A practical guide to cross-cultural and multi-sited data collection in the biological and behavioural sciences.

Researchers in the biological and behavioural sciences are increasingly conducting collaborative, multi-sited projects to address how phenomena vary across ecologies. These types of projects, however, pose additional workflow challenges beyond those typically encountered in single-sited projects. Through specific attention to cross-cultural research projects, we highlight four key aspects of multi-sited projects that must be considered during the design phase to ensure success: (1) project and team management; (2) protocol and instrument development; (3) data management and documentation; and (4) equitable and collaborative practices. Our recommendations are supported by examples from our experiences collaborating on the Evolutionary Demography of Religion project, a mixed-methods project collecting data across five countries in collaboration with research partners in each host country. To existing discourse, we contribute new recommendations around team and project management, introduce practical recommendations for exploring the validity of instruments through qualitative techniques during piloting, highlight the importance of good documentation at all steps of the project, and demonstrate how data management workflows can be strengthened through open science practices. While this project was rooted in cross-cultural human behavioural ecology and evolutionary anthropology, lessons learned from this project are applicable to multi-sited research across the biological and behavioural sciences.

Early iron supplementation in exclusively breastfed Gambian infants: a randomized controlled trial.

Objective: To investigate the effect of daily iron supplementation for 14 weeks on the serum iron concentration and other markers of iron status in exclusively breastfed infants in Gambia. Methods: A placebo-controlled, randomized, double-blind trial was performed in rural Gambia between 3 August 2021 and 9 March 2022. Overall, 101 healthy, exclusively breastfed infants aged 6 to 10 weeks were recruited at vaccination clinics and through community health workers. Infants were randomized to receive iron supplementation (7.5 mg/day as ferrous sulfate in sorbitol solution) or placebo for 98 days. Venous blood samples were collected at baseline and on day 99 to assess the serum iron concentration and other markers of iron and haematological status. Findings: At day 99, the serum iron concentration was significantly higher in the iron supplementation group than the placebo group (crude difference in means: 2.5 µmol/L; 95% confidence interval: 0.6 to 4.3) and there were significant improvements in other iron and haematological markers. There were 10 serious adverse events (five in each group), 106 non-serious adverse events (54 with iron supplementation; 52 with placebo) and no deaths. There was no marked difference between the groups in maternally reported episodes of diarrhoea, fever, cough, skin infection, eye infection or nasal discharge. Conclusion: In exclusively breastfed Gambian infants, iron supplementation from 6 weeks of age was associated with a significant improvement in markers of iron status at around 6 months of age. There was no indication of adverse effects on growth or infections.

Publisher Correction: Adolescence and the next generation.

In Fig. 4a of this Analysis, owing to an error during the production process, the year in the header of the right column was '2016' rather than '2010'. In addition, in the HTML version of the Analysis, Table 1 was formatted incorrectly. These errors have been corrected online.

Adolescence and the next generation.

Adolescent growth and social development shape the early development of offspring from preconception through to the post-partum period through distinct processes in males and females. At a time of great change in the forces shaping adolescence, including the timing of parenthood, investments in today's adolescents, the largest cohort in human history, will yield great dividends for future generations.

Religious Involvement Is Associated With Higher Fertility and Lower Maternal Investment, but More Alloparental Support Among Gambian Mothers.

OBJECTIVES: Human childrearing is cooperative, with women often able to achieve relatively high fertility through help from many individuals. Previous work has documented tremendous socioecological variation in who supports women in childrearing, but less is known about the intracultural correlates of variation in allomaternal support. In the highly religious, high-fertility setting of The Gambia, we studied whether religious mothers have more children and receive more support with their children. METHODS: We randomly sampled 395 mothers and 745 focal children enrolled in the Kiang West (The Gambia) Longitudinal Population Study cohort. Structured interviews asked mothers who and how often people invest in their children, and about their religious practices. Data were collected at participants' homes on electronic tablet-based long-form surveys and analyzed using the Bayesian hierarchical models. RESULTS: Religiosity was weakly associated with women's higher age-adjusted fertility. Maternal religiosity was negatively related to maternal investment in focal children, but positively associated with total allomaternal support. Specifically, a woman's religiosity was positively associated with allomaternal support from matrilineal kin, other offspring, and affinal kin, but unrelated to paternal, patrilineal, and non-kin investment. CONCLUSIONS: These results suggest that higher fertility among religious mothers may be supported by high levels of investment from biological and affinal kin. Matrilineal kin, other siblings, and affinal kin seem to be the most responsive to a woman's religiosity. Our findings cast doubt on interpretations of women's religious behaviors as signals of fidelity, and instead suggest they may be part of strategies to enable collective allomaternal resources and higher relative fertility.

Tissue- and ethnicity-independent hypervariable DNA methylation states show evidence of establishment in the early human embryo.

We analysed DNA methylation data from 30 datasets comprising 3474 individuals, 19 tissues and 8 ethnicities at CpGs covered by the Illumina450K array. We identified 4143 hypervariable CpGs ('hvCpGs') with methylation in the top 5% most variable sites across multiple tissues and ethnicities. hvCpG methylation was influenced but not determined by genetic variation, and was not linked to probe reliability, epigenetic drift, age, sex or cell heterogeneity effects. hvCpG methylation tended to covary across tissues derived from different germ-layers and hvCpGs were enriched for proximity to ERV1 and ERVK retrovirus elements. hvCpGs were also enriched for loci previously associated with periconceptional environment, parent-of-origin-specific methylation, and distinctive methylation signatures in monozygotic twins. Together, these properties position hvCpGs as strong candidates for studying how stochastic and/or environmentally influenced DNA methylation states which are established in the early embryo and maintained stably thereafter can influence life-long health and disease.

Genetic variations in human ATP2B4 gene alter Plasmodium falciparum in vitro growth in RBCs from Gambian adults.

BACKGROUND: Polymorphisms in ATP2B4 coding for PMCA4b, the primary regulator of erythrocyte calcium concentration, have been shown by GWAS and cross-sectional studies to protect against severe malaria but the mechanism remains unknown. METHODS: Using a recall-by-genotype design, we investigated the impact of a common haplotype variant in ATP2B4 using in vitro assays that model erythrocyte stage malaria pathogenesis. Ninety-six donors representing homozygote (carriers of the minor allele, C/C), heterozygote (T/C) and wildtype (T/T) carriers of the tagging SNP rs1541252 were selected from a cohort of over 12,000 participants in the Keneba Biobank. RESULTS: Red blood cells (RBCs) from homozygotes showed reduced PMCA4b protein expression (mean fluorescence intensities (MFI = 2428 ± 124, 3544 ± 159 and 4261 ± 283], for homozygotes, heterozygotes and wildtypes respectively, p < 0.0001) and slower rates of calcium expulsion (calcium t½ ± SD = 4.7 ± 0.5, 1.8 ± 0.3 and 1.9 ± 0.4 min, p < 0.0001). Growth of a Plasmodium falciparum laboratory strain (FCR3) and two Gambian field isolates was decreased in RBCs from homozygotes compared to heterozygotes and wildtypes (p < 0.01). Genotype group did not affect parasite adhesion in vitro or var-gene expression in malaria-infected RBCs. Parasite growth was inhibited by a known inhibitor of PMCA4b, aurintricarboxylic acid (IC50 = 122uM CI: 110-134) confirming its sensitivity to calcium channel blockade. CONCLUSION: The data support the hypothesis that this ATP2B4 genotype, common in The Gambia and other malaria-endemic areas, protects against severe malaria through the suppression of parasitaemia during an infection. Reduction in parasite density plays a pivotal role in disease outcome by minimizing all aspects of malaria pathogenesis. Follow up studies are needed to further elucidate the mechanism of protection and to determine if this ATP2B4 genotype carries a fitness cost or increases susceptibility to other human disease.

Catch-Up Growth in Infants and Young Children With Faltering Growth: Expert Opinion to Guide General Clinicians.

Faltering growth (FG) is a problem regularly seen by clinicians in infants and young children (<2 years of age). It can occur due to non-disease-related and disease-related causes and is associated with a wide range of adverse outcomes, including shorter-term effects such as impaired immune responses and increased length of hospital stay, and longer-term consequences, including an impact on schooling and cognitive achievements, short stature, and socioeconomic outcomes. It is essential to detect FG, address underlying causes and support catch-up growth where this is indicated. However, anecdotal reports suggest misplaced fear of promoting accelerated (too rapid) growth may deter some clinicians from adequately addressing FG. An invited international group of experts in pediatric nutrition and growth reviewed the available evidence and guidelines on FG resulting from disease-related and non-disease-related effects on nutritional status in healthy term and small for gestational age infants and children up to the age of 2 years in low-, middle-, and high-income countries. Using a modified Delphi process, we developed practical consensus recommendations to provide clarity and practical recommendations for general clinicians on how FG should be defined in different young child populations at risk, how FG should be assessed and managed, and the role of catch-up growth after a period of FG. We also suggested areas where further research is needed to answer remaining questions on this important issue.

Concealed pregnancy as an act of care? A qualitative analysis of motivations for concealing and non-disclosure of early pregnancy in The Gambia.

BACKGROUND: A barrier to achieving first trimester antenatal care (ANC) attendance in many countries has been the widespread cultural practice of not discussing pregnancies in the early stages. Motivations for concealing pregnancy bear further study, as the interventions necessary to encourage early ANC attendance may be more complicated than targeting infrastructural barriers to ANC attendance such as transportation, time, and cost. METHODS: Five focus groups with a total of 30 married, pregnant women were conducted to assess the feasibility of conducting a randomised controlled trial to evaluate the effectiveness of early initiation of physical activity and/or yoghurt consumption in reducing Gestational Diabetes Mellitus in pregnant women in The Gambia. Focus group transcripts were coded through a thematic analysis approach, assessing themes as they arose in relation to failure to attend early ANC. RESULTS: Two reasons for the concealment of pregnancies in the first trimester or ahead of a pregnancy's obvious visibility to others were given by focus group participants. These were 'pregnancy outside of marriage' and 'evil spirits and miscarriage.' Concealment on both grounds was motivated through specific worries and fears. In the case of a pregnancy outside of marriage, this was worry over social stigma and shame. Evil spirits were widely considered to be a cause of early miscarriage, and as such, women may choose to conceal their pregnancies in the early stages as a form of protection. CONCLUSION: Women's lived experiences of evil spirits have been under-explored in qualitative health research as they relate specifically to women's access to early antenatal care. Better understanding of how such sprits are experienced and why some women perceive themselves as vulnerable to related spiritual attacks may help healthcare workers or community health workers to identify in a timely manner the women most likely to fear such situations and spirits and subsequently conceal their pregnancies.

Human milk immune factors, maternal nutritional status, and infant sex: The INSPIRE study.

OBJECTIVES: Breastfeeding is an energetically costly and intense form of human parental investment, providing sole-source nutrition in early infancy and bioactive components, including immune factors. Given the energetic cost of lactation, milk factors may be subject to tradeoffs, and variation in concentrations have been explored utilizing the Trivers-Willard hypothesis. As human milk immune factors are critical to developing immune system and protect infants against pathogens, we tested whether concentrations of milk immune factors (IgA, IgM, IgG, EGF, TGFß2, and IL-10) vary in response to infant sex and maternal condition (proxied by maternal diet diversity [DD] and body mass index [BMI]) as posited in the Trivers-Willard hypothesis and consider the application of the hypothesis to milk composition. METHODS: We analyzed concentrations of immune factors in 358 milk samples collected from women residing in 10 international sites using linear mixed-effects models to test for an interaction between maternal condition, including population as a random effect and infant age and maternal age as fixed effects. RESULTS: IgG concentrations were significantly lower in milk produced by women consuming diets with low diversity with male infants than those with female infants. No other significant associations were identified. CONCLUSIONS: IgG concentrations were related to infant sex and maternal diet diversity, providing minimal support for the hypothesis. Given the lack of associations across other select immune factors, results suggest that the Trivers-Willard hypothesis may not be broadly applied to human milk immune factors as a measure of maternal investment, which are likely buffered against perturbations in maternal condition.

Lipoprotein subfraction patterns throughout gestation in The Gambia: changes in subfraction composition and their relationships with infant birth weights.

BACKGROUND: Lipoprotein subfraction concentrations have been shown to change as gestation progresses in resource-rich settings. The objective of the current study was to evaluate the impact of pregnancy on different-sized lipoprotein particle concentrations and compositions in a resource-poor setting. METHOD: Samples were collected from pregnant women in rural Gambia at enrollment (8-20 weeks), 20 weeks, and 30 weeks of gestation. Concentrations of different-sized high-density, low-density, and triglyceride-rich lipoprotein particles (HDL, LDL, and TRL, respectively) were measured by nuclear magnetic resonance in 126 pooled plasma samples from a subset of women. HDL was isolated and the HDL proteome evaluated using mass spectroscopy. Subfraction concentrations from women in The Gambia were also compared to concentrations in women in the U.S. in mid gestation. RESULTS: Total lipoprotein particles and all-sized TRL, LDL, and HDL particle concentrations increased during gestation, with the exception of medium-sized LDL and HDL particles which decreased. Subfraction concentrations were not associated with infant birth weights, though relationships were found between some lipoprotein subfraction concentrations in women with normal versus low birth weight infants (< 2500 kg). HDL's proteome also changed during gestation, showing enrichment in proteins associated with metal ion binding, hemostasis, lipid metabolism, protease inhibitors, proteolysis, and complement activation. Compared to women in the U.S., Gambian women had lower large- and small-sized LDL and HDL concentrations, but similar medium-sized LDL and HDL concentrations. CONCLUSIONS: Most lipoprotein subfraction concentrations increase throughout pregnancy in Gambian women and are lower in Gambian vs U.S. women, the exception being medium-sized LDL and HDL particle concentrations which decrease during gestation and are similar in both cohorts of women. The proteomes of HDL also change in ways to support gestation. These changes warrant further study to determine how a lack of change or different changes could impact negative pregnancy outcomes.

Possible mediators of metabolic endotoxemia in women with obesity and women with obesity-diabetes in The Gambia.

AIMS/HYPOTHESIS: Translocation of bacterial debris from the gut causes metabolic endotoxemia (ME) that results in insulin resistance, and may be on the causal pathway to obesity-related type 2 diabetes. To guide interventions against ME we tested two hypothesised mechanisms for lipopolysaccharide (LPS) ingress: a leaky gut and chylomicron-associated transfer following a high-fat meal. METHODS: In lean women (n = 48; fat mass index (FMI) 9.6 kg/m2), women with obesity (n = 62; FMI 23.6 kg/m2) and women with obesity-diabetes (n = 38; FMI 24.9 kg/m2) we used the lactulose-mannitol dual-sugar permeability test (LM ratio) to assess gut integrity. Markers of ME (LPS, EndoCAb IgG and IgM, IL-6, CD14 and lipoprotein binding protein) were assessed at baseline, 2 h and 5 h after a standardised 49 g fat-containing mixed meal. mRNA expression of markers of inflammation, macrophage activation and lipid metabolism were measured in peri-umbilical adipose tissue (AT) biopsies. RESULTS: The LM ratio did not differ between groups. LPS levels were 57% higher in the obesity-diabetes group (P < 0.001), but, contrary to the chylomicron transfer hypothesis, levels significantly declined following the high-fat challenge. EndoCAb IgM was markedly lower in women with obesity and women with obesity-diabetes. mRNA levels of inflammatory markers in adipose tissue were consistent with the prior concept that fat soluble LPS in AT attracts and activates macrophages. CONCLUSIONS/INTERPRETATION: Raised levels of LPS and IL-6 in women with obesity-diabetes and evidence of macrophage activation in adipose tissue support the concept of metabolic endotoxemia-mediated inflammation, but we found no evidence for abnormal gut permeability or chylomicron-associated post-prandial translocation of LPS. Instead, the markedly lower EndoCAb IgM levels indicate a failure in sequestration and detoxification.

Implications for quantifying early life growth trajectories of term-born infants using INTERGROWTH-21st newborn size standards at birth in conjunction with World Health Organization child growth standards in the postnatal period.

BACKGROUND: The INTERGROWTH-21st sex and gestational age (GA) specific newborn size standards (IG-NS) are intended to complement the World Health Organization Child Growth Standards (WHO-GS), which are not GA-specific. We examined the implications of using IG-NS at birth and WHO-GS at postnatal ages in longitudinal epidemiologic studies. OBJECTIVES: The aim of this study was to quantify the extent to which standardised measures of newborn size and growth are affected when using WHO-GS versus IG-NS at birth among term-born infants. METHODS: Data from two prenatal trials in Bangladesh (n = 755) and The Gambia (n = 522) were used to estimate and compare size at birth and growth from birth to 3 months when using WHO-GS only ('WHO-GS') versus IG-NS at birth and WHO-GS postnatally ('IG-NS'). Mean length-for-age (LAZ), weight-for-age (WAZ) and head circumference-for-age (HCAZ), and the prevalence of undernutrition (stunting: LAZ < -2SD; underweight: WAZ < -2SD; and microcephaly: HCAZ < -2SD) were estimated overall and by GA strata [early-term (370/7 -386/7 ), full-term (390/7 -406/7 ) and late-term (410/7 -430/7 )]. We used Bland-Altman plots to compare continuous indices and Kappa statistic to compare categorical indicators. RESULTS: At birth, mean LAZ, WAZ and HCAZ, and the prevalence of undernutrition were most similar among newborns between 39 and 40 weeks of GA when using WHO-GS versus IG-NS. However, anthropometric indices were systematically lower among early-term infants and higher among late-term infants when using WHO-GS versus IG-NS. Early-term and late-term infants demonstrated relatively faster and slower growth, respectively, when using WHO-GS versus IG-NS, with the direction and magnitude of differences varying between anthropometric indices. Individual-level differences in attained size and growth, when using WHO-GS versus IG-NS, were greater than 0.2 SD in magnitude for >60% of infants across all anthropometric indices. CONCLUSIONS: Using IG-NS at birth with WHO-GS postnatally is acceptable for full-term infants but may give a misleading interpretation of growth trajectories among early- and late-term infants.

Breastfeeding in the Modern World.

BACKGROUND: Social changes in the 20th century resulted in substantial reductions in the prevalence of breastfeeding in many countries but especially in those with high and increasing wealth. Concerns about this decline prompted widespread research to quantify the benefits of breastfeeding and the mechanisms by which it exerts protective effects for mothers and children. Pro-breastfeeding advocacy resulted in the WHO International Code of Marketing of Breastmilk Substitutes in 1981 and the Innocenti Declaration on Breastfeeding in 1990, which, together with numerous other initiatives, have helped to turn the tide. SUMMARY: A tranche of recent meta-analyses of dozens of individual studies provide very strong evidence that breastfeeding has substantial benefits to babies, infants, and young children. The benefits and strengths of association vary according to the background environmental and hygiene conditions in different settings. In low-income settings, the chief measurable benefits for the child are in respect of reductions in diarrhea and respiratory infections, and in mortality. In high-income settings, breastfeeding protects against otitis media, likely protects against type 2 diabetes and overweight and obesity, and possibly protects against type 1 diabetes. It likely improves IQ by 2-3 percentage points. In mothers, breastfeeding reduces a mother's likelihood of breast and ovarian cancers. Feeding these data into the Lives Saved Tool suggests that these benefits could prevent 823,000 deaths in children and 22,000 among women.

Key genetic variants associated with variation of milk oligosaccharides from diverse human populations.

Human milk oligosaccharides (HMO), the third most abundant component of human milk, are thought to be important contributors to infant health. Studies have provided evidence that geography, stage of lactation, and Lewis and secretor blood groups are associated with HMO profile. However, little is known about how variation across the genome may influence HMO composition among women in various populations. In this study, we performed genome-wide association analyses of 395 women from 8 countries to identify genetic regions associated with 19 different HMO. Our data support FUT2 as the most significantly associated (P < 4.23-9 to P < 4.5-70) gene with seven HMO and provide evidence of balancing selection for FUT2. Although polymorphisms in FUT3 were also associated with variation in lacto-N-fucopentaose II and difucosyllacto-N-tetrose, we found little evidence of selection on FUT3. To our knowledge, this is the first report of the use of genome-wide association analyses on HMO.

Intense and Mild First Epidemic Wave of Coronavirus Disease, The Gambia.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is evolving differently in Africa than in other regions. Africa has lower SARS-CoV-2 transmission rates and milder clinical manifestations. Detailed SARS-CoV-2 epidemiologic data are needed in Africa. We used publicly available data to calculate SARS-CoV-2 infections per 1,000 persons in The Gambia. We evaluated transmission rates among 1,366 employees of the Medical Research Council Unit The Gambia (MRCG), where systematic surveillance of symptomatic cases and contact tracing were implemented. By September 30, 2020, The Gambia had identified 3,579 SARS-CoV-2 cases, including 115 deaths; 67% of cases were identified in August. Among infections, MRCG staff accounted for 191 cases; all were asymptomatic or mild. The cumulative incidence rate among nonclinical MRCG staff was 124 infections/1,000 persons, which is >80-fold higher than estimates of diagnosed cases among the population. Systematic surveillance and seroepidemiologic surveys are needed to clarify the extent of SARS-CoV-2 transmission in Africa.

Measurement of long-term iron absorption and loss during iron supplementation using a stable isotope of iron (57 Fe).

We report the first measurements of long-term iron absorption and loss during iron supplementation in African children using a stable isotope of iron (57 Fe). After uniform labelling of body iron with 57 Fe, iron absorption is proportional to the rate of decrease in the 57 Fe tracer concentration, while iron loss is proportional to the rate of decrease in the 57 Fe tracer amount. Anaemic Gambian toddlers were given 2 mg 57 Fe orally to equilibrate with total body iron over 8-11 months. After assignment to the positive control arm of the HIGH study, 22 toddlers consumed a micronutrient powder containing 12 mg iron for 12 weeks followed by 12 weeks without iron supplementation. Their daily iron absorption increased 3·8-fold during the iron supplementation period compared to the control period [median (interquartile range, IQR): 1·00 (0·82; 1·28) mg/day vs. 0·26 (0·22; 0·35) mg/day; P = 0·001]. Unexpectedly, during the supplementation period, daily iron loss also increased by 3·4-fold [0·75 (0·55; 0·87) mg/day vs. 0·22 (0·19; 0·29) mg/day; P = 0·005]. Consequently, most (~72%) of the absorbed iron was lost during supplementation. Long-term studies of iron absorption and loss are a promising and accurate method for assessing and quantifying long-term iron balance and may provide a reference method for evaluating iron intervention programs in vulnerable population groups. This study was registered as ISRCTN 0720906.

Prevalence and predictors of vitamin D deficiency in young African children.

BACKGROUND: Children living in sub-Saharan Africa have a high burden of rickets and infectious diseases, conditions that are linked to vitamin D deficiency. However, data on the vitamin D status of young African children and its environmental and genetic predictors are limited. We aimed to examine the prevalence and predictors of vitamin D deficiency in young African children. METHODS: We measured 25-hydroxyvitamin D (25(OH)D) and typed the single nucleotide polymorphisms, rs4588 and rs7041, in the GC gene encoding the vitamin D binding protein (DBP) in 4509 children aged 0-8 years living in Kenya, Uganda, Burkina Faso, The Gambia and South Africa. We evaluated associations between vitamin D status and country, age, sex, season, anthropometric indices, inflammation, malaria and DBP haplotypes in regression analyses. RESULTS: Median age was 23.9 months (interquartile range [IQR] 12.3, 35.9). Prevalence of vitamin D deficiency using 25(OH)D cut-offs of < 30 nmol/L and < 50 nmol/L was 0.6% (95% CI 0.4, 0.9) and 7.8% (95% CI 7.0, 8.5), respectively. Overall median 25(OH)D level was 77.6 nmol/L (IQR 63.6, 94.2). 25(OH)D levels were lower in South Africa, in older children, during winter or the long rains, and in those with afebrile malaria, and higher in children with inflammation. 25(OH)D levels did not vary by stunting, wasting or underweight in adjusted regression models. The distribution of Gc variants was Gc1f 83.3%, Gc1s 8.5% and Gc2 8.2% overall and varied by country. Individuals carrying the Gc2 variant had lower median 25(OH)D levels (72.4 nmol/L (IQR 59.4, 86.5) than those carrying the Gc1f (77.3 nmol/L (IQR 63.5, 92.8)) or Gc1s (78.9 nmol/L (IQR 63.8, 95.5)) variants. CONCLUSIONS: Approximately 0.6% and 7.8% of young African children were vitamin D deficient as defined by 25(OH)D levels < 30 nmol/L and < 50 nmol/L, respectively. Latitude, age, season, and prevalence of inflammation and malaria should be considered in strategies to assess and manage vitamin D deficiency in young children living in Africa.

The Role of Nutrition in COVID-19 Susceptibility and Severity of Disease: A Systematic Review.

BACKGROUND: Many nutrients have powerful immunomodulatory actions with the potential to alter susceptibility to coronavirus disease 2019 (COVID-19) infection, progression to symptoms, likelihood of severe disease, and survival. OBJECTIVE: The aim was to review the latest evidence on how malnutrition across all its forms (under- and overnutrition and micronutrient status) may influence both susceptibility to, and progression of, COVID-19. METHODS: We synthesized information on 13 nutrition-related components and their potential interactions with COVID-19: overweight, obesity, and diabetes; protein-energy malnutrition; anemia; vitamins A, C, D, and E; PUFAs; iron; selenium; zinc; antioxidants; and nutritional support. For each section we provide: 1) a landscape review of pertinent material; 2) a systematic search of the literature in PubMed and EMBASE databases, including a wide range of preprint servers; and 3) a screen of 6 clinical trial registries. All original research was considered, without restriction to study design, and included if it covered: 1) severe acute respiratory syndrome coronavirus (CoV) 2 (SARS-CoV-2), Middle East respiratory syndrome CoV (MERS-CoV), or SARS-CoV viruses and 2) disease susceptibility or 3) disease progression, and 4) the nutritional component of interest. Searches took place between 16 May and 11 August 2020. RESULTS: Across the 13 searches, 2732 articles from PubMed and EMBASE, 4164 articles from the preprint servers, and 433 trials were returned. In the final narrative synthesis, we include 22 published articles, 38 preprint articles, and 79 trials. CONCLUSIONS: Currently there is limited evidence that high-dose supplements of micronutrients will either prevent severe disease or speed up recovery. However, results of clinical trials are eagerly awaited. Given the known impacts of all forms of malnutrition on the immune system, public health strategies to reduce micronutrient deficiencies and undernutrition remain of critical importance. Furthermore, there is strong evidence that prevention of obesity and type 2 diabetes will reduce the risk of serious COVID-19 outcomes. This review is registered at PROSPERO as CRD42020186194.

A Novel method for the identification and quantification of weight faltering.

OBJECTIVE: We describe a new method for identifying and quantifying the magnitude and rate of short-term weight faltering episodes, and assess how (a) these episodes relate to broader growth outcomes, and (b) different data collection intervals influence the quantification of weight faltering. MATERIALS AND METHODS: We apply this method to longitudinal growth data collected every other day across the first year of life in Gambian infants (n = 124, males = 65, females = 59). Weight faltering episodes are identified from velocity peaks and troughs. Rate of weight loss and regain, maximum weight loss, and duration of each episode were calculated. We systematically reduced our dataset to mimic various potential measurement intervals, to assess how these intervals affect the ability to derive information about short-term weight faltering episodes. We fit linear models to test whether metrics associated with growth faltering were associated with growth outcomes at 1 year, and generalized additive mixed models to determine whether different collection intervals influence episode identification and metrics. RESULTS: Three hundred weight faltering episodes from 119 individuals were identified. The number and magnitude of episodes negatively impacted growth outcomes at 1 year. As data collection interval increases, weight faltering episodes are missed and the duration of episodes is overestimated, resulting in the rate of weight loss and regain being underestimated. CONCLUSIONS: This method identifies and quantifies short-term weight faltering episodes, that are in turn negatively associated with growth outcomes. This approach offers a tool for investigators interested in understanding how short-term weight faltering relates to longer-term outcomes.