Derivation and Internal Validation of a Novel Risk Assessment Tool to Identify Infants and Young Children at Risk for Post-Discharge Mortality in Dar es Salaam, Tanzania and Monrovia, Liberia.

OBJECTIVE: To derive and validate internally a novel risk assessment tool to identify young children at risk for all-cause mortality ≤60 days of discharge from hospitals in sub-Saharan Africa. STUDY DESIGN: We performed a prospective observational cohort study of children aged 1-59 months discharged from Muhimbili National Hospital in Dar es Salaam, Tanzania and John F. Kennedy Medical Center in Monrovia, Liberia (2019 to 2022). Caregivers received telephone calls up to 60 days after discharge to ascertain participant vital status. We collected socioeconomic, demographic, clinical, and anthropometric data during hospitalization. Candidate variables with P<0.20 in bivariate analyses were included in a multivariable logistic regression model with best subset selection to identify risk factors for the outcome. We internally validated our tool using bootstrapping with 500 repetitions. RESULTS: There were 1,933 young children enrolled in the study. The median (interquartile range) age was 11 (4, 23) months and 58.7% were male. In total, 67 (3.5%) died during follow-up. Ten variables contributed to our tool (total possible score 82). Cancer (adjusted odds ratio [aOR] 10.6, 95% CI 2.58, 34.6), pedal edema (aOR 6.94, 95% CI 1.69, 22.6), and leaving against medical advice (aOR 6.46, 95% CI 2.46, 15.3) were most predictive of post-discharge mortality. Our risk assessment tool demonstrated good discriminatory value (optimism corrected area under the receiver operating characteristic curve 0.77), high precision, and sufficient calibration. CONCLUSIONS: After validation, this tool may be used to identify young children at risk for post-discharge mortality to direct resources for follow-up of high-risk children.

The Association Between Breastfeeding and Growth Among Infants with Moderately Low Birth Weight: A Prospective Cohort Study.

OBJECTIVE: To assess the association between breastfeeding competency, as determined by Latch, Audible swallowing, Type of nipple, Comfort, and Hold (LATCH) and Preterm Infant Breastfeeding Behavior Scale (PIBBS) scores, and exclusive breastfeeding and growth among infants with low birth weight (LBW) in India, Malawi, and Tanzania. STUDY DESIGN: We conducted LATCH and PIBBS assessments among mother-infant dyads enrolled in the Low Birthweight Infant Feeding Exploration (LIFE) observational study of infants with moderately LBW (1500g-2499 g) in India, Malawi, and Tanzania. We analyzed feeding and growth patterns among this cohort. RESULTS: We observed 988 infants. We found no association between LATCH or PIBBS scores and rates of exclusive breastfeeding at 4 or 6 months. Higher week 1 LATCH and PIBBS scores were associated with increased likelihood of regaining birth weight by 2 weeks of age [LATCH: aRR 1.42 (95% CI 1.15, 1.76); PIBBS: aRR 1.15 (95% CI 1.07, 1.23); adjusted for maternal age, parity, education, residence, delivery mode, LBW type, number of offspring, and site]. Higher PIBBS scores at 1 week were associated with improved weight gain velocity (weight-for-age z-score change) at 1, 4, and 6 months [adjusted beta coefficient: 1 month 0.04 (95% CI 0.01, 0.06); 4 month 0.04 (95% CI 0.01, 0.06); and 6 month 0.04 (95% CI 0.00, 0.08)]. CONCLUSION: Although week 1 LATCH and PIBBS scores were not associated with rates of exclusive breastfeeding, higher scores were positively associated with growth metrics among infants with LBW, suggesting that these tools may be useful to identify dyads who would benefit from early lactation support.

Effects of Zinc Supplementation on Metabolomic Profiles in Tanzanian Infants: A Randomized Trial.

BACKGROUND: Provision of zinc supplementation to young children has been associated with reduced infectious morbidity and better growth outcomes. However, the metabolic pathways underlying these outcomes are unclear, and metabolomic data from humans undergoing zinc supplementation, particularly infants, are generally lacking. OBJECTIVES: This study aimed to examine the effect of zinc supplementation on metabolic profiles in Tanzanian infants aged 6 wk and 6 mo. METHODS: Blood samples were collected at age 6 wk and 6 mo from 50 Tanzanian infants who were enrolled in a randomized placebo-controlled trial of zinc supplementation (5 mg oral daily). Metabolomic analysis using an ultrahigh-performance liquid chromatography/tandem mass spectroscopy platform was performed to identify potential metabolomic profiles and biomarkers associated with zinc supplementation. Principal component analysis (PCA) was used to summarize metabolomic data from all samples. Two-way repeated measures analysis of variance with compound symmetry covariance structures were used to compare metabolome levels over time between infants in the 2 treatment arms. RESULTS: In PCA, the samples tended to be more separated by child age (6 wk compared with 6 mo) than by zinc supplementation status. We found that zinc supplementation affected a variety of metabolites associated with amino acid, lipid, nucleotide, and xenobiotic metabolism, including indoleacetate in the tryptophan metabolism pathway; 3-methoxytrosine and 4-hydrxoyphenylphruvate in the tyrosine pathway; eicosanedioate, 2-aminooctanoate, and N-acetyl-2-aminooctanoate in the fatty acid pathway; and N6-succinyladenosine in the purine metabolism pathway. Compared to the relatively small number of metabolites associated with zinc supplements, many infant metabolites changed significantly from age 6 wk to 6 mo. CONCLUSIONS: Zinc supplementation, despite having overall clinical benefits, appears to induce limited metabolomic changes in blood metabolites in young infants. Future larger studies may be warranted to further examine metabolic pathways associated with zinc supplementation. The parent trial was registered at clinicaltrials.gov as NCT00421668.

Risk factors for moderate acute malnutrition among children with acute diarrhoea in India and Tanzania: a secondary analysis of data from a randomized trial.

BACKGROUND: Moderate acute malnutrition (MAM) affects over 30 million children aged < 5 years worldwide. MAM may confer a greater risk of developing severe malnutrition and even mortality in children. Assessing risk factors for MAM may allow for earlier recognition of children at risk of deleterious health outcomes. OBJECTIVE: To determine risk factors associated with the prevalence and development of MAM among children aged 6 to 59 months with acute diarrhoea who received treatment with oral rehydration solution and zinc supplementation. METHODS: We conducted a secondary analysis of data from a randomized, dose-finding trial of zinc among children with acute diarrhoea in India and Tanzania. We used regression models to assess risk factors for prevalent MAM at the start of diarrhoea treatment and to identify risk factors associated with the development of MAM at 60 days. MAM was defined as weight for length (or height) Z score ≤-2 and > -3 or mid-upper arm circumference < 12.5 and ≥ 11.5 cm. RESULTS: A total of 4,500 children were enrolled; 593 (13.2%) had MAM at the baseline. MAM at baseline was significantly less common among children in Tanzania than in India (adjusted risk ratio [aRR] 0.37, 95% confidence interval [CI]: 0.30, 0.44, P < 0.001), in children aged 24- < 60 months versus 6- < 12 months (aRR 0.46, 95% CI: 0.38, 0.56, P < 0.001), and in families with household wealth index higher than the median (aRR 0.79, 95% CI: 0.68, 0.92, P = 0.002). Sixty days after outpatient treatment and follow-up, 87 (2.5%) children developed MAM. When compared to children aged 6- < 12 months, children aged 24- < 60 months had a 52% lower risk of developing MAM. Every one unit increase in weight for length (or height) Z score at enrolment was associated with a 93% lower risk of developing MAM during follow-up. CONCLUSIONS: Among children with diarrhoea, younger children and those from households with lower wealth were at greater risk of MAM. These children may benefit from targeted interventions focusing on feeding (targeted nutrition support for at-risk households) and follow up in order to reduce the occurrence of MAM and its consequences.

Lower-Dose Zinc for Childhood Diarrhea - A Randomized, Multicenter Trial.

BACKGROUND: The World Health Organization recommends 20 mg of zinc per day for 10 to 14 days for children with acute diarrhea; in previous trials, this dosage decreased diarrhea but increased vomiting. METHODS: We randomly assigned 4500 children in India and Tanzania who were 6 to 59 months of age and had acute diarrhea to receive 5 mg, 10 mg, or 20 mg of zinc sulfate for 14 days. The three primary outcomes were a diarrhea duration of more than 5 days and the number of stools (assessed in a noninferiority analysis) and the occurrence of vomiting (assessed in a superiority analysis) within 30 minutes after zinc administration. RESULTS: The percentage of children with diarrhea for more than 5 days was 6.5% in the 20-mg group, 7.7% in the 10-mg group, and 7.2% in the 5-mg group. The difference between the 20-mg and 10-mg groups was 1.2 percentage points (upper boundary of the 98.75% confidence interval [CI], 3.3), and that between the 20-mg and 5-mg groups was 0.7 percentage points (upper boundary of the 98.75% CI, 2.8), both of which were below the noninferiority margin of 4 percentage points. The mean number of diarrheal stools was 10.7 in the 20-mg group, 10.9 in the 10-mg group, and 10.8 in 5-mg group. The difference between the 20-mg and 10-mg groups was 0.3 stools (upper boundary of the 98.75% CI, 1.0), and that between the 20-mg and 5-mg groups was 0.1 stools (upper boundary of the 98.75% CI, 0.8), both of which were below the noninferiority margin (2 stools). Vomiting within 30 minutes after administration occurred in 19.3%, 15.6%, and 13.7% of the patients in the 20-mg, 10-mg, and 5-mg groups, respectively; the risk was significantly lower in the 10-mg group than in the 20-mg group (relative risk, 0.81; 97.5% CI, 0.67 to 0.96) and in the 5-mg group than in the 20-mg group (relative risk, 0.71; 97.5% CI, 0.59 to 0.86). Lower doses were also associated with less vomiting beyond 30 minutes after administration. CONCLUSIONS: Lower doses of zinc had noninferior efficacy for the treatment of diarrhea in children and were associated with less vomiting than the standard 20-mg dose. (Funded by the Bill and Melinda Gates Foundation; ZTDT ClinicalTrials.gov number, NCT03078842.).

Lessons learned in implementing the Low Birthweight Infant Feeding Exploration study: A large, multi-site observational study.

OBJECTIVE: Globally, early and optimal feeding practices and strategies for small and vulnerable infants are limited. We aim to share the challenges faced and implementation lessons learned from a complex, mixed methods research study on infant feeding. DESIGN: A formative, multi-site, observational cohort study using convergent parallel, mixed-methods design. SETTING: Twelve tertiary/secondary, public/private hospitals in India, Malawi and Tanzania. POPULATION OR SAMPLE: Moderately low birthweight infants (MLBW; 1.50-2.49 kg). METHODS: We assessed infant feeding and care practices through: (1) assessment of in-facility documentation of 603 MLBW patient charts; (2) intensive observation of 148 MLBW infants during facility admission; and (3) prospective 1-year follow-up of 1114 MLBW infants. Focus group discussions and in-depth interviews gathered perspectives on infant feeding among clinicians, families, and key stakeholders. MAIN OUTCOME MEASURES: The outcomes of the primary study were: (1) To understand the current practices and standard of care for feeding LBW infants; (2) To define and document the key outcomes (including growth, morbidity, and lack of success on mother's own milk) for LBW infants under current practices; (3) To assess the acceptability and feasibility of a system-level Infant and Young Child Feeding (IYCF) intervention and the proposed infant feeding options for LBW infants. RESULTS: Hospital-level guidelines and provision of care for MLBW infants varied across and within countries. In all, 89% of charts had missing data on time to first feed and 56% lacked discharge weights. Among 148 infants observed in-facility, 18.5% were discharged prior to meeting stated weight goals. Despite challenges during COVID, 90% of the prospective cohort was followed until 12 months of age. CONCLUSIONS: Enrolment and follow-up of this vulnerable population required additional effort from researchers and the community. Using a mixed-methods exploratory study allowed for a comprehensive understanding of MLBW health and evidence-based planning of targeted large-scale interventions. Multi-site partnerships in global health research, which require active and equal engagement, are instrumental in avoiding duplication and building a stronger, generalisable evidence base.

Gestational Age, Birth Weight, and Neurocognitive Development in Adolescents in Tanzania.

OBJECTIVES: To investigate the association between gestational age, birthweight, and birthweight adjusted for gestational age, with domains of neurocognitive development and behavioral problems in adolescents in Tanzania. STUDY DESIGN: Data from a long-term follow-up of adolescents aged 11-15 years born to women previously enrolled in a randomized controlled trial of prenatal multiple micronutrient supplementation in Dar es Salaam, Tanzania, were used. A battery of neurodevelopmental tests were administered to measure adolescent general intelligence, executive function, and behavioral problems. The INTERGROWTH-21st newborn anthropometric standards were used to derive birthweight for gestational age z-scores. We assessed the shape of relationships using restricted cubic splines and estimated the associations of gestational age, birthweight, and birthweight for gestational age z-score with adolescent development using multivariable linear regressions. RESULTS: Among adolescents studied (n = 421), higher gestational age (per week), birthweight (per 100 grams), and birthweight for gestational age z-score (per SD) were linearly associated with higher intelligence score (adjusted standardized mean difference, 0.05 SD [95% CI, 0.01-0.09], 0.04 SD [95% CI, 0.02-0.06], and 0.09 SD [95% CI, 0.01-0.17], respectively). Birthweight and birthweight for gestational age z-score, but not gestational age, were also associated with improved executive function. Low birthweight (<2500 g) was associated with lower intelligence and executive function scores. Associations between birthweight and executive function were stronger among adolescents born to women with higher education. CONCLUSIONS: The duration of gestation and birthweight were positively associated with adolescent neurodevelopment in Tanzania. These findings suggest that interventions to improve birth outcomes may also benefit adolescent cognitive function.

Prevalence and risk factors for Subclinical Rheumatic Heart Disease among primary school children in Dar es Salaam, Tanzania: a community based cross-sectional study.

BACKGROUND: Rheumatic heart disease (RHD) is the most common acquired heart disease occurring in children and adolescents. RHD is associated with significant morbidity and mortality particularly in low and middle- income countries (LMICs) where the burden is estimated to be higher compared to high income countries. Subclinical RHD is the presence of valvular lesion diagnosed by echocardiography in a person with no clinical manifestation of RHD. This study aimed at determining the prevalence, types and factors associated with subclinical RHD among primary school children in Dar Es Salaam, Tanzania. METHODS: A descriptive community-based cross-sectional study was conducted in primary school children from February to May 2019. A standardized structured questionnaire was used to collect demographic characteristics, history of upper respiratory tract infections (URTIs), anthropometric measurements, and chest auscultation findings. Moreover echocardiographic screening was done to all children recruited into the study. World Heart Federation echocardiographic classification was used to define the types and prevalence of subclinical RHD. RESULTS: A total of 949 primary school children were enrolled with females being predominant (57.1%). The prevalence of subclinical RHD was 34 per 1000. All the participants had mitral valve disease only whereby 17 had definite disease and 15 had a borderline disease. The associated factors for subclinical RHD were older age of more than 9 years (OR 10.8, 95% CI 1.4-82.2, P = 0.02) having three or more episodes of URTI in previous six months (OR 21, 95% CI 9.6-46, P = 0.00) and poor hygiene (OR 3, 95% CI 1.3-6.8, P = 0.009). CONCLUSION: Subclinical RHD as detected by echocardiographic screening is prevalent in primary school children, uniformly affects the mitral valve, and is associated with potentially modifiable risk factors. Children with a history of more than three episodes of URTI in six months represents a high-risk population that should be targeted for RHD screening.

Poor weight gain and its predictors among preterm neonates admitted at Muhimbili National Hospital in Dar-es-salaam, Tanzania: a prospective cohort study.

BACKGROUND: Preterm delivery is among the major public health problems worldwide and the leading cause of morbidity and mortality among neonates. Postnatal poor weight gain, which can contribute to mortality, can be influenced by feeding practices, medical complications and quality of care that is provided to these high-risk neonates. This study aimed to investigate the proportion and predictors of poor weight gain among preterm neonates at Muhimbili National Hospital (MNH), from September 2018 to February 2019. METHODS: A hospital-based prospective cohort study involving preterm neonates with Gestation age (GA) < 37 weeks receiving care at MNH. Eligible preterm, were consecutively recruited at admission and followed up until discharge, death or end of neonatal period. Poor weight gain was defined as weight gain less than 15 g per kg per day. The risk factors associated with poor weight gain were evaluated. Predictors of poor weight gain were evaluated using a multivariate analysis. Results were considered statistically significant if P -value was < 0.05 and 95% confidence interval (CI) did not include 1. RESULTS: A total of 227 preterm neonates < 37 weeks GA, with male to female ratio of 1:1.2 were enrolled in the study. The overall proportion of preterm with poor weight gain was 197/227 (86.8%). Proportion of poor weight gain among the early and late preterm babies, were 100/113 (88.5%) and 97/114 (85.1%) respectively. Predictors of poor weight gain were low level of maternal education (AOR = 2.58; 95%Cl: 1.02-6.53), cup feeding as the initial method of feeding (AOR = 8.65; 95%Cl: 1.59-16.24) and delayed initiation of the first feed more than 48 h (AOR = 10.06; 95%Cl: 4.14-24.43). A previous history of preterm delivery was protective against poor weight gain (AOR = 0.33; 95% Cl: 0.11-0.79). CONCLUSION AND RECOMMENDATION: Poor weight gain was a significant problem among preterm neonates receiving care at MNH. This can be addressed by emphasizing on early initiation of feed and tube feeding for neonates who are not able to breastfeed. Health education and counselling to mothers focusing on feeding practices as well as close supervision of feeding especially for mothers experiencing difficulties in feeding their preterm will potentially minimize risk of growth failure.

Rotavirus Diarrhoea among Children Aged <5 Years in Hospital Setting in Dar Es Salaam, Tanzania.

BACKGROUND: Diarrhoea remains among the highest causes of death in children under 5 years of age in developing countries. Before the introduction of rotavirus vaccine in Tanzania, rotavirus infection was the leading cause of severe diarrhoea in children below the age of 5 years but there is a paucity of studies reporting the severity of this infection after the introduction of rotavirus vaccine. This hospital-based study reports the proportion of children with rotavirus-associated diarrhoea in Dar es Salaam, its severity and associated factors. METHODS: A hospital-based cross-sectional study was conducted at the inpatient and outpatient paediatrics departments of the selected health facilities from September 2018 to February 2019. A total of 314 children meeting inclusion criteria were enrolled into the study. A structured questionnaire was used to collect demographic and medical history, anthropometric measurements were taken and a stool sample was collected from each patient for rotavirus antigen detection using CTK Biotech Onsite rotavirus antigen rapid test. RESULTS: A total of 314 children were included in the study with age range between 2 and 59 months. The median age was 12 months with an interquartile range of 8-19 months. Symptoms of rotavirus diarrhoea were vomiting (p-value = 0.018) and severe dehydration (p-value = 0.000). Independent associated factors of rotavirus diarrhoea included: age of mother between 35 and 49 years (AoR 4.1, 95% CI 1.0-17.1, p-value = 0.05), geographical distribution (Ilala District, AoR 4.0, 95% CI 1.1-10.4, p-value = 0.039), poor hand hygiene (AoR 8.5, 95% CI 2.6-28.1, p-value = 0.000) and drinking bottled/home-treated water (AoR 5.4, 95% CI 1.3-22.7, p-value = 0.02). CONCLUSION: Rotavirus infection is still prevalent and severe among children with diarrhoea. The difference in prevalence among the districts is also of concern and hence larger community-based cohort studies are needed to assess the association of rotavirus diarrhoea with the geographical variation across districts and regions. Improving sanitation and hygiene through health education amongst households is crucial for disease prevention.

Markers of Systemic Inflammation and Environmental Enteric Dysfunction Are Not Reduced by Zinc or Multivitamins in Tanzanian Infants: A Randomized, Placebo-Controlled Trial.

OBJECTIVE: To examine whether daily zinc and/or multivitamin supplementation reduce biomarkers of environmental enteric dysfunction (EED), systemic inflammation, or markers of growth in a sample of infants from Dar es Salaam, Tanzania. STUDY DESIGN: Subgroup analysis of infants participating in a randomized, double-blind, placebo-controlled trial received daily oral supplementation of zinc, multivitamins, zinc + multivitamins, or placebo for 18 months starting at 6 weeks of age. EED (anti-flagellin and anti-lipopolysaccharide immunoglobulins), systemic inflammation (C-reactive protein and alpha-1-acid glycoprotein), and growth biomarkers (insulin-like growth factor-1 and insulin-like growth factor binding protein-3) were measured via enzyme-linked immunosorbent assay in a subsample of 590 infants at 6 weeks and 6 months of age. EED biomarkers also were measured in 162 infants at 12 months of age. RESULTS: With the exception of anti-lipopolysaccharide IgG concentrations, which were significantly greater in infants who received multivitamins compared with those who did not (1.41 ± 0.61 vs 1.26 ± 0.65, P = .006), and insulin-like growth factor binding protein-3 concentrations, which were significantly lower in children who received zinc compared with those who did not (981.13 ± 297.59 vs 1019.10 ± 333.01, P = .03), at 6 months of age, we did not observe any significant treatment effects of zinc or multivitamins on EED, systemic inflammation, or growth biomarkers. CONCLUSIONS: Neither zinc nor multivitamin supplementation ameliorated markers of EED or systemic inflammation during infancy. Other interventions should be prioritized for future trials. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00421668.

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.

Association of vitamin D and diarrhoea in children aged less than five years at Muhimbili national hospital, Dar es Salaam: an unmatched case control study.

BACKGROUND: There has been a growing interest in the non-skeletal roles of vitamin D particularly its immune-modulatory properties which has been shown to influence the susceptibility and severity to infections. There is insufficient data globally on the association between Vitamin D levels and Diarrhoea in children. The objective of the study was to determine the association between vitamin D levels and diarrhoea in children aged less than five years. METHODS: Hospital based unmatched case-control study was carried out at MNH between September 2015 and January 2016. Cases were defined as patients with diarrhoea, Sick controls were patients who did not have diarrhoea but were admitted for other illnesses and Healthy controls were children who had neither diarrhoea nor other co-morbid conditions. Structured questionnaires were used to capture the demographic data and anthropometric measurements. Blood samples of study participants were tested for serum vitamin D levels and grouped as vitamin D sufficient, insufficient or deficient (VDD). SPSSv.20 was used to carry out the Statistical analysis. Binary logistic regression, Mann-Whitney and Kruskal-Wallis tests were used, a p-value≤ 0.05 was considered to be statistically significant. RESULTS: A total of 188 children under five were recruited in the study at the ratio of 1 case: 3 controls, of these 47 were Cases, 94 were Sick controls and remaining 47 were Healthy controls. The mean age was 17.01 ± 14.8 months. The mean vitamin D level was 51.18 ± 21.97 nmol/l. Majority of the participants 101 (53.7%) were vitamin D deficient, 64 (34%) were insufficient and 23 (12.2%) had sufficient vitamin D levels. Sick controls were 3.2 times more likely to be VDD compared to cases [95% CI 0.14-0.69; p = 0.0015] and 5.03 times when compared to Healthy controls [95% CI 2.22-11.55; p = 0.000]. Severe acute malnutrition (SAM) was independently associated with diarrhoea (95% CI: 1.26-5.39, p 0.01). CONCLUSIONS: High prevalence of vitamin D deficiency was found in the children under five years studied. Vitamin D levels was not found to be specifically associated with diarrhoea in children under five years of age.

Neonatal and Infant Mortality Risk Associated with Preterm and Small for Gestational Age Births in Tanzania: Individual Level Pooled Analysis Using the Intergrowth Standard.

OBJECTIVES: To evaluate the risk of newborn and infant mortality associated with preterm, small for gestational age (SGA), and low birth weight (LBW) stratified by maternal HIV status and the location of birth. STUDY DESIGN: We created a prospective cohort by pooling 5 individually randomized trials. We used Cox proportional hazard models to estimate the risk of mortality for SGA defined using the recently published Intergrowth standard, preterm, LBW, and gestational age and size for gestational age categories (preterm- appropriate for gestational age [AGA], term-SGA, and preterm-SGA). Effect modification by maternal HIV status and place of residence was assessed using the likelihood ratio test. RESULTS: Of the 31 988 infants, 15.3% were preterm, 16.6% were SGA, and 7.3% were LBW. The proportion of preterm and SGA births was higher among the HIV-infected cohort than in the uninfected cohort. Compared with term-AGA groups, infants born both preterm and SGA had a greater risk of neonatal mortality (hazard ratio [HR] 5.43, 95% CI 2.01-14.63) than preterm-AGA infants (HR 2.40, 95% CI 1.89-3.05) and term-SGA infants (HR 2.56, 95% CI 1.96-3.34). Maternal HIV infection modified the risk of infant mortality associated with being born preterm or LBW, with a higher relative risk among those born to HIV-uninfected women. Rural residence significantly modified the risk of neonatal mortality associated with being LBW (P for interaction = .005). CONCLUSIONS: Preterm and SGA newborns had an increased risk of mortality during the first year of life. Interventions targeting these conditions, especially in HIV-exposed and rural populations, should be integrated into existing maternal and child health programs.

Markers of Environmental Enteric Dysfunction Are Associated With Neurodevelopmental Outcomes in Tanzanian Children.

BACKGROUND: Chronic exposure to enteropathogens may result in environmental enteric dysfunction (EED), a subclinical condition associated with poor child growth. Growth faltering is strongly associated with poor neurodevelopment, and occurs during sensitive periods of postnatal brain development. We investigated the role of novel EED biomarkers, systemic inflammation, and micronutrient status on neurodevelopment in Tanzanian children. METHODS: Non-stunted subjects with 6-week and 6-month blood samples and neurodevelopmental measures (n = 107) were included in this study. Samples were tested for biomarkers of gastrointestinal function (citrulline, antibodies to lipopolysaccharide, and flagellin), micronutrient status (iron, retinol binding protein [RBP], and vitamin D), systemic inflammation (C-reactive protein [CRP] and alpha-1-acid glycoprotein), and growth (insulin-like growth factor and insulin-like growth factor binding protein 3). RESULTS: Cognitive scores at 15 months were associated with higher concentrations of 6-month anti-lipopolysaccharide IgG (ß = 1.95, P = 0.02), anti-flagellin IgA (ß = 2.41, P = 0.04), and IgG (ß = 2.99, P = 0.009). Higher receptive language scores were positively associated with anti-flagellin IgG (ß = 0.95, P = 0.05), and receptive language and gross motor scores were positively associated with citrulline at 6 months (ß = 0.09, P = 0.02; ß = 0.10, P = 0.03, respectively). Gross motor scores were positively associated with RBP at 6 months (ß = 1.70, P = 0.03). Markers of systemic inflammation were not significantly associated with neurodevelopment. CONCLUSIONS: Plasma citrulline, a marker of gastrointestinal mucosal surface area, and vitamin A status were associated with higher gross motor development scores. Novel markers for EED, but not inflammation, were positively associated with cognitive scores, suggesting a possible mechanistic pathway involving immune response and neuroprotection.

Mid-arm muscle area and anthropometry predict low birth weight and poor pregnancy outcomes in Tanzanian women with HIV.

BACKGROUND: An observational study was conducted to examine the role of maternal anthropometry, including mid-arm muscle area (MAMA) and others, as risk factors for low birth weight (LBW), small for gestational age (SGA) and preterm births in human immunodeficiency virus (HIV) infected pregnant women. HIV-positive women (N = 2369), between 12 and 32 weeks gestation were followed through delivery in Tanzania, from 2003 to 2008. Participants were women enrolled in a randomized, double-blind, placebo-controlled, clinical trial who delivered live births. METHODS: Binomial regression analysis was used to evaluate the association of maternal nutritional indicators of MAMA, mid-upper arm circumference (MUAC), body mass index (BMI) and maternal weight with LBW, SGA and preterm in multivariate analysis. RESULTS: Higher MAMA was associated with a 32% lower risk of LBW compared to lower measurements (RR = 0.68, 95% CI = 0.50-0.94). Similar protective associations were noted for higher BMI (RR = 0.58, 95% CI = 0.42-0.79); maternal weight (RR = 0.50, 95% CI = 0.36-0.69) and MUAC (RR = 0.62, 95% CI = 0.45-0.86). Higher MAMA was also associated with lower risk of SGA (RR = 0.78, 95% CI = 0.68-0.90) and marginally associated with preterm (RR = 0.85, 95% CI = 0.69-1.04). Beneficial associations of MUAC, BMI and maternal weight with SGA and preterm were also observed. CONCLUSION: MAMA performs comparably to MUAC, maternal weight and BMI, as a predictor of LBW and SGA in HIV-infected women. The possible role of MAMA and other indicators in screening HIV positive women at risk of adverse pregnancy outcomes should be investigated.

Delayed Breastfeeding Initiation Is Associated with Infant Morbidity.

OBJECTIVE: To assess the relationship between breastfeeding initiation time and postneonatal mortality, morbidity, and growth through 24 months in a cohort of Tanzanian infants. STUDY DESIGN: We included 4203 infants from 2 trials of micronutrient supplementation. We used Cox proportional hazards models or general estimating equations to estimate relative risks. RESULTS: A total of 13% of infants initiated breastfeeding >1 hour after birth (n = 536). There was no association between breastfeeding initiation time and risk of all-cause or cause-specific mortality, nor infant growth failure, from 6 weeks to 2 years of age. However, delayed breastfeeding was associated with an increased risk of several common infectious morbidities in early infancy, including upper respiratory infection symptoms and vomiting. Compared with those who initiated breastfeeding within the first hour of birth, delayed breastfeeding initiation was associated with an 11% increased risk of cough (relative risk 1.11, 95% CI 1.02-1.21) and a 48% increased risk of difficulty breathing (relative risk 1.48, 95% CI 1.09-2.01) during the first 6 months. Delayed initiation was associated with a greater risk of difficulty breathing from 6 to 12 months of age, but it was not associated with risk of any other morbidity during this time, nor any morbidity between 12 and 24 months. CONCLUSION: Delayed breastfeeding initiation is associated with an increased risk of infant morbidity during the first 6 months of life. Early breastfeeding initiation, along with exclusive and prolonged breastfeeding, should be prioritized and promoted in efforts to improve child health.

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.

Infant Nutritional Status and Markers of Environmental Enteric Dysfunction are Associated with Midchildhood Anthropometry and Blood Pressure in Tanzania.

OBJECTIVE: To assess whether growth and biomarkers of environmental enteric dysfunction in infancy are related to health outcomes in midchildhood in Tanzania. STUDY DESIGN: Children who participated in 2 randomized trials of micronutrient supplements in infancy were followed up in midchildhood (4.6-9.8 years of age). Anthropometry was measured at age 6 and 52 weeks in both trials, and blood samples were available from children at 6 weeks and 6 months from 1 trial. Linear regression was used for height-for-age z-score, body mass index-for-age z-score, and weight for age z-score, and blood pressure analyses; log-binomial models were used to estimate risk of overweight, obesity, and stunting in midchildhood. RESULTS: One hundred thirteen children were followed-up. Length-for-age z-score at 6 weeks and delta length-for-age z-score from 6 to 52 weeks were associated independently and positively with height-for-age z-score and inversely associated with stunting in midchildhood. Delta weight-for-length and weight-for-age z-score were also positively associated with midchildhood height-for-age z-score. The 6-week and delta weight-for-length z-scores were associated independently and positively with midchildhood body mass index-for-age z-score and overweight, as was the 6-week and delta weight-for-age z-score. Delta length-for-age z-score was also associated with an increased risk of overweight in midchildhood. Body mass index-for-age z-score in midchildhood was associated positively with systolic blood pressure. Serum anti-flagellin IgA concentration at 6 weeks was also associated with increased blood pressure in midchildhood. CONCLUSIONS: Anthropometry at 6 weeks and growth in infancy independently predict size in midchildhood, while anti-flagellin IgA, a biomarker of environmental enteric dysfunction, in early infancy is associated with increased blood pressure in midchildhood. Interventions in early life should focus on optimizing linear growth while minimizing excess weight gain and environmental enteric dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00197730 and NCT00421668.

Vitamin D Deficiency Is Not Associated With Growth or the Incidence of Common Morbidities Among Tanzanian Infants.

OBJECTIVE: The objective of this study was to examine risk factors for vitamin D deficiency and determine the association of vitamin D status with child growth and incidence of common morbidities among Tanzanian infants. METHODS: A prospective cohort of 581 Tanzanian infants born to human immunodeficiency virus (HIV)-uninfected mothers had serum 25-hydroxyvitamin D assessed at 6 weeks and 6 months of age. Infants were seen at monthly clinic visits for growth monitoring until 18 months of age. Physicians examined infants every 3 months or when an illness was noted to document morbidities. RESULTS: The prevalence of vitamin D deficiency (<20 ng/mL) declined from 76.4% at 6 weeks of age to 21.2% at 6 months. Infants who were exclusively breastfed at 6 weeks of age had 2.05 (95% confidence interval 1.11-3.79; P = 0.02) times the risk of vitamin D deficiency as compared formula-fed infants. After multivariate adjustment, there was no association of vitamin D status at 6 weeks or 6 months with the incidence of stunting, wasting, or underweight. There was also no association of low vitamin D with the incidence of diarrhea, upper respiratory infection, acute lower respiratory tract infection, or malaria. CONCLUSIONS: Vitamin D deficiency is common during early infancy, particularly among exclusively breastfed infants; however, these observational data suggest it may not be an important contributor to morbidity and growth among the general population of Tanzanian infants. Future studies of vitamin D among high-risk infants, including those with low birthweight and exposed to HIV, may be warranted.