Identifying neonates at risk for post-discharge mortality in Dar es Salaam, Tanzania, and Monrovia, Liberia: Derivation and internal validation of a novel risk assessment tool.

INTRODUCTION: The immediate period after hospital discharge carries a large burden of childhood mortality in sub-Saharan Africa. Our objective was to derive and internally validate a risk assessment tool to identify neonates discharged from the neonatal ward at risk for 60-day post-discharge mortality. METHODS: We conducted a prospective observational cohort study of neonates discharged from Muhimbili National Hospital in Dar es Salaam, Tanzania, and John F Kennedy Medical Centre in Monrovia, Liberia. Research staff called caregivers to ascertain vital status up to 60 days after discharge. We conducted multivariable logistic regression analyses with best subset selection to identify socioeconomic, demographic, clinical, and anthropometric factors associated with post-discharge mortality. We used adjusted log coefficients to assign points to each variable and internally validated our tool with bootstrap validation with 500 repetitions. RESULTS: There were 2344 neonates discharged and 2310 (98.5%) had post-discharge outcomes available. The median (IQR) age at discharge was 8 (4, 15) days; 1238 (53.6%) were male. In total, 71 (3.1%) died during follow-up (26.8% within 7 days of discharge). Leaving against medical advice (adjusted OR [aOR] 5.62, 95% CI 2.40 to 12.10) and diagnosis of meconium aspiration (aOR 6.98, 95% CI 1.69 to 21.70) conferred the greatest risk for post-discharge mortality. The risk assessment tool included nine variables (total possible score=63) and had an optimism corrected area under the receiver operating characteristic curve of 0.77 (95% CI 0.75 to 0.80). A score of ≥6 was most optimal (sensitivity 68.3% [95% CI 64.8% to 71.5%], specificity 72.1% [95% CI 71.5% to 72.7%]). CONCLUSIONS: A small number of factors predicted all-cause, 60-day mortality after discharge from neonatal wards in Tanzania and Liberia. After external validation, this risk assessment tool may facilitate clinical decision making for eligibility for discharge and the direction of resources to follow-up high risk neonates.

Safe infant feeding in healthcare facilities: Assessment of infection prevention and control conditions and behaviors in India, Malawi, and Tanzania.

Infants need to receive care in environments that limit their exposure to pathogens. Inadequate water, sanitation, and hygiene (WASH) environments and suboptimal infection prevention and control practices in healthcare settings contribute to the burden of healthcare-associated infections, which are particularly high in low-income settings. Specific research is needed to understand infant feeding preparation in healthcare settings, a task involving multiple behaviors that can introduce pathogens and negatively impact health. To understand feeding preparation practices and potential risks, and to inform strategies for improvement, we assessed facility WASH environments and observed infant feeding preparation practices across 12 facilities in India, Malawi, and Tanzania serving newborn infants. Research was embedded within the Low Birthweight Infant Feeding Exploration (LIFE) observational cohort study, which documented feeding practices and growth patterns to inform feeding interventions. We assessed WASH-related environments and feeding policies of all 12 facilities involved in the LIFE study. Additionally, we used a guidance-informed tool to carry out 27 feeding preparation observations across 9 facilities, enabling assessment of 270 total behaviors. All facilities had 'improved' water and sanitation services. Only 50% had written procedures for preparing expressed breastmilk; 50% had written procedures for cleaning, drying, and storage of infant feeding implements; and 33% had written procedures for preparing infant formula. Among 270 behaviors assessed across the 27 feeding preparation observations, 46 (17.0%) practices were carried out sub-optimally, including preparers not handwashing prior to preparation, and cleaning, drying, and storing of feeding implements in ways that do not effectively prevent contamination. While further research is needed to improve assessment tools and to identify specific microbial risks of the suboptimal behaviors identified, the evidence generated is sufficient to justify investment in developing guidance and programing to strengthen infant feeding preparation practices to ensure optimal newborn health.

Reporting of Important Social Determinants of Health in Pediatric Clinical Trials.

INTRODUCTION: The objective of this study was to determine the rates and trends in the reporting of preferred language, socioeconomic factors, sexual orientation, and gender identity in published pediatric clinical trials. METHODS: A cross-sectional study of pediatric clinical trials conducted in the U.S. published from January 1, 2011 through December 31, 2020 in 5 general pediatric and 5 general medical journals with the highest impact factor in their respective fields was performed. Outcomes were reporting of preferred language, socioeconomic factors, sexual orientation, and gender identity. In late 2021, descriptive statistics and logistic regression to understand how reporting of preferred language and socioeconomic factors changed over time were performed. RESULTS: Of 612 trials, 29.6% (n=181) reported preferred language. Among these, 64.6% (n=117 of 181) exclusively enrolled participants whose preferred language was English. From 2011 to 2020, there was a relative increase in the reporting of preferred language (8.6% per year, 95% CI=1.8, 16.0). Socioeconomic factors were reported in 47.9% (n=293) of trials. There was no significant change in the reporting of socioeconomic factors (8.2% per year, 95% CI= -1.9, 15.1). Only 5.1% (9 of 179) of published trial results among adolescent participants reported any measure of sexual orientation, and 1.1% (2 of 179) reported gender identity. CONCLUSIONS: Preferred language, socioeconomic factors, sexual orientation, and gender identity were infrequently reported in pediatric clinical trial results despite these characteristics being increasingly recognized as social determinants of health. To achieve more inclusiveness and to reduce unmeasured disparities, these characteristics should be incorporated into routine trial registration, design, funding decisions, and reporting.

Mortality During Readmission Among Children in United States Children's Hospitals.

OBJECTIVE: To identify demographic, clinical, and hospital factors associated with mortality on readmission within 180 days following an inpatient hospitalization. STUDY DESIGN: We conducted a retrospective cohort study including 33 US children's hospitals in the Pediatric Health Information System from January 2010 to June 2020. Our primary outcome was death during readmission within 180 days of an index hospitalization among children aged 0-18 years. Illness severity during the index hospitalization was defined according to the All Patient-Refined Diagnosis-Related Group-categorized illness severity (ie, minor, moderate, or major/extreme). We performed multivariable logistic regression analysis to identify factors during the index hospitalization associated with mortality during readmission. RESULTS: Among 2 677 111 children discharged, 337 385 (12.6%) were readmitted within 180 days of the index hospitalization and 2913 (0.8%) died during readmission. More than one-quarter (26.2%) of deaths among children who were readmitted and died occurred within 10 days after discharge from the index hospitalization. Factors independently associated with mortality during readmission included multiple complex chronic conditions, index admissions lasting >7 days, moderate or severe/extreme illness during the index hospitalization, and public insurance. Children whose race was reported as Black had greater odds of mortality during readmission compared with children of other races. CONCLUSIONS: Among hospitalized children, several demographic and clinical factors present during index hospitalizations were associated with mortality during readmission. Greater odds of mortality during readmission among children whose race was reported as Black likely reflects disparities in social determinants of health and clinical care. Interventions to reduce mortality during readmission may target high-risk populations in the period immediately following discharge.

Cost-effectiveness of Zinc Supplementation for Prevention of Childhood Diarrhoea in Tanzania.

OBJECTIVE: To assess the cost-effectiveness of prophylactic zinc supplementation for preventing diarrhoea in young children in Tanzania. DESIGN: Cost-effectiveness analysis using decision-analytic modelling. Cost-effectiveness ratios were calculated as the incremental cost (2019 USD) per disability-adjusted life year (DALY) averted, from a societal perspective, and with a 3% discount rate applied to future outcomes. Sensitivity analyses were performed to test the robustness of results to alternative assumptions. SETTING: Tanzania. PARTICIPANTS: A hypothetical cohort of 10,000 children ages 6 weeks to 18 months. RESULTS: The intervention costs of zinc supplementation were estimated as $109,800 (95% uncertainty interval: 61,716-171,507). Zinc supplementation was estimated to avert 2,200 (776-3,737) diarrhoeal episodes, 14,080 (4,692-25,839) sick days, 1,584 (522-2,927) outpatient visits, 561 (160-1,189) inpatient bed-days, 0.51 (0.15-1.03) deaths, and 19.3 (6.1-37.5) DALYs (discounted at 3% per year). Zinc supplementation reduced diarrhoea care costs by $12, 887 (4,089-25,058). The incremental cost per DALY averted was $4,950 (1,678-17,933). Incremental cost-effectiveness ratios (ICERs) estimated from a health system perspective were similar to the results from the societal perspective. ICERs were substantially lower (more favourable) when future outcomes were not discounted, but all ICERs were above contemporary thresholds for cost-effectiveness in this setting. CONCLUSION: Prophylactic zinc reduced diarrhoea incidence and associated healthcare utilization; however it did not appear to be cost-effective for prevention of childhood diarrhoea in the scenario examined in this study. Reducing intervention costs, or identifying high risk groups for intervention targeting, may be needed to improve cost-effectiveness in this setting.

Effect of Maternal Vitamin B12 Supplementation on Cognitive Outcomes in South Indian Children: A Randomized Controlled Clinical Trial.

Objectives To examine the effects of oral maternal vitamin B12 supplementation during pregnancy and early lactation on cognitive development in children. Method We studied 218 children born to mothers enrolled in a placebo-controlled, randomized trial of vitamin B12 supplementation during pregnancy through 6 weeks post-partum. Cognitive functions were assessed at 30 months using the Bayley Scales of Infant Development- 3rd edition (BSID III). The association of maternal sociodemographic characteristics, maternal biochemical status during pregnancy, birth weight and home environment with each sub-domain of BSID-III was examined using linear regression analysis. Separate multiple linear regression analyses for each of the BSID-III sub-domains with maternal trimester specific nutritional biomarker status was conducted. Results Children of mothers who received oral vitamin B12 supplementation had significantly higher scores on expressive language compared to children of mothers who received placebo (ß = 0.14, P = 0.03). Children of mothers with elevated serum total homocysteine (tHcy) in the second and third trimesters of pregnancy had significantly lower scores on expressive language (ß = - 0.18, P = 0.03 and ß = - 0.19, P = 0.02, respectively) and gross motor domains (ß = - 0.23, P = 0.008 and ß = - 0.30, P = 0.001, respectively) of BSID-III adjusted for treatment arm and multiple confounders, compared with children whose mothers did not have elevated tHcy. Conclusions for practice Maternal B12 supplementation during pregnancy was associated with higher expressive language scores in children at 30 months. Elevated maternal tHcy levels during pregnancy had negative associations with expressive language and gross motor domains of BSID-III. Larger trials of maternal B12 supplementation are needed to confirm these findings.

Nutritional, Socioeconomic, and Delivery Characteristics Are Associated with Neurodevelopment in Tanzanian Children.

OBJECTIVES: To evaluate the hypothesis that various maternal, socioeconomic, delivery, and infant nutritional characteristics are associated with early childhood development in young Tanzanian children. STUDY DESIGN: We performed a prospective cohort study among 206 HIV-exposed, uninfected and 247 HIV-unexposed Tanzanian infants who had been enrolled in 2 separate micronutrient trials (NCT00197730 and NCT00421668). Trained nurses administered culturally modified Bayley Scales of Infant and Toddler Development, 3rd edition (BSID-III), to evaluate cognitive, motor, and language development at 15 months of age. This analysis explored predictors of BSID-III z-scores using multivariable linear regression. RESULTS: Among maternal determinants, we found that low maternal height predicted all BSID-III domains in HIV-unexposed children; low maternal education predicted lower cognitive (standardized mean difference, -0.41; 95% CI, -0.74 to -0.08) and lower gross motor scores (standardized mean difference, -0.32; 95% CI, -0.61 to -0.04) in HIV-exposed children. Among delivery characteristics, facility delivery predicted higher cognitive scores (standardized mean difference, 1.36; 95% CI, 0.26-2.46); and oxytocin administration predicted lower fine motor scores (standardized mean difference, -0.48; 95% CI, -0.87 to -0.09) in HIV-exposed children. Higher length-for-age z-scores at 6 weeks of age predicted better cognitive (standardized mean difference, 0.15; 95% CI, 0.01-0.29) and expressive language scores (standardized mean difference, 0.16; 95% CI, 0.02-0.29) at 15 months in HIV-exposed infants. CONCLUSIONS: This hypothesis-generating study found significant associations between nutritional status and health of the mother and child, and maternal educational attainment, with direct measures of early childhood development at 15 months of age. In addition, several aspects of delivery (facility birth and oxytocin administration) were associated with early childhood development. Future intervention trials should focus on modifiable maternal, infant, and obstetric factors to strengthen the evidence base concerning early childhood development. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00197730 and NCT00421668.

Body Composition in Children with Chronic Illness: Accuracy of Bedside Assessment Techniques.

OBJECTIVE: To evaluate the accuracy of estimated fat mass and fat-free mass from bedside methods compared with reference methods in children with chronic illnesses. STUDY DESIGN: Fat mass and fat-free mass values were obtained by skinfold, bioelectrical impedance analysis (BIA), dual-energy x-ray absorptiometry (DXA), and deuterium dilution method in children with spinal muscular atrophy, intestinal failure, and post hematopoietic stem cell transplantation (HSCT). Spearman's correlation and agreement analyses were performed between (1) fat mass values estimated by skinfold equations and by DXA and (2) fat-free mass values estimated by BIA equations and by DXA and deuterium dilution methods. Limits of agreement between estimating and reference methods within ±20% were deemed clinically acceptable. RESULTS: Fat mass and fat-free mass values from 90 measurements in 56 patients, 55% male, and median age of 11.6 years were analyzed. Correlation coefficients between the skinfold-estimated fat mass values and DXA were 0.93-0.94 and between BIA-estimated fat-free mass values and DXA were 0.92-0.97. Limits of agreement between estimated and DXA values of fat mass and fat-free mass were greater than ±20% for all equations. Correlation coefficients between estimated fat-free mass values and deuterium dilution method in 35 encounters were 0.87-0.91, and limits of agreement were greater than ±20%. CONCLUSION: Estimated body composition values derived from skinfold and BIA may not be reliable in children with chronic illnesses. An accurate noninvasive method to estimate body composition in this cohort is desirable.

The effect of daily zinc and/or multivitamin supplements on early childhood development in Tanzania: results from a randomized controlled trial.

Impaired childhood development has lifelong consequences for educational attainment and wage-earning potential. Micronutrient supplements have the potential to improve development. The objective of this study was to determine the effect of daily zinc and/or multivitamin (vitamins C, E and B-complex) supplements on development among Tanzanian infants. In this randomized, 2 × 2 factorial, double-blind trial, 2400 infants were randomized to zinc (Zn), multivitamins (MV), zinc and multivitamins (Zn + MV) or placebo at 6 weeks of age. At approximately 15 months, a sub-sample of 247 children underwent developmental assessment using the cognitive, language (receptive and expressive) and motor (fine and gross) scales of the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III). Mean BSID-III scores were compared using univariate and multivariate linear regression models adjusted for child's sex, post-conceptual age and test administrator. Logistic regressions were used to assess odds of low developmental scores. We did not detect a significant difference in mean BSID-III scores in any of the five domains in univariate or multivariate models comparing each of the four treatment groups. We also did not detect a significant difference in mean BSID-III scores when comparing children who received zinc supplements versus those who did not, or in comparisons of children who received multivitamin supplements versus those who did not. There was no significant difference in odds of a low BSID-III score in any of the five domains in treatment arms either. Because neither daily zinc nor multivitamin (vitamins B-complex, C and E) supplementation led to improvements in any of the developmental domains assessed using the BSID-III, we recommend pursuing alternative interventions to promote early childhood development in vulnerable populations. © 2016 John Wiley & Sons Ltd.

High Burden of Morbidity and Mortality but Not Growth Failure in Infants Exposed to but Uninfected with Human Immunodeficiency Virus in Tanzania.

OBJECTIVE: To compare health and growth outcomes in children infected with HIV, children exposed to but uninfected with HIV, and children unexposed to HIV. STUDY DESIGN: Our cohort included 3554 Tanzanian children enrolled in 2 trials of micronutrient supplementation. Among infants born to mothers infected with HIV, 264 were infected with HIV and 2088 were exposed to but uninfected at 6 weeks of age. An additional 1202 infants were unexposed to HIV. Infants were followed until 18 months of age, death, or loss to follow-up. Morbidity and growth were assessed at monthly nurse visits. RESULTS: Compared with unexposed infants, hazard ratios (95% CI) for all-cause mortality in infants infected with HIV and infants who were exposed to but uninfected with HIV were 28.99 (14.83-56.66) and 2.79 (1.41-5.53), respectively, after adjusting for demographic and nutritional covariates. Compared with infants unexposed to HIV, infants infected with HIV also had a significantly greater risk of all measured morbidities, while infants who were exposed to but uninfected with HIV were significantly more likely to suffer from cough, fever, unscheduled outpatient visits, and hospitalizations. Infants infected with HIV also were more likely to experience stunting, wasting, and underweight at baseline and during follow-up. Infants exposed to but uninfected with HIV were more likely to be underweight at baseline (adjusted relative risk, 2.05; 95% CI, 1.45-2.89), but on average, experienced slower declines in height-for-age z-score, weight-for-age z-score, and weight-for-height z-score as well as a lower rate of stunting over follow-up, compared with unexposed infants. CONCLUSION: In addition to preventing and treating HIV infection in infants, prevention-of-mother-to-child-transmission of HIV and child health services should also target children exposed to but uninfected with HIV to improve health outcomes in this vulnerable population. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00197730 and NCT00421668.

Accuracy of a simplified equation for energy expenditure based on bedside volumetric carbon dioxide elimination measurement--a two-center study.

BACKGROUND & AIMS: Accurate assessment of resting energy expenditure (REE) and metabolic state is essential to optimize nutrient intake in critically ill patients. We aimed to examine the accuracy of a simplified equation for predicting REE using carbon dioxide elimination (VCO2) values. METHODS: We conducted a two-center study of metabolic data from mechanically ventilated children less than 18 years of age. Mean respiratory quotient (RQ) from the derivation set (n = 72 subjects) was used to modify the Weir equation to obtain a simplified equation based on VCO2 measurements alone. This equation was then applied to subjects at the second institution (validation dataset, n = 94) to predict resting energy expenditure. Bland-Altman analysis was used to assess the agreement between measured REE values, and REE estimated by the new equation as well as the Schofield equation. We also examined the accuracy of the new equation in classifying patients according to their metabolic state. RESULTS: Mean respiratory quotient (± SD) of 0.89 ± 0.09 in the derivation set was used to obtain a simplified equation, REE (kcal/day) = 5.534*VCO2 (L/min)*1440. In relation to the measured REE in the validation set, the mean bias (limits of agreement) for the REE predicted by this equation was -0.65% (-14.4-13.1%); and the overall diagnostic accuracy for classifying subjects as hypometabolic or hypermetabolic was 84%. Mean bias (limits) of agreement between measured and Schofield equation estimated REE was -0.1% (-40.5-40.7%). CONCLUSIONS: A simplified metabolic equation using VCO2 values was superior to the standard equation in estimating REE, and provided a reasonably accurate metabolic classification in mechanically ventilated children. In the absence of indirect calorimetry, bedside VCO2 monitoring could provide valuable continuous metabolic information to guide optimal nutrient intake.

Comparison of body composition assessment methods in pediatric intestinal failure.

OBJECTIVES: The aim of the study was to examine the agreement of multifrequency bioelectric impedance analysis (BIA) and anthropometry with reference methods for body composition assessment in children with intestinal failure (IF). METHODS: We conducted a prospective pilot study in children 14 years or younger with IF resulting from either short bowel syndrome or motility disorders. Bland-Altman analysis was used to examine the agreement between BIA and deuterium dilution in measuring total body water (TBW) and lean body mass (LBM), and between BIA and dual-energy x-ray absorptiometry (DXA) techniques in measuring LBM and fat mass (FM). FM and percent body fat (%BF) measurements by BIA and anthropometry were also compared in relation to those measured by deuterium dilution. RESULTS: Fifteen children with IF, median (interquartile range) age 7.2 (5.0, 10.0) years, and 10 (67%) boys, were studied. BIA and deuterium dilution were in good agreement with a mean bias (limits of agreement) of 0.9 (-3.2 to 5.0) for TBW (L) and 0.1 (-5.4 to 5.6) for LBM (kg) measurements. The mean bias (limits) for FM (kg) and %BF measurements were 0.4 (-3.8 to 4.6) kg and 1.7 (-16.9 to 20.3)%, respectively. The limits of agreement were within 1 standard deviation of the mean bias in 12 of 14 (86%) subjects for TBW and LBM, and in 11 of 14 (79%) for FM and %BF measurements. Mean bias (limits) for LBM (kg) and FM (kg) between BIA and DXA were 1.6 (-3.0 to 6.3) kg and -0.1 (-3.2 to 3.1) kg, respectively. Mean bias (limits) for FM (kg) and %BF between anthropometry and deuterium dilution were 0.2 (-4.2 to 4.6) and -0.2 (-19.5 to 19.1), respectively. The limits of agreement were within 1 standard deviation of the mean bias in 10 of 14 (71%) subjects. CONCLUSIONS: In children with IF, TBW and LBM measurements by multifrequency BIA method were in agreement with isotope dilution and DXA methods, with small mean bias and clinically acceptable limits of agreement. In comparison with deuterium dilution, BIA was comparable to anthropometry for FM and %BF assessments with small mean bias, but the limits of agreement were large. BIA is a reliable method for TBW and LBM assessments in population studies; however, its reliability in individual patients, especially for FM assessments, cannot be guaranteed.

Resting energy expenditure after Fontan surgery in children with single-ventricle heart defects.

BACKGROUND: Data on resting energy expenditure (REE) and oxygen consumption (VO(2)) after pediatric cardiopulmonary bypass (CPB) will facilitate optimal nutrient prescription. METHODS: The authors measured continuous REE and VO(2), using an in-line indirect calorimetery (IC) in 30 consecutive children with single-ventricle physiology immediately after Fontan surgery. REE during steady state at 8 hours after surgery was compared with standard equation-estimated energy expenditure (EEE). Patients were classified into 3 groups: hypermetabolic (measured REE [MREE]/EEE ratio >1.2), hypometabolic (MREE/EEE ratio <0.8), and normometabolic (MREE/EEE ratio 0.8-1.2). Demographic, anthropometric, and perioperative clinical characteristics were examined for their correlation with metabolic status. RESULTS: In 26 of 30 patients with completed IC, mean REE at 8 hours after surgery was 57 ± 20 kcal/kg/d, and mean VO(2) was 110 ± 35 mL/min. Mean values of VO(2) and REE did not change within the first 24 hours after surgery. There was poor correlation between MREE at 8 hours and the EEE using the World Health Organization equation (r = 0.32, P = .11). Most patients (n = 19, 73%) were either normometabolic or hypometabolic. Lack of hypermetabolism was significantly associated with higher intraoperative serum lactate level and positive fluid balance compared with the rest of the group. CONCLUSIONS: The authors report a low prevalence of hypermetabolism in children with single-ventricle defects after Fontan surgery. Measured REE had poor correlation with equation-estimated energy expenditure in a majority of the cohort. The absence of increased energy expenditure after CPB will influence energy prescription in this group.