Weight change in the first 30 days among infants born less than 2000 grams in Guinea-Bissau and Uganda.

Despite the high prevalence of low birth weight infants in sub-Saharan Africa and the associated poor outcomes, weight change during the newborn period has not been well characterized for this population. We prospectively assessed growth over the first 30 days among 120 infants born < 2000 g (g) in Guinea-Bissau and Uganda, and compared it to a similar cohort of 420 infants born ≥ 2000 g. Among those born < 2000 g, mean birth weight was 1747 ± 164 g, and initial weight loss was 8.25 ± 4.40% of birth weight prior to the initiation of weight gain at a median of 3 (interquartile range 2, 4) days of age. This initial weight loss was more pronounced (8.25 vs 6.06%; p < 0.001) and lasted longer (median 3 vs 2 days; p < 0.001) than for infants born ≥ 2000 g. The initial period of weight loss was an important predictor of growth at 30 days in both cohorts. Infants born < 2000 g on average grew proportionately to their size at birth but did not experience catch-up growth; their weights at 30 days remained much lower than that of infants born ≥ 2000 g and most remained severely underweight. Targeted interventions to optimize early growth should be investigated.

Newborn weight nomograms in selected low and middle-income countries.

Growth impairment is common in low- and middle-income countries (LMIC) and may begin during early infancy, increasing morbidity and mortality. To ensure healthy infant growth, healthcare providers in high-income countries (HIC) track newborn weight change using tools developed and validated in HIC. To understand the utility of these tools for LMIC, we conducted a secondary analysis to compare weight trajectories in the first 5 days of life among newborns born in our LMIC cohort to an existing HIC newborn weight tool designed to track early weight change. Between April 2019 and March 2020, a convenience sample of 741 singleton healthy breastfeeding newborns who weighed ≥ 2000 g at birth were enrolled at selected health facilities in Guinea-Bissau, Nepal, Pakistan, and Uganda. Using a standardized protocol, newborn weights were obtained within 6 h of birth and at 1, 2, 3, 4, and 5 days, and nomograms depicting newborn weight change were generated. The trajectories of early newborn weight change in our cohort were largely similar to published norms derived from HIC infants, with the exceptions that initial newborn weight loss in Guinea-Bissau was more pronounced than HIC norms and newborn weight gain following weight nadir was more pronounced in Guinea-Bissau, Pakistan, and Uganda than HIC norms. These data demonstrate that HIC newborn weight change tools may have utility in LMIC settings.

Randomized controlled trial of early, small-volume formula supplementation among newborns: A study protocol.

Childhood undernutrition is a major health burden worldwide that increases childhood morbidity and mortality and causes impairment in infant growth and developmental delays that can persist into adulthood. The first weeks and months after birth are critical to the establishment of healthy growth and development during childhood. The World Health Organization recommends immediate and exclusive breastfeeding (EBF). In infants for whom EBF may not meet nutritional and caloric demands, early, daily, small-volume formula supplementation along with breastfeeding may more effectively avoid underweight wasting and stunting in early infancy than breastfeeding alone. The primary objective of this randomized controlled trial is to evaluate the efficacy of formula for 30 days among low birth weight (LBW) infants <6 hours of age and those not LBW with weights <2600 grams at 4 days of age. We will compare breastfeeding and formula (up to 59 milliliters administered daily) through 30 days of infant age vs recommendations for frequent EBF without supplementation, and test the hypothesis that formula increases weight-for-age z-score at 30 days of infant age. The trial will enroll and randomize 324 mother-infant pairs in Guinea-Bissau and Uganda, and follow them for 6 months for outcomes including growth, intestinal microbiota, breastfeeding duration, infant dietary intake, and adverse events. Conservatively estimating 20% loss to follow up, this sample size provides ≥80% power per weight stratum for intervention group comparison to detect a difference of 0.20 with respect to the outcome of WAZ at day 30. This trial was approved by the University of California, San Francisco Institutional Review Board (19-29405); the Guinea-Bissau National Committee on Ethics in Health (Comite Nacional de Etica na Saude, 075/CNES/INASA/2020); the Higher Degrees, Research and Ethics Committee of Makerere University (871); and the Uganda National Council of Science and Technology (HS1226ES). We plan to disseminate study results in peer-reviewed journals and international conferences. Trial registration number: NCT04704076.

Effects of food supplementation on cognitive function, cerebral blood flow, and nutritional status in young children at risk of undernutrition: randomized controlled trial.

OBJECTIVE: To assess the effects of food supplementation on improving working memory and additional measures including cerebral blood flow in children at risk of undernutrition. DESIGN: Randomized controlled trial. SETTING: 10 villages in Guinea-Bissau. PARTICIPANTS: 1059 children aged 15 months to 7 years; children younger than 4 were the primary population. INTERVENTIONS: Supervised isocaloric servings (≈1300 kJ, five mornings each week, 23 weeks) of a new food supplement (NEWSUP, high in plant polyphenols and omega 3 fatty acids, within a wide variety and high fortification of micronutrients, and a high protein content), or a fortified blended food (FBF) used in nutrition programs, or a control meal (traditional rice breakfast). MAIN OUTCOME MEASUREMENTS: The primary outcome was working memory, a core executive function predicting long term academic achievement. Additional outcomes were hemoglobin concentration, growth, body composition, and index of cerebral blood flow (CBFi). In addition to an intention-to-treat analysis, a predefined per protocol analysis was conducted in children who consumed at least 75% of the supplement (820/925, 89%). The primary outcome was assessed by a multivariable Poisson model; other outcomes were assessed by multivariable linear mixed models. RESULTS: Among children younger than 4, randomization to NEWSUP increased working memory compared with the control meal (rate ratio 1.20, 95% confidence interval 1.02 to 1.41, P=0.03), with a larger effect in the per protocol population (1.25, 1.06 to 1.47, P=0.009). NEWSUP also increased hemoglobin concentration among children with anemia (adjusted mean difference 0.65 g/dL, 95% confidence interval 0.23 to 1.07, P=0.003) compared with the control meal, decreased body mass index z score gain (-0.23, -0.43 to -0.02, P=0.03), and increased lean tissue accretion (2.98 cm2, 0.04 to 5.92, P=0.046) with less fat (-5.82 cm2, -11.28 to -0.36, P=0.04) compared with FBF. Additionally, NEWSUP increased CBFi compared with the control meal and FBF in both age groups combined (1.14 mm2/s×10-8, 0.10 to 2.23, P=0.04 for both comparisons). Among children aged 4 and older, NEWSUP had no significant effect on working memory or anemia, but increased lean tissue compared with FBF (4.31 cm2, 0.34 to 8.28, P=0.03). CONCLUSIONS: Childhood undernutrition is associated with long term impairment in cognition. Contrary to current understanding, supplementary feeding for 23 weeks could improve executive function, brain health, and nutritional status in vulnerable young children living in low income countries. Further research is needed to optimize nutritional prescriptions for regenerative improvements in cognitive function, and to test effectiveness in other vulnerable groups. TRIAL REGISTRATION: ClinicalTrials.gov NCT03017209.

A Pilot Randomized Controlled Trial of a New Supplementary Food Designed to Enhance Cognitive Performance during Prevention and Treatment of Malnutrition in Childhood.

BACKGROUND: Cognitive impairment associated with childhood malnutrition and stunting is generally considered irreversible. OBJECTIVE: The aim was to test a new nutritional supplement for the prevention and treatment of moderate-acute malnutrition (MAM) focused on enhancing cognitive performance. METHODS: An 11-wk, village-randomized, controlled pilot trial was conducted in 78 children aged 1-3 or 5-7 y living in villages in Guinea-Bissau. The supplement contained 291 kcal/d for young children and 350 kcal/d for older children and included 5 nutrients and 2 flavan-3-ol-rich ingredients not present in current food-based recommendations for MAM. Local bakers prepared the supplement from a combination of locally sourced items and an imported mix of ingredients, and it was administered by community health workers 5 d/wk. The primary outcome was executive function abilities at 11 wk. Secondary outcomes included additional cognitive measures and changes in z scores for weight (weight-for-age) and height (height-for-age) and hemoglobin concentrations at 11 wk. An index of cerebral blood flow (CBF) was also measured at 11 wk to explore the use of this measurement as a biological index of cognitive impairment. RESULTS: There were no significant differences in any outcome between groups at baseline. There was a beneficial effect of random assignment to the supplement group on working memory at 11 wk in children aged 1-3 y (P < 0.05). This difference contrasted with no effect in older children and was not associated with faster growth rate. In addition, CBF correlated with task-switching performance (P < 0.05). CONCLUSIONS: These preliminary data suggest that cognitive impairment can be monitored with measurement of CBF. In addition, the findings provide preliminary data that suggest that it may be possible to improve poor cognitive performance in young children through changes in the nutritional formulation of supplementary foods used to prevent and treat MAM. Powered studies of the new supplement formulation are needed. This trial was registered at clinicaltrials.gov as NCT03017209.