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.

Cognitive control in infancy: Attentional predictors using a tablet-based measure.

Cognitive control is a predictor of later-life outcomes and may underpin higher order executive processes. The present study examines the development of early cognitive control during the first 24-month. We evaluated a tablet-based assessment of cognitive control among infants aged 18- and 24-month. We also examined concurrent and longitudinal associations between attentional disengagement, general cognitive skills and cognitive control. Participants (N = 60, 30 female) completed the tablet-task at 18- and 24-month of age. Attentional disengagement and general cognitive development were assessed at 5-, 8-, 12-, 18- and 24-month using an eye-tracking measure and the Mullen Scales of Early Learning (MSEL), respectively. The cognitive control task demonstrated good internal consistency, sensitivity to age-related change in performance and stable individual differences. No associations were found between infant cognitive control and MSEL scores longitudinally or concurrently. The eye-tracking task revealed that slower attentional disengagement at 8-month, but faster disengagement at 18-month, predicted higher cognitive control scores at 24-month. This task may represent a useful tool for measuring emergent cognitive control. The multifaceted relationship between attention and infant cognitive control suggests that the rapid development of the attentional system in infancy results in distinct attentional skills, at different ages, being relevant for cognitive control development.

Longitudinal fNIRS and EEG metrics of habituation and novelty detection are correlated in 1-18-month-old infants.

INTRODUCTION: Habituation and novelty detection are two fundamental and widely studied neurocognitive processes. Whilst neural responses to repetitive and novel sensory input have been well-documented across a range of neuroimaging modalities, it is not yet fully understood how well these different modalities are able to describe consistent neural response patterns. This is particularly true for infants and young children, as different assessment modalities might show differential sensitivity to underlying neural processes across age. Thus far, many neurodevelopmental studies are limited in either sample size, longitudinal scope or breadth of measures employed, impeding investigations of how well common developmental trends can be captured via different methods. METHOD: This study assessed habituation and novelty detection in N = 204 infants using EEG and fNIRS measured in two separate paradigms, but within the same study visit, at 1, 5 and 18 months of age in an infant cohort in rural Gambia. EEG was acquired during an auditory oddball paradigm during which infants were presented with Frequent, Infrequent and Trial Unique sounds. In the fNIRS paradigm, infants were familiarised to a sentence of infant-directed speech, novelty detection was assessed via a change in speaker. Indices for habituation and novelty detection were extracted for both EEG and NIRS RESULTS: We found evidence for weak to medium positive correlations between responses on the fNIRS and the EEG paradigms for indices of both habituation and novelty detection at most age points. Habituation indices correlated across modalities at 1 month and 5 months but not 18 months of age, and novelty responses were significantly correlated at 5 months and 18 months, but not at 1 month. Infants who showed robust habituation responses also showed robust novelty responses across both assessment modalities. DISCUSSION: This study is the first to examine concurrent correlations across two neuroimaging modalities across several longitudinal age points. Examining habituation and novelty detection, we show that despite the use of two different testing modalities, stimuli and timescale, it is possible to extract common neural metrics across a wide age range in infants. We suggest that these positive correlations might be strongest at times of greatest developmental change.

Human milk: From complex tailored nutrition to bioactive impact on child cognition and behavior.

Human milk is a highly complex liquid food tailor-made to match an infant's needs. Beyond documented positive effects of breastfeeding on infant and maternal health, there is increasing evidence that milk constituents also impact child neurodevelopment. Non-nutrient milk bioactives would contribute to the (long-term) development of child cognition and behavior, a process termed 'Lactocrine Programming'. In this review we discuss the current state of the field on human milk composition and its links with child cognitive and behavioral development. To promote state-of-the-art methodologies and designs that facilitate data pooling and meta-analytic endeavors, we present detailed recommendations and best practices for future studies. Finally, we determine important scientific gaps that need to be filled to advance the field, and discuss innovative directions for future research. Unveiling the mechanisms underlying the links between human milk and child cognition and behavior will deepen our understanding of the broad functions of this complex liquid food, as well as provide necessary information for designing future interventions.

An evidence review and nutritional conceptual framework for pre-eclampsia prevention.

Pre-eclampsia is a serious complication of pregnancy, and maternal nutritional factors may play protective roles or exacerbate risk. The tendency to focus on single nutrients as a risk factor obscures the complexity of possible interactions, which may be important given the complex nature of pre-eclampsia. An evidence review was conducted to compile definite, probable, possible and indirect nutritional determinants of pre-eclampsia to map a nutritional conceptual framework for pre-eclampsia prevention. Determinants of pre-eclampsia were first compiled through an initial consultation with experts. Second, an expanded literature review was conducted to confirm associations, elicit additional indicators and evaluate evidence. The strength of association was evaluated as definite relative risk (RR) < 0·40 or ≥3·00, probable RR 0·40-0·69 or 1·50-2·99, possible RR 0·70-0·89 or 1·10-1·49 or not discernible RR 0·90-1·09. The quality of evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluation. Twenty-five nutritional factors were reported in two umbrella reviews and twenty-two meta-analyses. Of these, fourteen were significantly associated with pre-eclampsia incidence. Higher serum Fe emerged as a definite nutritional risk factors for pre-eclampsia incidence across populations, while low serum Zn was a risk factor in Asia and Africa. Maternal vitamin D deficiency was a probable risk factor and Ca and/or vitamin D supplementation were probable protective nutritional factors. Healthy maternal dietary patterns were possibly associated with lower risk of developing pre-eclampsia. Potential indirect pathways of maternal nutritional factors and pre-eclampsia may exist through obesity, maternal anaemia and gestational diabetes mellitus. Research gaps remain on the influence of household capacities and socio-cultural, economic and political contexts, as well as interactions with medical conditions.

Executive functioning skills and their environmental predictors among pre-school aged children in South Africa and The Gambia.

Executive functions (EFs) in early childhood are predictors of later developmental outcomes and school readiness. Much of the research on EFs and their psychosocial correlates has been conducted in high-income, minority world countries, which represent a small and biased portion of children globally. The aim of this study is to examine EFs among children aged 3-5 years in two African countries, South Africa (SA) and The Gambia (GM), and to explore shared and distinct predictors of EFs in these settings. The SA sample (N = 243, 51.9% female) was recruited from low-income communities within the Cape Town Metropolitan area. In GM, participants (N = 171, 49.7% female) were recruited from the rural West Kiang region. EFs, working memory (WM), inhibitory control (IC) and cognitive flexibility (CF), were measured using tablet-based tasks. Associations between EF task performance and indicators of socioeconomic status (household assets, caregiver education) and family enrichment factors (enrichment activities, diversity of caregivers) were assessed. Participants in SA scored higher on all EF tasks, but children in both sites predominantly scored within the expected range for their age. There were no associations between EFs and household or familial variables in SA, except for a trend-level association between caregiver education and CF. Patterns were similar in GM, where there was a trend-level association between WM and enrichment activities but no other relationships. We challenge the postulation that children in low-income settings have poorer EFs, simply due to lower socioeconomic status, but highlight the need to identify predictors of EFs in diverse, global settings. RESEARCH HIGHLIGHTS: Assessed Executive Functioning (EF) skills and their psychosocial predictors among pre-school aged children (aged 3-5 years) in two African settings (The Gambia and South Africa). On average, children within each setting performed within the expected range for their age, although children in South Africa had higher scores across tasks. There was little evidence of any association between socioeconomic variables and EFs in either site. Enrichment activities were marginally associated with better working memory in The Gambia, and caregiver education with cognitive flexibility in South Africa, both associations were trend-level significance.

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.

Caregiver perceptions of nutrition interventions in infants and children under 24 months of age: a systematic review.

OBJECTIVE: Efficacy studies show early nutrition interventions improving infant nutrition status, but understanding caregiver acceptability is required for implementation of such interventions. This systematic review examines caregivers' perceptions of nutrition interventions in young children. DESIGN: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL and PsychINFO from date of online journal inception through December 2020. Interventions included oral (powder/liquid/tablet) and/or intravenous supplementation, food fortification and nutrition counselling. Inclusion criteria included primary research, data presented on caregiver perception and studies published in English. Quality assessment was performed using the Critical Appraisal Skills Programme tool. Studies underwent narrative synthesis using inductive thematic analysis. SETTING: No restriction. PARTICIPANTS: Caregivers of children under 24 months of age. RESULTS: Of 11 798 records identified, thirty-seven publications were included. Interventions included oral supplementation, food fortification and nutrition counselling. Caregivers included mothers (83 %), fathers, grandparents and aunts. Perceptions were gathered through individual interviews, focus group discussions, questionnaires, surveys and ratings. Totally, 89 % of studies noted high acceptability (n 33 most notably increased appetite (n 17). In total, 57 % of studies (n 21) cited low acceptability, commonly from side effects (n 13) such as gastrointestinal issues, appetite loss and stained teeth. CONCLUSIONS: Positive perceptions and enthusiasm for interventions were frequently reported. Key to implementation was the increased appetite noted by caregivers. A substantial proportion of studies reported negative perceptions, mainly due to side effects. In future interventions, mitigation and education around common side effects are crucial for acceptability. Understanding both positive and negative caregiver perceptions is important for informing future nutrition interventions and strengthening sustainability and implementation.

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.

Applying the cultural adaption framework to the Early Youth Engagement (EYE-2) approach to early intervention in psychosis.

OBJECTIVES: Disengagement from Early Intervention in Psychosis (EIP) services is pronounced in individuals from racially minoritized or diverse ethnic backgrounds, lesbian, gay, bisexual, transgender, and queer or questioning individuals, and individuals from some religious or spiritual backgrounds. The Early Youth Engagement in first episode psychosis study (EYE-2) is a cluster randomized controlled trial that tests a new engagement intervention. The current study aimed to (i) explore perspectives of service users from diverse backgrounds in relation to spirituality, ethnicity, culture and sexuality on engagement and the EYE-2 approach and (ii) use an evidence-based adaptation framework to incorporate their needs and perspectives into the EYE-2 resources and training. METHODS: This qualitative study used semi-structured interviews to explore service users' experiences and perspectives on EYE-2 approaches and resources. The study was conducted within EIP teams across three inner-city sites in England chosen to reflect diverse urban populations. Topic guides covered participant's identity, perceptions of EYE-2 resources, and experience of using mental health services. Transcribed interviews underwent thematic analysis. RESULTS: In this study, 21 service users aged 18 to 35 (M = 25.4; SD = 5.5) participated in semi-structured interviews. Seven key themes were identified across the four domains of the cultural adaptation framework: Differing cognitions and beliefs; multiple facets of culture; language as a barrier to engagement; stigma and discrimination; adaptations to EYE-2 resources; trust in therapeutic alliance; and individual differences in therapeutic preferences. CONCLUSIONS: The emergent themes highlighted a need to cater to various aspects of cultural diversity when developing EIP materials and services.

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.

Calcium for pre-eclampsia prevention: A systematic review and network meta-analysis to guide personalised antenatal care.

BACKGROUND: Calcium supplementation reduces the risk of pre-eclampsia, but questions remain about the dosage to prescribe and who would benefit most. OBJECTIVES: To evaluate the effectiveness of high (≥1 g/day) and low (<1 g/day) calcium dosing for pre-eclampsia prevention, according to baseline dietary calcium, pre-eclampsia risk and co-interventions, and intervention timing. SEARCH STRATEGY: CENTRAL, PubMed, Global Index Medicus and CINAHL, from inception to 2 February 2021, clinical trial registries, reference lists and expert input (CRD42018111239). SELECTION CRITERIA: Randomised controlled trials of calcium supplementation for pre-eclampsia prevention, for women before or during pregnancy. Network meta-analysis (NMA) also included trials of different calcium doses. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted published data. The meta-analysis employed random-effects models and the NMA, a Bayesian random-effects model, to obtain direct and indirect effect estimates. MAIN RESULTS: The meta-analysis included 30 trials (N = 20 445 women), and the NMA to evaluate calcium dosage included 25 trials (N = 15 038). Calcium supplementation prevented pre-eclampsia similarly with a high dose (RR 0.49, 95% CI 0.36-0.66) or a low dose (RR 0.49, 95% CI 0.36-0.65). By NMA, high-dose (vs low-dose) calcium did not differ in effect (RR 0.79, 95% CI 0.43-1.40). Calcium was similarly effective regardless of baseline pre-eclampsia risk, vitamin D co-administration or timing of calcium initiation, but calcium was ineffective among women with adequate average baseline calcium intake. CONCLUSIONS: Low- and high-dose calcium supplementation are effective for pre-eclampsia prevention in women with low calcium intake. This has implications for population-level implementation where dietary calcium is low, and targeted implementation where average intake is adequate. TWEETABLE ABSTRACT: A network meta-analysis of 25 trials found that low-dose calcium supplementation (<1 g/day) is as effective as high-dose calcium supplementation (≥1 g/day) in halving the risk of pre-eclampsia when baseline calcium intake is low.

Maternal nutritional risk factors for pre-eclampsia incidence: findings from a narrative scoping review.

BACKGROUND: Pre-eclampsia is a leading cause of maternal mortality and morbidity that involves pregnancy-related stressors on the maternal cardiovascular and metabolic systems. As nutrition is important to support optimal development of the placenta and for the developing fetus, maternal diets may play a role in preventing pre-eclampsia. The purpose of this scoping review is to map the maternal nutritional deficiencies and imbalances associated with pre-eclampsia incidence and discuss evidence consistency and linkages with current understandings of the etiology of pre-eclampsia. METHODS: A narrative scoping review was conducted to provide a descriptive account of available research, summarize research findings and identify gaps in the evidence base. Relevant observational studies and reviews of observational studies were identified in an iterative two-stage process first involving electronic database searches then more sensitive searches as familiarity with the literature increased. Results were considered in terms of their consistency of evidence, effect sizes and biological plausibility. RESULTS: The review found evidence for associations between nutritional inadequacies and a greater risk of pre-eclampsia. These associations were most likely mediated through oxidative stress, inflammation, maternal endothelial dysfunction and blood pressure in the pathophysiology of pre-eclampsia. Maternal nutritional risk factors for pre-eclampsia incidence with the strongest consistency, effect and biological plausibility include vitamin C and its potential relationship with iron status, vitamin D (both on its own and combined with calcium and magnesium), and healthy dietary patterns featuring high consumption of fruits, vegetables, whole grains, fish, seafood and monounsaturated vegetable oils. Foods high in added sugar, such as sugary drinks, were associated with increased risk of pre-eclampsia incidence. CONCLUSION: A growing body of literature highlights the involvement of maternal dietary factors in the development of pre-eclampsia. Our review findings support the need for further investigation into potential interactions between dietary factors and consideration of nutritional homeostasis and healthy dietary patterns. Further research is recommended to explore gestational age, potential non-linear relationships, dietary diversity and social, cultural contexts of food and meals.

Pre-eclampsia is a condition of high blood pressure during the second half of pregnancy with signs of damage to another organ system, often the liver and kidneys. It is a serious and potentially deadly disease and is the second top cause of deaths related to pregnancy and childbirth globally. Though the exact cause of pre-eclampsia is unclear, researchers have discovered that pre-eclampsia develops through abnormal development of the placenta, which is the interface between the growing baby and the mother in the womb. The placenta helps to transfer nutrients, oxygen and waste between the mother and fetus. Nutrition has important roles to play in the development of the placenta and certain vitamins and minerals have clinical properties that may help prevent pre-eclampsia. We conducted a review to summarize observational studies on maternal nutritional risk factors associated with the development of pre-eclampsia. Promising maternal dietary factors that fit with current understandings of how pre-eclampsia develops include vitamin C and its potential relationship with iron, calcium and vitamin D. Healthy dietary patterns with high consumption of fruits, vegetables, whole grains, fish and seafood and monounsaturated vegetable oils are likely beneficial. Foods high in added sugar, such as sugary drinks, may be linked to higher rates of developing pre-eclampsia. Instead of focusing on single nutrient deficiencies, our findings support a broader approach to explore interrelationships between dietary factors and balanced healthy dietary intake for the prevention of pre-eclampsia.

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.

Longitudinal infant fNIRS channel-space analyses are robust to variability parameters at the group-level: An image reconstruction investigation.

The first 1000 days from conception to two-years of age are a critical period in brain development, and there is an increasing drive for developing technologies to help advance our understanding of neurodevelopmental processes during this time. Functional near-infrared spectroscopy (fNIRS) has enabled longitudinal infant brain function to be studied in a multitude of settings. Conventional fNIRS analyses tend to occur in the channel-space, where data from equivalent channels across individuals are combined, which implicitly assumes that head size and source-detector positions (i.e. array position) on the scalp are constant across individuals. The validity of such assumptions in longitudinal infant fNIRS analyses, where head growth is most rapid, has not previously been investigated. We employed an image reconstruction approach to analyse fNIRS data collected from a longitudinal cohort of infants in The Gambia aged 5- to 12-months. This enabled us to investigate the effect of variability in both head size and array position on the anatomical and statistical inferences drawn from the data at both the group- and the individual-level. We also sought to investigate the impact of group size on inferences drawn from the data. We found that variability in array position was the driving factor between differing inferences drawn from the data at both the individual- and group-level, but its effect was weakened as group size increased towards the full cohort size (N = 53 at 5-months, N = 40 at 8-months and N = 45 at 12-months). We conclude that, at the group sizes in our dataset, group-level channel-space analysis of longitudinal infant fNIRS data is robust to assumptions about head size and array position given the variability in these parameters in our dataset. These findings support a more widespread use of image reconstruction techniques in longitudinal infant fNIRS studies.

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.

The missing focus on women's health in the First 1,000 days approach to nutrition.

The First 1,000 Days approach highlights the time between conception and a child's second birthday as a critical period where adequate nutrition is essential for adequate development and growth throughout the child's life and potentially onto their own offspring. Based on a review of relevant literature, this commentary explores the First 1,000 Days approach with a maternal lens. While the primary objective of the First 1,000 Days approach to nutrition is to reduce child malnutrition rates, particularly chronic undernutrition in the form of stunting, interventions are facilitated through mothers in terms of promoting healthy behaviours such as exclusive breast-feeding and attention to her nutritional status during pregnancy and lactation. Though these interventions were facilitated through women, women's health indicators are rarely tracked and measured, which we argue represents a missed opportunity to strengthen the evidence base for associations between maternal nutrition and women's health outcomes. Limited evidence on the effects of dietary interventions with pregnant and lactating mothers on women's health outcomes hinders advocacy efforts, which then contributes to lower prioritisation and less research.

Exploring influences on adolescent diet and physical activity in rural Gambia, West Africa: food insecurity, culture and the natural environment.

OBJECTIVE: To explore, from the perspectives of adolescents and caregivers, and using qualitative methods, influences on adolescent diet and physical activity in rural Gambia. DESIGN: Six focus group discussions (FGD) with adolescents and caregivers were conducted. Thematic analysis was employed across the data set. SETTING: Rural region of The Gambia, West Africa. PARTICIPANTS: Participants were selected using purposive sampling. Four FGD, conducted with forty adolescents, comprised: girls aged 10-12 years; boys aged 10-12 years; girls aged 15-17 years, boys aged 15-17 years. Twenty caregivers also participated in two FGD (mothers and fathers). RESULTS: All participants expressed an understanding of the association between salt and hypertension, sugary foods and diabetes, and dental health. Adolescents and caregivers suggested that adolescent nutrition and health were shaped by economic, social and cultural factors and the local environment. Adolescent diet was thought to be influenced by: affordability, seasonality and the receipt of remittances; gender norms, including differences in opportunities afforded to girls, and mother-led decision-making; cultural ceremonies and school holidays. Adolescent physical activity included walking or cycling to school, playing football and farming. Participants felt adolescent engagement in physical activity was influenced by gender, seasonality, cultural ceremonies and, to some extent, the availability of digital media. CONCLUSIONS: These novel insights into local understanding should be considered when formulating future interventions. Interventions need to address these interrelated factors, including misconceptions regarding diet and physical activity that may be harmful to health.

Seasonal modulation of antibody response to diphtheria-tetanus-pertussis vaccination in infants: a cohort study in rural Gambia.

BACKGROUND: In rural Gambia, rates of malnutrition and infection are higher during the annual rainy/'hungry' season (June-October) in comparison to the dry/'harvest' season (November-May). The effects of this seasonal pattern on an infant's immune development and their capacity to respond to childhood vaccinations remain unclear. The aim of the current analysis was to determine whether antibody responses to diphtheria-tetanus-pertussis (DTP) vaccinations in infants differ between seasons. METHODS: Infants received the DTP vaccine at 8, 12 and 16 weeks of age and antibody titres were measured in blood samples collected at 12 (n = 710) and 24 (n = 662) weeks of age. Mean DTP antibody titres, adjusted for maternal and infant confounders, were compared by t-tests and the effect sizes of the mean differences were calculated between seasons at mid-gestation (20 weeks gestation) and first vaccination (8 weeks of infant age). RESULTS: A smaller number of infants received their first vaccination during the rainy/hungry season months compared to the dry/harvest season (n = 224 vs. n = 486). At 12 weeks, infants vaccinated during the rainy/hungry season had lower weight-for-length Z-scores (p = 0.01) and were more likely to be anaemic (p < 0.001). Their mothers, however, were pregnant mostly during the dry/harvest season, had higher weight gain (p < 0.001) and were less likely to be anaemic during pregnancy (p < 0.001). At 12 weeks, infants vaccinated during the rainy/hungry season had significantly higher mean diphtheria, tetanus and pertussis antibody titres; by 62.3, 16.9 and 19.7%, respectively (all, p < 0.001). However, at 24 weeks, they had lower mean anti-diphtheria titres (by 20.6%, p < 0.001) compared with infants vaccinated during the dry/harvest season, and no differences were observed in mean tetanus and pertussis antibody titres by vaccination season. CONCLUSIONS: Infant antibody response to the primary dose of the DTP vaccine was influenced by both season of pregnancy and infancy, although effects were diminished following three doses. Environmental exposures, including nutrition, to both the mother and infant are hypothesised as likely drivers of these seasonal effects.