Clinical and nutritional correlates of bacterial diarrhoea aetiology in young children: a secondary cross-sectional analysis of the ABCD trial.

OBJECTIVE: The objective was to assess the association between nutritional and clinical characteristics and quantitative PCR (qPCR)-diagnosis of bacterial diarrhoea in a multicentre cohort of children under 2 years of age with moderate to severe diarrhoea (MSD). DESIGN: A secondary cross-sectional analysis of baseline data collected from the AntiBiotics for Children with Diarrhoea trial (NCT03130114). PATIENTS: Children with MSD (defined as >3 loose stools within 24 hours and presenting with at least one of the following: some/severe dehydration, moderate acute malnutrition (MAM) or severe stunting) enrolled in the ABCD trial and collected stool sample. STUDY PERIOD: June 2017-July 2019. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Likely bacterial aetiology of diarrhoea. Secondary outcomes included specific diarrhoea aetiology. RESULTS: A total of 6692 children with MSD had qPCR results available and 28% had likely bacterial diarrhoea aetiology. Compared with children with severe stunting, children with MAM (adjusted OR (aOR) (95% CI) 1.56 (1.18 to 2.08)), some/severe dehydration (aOR (95% CI) 1.66 (1.25 to 2.22)) or both (aOR (95% CI) 2.21 (1.61 to 3.06)), had higher odds of having likely bacterial diarrhoea aetiology. Similar trends were noted for stable toxin-enterotoxigenic Escherichia coli aetiology. Clinical correlates including fever and prolonged duration of diarrhoea were not associated with likely bacterial aetiology; children with more than six stools in the previous 24 hours had higher odds of likely bacterial diarrhoea (aOR (95% CI) 1.20 (1.05 to 1.36)) compared with those with fewer stools. CONCLUSION: The presence of MAM, dehydration or high stool frequency may be helpful in identifying children with MSD who might benefit from antibiotics.

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.

Factors associated with D-lactic acidosis in pediatric intestinal failure: A case-control study.

BACKGROUND: D-lactic acidosis (DLA) is a serious complication of short bowel syndrome (SBS) in children with intestinal failure (IF). Malabsorbed carbohydrates are metabolized by bacteria in the intestine to D-lactate which can lead to metabolic acidosis and neurologic symptoms. METHODS: A retrospective chart review was performed in children ≤18 years old with SBS who had one of the following criteria: unexplained metabolic acidosis, neurologic signs or symptoms, history of antibiotic therapy for small bowel bacterial overgrowth, or high clinical suspicion of DLA. Cases had serum D-lactate concentration >0.25 mmol/L; controls with concentrations ≤0.25 mmol/L. RESULTS: Of forty-six children, median age was 3.16 (interquartile range (IQR): 1.98, 5.82) years, and median residual bowel length was 40 (IQR: 25, 59) cm. There were 23 cases and 23 controls. Univariate analysis showed that cases had significantly lower median bicarbonate (19 vs. 24 mEq/L, p = 0.001), higher anion gap (17 vs. 14 mEq/L, p < 0.001) and were less likely to be receiving parenteral nutrition, compared with children without DLA. Multivariable analysis identified midgut volvulus, history of intestinal lengthening procedure, and anion gap as significant independent risk factors. Midgut volvulus was the strongest independent factor associated with DLA (adjusted odds ratio = 17.1, 95% CI: 2.21, 133, p = 0.007). CONCLUSION: DLA is an important complication of pediatric IF due to SBS. Patients with IF, particularly those with history of midgut volvulus, having undergone intestinal lengthening, or with anion gap acidosis, should be closely monitored for DLA.

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.

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.

Two Randomized Trials of Low-Dose Calcium Supplementation in Pregnancy.

BACKGROUND: The World Health Organization recommends 1500 to 2000 mg of calcium daily as supplementation, divided into three doses, for pregnant persons in populations with low dietary calcium intake in order to reduce the risk of preeclampsia. The complexity of the dosing scheme, however, has led to implementation barriers. METHODS: We conducted two independent randomized trials of calcium supplementation, in India and Tanzania, to assess the noninferiority of a 500-mg daily dose to a 1500-mg daily dose of calcium supplementation. In each trial, the two primary outcomes were preeclampsia and preterm birth, and the noninferiority margins for the relative risks were 1.54 and 1.16, respectively. RESULTS: A total of 11,000 nulliparous pregnant women were included in each trial. The cumulative incidence of preeclampsia was 3.0% in the 500-mg group and 3.6% in the 1500-mg group in the India trial (relative risk, 0.84; 95% confidence interval [CI], 0.68 to 1.03) and 3.0% and 2.7%, respectively, in the Tanzania trial (relative risk, 1.10; 95% CI, 0.88 to 1.36) - findings consistent with the noninferiority of the lower dose in both trials. The percentage of live births that were preterm was 11.4% in the 500-mg group and 12.8% in the 1500-mg group in the India trial (relative risk, 0.89; 95% CI, 0.80 to 0.98), which was within the noninferiority margin of 1.16; in the Tanzania trial, the respective percentages were 10.4% and 9.7% (relative risk, 1.07; 95% CI, 0.95 to 1.21), which exceeded the noninferiority margin. CONCLUSIONS: In these two trials, low-dose calcium supplementation was noninferior to high-dose calcium supplementation with respect to the risk of preeclampsia. It was noninferior with respect to the risk of preterm live birth in the trial in India but not in the trial in Tanzania. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT03350516; Clinical Trials Registry-India number, CTRI/2018/02/012119; and Tanzania Medicines and Medical Devices Authority Trials Registry number, TFDA0018/CTR/0010/5).

Stress Ulcer Prophylaxis Versus Placebo-A Blinded Pilot Randomized Controlled Trial to Evaluate the Safety of Two Strategies in Critically Ill Infants With Congenital Heart Disease.

OBJECTIVES: The routine use of stress ulcer prophylaxis (SUP) in infants with congenital heart disease (CHD) in the cardiac ICU (CICU) is controversial. We aimed to conduct a pilot study to explore the feasibility of performing a subsequent larger trial to assess the safety and efficacy of withholding SUP in this population (NCT03667703). DESIGN, SETTING, PATIENTS: Single-center, prospective, double-blinded, parallel group (SUP vs. placebo), pilot randomized controlled pilot trial (RCT) in infants with CHD admitted to the CICU and anticipated to require respiratory support for greater than 24 hours. INTERVENTIONS: Patients were randomized 1:1 (stratified by age and admission type) to receive a histamine-2 receptor antagonist or placebo until respiratory support was discontinued, up to 14 days, or transfer from the CICU, if earlier. MEASUREMENTS AND MAIN RESULTS: Feasibility was defined a priori by thresholds of screening rate, consent rate, timely drug allocation, and protocol adherence. The safety outcome was the rate of clinically significant upper gastrointestinal (UGI) bleeding. We screened 1,426 patients from February 2019 to March 2022; of 132 eligible patients, we gained informed consent in 70 (53%). Two patients did not require CICU admission after obtaining consent, and the remaining 68 patients were randomized to SUP (n = 34) or placebo (n = 34). Ten patients were withdrawn early, because of a change in eligibility (n = 3) or open-label SUP use (n = 7, 10%). Study procedures were completed in 58 patients (89% protocol adherence). All feasibility criteria were met. There were no clinically significant episodes of UGI bleeding during the pilot RCT. The percentage of patients with other nonserious adverse events did not differ between groups. CONCLUSIONS: Withholding of SUP in infants with CHD admitted to the CICU was feasible. A larger multicenter RCT designed to confirm the safety of this intervention and its impact on incidence of UGI bleeding, gastrointestinal microbiome, and other clinical outcomes is warranted.

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.

Improving anthropometric measurements in hospitalized children: A quality-improvement project.

BACKGROUND: The objective of this quality-improvement project was to increase documentation rates of anthropometrics (measured weight, length/height, and body mass index [BMI], which are critical to identify patients at malnutrition (undernutrition) risk) from <50% to 80% within 24 hours of hospital admission for pediatric patients. METHODS: Multidisciplinary champion teams on surgical, cardiac, and intensive care (ICU) pilot units were established to identify and iteratively test interventions addressing barriers to documentation from May 2016 to June 2018. Percentage of patients with documented anthropometrics <24 h of admission was assessed monthly by statistical process control methodology. Percentage of patients at malnutrition (undernutrition) risk by anthropometrics was compared by χ2 for 4 months before and after intervention. RESULTS: Anthropometric documentation rates significantly increased (P < 0.001 for all): BMI, from 11% to 89% (surgical), 33% to 57% (cardiac), and 16% to 51% (ICU); measured weight, from 24% to 88% (surgical), 69% to 83% (cardiac), and 51% to 67% (ICU); and length/height, from 12% to 89% (surgical), 38% to 57% (cardiac), and 26% to 63% (ICU). Improvement hospital-wide was observed (BMI, 42% to 70%, P < 0.001) with formal dissemination tactics. For pilot units, moderate/severe malnutrition (undernutrition) rates tripled (1.2% [24 of 2081] to 3.4% [81 of 2374], P < 0.001). CONCLUSION: Documentation of anthropometrics on admission substantially improved after establishing multidisciplinary champion teams. Goal rate (80%) was achieved within 26 months for all anthropometrics in the surgical unit and for weight in the cardiac unit. Improved documentation rates led to significant increase in identification of patients at malnutrition (undernutrition) risk.

Facilitators, barriers, and key influencers of breastfeeding among low birthweight infants: a qualitative study in India, Malawi, and Tanzania.

BACKGROUND: Low birthweight (LBW) infants are at increased risk of morbidity and mortality. Exclusive breastfeeding up to six months is recommended to help them thrive through infection prevention, growth improvements, and enhancements in neurodevelopment. However, limited data exist on the feeding experiences of LBW infants, their caregivers and key community influencers. The qualitative component of the Low Birthweight Infant Feeding Exploration (LIFE) study aimed to understand practices, facilitators, and barriers to optimal feeding options in the first six months for LBW infants in low-resource settings. METHODS: This study was conducted in four sites in India, Malawi, and Tanzania from July 2019 to August 2020. We conducted 37 focus group discussions with mothers and family members of LBW infants and community leaders and 142 in-depth interviews with healthcare providers, government officials, and supply chain and donor human milk (DHM) experts. Data were analyzed using a framework approach. RESULTS: All participants believed that mother's own milk was best for LBW infants. Direct breastfeeding was predominant and feeding expressed breast milk and infant formula were rare. DHM was a new concept for most. Adequate maternal nutrition, lactation support, and privacy in the facility aided breastfeeding and expression, but perceived insufficient milk, limited feeding counseling, and infant immaturity were common barriers. Most believed that DHM uptake could be enabled through community awareness by overcoming misconceptions, safety concerns, and perceived family resistance. CONCLUSION: This study fills an evidence gap in LBW infant feeding practices and their facilitators and barriers in resource-limited settings. LBW infants face unique feeding challenges such as poor latching and tiring at the breast. Similarly, their mothers are faced with numerous difficulties, including attainment of adequate milk supply, breast pain and emotional stress. Lactation support and feeding counseling could address obstacles faced by mothers and infants by providing psychosocial, verbal and physical support to empower mothers with skills, knowledge and confidence and facilitate earlier, more and better breast milk feeding. Findings on DHM are critical to the future development of human milk banks and highlight the need to solicit partnership from stakeholders in the community and health system.

Gastric Foveolar Hyperplastic Polyps in 2 Children With Short Bowel Syndrome on Long-Term Teduglutide.

The natural history of short bowel syndrome involves intestinal adaptation wherein the remnant small intestine undergoes histologic and anatomic changes aimed at increasing absorption. Teduglutide-a glucagon-like peptide 2 analog approved for pediatric use in 2019-stimulates this process by causing proliferation of intestinal epithelial cells resulting in increased villous height and crypt depth. Food and Drug Administration approval for pediatric patients followed safety and efficacy studies in children that were limited to 24-week duration. Pediatric-specific postmarketing studies evaluating long-term safety and efficacy are underway. Formation of colorectal polyps has been repeatedly observed in studies of adult patients on long-term teduglutide, including in individuals without endoscopic evidence of polyps before treatment initiation. Recent studies, however, suggest increased risk of small bowel hyperplastic and dysplastic polyp formation with long-term glucagon-like peptide 2 analog use. We report 2 cases of small bowel foveolar hyperplastic polyps found during surveillance endoscopies after 1 year of treatment with teduglutide.

Role of Pediatricians in Promoting and Supporting Breastfeeding: A Position Paper of the International Pediatric Association Strategic Advisory Group on Infant, Child, and Adolescent Nutrition.

BACKGROUND: Promoting and supporting breastfeeding is an important public health intervention with multiple benefits for both infants and mothers. Even modest increases in the prevalence and duration of breastfeeding could significantly reduce healthcare costs and improve maternal and child health outcomes. However, widespread adoption of breastfeeding recommendations remains poor in most settings, which contributes to widening health and social inequalities. Pediatricians have a duty to advocate for improving child health, including promoting and supporting breastfeeding. SUMMARY: This paper, from the International Pediatric Association Special Advisory Group on Nutrition, considers common barriers to breastfeeding and addresses how pediatricians can better promote and support breastfeeding, both at an individual level and by influencing practice and policy. All pediatricians need to understand the basics of breastfeeding, including lactation physiology, recognize common breastfeeding problems, and advise mothers or refer them for appropriate support; training curricula for general pediatricians and all pediatric subspecialties should reflect this. Even in the situation where their day-to-day work does not involve direct contact with mothers and infants, pediatricians can have an important influence on policy and practice. They should support colleagues who work directly with mothers and infants, ensuring that systems and environments are conducive to breastfeeding and, where appropriate, milk expression. Pediatricians and pediatric organizations should also promote policies aimed at promoting and supporting breastfeeding at local, regional, national, and international levels. KEY MESSAGES: Pediatricians have a duty to promote and support breastfeeding, regardless of their day-to-day role and responsibilities. Pediatric training curricula should ensure that all trainees acquire a good understanding of breastfeeding so they are able to effectively support mothers in their personal practice but also influence breastfeeding practice and policy at a local, regional, national, and international level.

Azithromycin for bacterial watery diarrhea: A reanalysis of the AntiBiotics for Children with severe Diarrhea (ABCD) trial incorporating molecular diagnostics.

BACKGROUND: Bacterial pathogens cause substantial diarrhea morbidity and mortality among children living in endemic settings, yet antimicrobial treatment is only recommended for dysentery or suspected cholera. METHODS: AntiBiotics for Children with severe Diarrhea was a 7-country placebo-controlled double-blind efficacy trial of azithromycin in children 2-23 months of age with watery diarrhea accompanied by dehydration or malnutrition. We tested fecal samples for enteric pathogens utilizing quantitative PCR and employed pathogen-specific cutoffs based on genomic target quantity in previous case control diarrhea etiology studies to identify likely and possible bacterial etiologies. RESULTS: Among 6,692 children, the leading likely etiologies were rotavirus(21.1%), ST-ETEC(13.3%), Shigella(12.6%) and Cryptosporidium(9.6%). More than one quarter (1894[28.3%]) had a likely and 1,153(17.3%) a possible bacterial etiology. Day 3 diarrhea was less common in those randomized to azithromycin vs. placebo among children with a likely bacterial etiology (Risk Difference[RD]likely: -11.6[95%CI:-15.6, -7.6] and possible bacterial etiology (RDpossible:-8.7 [95%CI:-13.0, -4.4]) but not in other children (RDunlikely:-0.3%[95%CI:-2.9%,2.3%]). A similar association was observed for 90-day hospitalization or death (RDlikely:-3.1[95%CI:-5.3, -1.0], RDpossible: -2.3[95%CI: -4.5, -0.01], and (RDunlikely:-0.6 [95%CI:-1.9,0.6]). The magnitude of risk differences were similar among specific likely bacterial etiologies, including Shigella. CONCLUSION: Acute watery diarrhea confirmed or presumed to be of bacterial etiology may benefit from azithromycin treatment.

Air Displacement Plethysmography is an Accurate and Feasible Noninvasive Measure of Fat-Free Mass in Children With Intestinal Failure.

BACKGROUND: The nutritional status of children with intestinal failure (IF) can be difficult to determine using body weight and currently available anthropometric techniques. Air displacement plethysmography (ADP) is a noninvasive measure of whole-body composition that measures body mass and volume, with a calculation of percent body fat (%BF) and fat-free mass (FFM) that may be useful during the provision of specialized nutrition. OBJECTIVES: To evaluate the validity and feasibility of measuring body composition in children with IF using ADP compared with deuterium dilution (DD), as well as secondarily with other measures of body composition, namely bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), and four-site skinfold anthropometry. METHODS: We conducted a prospective cohort study of 18 children recruited through the Center for Advanced Intestinal Rehabilitation at Boston Children's Hospital. Patients 2-17 years of age with IF dependent on parenteral nutrition (PN) for more than 90 days were included. Spearman rank correlation and Bland-Altman limits of agreement (LOA) analysis were used to compare ADP to 4 alternative measures of body composition. RESULTS: Eighteen children with IF, median age 7.1 [interquartile range (IQR) 5.4-9.3] years, 9 female (50%), and median residual bowel length 31 (IQR 22-85) cm were enrolled. Median PN energy intake was 46 (IQR 39-49) kcal/kg/day. Incomplete bladder emptying lead to invalid measures of DD in 4 subjects. Spearman correlation coefficients for %BF were low to moderate between ADP and DD ( r = 0.29), DXA ( r = 0.62), BIA ( r = 0.50), and skinfold ( r = 0.40). Correlations for FFM were high between ADP and these other measures (range 0.95-0.98). Comparing ADP with DD and skinfold measures, Bland-Altman analysis showed small mean bias (-1.9 and +1.5 kg) and acceptable 95% LOA ranges (10.7 and 22.9 kg), respectively, with larger bias (-10.7 and -7.7 kg) and LOA ranges (38.7 and 45.2 kg) compared to DXA and BIA. %BF by ADP and skinfold thickness were moderately correlated ( r = 0.43) with low bias (-0.2%) but very wide LOA (25.7%). CONCLUSIONS: Body composition via ADP is feasible and valid in children with IF as a measure of FFM but appears less suitable for the measurement of %BF. The technique holds promise as a noninvasive measure of body composition to assess the efficacy of nutritional, medical, and surgical interventions.

Antenatal depression and adverse birth outcomes among pregnant women living with HIV in Dar es Salaam, Tanzania.

BACKGROUND: Women who experience antenatal depression may be at increased risk of adverse birth outcomes. Few studies have examined this association among women living with HIV (WHIV). METHODS: We conducted a prospective cohort study of 2298 pregnant WHIV on antiretroviral therapy (ART) in Dar es Salaam, Tanzania, who were participants in a randomized trial of vitamin D3 supplementation. Depressive symptoms were assessed at 12-27 weeks gestation using the Hopkins Symptoms Checklist (HSCL-25). Generalized estimating equations to account for twins were used to assess the relative risks of adverse birth outcomes. RESULTS: Approximately 67 % of the women in our study population reported symptoms consistent with depression. We observed a 4.0 % prevalence of stillbirth and a 25.1 % prevalence of preterm birth. We found that low social support, higher education, and more recent initiation of ART were associated with a greater risk of antenatal depression. There was no association of antenatal depression with risk of fetal loss, stillbirth, low birth weight, birth weight, preterm birth, gestational age at delivery, or small-for-gestational age. LIMITATIONS: Depression was self-reported and only collected at one timepoint in pregnancy. Our findings may not be generalizable to all WHIV. CONCLUSIONS: Our findings illustrate the high risk of both depression and adverse birth outcomes among WHIV and underscore the need for interventions to improve their mental health and the health of their infants; however, the relationship between depression and birth outcomes remains unclear. Further research on this topic is merited, particularly examining the chronicity and timing of depression in pregnancy.

What more can be done? Prioritizing the most promising antenatal interventions to improve birth weight.

BACKGROUND: Low birth weight (LBW) is associated with neonatal mortality and sequelae of lifelong health problems; prioritizing the most promising antenatal interventions may guide resource allocation and improve health outcomes. OBJECTIVE: We sought to identify the most promising interventions that are not yet included in the policy recommendations of the World Health Organization (WHO) but could complement antenatal care and reduce the prevalence of LBW and related adverse birth outcomes in low- and middle-income settings. METHODS: We utilized an adapted Child Health and Nutrition Research Initiative (CHNRI) prioritization method. RESULTS: In addition to procedures already recommended by WHO for the prevention of LBW, we identified six promising antenatal interventions that are not currently recommended by WHO with an indication for LBW prevention, namely: (1) provision of multiple micronutrients; (2) low-dose aspirin; (3) high-dose calcium; (4) prophylactic cervical cerclage; (5) psychosocial support for smoking cessation; and (6) other psychosocial support for targeted populations and settings. We also identified seven interventions for further implementation research and six interventions for efficacy research. CONCLUSION: These promising interventions, coupled with increasing coverage of currently recommended antenatal care, could accelerate progress toward the global target of a 30% reduction in the number of LBW infants born in 2025 compared to 2006-10.

Predictive value of clinician impression for readmission and postdischarge mortality among neonates and young children in Dar es Salaam, Tanzania and Monrovia, Liberia.

BACKGROUND: There are no validated clinical decision aids to identify neonates and young children at risk of hospital readmission or postdischarge mortality in sub-Saharan Africa, leaving the decision to discharge a child to a clinician's impression. Our objective was to determine the precision of clinician impression to identify neonates and young children at risk for readmission and postdischarge mortality. METHODS: We conducted a survey study nested in a prospective observational cohort of neonates and children aged 1-59 months followed 60 days after hospital discharge from Muhimbili National Hospital in Dar es Salaam, Tanzania or John F. Kennedy Medical Center in Monrovia, Liberia. Clinicians who discharged each enrolled patient were surveyed to determine their perceived probability of the patient's risk of 60-day hospital readmission or postdischarge mortality. We calculated the area under the precision-recall curve (AUPRC) to determine the precision of clinician impression for both outcomes. RESULTS: Of 4247 discharged patients, 3896 (91.7%) had available clinician surveys and 3847 (98.7%) had 60-day outcomes available: 187 (4.8%) were readmitted and 120 (3.1%) died within 60 days of hospital discharge. Clinician impression had poor precision in identifying neonates and young children at risk of hospital readmission (AUPRC: 0.06, 95% CI: 0.04 to 0.08) and postdischarge mortality (AUPRC: 0.05, 95% CI: 0.03 to 0.08). Patients for whom clinicians attributed inability to pay for future medical treatment as the reason for risk for unplanned hospital readmission had 4.76 times the odds hospital readmission (95% CI: 1.31 to 17.25, p=0.02). CONCLUSIONS: Given the poor precision of clinician impression alone to identify neonates and young children at risk of hospital readmission and postdischarge mortality, validated clinical decision aids are needed to aid in the identification of young children at risk for these outcomes.

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.

Associations Between Social Support and Symptoms of Antenatal Depression with Infant Growth and Development Among Mothers Living with HIV in Tanzania.

Children born to mothers living with HIV may experience greater risk of poor growth and development outcomes than their HIV-unexposed peers. Few studies have examined the relationship between maternal depression and social support with infant growth and development in the context of HIV. We conducted a prospective cohort study of 2,298 pregnant women living with HIV in Dar es Salaam, Tanzania, assessing antenatal depression (Hopkins Symptoms Checklist-25) and social support (Duke-UNC Functional Social Support Questionnaire) at 12-27 weeks of gestation. At one-year age, infant anthropometry and caregiver-reported infant development were assessed. Generalized estimating equations were used to assess mean differences (MD) and relative risks (RR) for growth and developmental outcomes. Symptoms consistent with maternal antenatal depression had 67% prevalence and were associated with infant wasting (RR 2.61; 95% confidence interval (CI) 1.03-6.65; z = 2.02; p = 0.04), but no other growth or developmental outcomes. Greater maternal social support was not associated with infant growth outcomes. Greater affective support was associated with better cognitive (MD 0.18; CI 0.01-0.35; z = 2.14; p = 0.03) and motor (MD 0.16; CI 0.01-0.31; z = 2.04; p = 0.04) development scores. Greater instrumental support was associated with better cognitive (MD 0.26; CI 0.10-0.42; z = 3.15; p < 0.01), motor (MD 0.17; CI 0.02-0.33; z = 2.22; p = 0.03), and overall (MD 0.19; CI 0.03-0.35; z = 2.35; p = 0.02) development scores. Depressive symptoms were associated with greater risk of wasting, while social support was associated with better infant development scores. Strategies to improve mental health and social support for mothers living with HIV during the antenatal period may benefit infant growth and development.