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).

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 polymerase chain reaction to identify likely and possible bacterial etiologies 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 6692 children, the leading likely etiologies were rotavirus (21.1%), enterotoxigenic Escherichia coli encoding heat-stable toxin (13.3%), Shigella (12.6%), and Cryptosporidium (9.6%). More than one-quarter (1894 [28.3%]) had a likely and 1153 (17.3%) a possible bacterial etiology. Day 3 diarrhea was less common in those randomized to azithromycin versus placebo among children with a likely bacterial etiology (risk difference [RD]likely, -11.6 [95% confidence interval {CI}, -15.6 to -7.6]) and possible bacterial etiology (RDpossible, -8.7 [95% CI, -13.0 to -4.4]) but not in other children (RDunlikely, -0.3% [95% CI, -2.9% to 2.3%]). A similar association was observed for 90-day hospitalization or death (RDlikely, -3.1 [95% CI, -5.3 to -1.0]; RDpossible, -2.3 [95% CI, -4.5 to -.01]; RDunlikely, -0.6 [95% CI, -1.9 to .6]). The magnitude of risk differences was similar among specific likely bacterial etiologies, including Shigella. CONCLUSIONS: Acute watery diarrhea confirmed or presumed to be of bacterial etiology may benefit from azithromycin treatment. CLINICAL TRIALS REGISTRATION: NCT03130114.

Biological and pathological mechanisms leading to the birth of a small vulnerable newborn.

The pathway to a thriving newborn begins before conception and continues in utero with a healthy placenta and the right balance of nutrients and growth factors that are timed and sequenced alongside hormonal suppression of labour until a mature infant is ready for birth. Optimal nutrition that includes adequate quantities of quality protein, energy, essential fats, and an extensive range of vitamins and minerals not only supports fetal growth but could also prevent preterm birth by supporting the immune system and alleviating oxidative stress. Infection, illness, undernourishment, and harmful environmental exposures can alter this trajectory leading to an infant who is too small due to either poor growth during pregnancy or preterm birth. Systemic inflammation suppresses fetal growth by interfering with growth hormone and its regulation of insulin-like growth factors. Evidence supports the prevention and treatment of several maternal infections during pregnancy to improve newborn health. However, microbes, such as Ureaplasma species, which are able to ascend the cervix and cause membrane rupture and chorioamnionitis, require new strategies for detection and treatment. The surge in fetal cortisol late in pregnancy is essential to parturition at the right time, but acute or chronically high maternal cortisol levels caused by psychological or physical stress could also trigger labour onset prematurely. In every pathway to the small vulnerable newborn, there is a possibility to modify the course of pregnancy by supporting improved nutrition, protection against infection, holistic maternal wellness, and healthy environments.

Small vulnerable newborns-big potential for impact.

Despite major achievements in child survival, the burden of neonatal mortality has remained high and even increased in some countries since 1990. Currently, most neonatal deaths are attributable to being born preterm, small for gestational age (SGA), or with low birthweight (LBW). Besides neonatal mortality, these conditions are associated with stillbirth and multiple morbidities, with short-term and long-term adverse consequences for the newborn, their families, and society, resulting in a major loss of human capital. Prevention of preterm birth, SGA, and LBW is thus critical for global child health and broader societal development. Progress has, however, been slow, largely because of the global community's failure to agree on the definition and magnitude of newborn vulnerability and best ways to address it, to frame the problem attractively, and to build a broad coalition of actors and a suitable governance structure to implement a change. We propose a new definition and a conceptual framework, bringing preterm birth, SGA, and LBW together under a broader umbrella term of the small vulnerable newborn (SVN). Adoption of the framework and the unified definition can facilitate improved problem definition and improved programming for SVN prevention. Interventions aiming at SVN prevention would result in a healthier start for live-born infants, while also reducing the number of stillbirths, improving maternal health, and contributing to a positive economic and social development in the society.

Achieving Enteral Autonomy in Children with Intestinal Failure Following Inpatient Admission: A Case Series.

We describe cases of intestinal failure wherein inpatient admission was critical toward enteral autonomy. We performed a retrospective chart review of 6 children with long-term parenteral nutrition dependence who were weaned from parenteral nutrition after admission. Admissions included feeding and medication titration, interdisciplinary care, and a home parenteral nutrition team consultation.

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 (2019-2022). 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 < .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 1933 young children enrolled in the study. The median (IQR) age was 11 (4, 23) months and 58.7% were males. In total, 67 (3.5%) died during follow-up. Ten variables contributed to our tool (total possible score 82). Cancer (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.

Effects of Vitamin D-3 Supplementation During Pregnancy and Lactation on Maternal and Infant Biomarkers of Environmental Enteric Dysfunction, Systemic Inflammation, and Growth: A Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Environmental enteric dysfunction (EED) is an acquired, subclinical state of intestinal inflammation common in children and adults in low-income and middle-income countries. Although vitamin D-3 supplementation has purported anti-inflammatory properties, its ability to ameliorate biomarkers of EED remains unclear. OBJECTIVES: This study aimed to examine the effects of maternal vitamin D-3 supplementation during pregnancy and lactation on biomarkers of EED, systemic inflammation, and growth in women living with HIV and their infants in Dar es Salaam, Tanzania. METHODS: We conducted subgroup analyses among randomly selected mothers (n = 720) and infants (n = 365 at 6 wk of age, and n = 266 at 6 mo of age) who participated in a randomized, triple-blind, placebo-controlled trial of daily maternal 3000 IU vitamin D-3 supplementation from the second trimester of pregnancy until 1 y postpartum. Biomarkers of EED (soluble CD14 and intestinal fatty acid-binding protein), systemic inflammation (C-reactive protein and α1-acid glycoprotein), and growth factors (insulin-like growth factor 1 and fibroblast growth factor 21) were measured via the Micronutrient and Environmental Enteric Dysfunction Assessment Tool. Anti-flagellin and anti-lipopolysaccharide immunoglobulins were measured via enzyme-linked immunosorbent assay. Comparisons by randomized treatment arm were performed using ordinary least squares regression models with log2-transformed biomarkers. RESULTS: At 32 wk of gestation, intestinal fatty acid-binding protein (ß: -0.19; P = 0.03) and α1-acid glycoprotein (ß:-0.11; P = 0.04) were significantly lower in mothers in the vitamin D-3 group than those in mothers in the placebo group. At 6 wk of age, insulin-like growth factor 1 (ß:-0.31; P = 0.03) was significantly lower in infants whose mothers were in the vitamin D-3 group than that in infants whose mothers were in the placebo group. CONCLUSIONS: Vitamin D-3 supplementation during pregnancy and lactation reduced selected EED and systemic inflammation biomarkers among women living with HIV. While the effects of maternal vitamin D-3 supplementation do not appear to extend to infants, there may be an effect on growth factors. This trial was registered at clinicaltrials.gov as NCT02305927 (https://clinicaltrials.gov/study/NCT02305927).

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.

Performance of pan-enteroscopy in children with intestinal failure due to short bowel syndrome: A single-center retrospective study.

OBJECTIVES: In pediatric patients with intestinal failure (IF) due to short bowel syndrome (SBS), we hypothesized that young children, those with shorter residual small bowel and those with congenital malrotation of the bowel would be more likely to undergo pan-enteroscopy. We aimed to determine the feasibility and diagnostic yield of pan-enteroscopy in this cohort. METHODS: We performed a single-center, retrospective study of pediatric patients with IF due to SBS who had undergone at least one GI endoscopic evaluation between January 1, 2018 and January 1, 2023. RESULTS: A pan-enteroscopy might have been possible in 381 of the 431 procedures (206 patients) reviewed. Forty-four (21%) patients underwent 54 pan-enteroscopies. Children with a residual bowel length <35 cm had higher odds of undergoing pan-enteroscopy (odds ratio [OR] 3.72, 95% confidence interval [CI] [1.32, 10.48], p = 0.01), as did patients with periprocedural glucagon-like peptide 2 (GLP-2) analog use (OR 4.30, 95% CI [1.24, 14.95], p = 0.02). Patients with diagnoses other than necrotizing enterocolitis (NEC) tended to be more likely to achieve a pan-enteroscopy (OR 2.73, 95% CI [0.95,7.88], p = 0.06). Evidence of gross and histopathologic abnormalities were found in 77.8% and 78% of the procedures, respectively. No complications were identified. CONCLUSION: In a large cohort of children with SBS, pan-enteroscopy was successfully performed in 14.2% of the procedures and microscopic abnormalities were common. Shorter residual bowel length, underlying diagnoses of non-NEC, and GLP-2 analog use were generally associated with successful pan-enteroscopy, independent of age and several other factors. These data suggest that pan-enteroscopy is feasible and of high-yield in a subset of patients with SBS.

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.

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.

Experiences, acceptability and barriers to calcium supplementation during pregnancy in Dar es Salaam, Tanzania.

Calcium supplementation in pregnancy is recommended in contexts with low dietary calcium intake to reduce the risk of pre-eclampsia and its complications. The World Health Organisation suggested high-dose calcium supplementation (1500-2000 mg/day), divided into three doses and taken at different times from daily iron-folic supplements. We conducted a mixed methods evaluation study to assess experiences, acceptability and barriers to high-dose calcium supplementation from the perspectives of pregnant women and antenatal health care providers at two public health facilities in Dar es Salaam, Tanzania. Descriptive statistics and thematic analysis were used to characterise acceptability, barriers and overall experiences of using high-dose calcium supplementation. Pregnant women in the cohort were aged 19-41 years, with 32.4% being primiparous. The proportion of pregnant women who liked calcium supplements 'a lot' decreased from 50.2% at the first visit to 31.8% at the last antenatal follow-up visit. Adherence was 71.3% (interquartile range: 50.5%, 89.3%), with only 24.0% of the participants taking 90% or more of the required supplements. Although participants expressed positive attitudes towards using calcium supplements, they also voiced concerns about the large size, side effects, the potential to forget and the burden of taking calcium supplements three times per day. Antenatal health care providers also affirmed the high burden of taking calcium supplements in addition to iron-folic acid supplements. Participants expressed the acceptability of using calcium supplements during pregnancy, but adherence to three doses per day posed challenges to pregnant women. Reducing the number of calcium supplement doses per day may improve adherence.

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.).

Nutritional and medical approaches to intestinal failure.

PURPOSE OF REVIEW: Advances in the field of intestinal failure continue to reduce mortality rates of this complex syndrome. Over the last 20 months (January 2021- October 2022), several important papers were published that relate to the nutritional and medical management of intestinal failure and rehabilitation. RECENT FINDINGS: New reports on the epidemiology of intestinal failure have shown that short bowel syndrome (SBS) remains the most common cause of intestinal failure worldwide in both adults and children. Advances in the provision of parenteral nutrition (PN), the advent of Glucagon-like peptide-2 (GLP-2) analogs, and the development of interdisciplinary centers have allowed for safer and longer courses of parenteral support. Unfortunately, rates of enteral anatomy continue to lag behind these advancements, requiring greater focus on quality of life, neurodevelopmental outcomes, and management of sequalae of long-term PN such as Intestinal Failure Associated Liver Disease (IFALD), small bowel bacterial overgrowth (SBBO), and Metabolic Bone Disease (MBD). SUMMARY: There have been significant advances in the nutritional and medical approaches in intestinal failure, including advances in PN, use of GLP-2 analogs, and key developments in the medical management of this condition. As children with intestinal failure increasingly survive to adulthood, new challenges exist with respect to the management of a changing population of patients with SBS. Interdisciplinary centers remain standard of care for this complex patient population.

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.

The effect of iron supplementation on maternal iron deficiency anemia does not differ by baseline anemia type among Tanzanian pregnant women without severe iron deficiency anemia.

PURPOSE: Whether anemia type modifies the risk of pregnancy and newborn outcomes and the effectiveness of iron supplementation is unclear. We examined the association of iron deficiency anemia (IDA) and non-iron deficiency anemia (NIDA) on the risks of these outcomes and the extent to which anemia type modifies the impact of prenatal iron supplementation. METHODS: This was a secondary analysis of a placebo-controlled trial of iron supplementation among 1450 HIV-negative women in Tanzania. Eligibility criteria included gestational age < 27 weeks, hemoglobin > 85 g/L, and ferritin > 12 µg/L. Individuals were categorized as non-anemia, IDA or NIDA using hemoglobin, ferritin and CRP. Analyses were conducted using regression models and likelihood ratio tests. RESULTS: Compared to the non-anemia group, delivery hemoglobin was lower by 15 g/L (95% CI 10.9, 19.3) in the baseline IDA group, and 7.3 g/L (95% CI 3.1, 11.5) in the baseline NIDA group. The RRs of anemia severity, iron deficiency, placental malaria, stillbirths, perinatal mortality, birthweight, and preterm birth were not different among women in the baseline NIDA group (vs. non-anemia) compared to the baseline IDA group (vs. non-anemia). The difference in the mean delivery hemoglobin for iron supplementation and placebo arms was 8 g/L (95% CI 6, 11) in the non-anemia group, 7 g/L (95% CI 2, 13) in the NIDA group, and 16 g/L (95% CI 10, 22) in the IDA group. CONCLUSION: Iron supplementation is effective even among pregnant women with NIDA. TRIAL REGISTRATION: NCT01119612 (May 7, 2010).

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.

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.