Explore the vast range of titles available.

Undernutrition in early life remains a significant public health challenge affecting millions of infants and young children globally. Children who are wasted, stunted or underweight are at increased risk of morbidity and mortality. Undernutrition at critical periods also impacts on aspects of neurodevelopment, with longer-term consequences to educational performance and mental health outcomes. Despite consistent evidence highlighting an increased risk of neonatal and infant mortality among boys, a common assumption held across many disciplines is that girls are more vulnerable with respect to early-life exposures. In relation to undernutrition, however, recent evidence indicates the reverse, and in contexts of food insecurity, boys are at increased risk of undernutrition in early life compared to girls, with sex-specific risks for neurodevelopmental deficits. These effects appear independent of social factors that may favour boys, such as gender disparities in infant feeding practices and health-seeking behaviours. The observed vulnerability among boys may therefore be underpinned by biological processes such as differential energy requirements during periods of rapid growth. As boys have greater needs for growth and maintenance, then, in times of nutritional hardship, these needs may not be met resulting in risk of undernutrition and subsequent health consequences. In view of this emerging evidence, a greater understanding of the mechanisms behind this vulnerability among boys is needed and policy considerations to protect boys should be considered. This review will explore sex differences in risk of undernutrition and consider these in the context of existing programmes and policies.

One-third of children falter in cognitive development by pre-school age. Iron plays an important role in many neurodevelopmental processes, and animal studies suggest that iron sufficiency in pregnancy and infancy is particularly important for neurodevelopment. However, it is not clear whether iron deficiency directly impacts developmental outcomes, and, if so, whether impact differs by timing of exposure or developmental domain. We searched four databases for studies on iron deficiency or iron supplementation in pregnancy, or at 0–6 months, 6–24 months, or 2–4 years of age. All studies included neurodevelopmental assessments in infants or children up to 4 years old. We then qualitatively synthesized the literature. There was no clear relationship between iron status and developmental outcomes across any of the time windows or domains included. We identified a large quantity of low-quality studies, significant heterogeneity in study design and a lack of research focused on pregnancy and early infancy. In summary, despite good mechanistic evidence for the role of iron in brain development, evidence for the impact of iron deficiency or iron supplementation on early development is inconsistent. Further high-quality research is needed, particularly within pregnancy and early infancy, which has previously been neglected.

BackgroundThe natural history of chronic HBV infection in sub-Saharan Africa is unknown. Data are required to inform WHO guidelines that are currently based on studies in Europe and Asia.MethodsBetween 1974 and 2008, serosurveys were repeated in two Gambian villages, and an open cohort of treatment-naive chronic HBV carriers was recruited. Participants were followed to estimate the rates of hepatitis B e (HBeAg) and surface antigen (HBsAg) clearance and incidence of hepatocellular carcinoma (HCC). In 2012–2013, a comprehensive liver assessment was conducted to estimate the prevalence of severe liver disease.Results405 chronic carriers (95% genotype E), recruited at a median age of 10.8 years, were followed for a median length of 28.4 years. Annually, 7.4% (95% CI 6.3% to 8.8%) cleared HBeAg and 1.0% (0.8% to 1.2%) cleared HBsAg. The incidence of HCC was 55.5/100 000 carrier-years (95% CI 24.9 to 123.5). In the 2012–2013 survey (n=301), 5.5% (95% CI 3.4% to 9.0%) had significant liver fibrosis. HBV genotype A (versus E), chronic aflatoxin B1 exposure and an HBsAg-positive mother, a proxy for mother-to-infant transmission, were risk factors for liver fibrosis. A small proportion (16.0%) of chronic carriers were infected via mother-to-infant transmission; however, this population represented a large proportion (63.0%) of the cases requiring antiviral therapy.ConclusionsThe incidence of HCC among chronic HBV carriers in West Africa was higher than that in Europe but lower than rates in East Asia. High risk of severe liver disease among the few who are infected by their mothers underlines the importance of interrupting perinatal transmission in sub-Saharan Africa.

Micronutrients are fundamental for healthy brain development and deficiencies during early development can have a severe and lasting impact on cognitive outcomes. Evidence indicates that undernourished lactating individuals may produce breast milk containing lower concentrations of certain vitamins and minerals. Exclusively breastfed infants born to mothers deficient in micronutrients may therefore be at risk of micronutrient deficiencies, with potential implications for neurodevelopment. This systematic review aims to consider current knowledge on the effects of breast milk micronutrients on the developmental outcomes of infants. The databases Medline, Global Health, PsychInfo, Open Grey, and the Web of Science were searched for papers published before February 2021. Studies were included if they measured micronutrients in breast milk and their association with the neurodevelopmental outcomes of exclusively breastfed infants. Also, randomised control trials investigating neurocognitive outcomes following maternal supplementation during lactation were sought. From 5477 initial results, three observational studies were eligible for inclusion. These investigated associations between breast milk levels of vitamin B6, carotenoids, or selenium and infant development. Results presented suggest that pyroxidal, β-carotene, and lycopene are associated with infant neurodevelopmental outcomes. Limited eligible literature and heterogeneity between included papers prevented quantitative synthesis. Insufficient evidence was identified, precluding any conclusions on the relationship between breast milk micronutrients and infant developmental outcomes. Further, the evidence available was limited by a high risk of bias. This highlights the need for further research in this area to understand the long-term influence of micronutrients in breast milk, the role of other breast milk micronutrients in infant neurodevelopmental outcomes, and the impact of possible lactational interventions.

The placenta is a vital, multi-functional organ that acts as an interface between maternal and fetal circulation during pregnancy. Nutritional deficiencies during pregnancy alter placental development and function, leading to adverse pregnancy outcomes, such as pre-eclampsia, infants with small for gestational age and low birthweight, preterm birth, stillbirths and maternal mortality. Maternal nutritional supplementation may help to mitigate the risks, but the evidence base is difficult to navigate. The primary purpose of this umbrella review is to map the evidence on the effects of maternal nutritional supplements and dietary interventions on pregnancy outcomes related to placental disorders and maternal mortality. A systematic search was performed on seven electronic databases, the PROSPERO register and references lists of identified papers. The results were screened in a three-stage process based on title, abstract and full-text by two independent reviewers. Randomized controlled trial meta-analyses on the efficacy of maternal nutritional supplements or dietary interventions were included. There were 91 meta-analyses included, covering 23 types of supplements and three types of dietary interventions. We found evidence that supports supplementary vitamin D and/or calcium, omega-3, multiple micronutrients, lipid-based nutrients, and balanced protein energy in reducing the risks of adverse maternal and fetal health outcomes. However, these findings are limited by poor quality of evidence. Nutrient combinations show promise and support a paradigm shift to maternal dietary balance, rather than single micronutrient deficiencies, to improve maternal and fetal health. The review is registered at PROSPERO (CRD42020160887).

To determine the duration of protection from hepatitis B vaccine given in infancy and early childhood and asses risk factors for HBV infection and chronic infection. In 1984 infant HBV vaccination was started in two Gambian villages. Cross sectional serological surveys have been undertaken every 4 years to determine vaccine efficacy. In the current survey 84.6% of 1508 eligible participants aged 1-28 years were tested. A spouse study was conducted in females (aged 14 years and above) and their male partners. Vaccine efficacy against chronic infection with hepatitis B virus was 95.1% (95% confidence interval 91.5% to 97.1%), which did not vary significantly between age groups or village. Efficacy against infection was 85.4% (82.7% to 87.7%), falling significantly with age. Concentrations of hepatitis B antibody fell exponentially with age varying according to peak response: 20 years after vaccination only 17.8% (95% CI 10.1-25.6) of persons with a low peak response (10-99 mIU/ml) had detectable HBs antibody compared to 27% (21.9% to 32.2%) of those with a high peak response (>999 mIU/ml). Time since vaccination and a low peak response were the strongest risk factors for HBV infections; males were more susceptible, marriage was not a significant risk for females. Hepatitis B DNA was not detected after infection, which tested soley core antibody positive. An undetectable peak antibody response of <10 mIU/ml and a mother who was hepatitis B e antigen positive were powerful risk factors for chronic infection. Adolescents and young adults vaccinated in infancy are at increased risk of hepatitis B infection, but not chronic infection. Married women were not at increased risk. There is no compelling evidence for the use of a booster dose of HBV vaccine in The Gambia.

In experimental animals, maternal diet during the periconceptional period influences the establishment of DNA methylation at metastable epialleles in the offspring, with permanent phenotypic consequences. Pronounced naturally occurring seasonal differences in the diet of rural Gambian women allowed us to test this in humans. We show that significant seasonal variations in methyl-donor nutrient intake of mothers around the time of conception influence 13 relevant plasma biomarkers. The level of several of these maternal biomarkers predicts increased/decreased methylation at metastable epialleles in DNA extracted from lymphocytes and hair follicles in infants postnatally. Our results demonstrate that maternal nutritional status during early pregnancy causes persistent and systemic epigenetic changes at human metastable epialleles. Maternal diet affects DNA methylation in the developing offspring, leading to phenotypic changes. Here, Dominguez-Salas et al . exploit seasonal variation in the diet of Gambian women to show that maternal methyl donor nutrient status around the time of conception predicts methylation levels at metastable epialleles in infants.

•We studied habituation and novelty detection via EEG and fNIRS at 1, 5 & 18 months.•fNIRS and EEG responses were correlated for habituation (1&5 m) and novelty (5&18 m).•Findings represent the first converging longitudinal infant fNIRS and EEG responses.•Responses were associated across a wide age band despite using different stimuli.•Cross-modality correlations may be strongest at times of great developmental change. 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. 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 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. 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.

In resource-poor settings, mother-infant dyads are commonly exposed to environmental factors increasing the risk of infectious diseases and possibly influencing the cytokine profile of human milk (HM). Hormones in HM have been proposed to influence appetite-regulation and possibly growth in exclusively breastfed infants. To compare cytokines and appetite-regulating hormone (ARH) concentrations in HM of mothers from four contrasting populations and investigate associations with infant growth. HM samples from 825 mothers participating in the Mothers, Infants and Lactation Quality Study from Bangladesh (BD), Brazil (BR), Denmark (DK) and The Gambia (GM) were collected between 1-3.5 months postpartum and analysed for tumour-necrosis factor-α, interferon (IFN)-γ, interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10, IL-33, and insulin, leptin and adiponectin. Infant growth was measured twice between 1-5.99 months postpartum. Analysis of covariance was used to compare geometric means of HM markers between the four sites and associations between HM markers and infant growth were investigated using linear regression analysis. Differences in geometric means of all HM cytokines and ARHs were found among the four study sites after adjustment for possible explanatory variables. Lowest levels of most HM cytokines were found in BD, whereas highest levels of IFN-γ, IL-4, IL-10 and IL-33 were found in DK. In GM, cytokines and ARHs were inversely associated with weight-for-age and weight-for-length Z-scores. We showed significant differences in HM composition of cytokines and ARHs among the four countries. Highest levels of T helper cell type 2 cytokines, which is typically related to increased risk of atopic diseases, were found in DK. The results may reflect the influence of different environmental exposures in the four sites on HM composition, which may be associated with infant growth in GM.