based Surveillance Study

Background

Children under five bear the largest cholera burden. We therefore sought to identify modifiable risk factors among Bangladeshi children.

Methodology/Principal Findings

We used multivariate Poisson regression to assess risk factors for severe cholera among diarrheal patients presenting at hospitals in Matlab (rural) and Dhaka (urban), Bangladesh. Risk increased with age. Compared to those under one, rural and urban four-year-olds had adjusted risk ratios (aRR) of 4.17 (95% confidence interval (CI) 2.43–7.15) and 6.32 (95% CI: 4.63–8.63), respectively. Breastfeeding halved the risk in both rural (aRR = 0.49, 95% CI: 0.35–0.67) and urban (aRR = 0.51, 95% CI: 0.41–0.62) settings. Rural children’s risk decreased with maternal education (P-trend: <0.001) and increased among those with a family member with diarrhea in the past week (aRR = 1.61, 95% CI: 1.22–2.14) and those with prior vitamin A supplementation (aRR = 1.65, 95% CI: 1.12–2.43). Urban children whose mothers daily (aRR = 0.41, 95% CI: 0.21–0.79) or occasionally (aRR = 0.55, 95% CI: 0.36–0.84) read a newspaper experienced reduced risk. Urban children from households with incomes between 34–84 USD/month had a 30% increased risk compared to those from households with incomes >84 USD/month.

Conclusion/Significance

Increasing age, lower socioeconomic status, and lack of breastfeeding are key correlates of increased risk for cholera hospitalization among those under five in rural and urban Bangladesh. In addition, having a family member with diarrhea in the past week was associated with increased risk among rural children. Continued attention should be directed to the promotion of breastfeeding. Further research is needed to elucidate the relationship between maternal education and cholera risk. Renewed research regarding the use of chemoprophylaxis among family members of cholera cases may be warranted in rural endemic settings.     

Influence of the Lactotripeptides Isoleucine–Proline–Proline and Valine–Proline–Proline on Systolic Blood Pressure in Japanese Subjects: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

The lactotripeptides isoleucine–proline–proline (IPP) and valine–proline–proline (VPP) have been shown to decrease systolic blood pressure (SBP) in several populations, but the size of the effect varies among studies. We performed a meta-analysis including all published studies to evaluate the SBP-lowering effect of IPP/VPP in Japanese subjects more comprehensively.

Methods and Findings

Eligible randomized controlled trials were searched for within four bibliographic databases, including two Japanese ones. Eighteen studies (including a total of 1194 subjects) were included in the meta-analysis. A random effect model using the restricted maximum likelihood (REML) estimator was used for the analysis. The analysis showed that consumption of IPP/VPP induced a significant reduction in SBP as compared with placebo in Japanese subjects, with an estimated effect of -5.63 mm Hg (95% CI, -6.87 to -4.39, P<0.0001) and no evidence of publication bias. A significant heterogeneity between series was evident, which could be explained by a significant influence of the baseline blood pressure status of the subjects, the effect of IPP/VPP on SBP being stronger in hypertensive subjects (-8.35 mm Hg, P<0.0001) than in non-hypertensive subjects (-3.42mm Hg, P<0.0001). Furthermore, the effect of IPP/VPP on SBP remained significant when limiting the analysis to series that tested the usual doses of IPP/VPP consumed daily (below 5 mg/d), with estimated effects of -6.01 mm Hg in the overall population and -3.32 mm Hg in non-hypertensive subjects.

Conclusions

Results from this meta-analysis show that IPP/VPP lactotripeptides can significantly reduce office SBP in Japanese subjects with or without overt hypertension, and for doses that can potentially be consumed as an everyday supplement. This suggests that these peptides could play a role in controlling blood pressure in Japanese subjects. The systematic review protocol was published on the PROSPERO register (CRD42014014322).     

Impact of Vitamin D Replacement on Markers of Glucose Metabolism and Cardio-Metabolic Risk in Women with Former Gestational Diabetes—A Double-Blind,Randomized Controlled Trial

Gestational Diabetes Mellitus (GDM) and vitamin D deficiency are related to insulin resistance and impaired beta cell function, with heightened risk for future development of diabetes. We evaluated the impact of vitamin D supplementation on markers of glucose metabolism and cardio metabolic risk in Asian women with former GDM and hypovitaminosis D. In this double blind, randomized controlled trial, 26 participants were randomized to receive either daily 4000 IU vitamin D3 or placebo capsules. 75g Oral Glucose Tolerance Test (OGTT) and biochemistry profiles were performed at baseline and 6 month visits. Mathematical models, using serial glucose, insulin and C peptide measurements from OGTT, were employed to calculate insulin sensitivity and beta cell function. Thirty three (76%) women with former GDM screened had vitamin D level of <50 nmol/L at baseline. Supplementation, when compared with placebo, resulted in increased vitamin D level (+51.1 nmol/L vs 0.2 nmol/L, p<0.001) and increased fasting insulin (+20% vs 18%, p = 0.034). The vitamin D group also demonstrated a 30% improvement in disposition index and an absolute 0.2% (2 mmol/mol) reduction in HbA_1c. There was no clear change in insulin sensitivity or markers of cardio metabolic risk. This study highlighted high prevalence of vitamin D deficiency among Asian women with former GDM. Six months supplementation with 4000 IU of vitamin D3 safely restored the vitamin D level, improved basal pancreatic beta-cell function and ameliorated the metabolic state. There was no effect on markers of cardio metabolic risk. Further mechanistic studies exploring the role of vitamin D supplementation on glucose homeostasis among different ethnicities may be needed to better inform future recommendations for these women with former GDM at high risk of both hypovitaminosis D and future diabetes.     

Prevalence and Risk Factors of Overweight and Obesity among Children Aged 6–59 Months in Cameroon: A Multistage,Stratified Cluster Sampling Nationwide Survey

Background

Childhood obesity is one of the most serious public health challenges of the 21st century. The prevalence of overweight and obesity among children (<5 years) in Cameroon, based on weight-for-height index, has doubled between 1991 and 2006. This study aimed to determine the prevalence and risk factors of overweight and obesity among children aged 6 months to 5 years in Cameroon in 2011.

Methods

Four thousand five hundred and eighteen children (2205 boys and 2313 girls) aged between 6 to 59 months were sampled in the 2011 Demographic Health Survey (DHS) database. Body Mass Index (BMI) z-scores based on WHO 2006 reference population was chosen to estimate overweight (BMI z-score > 2) and obesity (BMI for age > 3). Regression analyses were performed to investigate risk factors of overweight/obesity.

Results

The prevalence of overweight and obesity was 8% (1.7% for obesity alone). Boys were more affected by overweight than girls with a prevalence of 9.7% and 6.4% respectively. The highest prevalence of overweight was observed in the Grassfield area (including people living in West and North-West regions) (15.3%). Factors that were independently associated with overweight and obesity included: having overweight mother (adjusted odds ratio (aOR) = 1.51; 95% CI 1.15 to 1.97) and obese mother (aOR = 2.19; 95% CI = 155 to 3.07), compared to having normal weight mother; high birth weight (aOR = 1.69; 95% CI 1.24 to 2.28) compared to normal birth weight; male gender (aOR = 1.56; 95% CI 1.24 to 1.95); low birth rank (aOR = 1.35; 95% CI 1.06 to 1.72); being aged between 13–24 months (aOR = 1.81; 95% CI = 1.21 to 2.66) and 25–36 months (aOR = 2.79; 95% CI 1.93 to 4.13) compared to being aged 45 to 49 months; living in the grassfield area (aOR = 2.65; 95% CI = 1.87 to 3.79) compared to living in Forest area. Muslim appeared as a protective factor (aOR = 0.67; 95% CI 0.46 to 0.95).compared to Christian religion.

Conclusion

This study underlines a high prevalence of early childhood overweight with significant disparities between ecological areas of Cameroon. Risk factors of overweight included high maternal BMI, high birth weight, male gender, low birth rank, aged between 13–36 months, and living in the Grassfield area while being Muslim appeared as a protective factor. Preventive strategies should be strengthened especially in Grassfield areas and should focus on sensitization campaigns to reduce overweight and obesity in mothers and on reinforcement of measures such as surveillance of weight gain during antenatal consultation and clinical follow-up of children with high birth weight. Meanwhile, further studies including nutritional characteristics are of great interest to understand the association with religion, child age and ecological area in this age group, and will help in refining preventive strategies against childhood overweight and obesity in Cameroon.