Impact of emollient therapy for preterm infants in the neonatal period on child neurodevelopment in Bangladesh: an observational cohort study.

BACKGROUND: Topical treatment with sunflower seed oil (SSO) or Aquaphor® reduced sepsis and neonatal mortality in hospitalized preterm infants <33 weeks' gestational age in Bangladesh. We sought to determine whether the emollient treatments improved neurodevelopmental outcomes during early childhood. METHODS: 497 infants were randomized to receive SSO, Aquaphor®, or neither through the neonatal period or hospital discharge. 159 infant survivors were enrolled in the longitudinal follow-up study using a validated Rapid Neurodevelopmental Assessment tool and the Bayley Scales of Infant Development II (BSID II) administered at three-monthly intervals for the first year and thereafter at six-monthly intervals. Lowess smoothing was used to display neurodevelopmental status across multiple domains by age and treatment group, and Generalized Estimating Equations (GEE) were used to compare treatment groups across age points. RESULTS: 123 children completed at least one follow-up visit. Lowess graphs suggest that lower proportions of children who received massage with either SSO or Aquaphor® had neurodevelopmental delays than control infants in a composite outcome of disabilities. In GEE analysis, infants receiving SSO showed a significant protective effect on the development of fine motor skills [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.86-0.98, p=0.006]. The Psychomotor Development Index (PDI) in the BSID II showed significantly lower disability rates in the Aquaphor group (23.6%) compared to the control (55.2%) (OR 0.21, 95% CI 0.06-0.72, p=0.004). CONCLUSIONS: Emollient massage of very preterm, hospitalized newborn infants improved some child neurodevelopmental outcomes over the first 2 years of follow-up. Findings warrant further confirmatory research. TRIAL REGISTRATION: ClinicalTrials.gov (98-04-21-03-2) under weblink https://clinicaltrials.gov/ct2/show/NCT00162747.

Hierarchical Statistical Models to Represent and Visualize Survey Evidence for Program Evaluation: iCCM in Malawi.

Policy and Program evaluation for maternal, newborn and child health is becoming increasingly complex due to changing contexts. Monitoring and evaluation efforts in this area can take advantage of large nationally representative household surveys such as DHS or MICS that are increasing in size and frequency, however, this analysis presents challenges on several fronts. We propose an approach with hierarchical models for cross-sectional survey data to describe evidence relating to program evaluation, and apply this approach to the recent scale up of iCCM in Malawi. We describe careseeking for children sick with diarrhea, pneumonia, or malaria with empirical Bayes estimates for each district of Malawi at two time points, both for careseeking from any source, and for careseeking only from health surveillance assistants (HSA). We do not find evidence that children in areas with more HSA trained in iCCM are more likely to seek care for pneumonia, diarrhea, or malaria, despite evidence that many indeed are seeking care from HSA. Children in areas with more HSA trained in iCCM are more likely to seek care from a HSA, with 100 additional trained health workers in a district corresponding to a 2% average increase in careseeking from HSA. The hierarchical models presented here provide a flexible set of methods that describe the primary evidence for evaluating iCCM in Malawi and which could be extended to formal causal analyses, and to analysis for other similar evaluations with national survey data.

Treatment effects of maternal micronutrient supplementation vary by percentiles of the birth weight distribution in rural Nepal.

Certain antenatal micronutrient supplements increased birth weight by 40-70 g in rural Nepal. The effect was estimated by calculating the mean difference in birth weight between control and treatment groups, which assumes a constant treatment effect across the birth weight distribution. By estimating differences (and CI) in birth weight between treatment and control groups as a nonlinear, smooth function of the percentiles of the birth weight distribution, we can examine whether the shape of the birth weight distribution for a treatment group is different from that of the control group. Supplementation groups were folic acid, folic acid and iron, folic acid and iron and zinc, and a multiple micronutrient supplement all with vitamin A, compared with the control group of vitamin A alone. The shape of the birth weight distribution in the multiple micronutrient group was the same as that of the control group; however, the location of the distribution had shifted. The folic acid and iron group had fewer infants in the lower tail of its distribution but a similar proportion in the upper tail compared with the control group. The biologic pathways affecting intrauterine growth may vary by micronutrients such that some may confer a benefit among the most vulnerable infants, whereas others may have a more constant effect across the birth weight distribution. Future analytic approaches to estimating benefits of maternal supplementation on birth weight should examine whether there is a constant or variable treatment effect across the distribution of birth weight.

Familial risk for Alzheimer's disease alters fMRI activation patterns.

Alzheimer's disease poses a looming crisis for the health care system as well as society in general. The low efficacy of current treatments for those already affected with this disease has prompted the suggestion that interventions might be more successful if they were applied before the development of significant pathology, that is, when individuals are clinically asymptomatic. Currently, the field requires a sensitive and specific diagnostic tool for identifying those individuals destined to develop this disease. As a first step, we present here an analysis of cross-sectional data for 95 asymptomatic offspring (50-75 years of age) of autopsy-confirmed late-onset familial Alzheimer's disease cases and 90 age-matched controls, studied with functional magnetic resonance imaging (fMRI) to investigate brain activation patterns. Analysis of activation in response to a paired-associates memory paradigm found significantly different patterns in these groups. At-risk individuals showed more intense and extensive activation in the frontal and temporal lobes including the hippocampus during memory encoding, an increase unrelated to the APOE epsilon4 allele. They also showed decreased activation particularly in the cingulum and thalamus during both the encoding and recall phases of the task. These results demonstrate that asymptomatic individuals, at genetic risk for development of late-onset Alzheimer's disease by virtue of familial clustering, show functional activation patterns distinct from those without such risk more than a decade before their parent's onset age. While longitudinal study is needed to determine whether these patterns, or a subset of them, are predictive of disease onset, these findings suggest that functional neuroimaging holds promise as a method of identifying pre-clinical Alzheimer's disease.