Person:

Fink, Gunther

Background: Even though the WHO currently recommends zinc for diarrhea management, no consensus has been reached with respect to routine distribution of zinc for preventive reasons. We reviewed the health impact of preventive zinc interventions, and evaluated the relative cost effectiveness of currently feasible interventions. Methods: Using the latest relative risk estimates reported in the literature, we parameterized a health impact model, and calculated the expected benefits of zinc supplementation in a representative low-income country. We then computed the cost and cost-effectiveness for three delivery mechanisms: the direct distribution of zinc supplements, the distribution of micronutrient biscuits including zinc, and the distribution of zinc through water filtration systems. Results: Combining all health outcomes and impact estimates, we find that systematic zinc supplementation among children of ages one to five would avert 1.423 DALYs per 100 households and year in least developed countries. The estimated cost per DALY is US$ 606 for pill supplementation, US$ 1211 for micronutrient biscuits, and US$ 879 per DALY saved for water filtration systems. Conclusions: Preventive zinc supplementation to children of ages 1–5 appears to be a highly cost-effective intervention in typical developing country settings. More research will be needed to determine the most effective mechanism to deliver zinc to this target population.

Background: Low rates of adherence to artemisinin-based combination therapy (ACT) regimens increase the risk of treatment failure and may lead to drug resistance, threatening the sustainability of current anti-malarial efforts. We assessed the impact of text message reminders on adherence to ACT regimens. Methods: Health workers at hospitals, clinics, pharmacies, and other stationary ACT distributors in Tamale, Ghana provided flyers advertising free mobile health information to individuals receiving malaria treatment. The messaging system automatically randomized self-enrolled individuals to the control group or the treatment group with equal probability; those in the treatment group were further randomly assigned to receive a simple text message reminder or the simple reminder plus an additional statement about adherence in 12-hour intervals. The main outcome was self-reported adherence based on follow-up interviews occurring three days after treatment initiation. We estimated the impact of the messages on treatment completion using logistic regression. Results: 1140 individuals enrolled in both the study and the text reminder system. Among individuals in the control group, 61.5% took the full course of treatment. The simple text message reminders increased the odds of adherence (adjusted OR 1.45, 95% CI [1.03 to 2.04], p-value 0.028). Receiving an additional message did not result in a significant change in adherence (adjusted OR 0.77, 95% CI [0.50 to 1.20], p-value 0.252). Conclusion: The results of this study suggest that a simple text message reminder can increase adherence to antimalarial treatment and that additional information included in messages does not have a significant impact on completion of ACT treatment. Further research is needed to develop the most effective text message content and frequency. Trial Registration ClinicalTrials.gov NCT01722734

Objectives: To explore determinants of change in pediatrician supply in Japan, and examine impacts of a 2004 reform of postgraduate medical education on pediatricians’ practice location choice. Methods: Data were compiled from secondary data sources. The dependent variable was the change in the number of pediatricians at the municipality (“secondary tier of medical care” [STM]) level. To analyze the determinants of pediatrician location choices, we considered the following predictors: initial ratio of pediatricians per 1000 children under five years of age (pediatrician density) and under-5 mortality as measures of local area need, as well as measures of residential quality. Ordinary least-squares regression models were used to estimate the associations. A coefficient equality test was performed to examine differences in predictors before and after 2004. Basic comparisons of pediatrician coverage in the top and bottom 10% of STMs were conducted to assess inequality in pediatrician supply. Results: Increased supply was inversely associated with baseline pediatrician density both in the pre-period and post-period. Estimated impact of pediatrician density declined over time (P = 0.026), while opposite trends were observed for measures of residential quality. More specifically, urban centers and the SES composite index were positively associated with pediatrician supply for the post-period, but no such associations were found for the pre-period. Inequality in pediatrician distribution increased substantially after the reform, with the best-served 10% of communities benefitting from five times the pediatrician coverage compared to the least-served 10%. Conclusions: Residential quality increasingly became a function of location preference rather than public health needs after the reform. New placement schemes should be developed to achieve more equity in access to pediatric care.

Background: A growing literature suggests that low birth weight increases the risk of poor health outcomes in adulthood. We tested this hypothesis among young adults living in São Paulo State, Brazil. Methods and Findings: To identify the effects of low birth weight on young adulthood outcomes, a medical assessment of 297 individuals born between 1977 and 1989 was conducted at a primary care unit in São Paulo State, Brazil. We analyzed body mass index (BMI), waist-hip ratio, blood pressure, fasting glucose and total cholesterol levels using linear and logistic regressions. Low birth was negatively associated with BMI (β = −2.0, 95% CI: −3.69, −0.27, p = 0.02), fasting glucose levels (β = −1.9, 95% CI: −3.9, −0.07, p = 0.05), waist-hip ratio (β = −0.03, 95% CI: −0.07, −0.01, p = 0.10), systolic blood pressure (β = −3.32, 95% CI: −7.60, 0.96, p = 0.12), and total cholesterol levels (β = −3.19, 95% CI: −16.43, 10.05, p = 0.636). Low birth weight was also associated with lower odds of young adults being overweight and obese, but neither association was statistically significant. Weight gain in the first 12 months of life was associated with higher adult BMI (β = 0.79, 95% CI: −0.0455, 1.623, p = 0.064) and blood pressure (β = 2.79, 95% CI: 0.22, 5.35, p = 0.034). No associations were found between low birth weight and early life (catch-up) growth. Conclusions: Low birth weight was not associated with poor health outcomes among young adults in Brazil. These results appear inconsistent with the original Barker hypothesis, but will need to be corroborated in larger samples with longer follow-ups to allow a more general evaluation of the validity of the hypothesis in low and middle income countries.

Background: Stunting affects one-third of children under 5 y old in developing countries, and 14% of childhood deaths are attributable to it. A large number of risk factors for stunting have been identified in epidemiological studies. However, the relative contribution of these risk factors to stunting has not been examined across countries. We estimated the number of stunting cases among children aged 24–35 mo (i.e., at the end of the 1,000 days’ period of vulnerability) that are attributable to 18 risk factors in 137 developing countries. Methods and Findings: We classified risk factors into five clusters: maternal nutrition and infection, teenage motherhood and short birth intervals, fetal growth restriction (FGR) and preterm birth, child nutrition and infection, and environmental factors. We combined published estimates and individual-level data from population-based surveys to derive risk factor prevalence in each country in 2010 and identified the most recent meta-analysis or conducted de novo reviews to derive effect sizes. We estimated the prevalence of stunting and the number of stunting cases that were attributable to each risk factor and cluster of risk factors by country and region. The leading risk worldwide was FGR, defined as being term and small for gestational age, and 10.8 million cases (95% CI 9.1 million–12.6 million) of stunting (out of 44.1 million) were attributable to it, followed by unimproved sanitation, with 7.2 million (95% CI 6.3 million–8.2 million), and diarrhea with 5.8 million (95% CI 2.4 million–9.2 million). FGR and preterm birth was the leading risk factor cluster in all regions. Environmental risks had the second largest estimated impact on stunting globally and in the South Asia, sub-Saharan Africa, and East Asia and Pacific regions, whereas child nutrition and infection was the second leading cluster of risk factors in other regions. Although extensive, our analysis is limited to risk factors for which effect sizes and country-level exposure data were available. The global nature of the study required approximations (e.g., using exposures estimated among women of reproductive age as a proxy for maternal exposures, or estimating the impact of risk factors on stunting through a mediator rather than directly on stunting). Finally, as is standard in global risk factor analyses, we used the effect size of risk factors on stunting from meta-analyses of epidemiological studies and assumed that proportional effects were fairly similar across countries. Conclusions: FGR and unimproved sanitation are the leading risk factors for stunting in developing countries. Reducing the burden of stunting requires a paradigm shift from interventions focusing solely on children and infants to those that reach mothers and families and improve their living environment and nutrition.

Sex differences in the prevalence of psychiatric disorders are well documented, with exposure to stress during gestation differentially impacting females and males. We explored sex-specific DNA methylation in the cord blood of 39 females and 32 males born at term and with appropriate weight at birth regarding their potential connection to psychiatric outcomes. Mothers were interviewed to gather information about environmental factors (gestational exposure) that could interfere with the methylation profiles in the newborns. Bisulphite converted DNA was hybridized to Illumina HumanMethylation450 BeadChips. Excluding XYS probes, there were 2,332 differentially methylated CpG sites (DMSs) between sexes, which were enriched within brain modules of co-methylated CpGs during brain development and also differentially methylated in the brains of boys and girls. Genes associated with the DMSs were enriched for neurodevelopmental disorders, particularly for CpG sites found differentially methylated in brain tissue between patients with schizophrenia and controls. Moreover, the DMS had an overlap of 890 (38%) CpG sites with a cohort submitted to toxic exposition during gestation. This study supports the evidences that sex differences in DNA methylation of autosomes act as a primary driver of sex differences that are found in psychiatric outcomes.

Background: Ending preventable newborn deaths is a global health priority, but efforts to improve coverage of maternal and newborn care have not yielded expected gains in infant survival in many settings. One possible explanation is poor quality of clinical care. We assess facility quality and estimate the association of facility quality with neonatal mortality in Malawi. Methods and Findings: Data on facility infrastructure as well as processes of routine and basic emergency obstetric care for all facilities in the country were obtained from 2013 Malawi Service Provision Assessment. Birth location and mortality for children born in the preceding two years were obtained from the 2013–2014 Millennium Development Goals Endline Survey. Facilities were classified as higher quality if they ranked in the top 25% of delivery facilities based on an index of 25 predefined quality indicators. To address risk selection (sicker mothers choosing or being referred to higher-quality facilities), we employed instrumental variable (IV) analysis to estimate the association of facility quality of care with neonatal mortality. We used the difference between distance to the nearest facility and distance to a higher-quality delivery facility as the instrument. Four hundred sixty-seven of the 540 delivery facilities in Malawi, including 134 rated as higher quality, were linked to births in the population survey. The difference between higher- and lower-quality facilities was most pronounced in indicators of basic emergency obstetric care procedures. Higher-quality facilities were located a median distance of 3.3 km further from women than the nearest delivery facility and were more likely to be in urban areas. Among the 6,686 neonates analyzed, the overall neonatal mortality rate was 17 per 1,000 live births. Delivery in a higher-quality facility (top 25%) was associated with a 2.3 percentage point lower newborn mortality (95% confidence interval [CI] -0.046, 0.000, p-value 0.047). These results imply a newborn mortality rate of 28 per 1,000 births at low-quality facilities and of 5 per 1,000 births at the top 25% of facilities, accounting for maternal and newborn characteristics. This estimate applies to newborns whose mothers would switch from a lower-quality to a higher-quality facility if one were more accessible. Although we did not find an indication of unmeasured associations between the instrument and outcome, this remains a potential limitation of IV analysis. Conclusions: Poor quality of delivery facilities is associated with higher risk of newborn mortality in Malawi. A shift in focus from increasing utilization of delivery facilities to improving their quality is needed if global targets for further reductions in newborn mortality are to be achieved.

Background: Community-based programmes are a critical platform for improving child health and development. We tested the impact of a community-based early childhood intervention package in rural Zambia. Methods: We conducted a non-blinded cluster randomised controlled trial in Southern Province, Zambia. 30 clusters of villages were matched based on population density and distance from the nearest health centre, and randomly assigned to intervention (15 clusters and 268 caregiver–child dyads) or control (15 clusters and 258 caregiver–child dyads). Caregivers were eligible if they had a child aged 6–12 months at baseline. In intervention clusters, health workers screened children for infections and malnutrition, and invited caregivers to attend fortnightly group meetings covering a nutrition and child development curriculum. 220 intervention and 215 control dyads were evaluated after 1 year. The primary outcomes were stunting and INTERGROWTH-21st neurodevelopmental assessment (NDA) scores. Weight-for-age and height-for-age z-scores based on WHO growth standards were also analysed. Secondary outcomes were child illness symptoms, dietary intake and caregiver–child interactions based on self-report. Impact was estimated using intention-to-treat analysis. Results: The intervention package was associated with a 0.12 SD increase in weight-for-age (95% CI −0.14 to 0.38), a 0.15 SD increase in height-for-age (95% CI −0.18 to 0.48) and a reduction in stunting (OR 0.68; 95% CI 0.36 to 1.28), whereas there was no measurable impact on NDA score. Children receiving the intervention package had fewer symptoms, a more diverse diet and more caregiver interactions. Conclusions: In settings like Zambia, community-based early childhood programmes appear to be feasible and appreciated by caregivers, as evidenced by high rates of uptake. The intervention package improved parenting behaviours and had a small positive, though statistically insignificant, impact on child development. Given the short time frame of the project, larger developmental impact is likely if differential parenting behaviours persist. Trial registration number NCT02234726; Results.

In a reanalysis of our results,1 Michelle Remme and colleagues (October, 2015)2 found that “secondary schooling might [even] be as good an HIV investment as male circumcision”, not to mention more expensive biomedical options.2 As Remme and colleagues rightly point out, we had excluded from our cost-effectiveness calculations the myriad other benefits to secondary schooling beyond HIV. If the HIV community paid the costs of schooling net of those other benefits, secondary schooling would be extremely cost-effective.

We analyze the effect of fertility on income per capita with a particular focus on the experience of Europe. For European countries with below-replacement fertility, the cost of continued low fertility will only be observed in the long run. We show that in the short run, a fall in the fertility rate will lower the youth dependency ratio and increase the working-age share, thus raising income per capita. In the long run, however, the burden of old-age dependency dominates the youth dependency decline, and continued low fertility will lead to small working-age shares in the absence of large migration inflows. We show that the currently very high working-age shares generated by the recent declines in fertility and migration inflows are not sustainable, and that significant drops in the relative size of the working-age population should be expected. Without substantial adjustments in labor force participation or migration policies, the potential negative repercussions on the European economy are large.