Child, maternal, and adult mortality in rural Ethiopia in 2019: a cross-sectional mortality survey using electronic verbal autopsies.

Background: Ethiopia, with about 10% of Africa's population, has little direct information on causes of death, particularly in rural areas where 80% of Ethiopians live. In 2019-2020, we conducted electronic verbal autopsies (e-VA) to examine causes of death and quantify cause-specific mortality rates in rural Ethiopia. Methods: We examined deaths under 70 years in the three years prior to the survey dates (November 25, 2019-February 29, 2020) among 2% of East Gojjam Zone (Amhara Region) using registered deaths and adding random sampling in this cross-sectional study. Trained surveyors interviewed relatives of the deceased with central dual-physician assignment of causes as the main outcome. We documented details on age, sex and location of death, and derived overall rural death rates using 2007 Census data and the United Nations national estimates for 2019. To these, we applied our sample-weighted causes to derive cause-specific mortality rates. We calculated death risks for the leading causes for major age groups. Findings: We studied 3516 deaths: 55% male, 97% rural, and 68% occurring at home. At ages 5 and older, injuries were notable, accounting for over a third of deaths at 5-14 years, half of the deaths at ages 15-29 years, and a quarter of deaths at ages 30-69 years. Neonatal mortality was high, mostly from prematurity/low birthweight and infections. Among children under 5 (excluding neonates), infections caused nearly two-thirds of deaths. Most maternal deaths (84%) arose from direct causes. After injuries, especially suicide, assaults, and road traffic accidents, vascular disease (15%) and cancer (13%) were the leading causes among adults at 30-69 years. HIV/AIDS and tuberculosis deaths were also important causes among adults. Interpretation: Rural Ethiopia has a high burden of avoidable mortality, particularly injury, including suicide, assaults, and road traffic accidents. Funding: International Development Research Centre, and the Canadian Institutes of Health Research.

Adult malaria mortality during 2019 at Bo Government Hospital, Sierra Leone.

It is uncertain whether malaria is an important cause of death among adults in endemic areas. We performed a chart review of adults admitted to Bo Government Hospital during 2019. Of 893 admissions, 149 (59% female, mean age 58.5 years) had a laboratory diagnosis of malaria and 22 (14.8%) died. Mortality was significantly higher among patients with severe malaria compared with those who had non-severe malaria (6/20 [30%] versus 16/129 [12.4%], p=0.031).  Our results suggest that malaria is a common cause of death in hospitalized Sierra Leonian adults.

Could vaccinating adults against malaria materially reduce adult mortality in high-transmission areas?

After a period of unprecedented progress against malaria in the 2000s, halving the global disease burden by 2015, gains overall in sub-Saharan Africa have slowed and even reversed in some places, beginning well before the COVID-19 pandemic. The highly effective drugs, treated nets, and diagnostics that fueled the initial progress all face some threats to their effectiveness, and global funding to maintain and increase their use over the long term is not guaranteed. Malaria vaccines are among the most promising new interventions that could accelerate the elimination of malaria. Vaccines are still in early stages of rollout in children, the age group (along with pregnant women) that has been the focus of malaria strategies for a century. At the same time, over the past decade, a case has been made, based largely on evidence from verbal autopsies in at least a few high-transmission areas, that the malaria death rate among adults has been greatly underestimated. Could vaccinating adults help to bring down the adult malaria mortality rate, contribute to reduced transmission, or both? A randomized trial of a malaria vaccine is proposed in Sierra Leone, a highly endemic setting, to shed light on this proposition.

Complementary and alternative metrics for tracking population-level trends in child linear growth.

Stunting prevalence is commonly used to track population-level child nutritional status. However, other metrics derived from anthropometric datasets may be used as alternatives to stunting or provide complementary perspectives on the status of linear growth faltering in low- and middle-income countries (LMICs). Data from 156 Demographic and Health Surveys in 63 LMICs (years 2000 to 2020) were used to generate 2 types of linear growth metrics: (i) measures of location of height distributions (including stunting) for under-5 years (<5y) and 2 to 5 years (2-5y); (ii) model-derived metrics including predicted mean height-for-age z-score (HAZ) at 0, 2, and 5 years; interval slopes of HAZ, height-for-age difference (HAD), and growth delay (GD) from 1 month to 2 years (1mo-2y) and 2-5y; and the SITAR intensity parameter (SITAR-IP) for <5y. Using Spearman's rank correlation coefficient (r), metrics were considered alternatives to stunting if very strongly correlated with stunting (|r|≥0.95) and at least as strongly correlated as stunting with selected population indicators (under 5y mortality, gross domestic product, maternal education). Metrics were considered complementary if less strongly correlated with stunting (|r|<0.95) yet correlated with population indicators. We identified 6 of 15 candidate metrics (stunting 2-5y, mean HAZ <5y and 2-5y, p25 HAZ <5y and 2-5y, predicted HAZ at 2y) as potential alternatives to stunting and 6 as complementary metrics (SITAR-IP, predicted HAZ at 5y, HAZ slope 1m-2y, HAD slope 1m-2y, GD slopes 1m-2y and 2-5y). Three metrics (HAZ slope 2-5y, HAD slope 2-5y years and predicted HAZ at birth) had weak correlations with population indicators (|r| ≤ 0.43). In conclusion, several linear growth metrics could serve as alternatives to stunting prevalence and others may be complementary to stunting in tracking global progress in child health and nutrition. Further research is needed to explore the real-world utility of these alternative and complementary metrics.

Growth delay: an alternative measure of population health based on child height distributions.

BACKGROUND: Indicators of child height, such as mean height-for-age Z-scores (HAZ), height-for-age difference (HAD) and stunting prevalence, do not account for differences in population-average bone developmental stage. AIM: Propose a measure of child height that conveys the dependency of linear growth on stage rather than chronological age. SUBJECTS AND METHODS: Using Demographic and Health Surveys (2000-2018; 64 countries), we generated: (1) predicted HAZ at specific ages (HAZ regressed on age); (2) height-age (age at which mean height matches the WHO Growth Standards median); (3) Growth delay (GD), the difference between chronological age and height-age; (4) HAD; and (5) stunting prevalence. Metrics were compared based on secular trends within countries and age-related trajectories within surveys. RESULTS: In the most recent surveys (N = 64), GDs ranged from 1.9 to 19.1 months at 60 months chronological age. Cross-sectionally, HAZ, HAD and GD were perfectly correlated, and showed similar secular trends. However, age-related trajectories differed across metrics. Accumulating GD with age demonstrated growth faltering as slower than expected growth for children of the same height-age. Resumption of growth at the median for height-age was rarely observed. CONCLUSION: GD is a population-level measure of child health that reflects the role of delayed skeletal development in linear growth faltering.

Child, maternal, and adult mortality in Sierra Leone: nationally representative mortality survey 2018-20.

BACKGROUND: Sierra Leone's child and maternal mortality rates are among the highest in the world. However, little is known about the causes of premature mortality in the country. To rectify this, the Ministry of Health and Sanitation of Sierra Leone launched the Sierra Leone Sample Registration System (SL-SRS) of births and deaths. Here, we report cause-specific mortality from the first SL-SRS round, representing deaths from 2018 to 2020. METHODS: The Countrywide Mortality Surveillance for Action platform established the SL-SRS, which involved conducting electronic verbal autopsies in 678 randomly selected villages and urban blocks throughout the country. 61 surveyors, in teams of four or five, enrolled people and ascertained deaths of individuals younger than 70 years in 2019-20, capturing verbal autopsies on deaths from 2018 to 2020. Centrally, two trained physicians independently assigned causes of death according to the International Classification of Diseases (tenth edition). SL-SRS death proportions were applied to 5-year mortality averages from the UN World Population Prospects (2019) to derive cause-specific death totals and risks of death nationally and in four Sierra Leone regions, with comparisons made with the Western region where Freetown, the capital, is located. We compared SL-SRS results with the cause-specific mortality estimates for Sierra Leone in the 2019 WHO Global Health Estimates. FINDINGS: Between Sept 1, 2019, and Dec 15, 2020, we enrolled 343 000 people and ascertained 8374 deaths of individuals younger than 70 years. Malaria was the leading cause of death in children and adults, nationally and in each region, representing 22% of deaths under age 70 years in 2020. Other infectious diseases accounted for an additional 16% of deaths. Overall maternal mortality ratio was 510 deaths per 100 000 livebirths (95% CI 483-538), and neonatal mortality rate was 31·1 deaths per 1000 livebirths (95% CI 30·4-31·8), both among the highest rates in the world. Haemorrhage was the major cause of maternal mortality and birth asphyxia or trauma was the major cause of neonatal mortality. Excess deaths were not detected in the months of 2020 corresponding to the peak of the COVID-19 pandemic. Half of the deaths occurred in rural areas and at home. If the Northern, Eastern, and Southern regions of Sierra Leone had the lower death rates observed in the Western region, about 20 000 deaths (just over a quarter of national total deaths in people younger than 70 years) would have been avoided. WHO model-based data vastly underestimated malaria deaths and some specific causes of injury deaths, and substantially overestimated maternal mortality. INTERPRETATION: Over 60% of individuals in Sierra Leone die prematurely, before age 70 years, most from preventable or treatable causes. Nationally representative mortality surveys such as the SL-SRS are of high value in providing reliable cause-of-death information to set public health priorities and target interventions in low-income countries. FUNDING: Bill & Melinda Gates Foundation, Canadian Institutes of Health Research, Queen Elizabeth Scholarship Program.

Anthropometric data quality assessment in multisurvey studies of child growth.

BACKGROUND: Population-based surveys collect crucial data on anthropometric measures to track trends in stunting [height-for-age z score (HAZ) < -2SD] and wasting [weight-for-height z score (WHZ) < -2SD] prevalence among young children globally. However, the quality of the anthropometric data varies between surveys, which may affect population-based estimates of malnutrition. OBJECTIVES: We aimed to develop composite indices of anthropometric data quality for use in multisurvey analysis of child health and nutritional status. METHODS: We used anthropometric data for children 0-59 mo of age from all publicly available Demographic and Health Surveys (DHS) from 2000 onwards. We derived 6 indicators of anthropometric data quality at the survey level, including 1) date of birth completeness, 2) anthropometric measure completeness, 3) digit preference for height and age, 4) difference in mean HAZ by month of birth, 5) proportion of biologically implausible values, and 6) dispersion of HAZ and WHZ distribution. Principal component factor analysis was used to generate a composite index of anthropometric data quality for HAZ and WHZ separately. Surveys were ranked from the highest (best) to the lowest (worst) index values in anthropometric quality across countries and over time. RESULTS: Of the 145 DHS included, the majority (83 of 145; 57%) were conducted in Sub-Saharan Africa. Surveys were ranked from highest to lowest anthropometric data quality relative to other surveys using the composite index for HAZ. Although slightly higher values in recent DHS suggest potential improvements in anthropometric data quality over time, there continues to be substantial heterogeneity in the quality of anthropometric data across surveys. Results were similar for the WHZ data quality index. CONCLUSIONS: A composite index of anthropometric data quality using a parsimonious set of individual indicators can effectively discriminate among surveys with excellent and poor data quality. Such indices can be used to account for variations in anthropometric data quality in multisurvey epidemiologic analyses of child health.

Perspective: Understanding the Intersection of Climate/Environmental Change, Health, Agriculture, and Improved Nutrition - A Case Study: Type 2 Diabetes.

Efforts to promote health through improved diet and nutrition demand an appreciation of the nutritional ecology that accounts for the intersection of agriculture, food systems, health, disease and a changing environment. The complexity and implications of this ecology is exemplified by current trends and efforts to address nutrition-related non-communicable diseases (NCDs), most prominently type 2 diabetes. The global prevalence of type 2 diabetes continues to rise unabated. Of particular concern is how to address the unhealthy dietary patterns that are contributing to this pandemic in a changing environment. A multi- disciplinary approach is required that will engage those communities that comprise the continuum of effort from research to translation and implementation of evidence-informed interventions, programs and policies. Using the prevention of type 2 diabetes by increasing fruit and vegetable consumption as an exemplar, we argue that the ability to effect positive change in this and other persistent nutrition-related problems can be achieved by moving away from siloed approaches that limit the integration of key components of the diet-health continuum. Ultimately the impact of preventing type 2 diabetes via increased fruit and vegetable consumption will depend on how the entire diet changes, not just fruits and vegetables. In addition, the rapidly changing physical environment that will confront our food production system going forward will also shape the interventions that are possible. Nonetheless, the proposed "team science" approach that accounts for all the elements of the nutrition ecology will better position us to achieve public health goals through safe and sustainable food systems.

Impact of iron fortification on the geospatial patterns of malaria and non-malaria infection risk among young children: a secondary spatial analysis of clinical trial data from Ghana.

OBJECTIVES: Patterns of infection among children with varying levels of iron status in a malaria endemic area may vary spatially in ways requiring integrated infection and iron deficiency control programmes. The objective of this secondary analysis was to determine the geospatial factors associated with malaria and non-malaria infection status among young Ghanaian children at the end of a 5-month iron intervention trial. DESIGN: Cluster-randomised controlled trial. SETTING: Rural Ghana PARTICIPANTS: 1943 children (6-35 months of age) with geocoded compounds. INTERVENTIONS: Point-of-use fortification with micronutrient powders containing vitamins and minerals with or without iron. PRIMARY AND SECONDARY OUTCOME MEASURES: Generalised linear geostatistical models with a Matern spatial correlation function were used to analyse four infection response variables, defined using different combinations of inflammation (C-reactive protein, CRP >5 mg/L) and malaria parasitaemia. Analyses were also stratified by treatment group to assess the independent effects of the iron intervention. RESULTS: The by-group and combined-group analyses both showed that baseline infection status was the most consistent predictor of endline infection risk, particularly when infection was defined using parasitaemia. In the No-iron group, age above 24 months and weight-for-length z-score at baseline were associated with high CRP at endline. Higher asset score was associated with a 12% decreased odds of endline infection, defined as CRP >5 mg/L and/or parasitaemia (OR 0.88, 95% credible interval 0.78 to 0.98), regardless of group. Maps of the predicted risk and spatial random effects showed a defined low-risk area around the District centre, regardless of how infection was defined. CONCLUSION: In a clinical trial setting of iron fortification, where all children receive treated bed nets and access to malaria treatment, there may be geographical variation in the risk of infection with distinct high-risk and low-risk areas, particularly around municipal centres. TRIAL REGISTRATION NUMBER: clinicaltrials.gov, NCT01001871.

The intersection of climate/environment, food, nutrition and health: crisis and opportunity.

Climate/environmental change (C-E-C) is affecting human health and quality of life. Significant attention has been given to the impact of C-E-C on food supply, and food as a vehicle for exposure. However, C-E-C has been superimposed on prevalent malnutrition, infectious and non-communicable diseases. We discuss why nutrition is not synonymous with food and must be viewed as a biological variable that affects and is affected by both C-E-C as well as the current global health challenges. The nexus of C-E-C, food, nutrition and health must be considered in the development of safe and efficacious interventions. A case is presented for how the convergence of C-E-C, food/nutrition and health, presents an opportunity for more integrated approaches to achieve global health goals.

Geo-spatial factors associated with infection risk among young children in rural Ghana: a secondary spatial analysis.

BACKGROUND: Determining the spatial patterns of infection among young children living in a malaria-endemic area may provide a means of locating high-risk populations who could benefit from additional resources for treatment and improved access to healthcare. The objective of this secondary analysis of baseline data from a cluster-randomized trial among 1943 young Ghanaian children (6-35 months of age) was to determine the geo-spatial factors associated with malaria and non-malaria infection status. METHODS: Spatial analyses were conducted using a generalized linear geostatistical model with a Matern spatial correlation function and four definitions of infection status using different combinations of inflammation (C-reactive protein, CRP > 5 mg/L) and malaria parasitaemia (with or without fever). Potentially informative variables were included in a final model through a series of modelling steps, including: individual-level variables (Model 1); household-level variables (Model 2); and, satellite-derived spatial variables (Model 3). A final (Model 4) and maximal model (Model 5) included a set of selected covariates from Models 1 to 3. RESULTS: The final models indicated that children with inflammation (CRP > 5 mg/L) and/or any evidence of malaria parasitaemia at baseline were more likely to be under 2 years of age, stunted, wasted, live further from a health facility, live at a lower elevation, have less educated mothers, and higher ferritin concentrations (corrected for inflammation) compared to children without inflammation or parasitaemia. Similar results were found when infection was defined as clinical malaria or parasitaemia with/without fever (definitions 3 and 4). Conversely, when infection was defined using CRP only, all covariates were non-significant with the exception of baseline ferritin concentration. In Model 5, all infection definitions that included parasitaemia demonstrated a significant interaction between normalized difference vegetation index and land cover type. Maps of the predicted infection probabilities and spatial random effect showed defined high- and low-risk areas that tended to coincide with elevation and cluster around villages. CONCLUSIONS: The risk of infection among young children in a malaria-endemic area may have a predictable spatial pattern which is associated with geographical characteristics, such as elevation and distance to a health facility. Original trial registration clinicaltrials.gov (NCT01001871).

Effect of iron fortification on malaria incidence in infants and young children in Ghana: a randomized trial.

IMPORTANCE: In sub-Saharan Africa, malaria is a leading cause of childhood morbidity and iron deficiency is among the most prevalent nutritional deficiencies. In 2006, the World Health Organization and the United Nations Children's Fund released a joint statement that recommended limiting use of iron supplements (tablets or liquids) among children in malaria-endemic areas because of concern about increased malaria risk. As a result, anemia control programs were either not initiated or stopped in these areas. OBJECTIVE: To determine the effect of providing a micronutrient powder (MNP) with or without iron on the incidence of malaria among children living in a high malaria-burden area. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, cluster randomized trial of children aged 6 to 35 months (n = 1958 living in 1552 clusters) conducted over 6 months in 2010 in a rural community setting in central Ghana, West Africa. A cluster was defined as a compound including 1 or more households. Children were excluded if iron supplement use occurred within the past 6 months, they had severe anemia (hemoglobin level <7 g/dL), or severe wasting (weight-for-length z score <-3). INTERVENTIONS: Children were randomized by cluster to receive a MNP with iron (iron group; 12.5 mg/d of iron) or without iron (no iron group). The MNP with and without iron were added to semiliquid home-prepared foods daily for 5 months followed by 1-month of further monitoring. Insecticide-treated bed nets were provided at enrollment, as well as malaria treatment when indicated. MAIN OUTCOMES AND MEASURES: Malaria episodes in the iron group compared with the no iron group during the 5-month intervention period. RESULTS: In intention-to-treat analyses, malaria incidence overall was significantly lower in the iron group compared with the no iron group (76.1 and 86.1 episodes/100 child-years, respectively; risk ratio (RR), 0.87 [95% CI, 0.79-0.97]), and during the intervention period (79.4 and 90.7 episodes/100 child-years, respectively; RR, 0.87 [95% CI, 0.78-0.96]). In secondary analyses, these differences were no longer statistically significant after adjusting for baseline iron deficiency and anemia status overall (adjusted RR, 0.87; 95% CI, 0.75-1.01) and during the intervention period (adjusted RR, 0.86; 95% CI, 0.74-1.00). CONCLUSION AND RELEVANCE: In a malaria-endemic setting in which insecticide-treated bed nets were provided and appropriate malaria treatment was available, daily use of a MNP with iron did not result in an increased incidence of malaria among young children. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01001871.

A systematic review of the application and utility of geographical information systems for exploring disease-disease relationships in paediatric global health research: the case of anaemia and malaria.

Malaria and anaemia are important health problems among children globally. Iron deficiency anaemia may offer protection against malaria infection and iron supplementation may increase the risk of malaria-related hospitalization and mortality. The nature and mechanism of these relationships, however, remain largely unresolved, resulting in concern and uncertainty around policies for non-selective iron supplementation in malaria endemic areas. Use of geographical information systems (GIS) to investigate this disease-disease interaction could contribute important new information for developing safe and effective anaemia and malaria interventions. To assess the current state of knowledge we conducted a systematic review of peer-reviewed and grey literature. Our primary objective was to qualitatively assess the application and utility of geographical concepts or spatial analyses in paediatric global health research. The secondary objective was to identify geographical factors that may be associated with anaemia and malaria prevalence or incidence among children 0-5 years of age living in low- and middle-income countries. Evaluation tools for assessing the quality of geographical data could not be found in the peer-reviewed or grey literature, and thus adapted versions of the STROBE (Strengthening The Reporting of Observational Studies in Epidemiology) and GRADE (Grades of Recommendation, Assessment, Development and Evaluation) methods were used to create reporting, and overall evidence quality scoring systems. Among the 20 included studies, we found that both malaria and anaemia were more prevalent in rural communities compared to urban areas. Geographical factors associated with malaria prevalence included regional transmission stability, and proximity to a mosquito breeding area. The prevalence of anaemia tended to vary inversely with greater or poorer access to community services such as piped water. Techniques for investigating geographic relationships ranged from simple descriptive mapping of spatial distribution patterns, to more complex statistical models that incorporated environmental factors such as seasonal temperature and rain fall. Including GIS in paediatric global health research may be an effective approach to explore relationships between childhood diseases and contribute key evidence for safe implementation of anaemia control programs in malaria endemic areas. Further, GIS presentation of ecological health data could provide an efficient means of translating this knowledge to lay audiences.

Relative efficacy of micronutrient powders versus iron-folic acid tablets in controlling anemia in women in the second trimester of pregnancy.

BACKGROUND: Iron deficiency is a major cause of anemia and the most prevalent nutrient deficiency among pregnant women in developing countries. The use of iron and folic acid supplements to treat and prevent iron-deficiency anemia has limited effectiveness, mainly due to poor adherence. Home fortification with a micronutrient powder for pregnant women may be an effective and acceptable alternative to traditional drug models. OBJECTIVE: To determine whether home fortification with micronutrient powders is at least as efficacious as iron and folic acid tablets for improving hemoglobin concentration in pregnant women. METHODS: A cluster-randomized noninferiority trial was conducted in the rural subdistrict of Kaliganj in central Bangladesh. Pregnant women (gestational age 14-22 weeks, n=478), were recruited from 42 community-based Antenatal Care Centres. Each centre was randomly allocated to receive either a micronutrient powder (containing iron,folic acid, vitamin C, and zinc) or iron and folic acid tablets. Changes in hemoglobin from baseline were compared across groups using a linear mixed-effects regression model. RESULTS: At enrolment, the overall prevalence of anemia was 45% (n = 213/478). After the intervention period, the mean hemoglobin concentrations among women receiving the micronutrient powder were not inferior to those among women receiving tablets (109.5 ± 12.9 vs. 112.0 ± 11.2 g/L; 95% CI, -0.757 to 5.716). Adherence to the micronutrient powder was lower than adherence to tablets (57.5 ± 22.5% vs. 76.0 ± 13.7%; 95% CI, -22.39 to -12.94); however, in both groups, increased adherence was positively correlated with hemoglobin concentration. CONCLUSIONS: The micronutrient powder was at least as efficacious as the iron and folic acid tablets in controlling moderate to severe anemia during pregnancy.

Burden of anemia among indigenous populations.

An international perspective of the magnitude of anemia in indigenous peoples is currently lacking. The present systematic review was performed to characterize the global prevalence, severity, and etiology of anemia in indigenous peoples by conducting a systematic search of original research published in English from 1996 to February 2010 using PubMed, Medline, and Embase. A total of 50 studies, representing the following 13 countries, met the inclusion criteria: Australia, Brazil, Canada, Guatemala, India, Kenya, Malaysia, Mexico, New Zealand, Sri Lanka, Tanzania, the United States, and Venezuela. Results indicate major deficiencies in the coverage and quality of anemia monitoring data for indigenous populations worldwide. The burden of anemia is overwhelmingly higher among indigenous groups compared to the general population and represents a moderate (20-39.9%) to severe (≥40%) public health problem. For the most part, the etiology of anemia is preventable and includes inadequate diet, poor living conditions, and high infection rates (i.e., malaria and intestinal parasites). A concerted global effort is needed to reduce the worldwide burden of anemia in these marginalized populations.

A combination of pH-sensitive caplet coatings may be an effective noninvasive strategy to deliver bioactive substances, nutrients, or their precursors to the colon.

We hypothesize that bacterially synthesized nutrients in the large intestine may significantly influence the nutritional status of humans and, specifically, that of the colonocytes. In vivo research with human subjects in this area has been extremely limited because of the absence of a noninvasive means to quantitatively deliver test doses of nutrients, or their precursors, to the colon. The purpose of this study was to design and test the effectiveness of a pH-dependent coating in delivering intact placebo caplets to the large intestine. Barium sulphate caplet cores (19.1 mm x 9.7 mm) were coated with 2 different pH-dependent acrylic copolymer products, Eudragit L100 and S100, in either a 1:0 ratio (100% Eudragit L100) or 3:1 ratio (75% Eudragit L100 and 25% S100). The disintegration profile of each formulation was determined through in vitro testing, then caplets were sequentially administered to 10 healthy volunteers, and monitored in vivo via serial abdominal fluoroscopic images. Test caplets with the 3:1 coating formulation had a 40% higher colon-targeting specificity compared with the 1:0-coated caplets, and tended to begin disintegrating at a later time after administration (p = 0.09). The total time from administration to complete disintegration was also significantly longer for the 3:1-coated caplets (p = 0.003). These results suggest that barium sulphate caplets with a 3:1 acrylic copolymer coating formulation ratio (Eudragit L100 and S100) may be a suitable delivery system for quantifying the biosynthesis of nutrients in the human large intestine and measuring their absorption across the colonic epithelium.

Growth and body composition of human milk-fed premature infants provided with extra energy and nutrients early after hospital discharge: 1-year follow-up.

OBJECTIVES: Human milk (HM) is the optimal source of nutrition for premature infants; however, it is unclear whether HM alone is sufficient to meet their elevated nutritional requirements early after hospital discharge. We previously reported that premature infants (750-1800 g birth weight) fed HM containing extra nutrients for 12 weeks after discharge had dietary intakes closer to recommended levels and grew more rapidly than those fed HM alone. The objectives of the present article are to examine the impact of this intervention on bone mineralization, body composition, and HM use up to 1 year. Data are also presented on general developmental level at 18-month corrected age (CA). PATIENTS AND METHODS: At discharge, predominantly HM-fed infants were randomized to receive for 12 weeks either approximately half of their feedings containing a multinutrient fortifier (intervention, n=19) or all of their feedings as HM alone (control, n=20). RESULTS: Intervention infants remained longer (P<0.001) and had greater whole-body bone mineral content (P=0.02) until 12-month CA compared with controls. Intervention infants born less than or equal to 1250 g continued to have a larger mean head circumference throughout the first year of life (P<0.0001). Human milk feeding (mL.kg(-1).day(-1)) differed between groups at 6- (P=0.035), but not 12-month CA. No statistically significant differences were found between groups in the mental, motor, or behavior rating scale scores of the Bayley II at 18-month CA. CONCLUSIONS: Adding a multinutrient fortifier to HM provided to predominantly HM-fed premature infants early after discharge results in sustained differences in weight, length, and whole-body bone mineral content, and in smaller babies, head circumference for the first year of life.