Infants and children in low- and middle-income countries are frequently exposed to a range of poverty-related risk factors, increasing their likelihood of poor neurodevelopmental outcomes. There is a ...need for culturally objective markers, which can be used to study infants from birth, thereby enabling early identification and ultimately intervention during a critical time of neurodevelopment.
In this paper, we investigate developmental changes in auditory event related potentials (ERP) associated with habituation and novelty detection in infants between 1 and 5 months living in the United Kingdom and The Gambia, West Africa. Previous research reports that whereas newborns’ ERP responses are increased when presented with stimuli of higher intensity, this sensory driven response decreases over the first few months of life, giving rise to a cognitively driven, novelty-based response. Anthropometric measures were obtained concurrently with the ERP measures at 1 and 5 months of age. Neurodevelopmental outcome was measured using the Mullen Scales of Early Learning (MSEL) at 5 months of age.
The described developmental change was observed in the UK cohort, who exhibited an intensity-based response at 1 month and a novelty-based response at 5 months of age. This change was accompanied by greater habituation to stimulus intensity at 5 compared to 1 month. In the Gambian cohort we did not see a change from an intensity-to a novelty-based response, and no change in habituation to stimulus intensity across the two age points. The degree of change from an intensity towards a novelty-based response was further found to be associated with MSEL scores at 5 months of infant age, whereas infants’ growth between 1 and 5 months was not.
Our study highlights the utility of ERP-based markers to study young infants in rural Africa. By implementing a well-established paradigm in a previously understudied population we have demonstrated its use as a culturally objective tool to better understand early learning in diverse settings world-wide. Results offer insight into the neurodevelopmental processes underpinning early neurocognitive development, which may in the future contribute to early identification of infants at heightened risk of adverse neurodevelopmental outcome.
•Infants in low- and middle-income countries are at risk of poor cognitive outcomes.•There is a need for objective markers of infant brain development across settings.•We measured infants' event related potentials at 1–5 month in the UK and The Gambia.•Results show attenuated habituation and novelty responses in the Gambian cohort.•ERP P3, but not growth measures, were associated with neurodevelopment at 5 months.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective
Surgery for paediatric cancer presents many stresses on patients and families. The authors aimed to understand the long‐term impact of childhood cancer surgery on survivors and parents.
...Methods
The study recruited participants from 11 Australia/New Zealand hospitals for telephone interviews. The authors used descriptive statistics to analyse participants’ quantitative distress ratings and conducted thematic analysis of shared surgical experiences and needs.
Results
Of 32 participants (n = 17 survivors, n = 15 parents), survivors’ mean age at surgery was 6.9 (SD = 5.17) and parents’ children were 2.1 years old (SD = 1.41) at time of surgery. Survivors had surgery on average 15.2 years ago (SD = 6.72) and parents’ children 11.5 years ago (SD = 3.94). Parents and survivors rated surgery as highly distressing. Pre‐operatively, survivors recalled experiencing fear and pain mainly associated with pre‐operative procedures. Post‐operatively, survivors reported immobility and some lasting behavioural disturbances. Parents described pre‐ and intra‐operative anxiety and stress and some lasting post‐operative psychological disturbances. Experiences appeared to improve with clear/consistent communication from hospital staff, proximity to hospital, and with support for parents and children post‐operatively.
Conclusions
Surgical treatment for childhood cancer can have a lasting impact for survivors and parents. Better information provision may improve families’ surgical experience whilst reducing anxiety, distress and physical discomfort.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Vitamin D is important to maternal, fetal, and infant health, but quality data on vitamin D status in lowand middle-income countries and response to cholecalciferol supplementation in pregnancy are ...sparse.
We characterized vitamin D status and vitamin D metabolite change across pregnancy and in response to cholecalciferol supplementation in rural Gambia.
This study was a secondary analysis of samples collected in a 4-arm trial of maternal nutritional supplementation iron folic acid (FeFol); multiple micronutrients (MMN); protein energy (PE) as lipid-based supplement; PE + MMN; MMN included 10 µg/d cholecalciferol. Plasma 25-hydroxycholecalciferol 25(OH)D3, 24,25-dihydroxycholecalciferol 24,25(OH)2D3, and C3-epimer-25-hydroxycholecalciferol 3-epi-25(OH)D3 were measured by LC-MS/MS in 863 women aged 30 ± 7 y (mean ± SD) in early pregnancy (presupplementation) and late pregnancy, (gestational age 14 ± 3 and 30 ± 1 wk). Changes in 25(OH)D3and vitamin D metabolite concentrations and associations with pregnancy stage and maternal age and anthropometry were tested.
Early pregnancy 25(OH)D3concentration was 70 ± 15 nmol/L and increased according to pregnancy stage (82 ± 18 and 87 ± 17 nmol/L in the FeFol and PE-arms) and to cholecalciferol supplementation (95 ± 19 and 90 ± 20 nmol/L in the MMN and PE + MMN-arms) P < 0.0001). There was no difference between supplemented groups. Early pregnancy 25(OH)D3was positively associated with maternal age and gestational age. Change in 25(OH)D3was negatively associated with late pregnancy, but not early pregnancy, triceps skinfold thickness. The pattern of change of 24,25(OH)2D3mirrored that of 25(OH)D3and appeared to flatten as pregnancy progressed, whereas 3-epi-25(OH)D3concentration increased across pregnancy.
This study provides important data on the vitamin D status of a large cohort of healthy pregnant women in rural Africa. Without supplementation, vitamin D status increased during pregnancy, demonstrating that pregnancy stage should be considered when assessing vitamin D status. Nutritionally relevant cholecalciferol supplementation further increased vitamin D status. These data are relevant to the development of fortification and supplementation policies in pregnant women in West Africa.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The WHO recommends exclusive breastfeeding (EBF) for the first 6 mo of life.
The objective of this study was to assess the benefit of EBF to age 6 mo on growth in a large sample of rural Gambian ...infants at high risk of undernutrition.
Infants with growth monitoring from birth to 2 y of age (n = 756) from the ENID (Early Nutrition and Immune Development) trial were categorized as exclusively breastfed if only breast milk and no other liquids or foods were given. EBF status was entered into confounder-adjusted multilevel models to test associations with growth trajectories by using >11,000 weight-for-age (WAZ), length-for-age (LAZ), and weight-for-length (WLZ) z score observations.
Thirty-two percent of infants were exclusively breastfed to age 6 mo. The mean age of discontinuation of EBF was 5.2 mo, and growth faltering started at ∼3.5 mo of age. Some evidence for a difference in WAZ and WHZ was found between infants who were exclusively breastfed to age 6 mo (EBF-6) and those who were not (nEBF-6), at 6 and 12 mo of age, with EBF-6 children having a higher mean z score. The differences in z scores between the 2 groups were small in magnitude (at 6 mo of age: 0.147 WAZ; 95% CI: -0.001, 0.293 WAZ; 0.189 WHZ; 95% CI: 0.038, 0.341 WHZ). No evidence for a difference between EBF-6 and nEBF-6 infants was observed for LAZ at any time point (6, 12, and 24 mo of age). Furthermore, a higher mean WLZ at 3 mo of age was associated with a subsequent higher mean age at discontinuation of EBF, which implied reverse causality in this setting (coefficient: 0.060; 95% CI: 0.008, 0.120).
This study suggests that EBF to age 6 mo has limited benefit to the growth of rural Gambian infants. This trial was registered at http://www.isrctn.com as ISRCTN49285450.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Antenatal anemia is a risk factor for adverse maternal and fetal outcomes and is prevalent in sub-Saharan Africa. Less than half of antenatal anemia is considered responsive to iron; identifying ...women in need of iron may help target interventions. Iron absorption is governed by the iron-regulatory hormone hepcidin.
We sought to characterize changes in hepcidin and its associations with indexes of iron stores, erythropoiesis, and inflammation at weeks 14, 20, and 30 of gestation and to assess hepcidin's diagnostic potential as an index of iron deficiency.
We measured hemoglobin and serum hepcidin, ferritin, soluble transferrin receptor (sTfR), and C-reactive protein (CRP) at 14, 20, and 30 wk of gestation in a cohort of 395 Gambian women recruited to a randomized controlled trial. Associations with hepcidin were measured by using linear regression, and hepcidin's diagnostic test accuracy area under the receiver operating characteristic curve (AUC
), sensitivity, specificity, cutoffs for iron deficiency at each time point was analyzed.
The prevalence of anemia increased from 34.6% at 14 wk of gestation to 50.0% at 20 wk. Hepcidin concentrations declined between study enrollment and 20 wk, whereas ferritin declined between 20 and 30 wk of gestation. The variations in hepcidin explained by ferritin, sTfR, and CRP declined over pregnancy. The AUC
values for hepcidin to detect iron deficiency (defined as ferritin <15 μg/L) were 0.86, 0.83, and 0.84 at 14, 20, and 30 wk, respectively. Hepcidin was superior to hemoglobin and sTfR as an indicator of iron deficiency.
In Gambian pregnant women, hepcidin appears to be a useful diagnostic test for iron deficiency and may enable the identification of cases for whom iron would be beneficial. Hepcidin suppression in the second trimester suggests a window for optimal timing for antenatal iron interventions. Hemoglobin does not effectively identify iron deficiency in pregnancy. This trial was registered at www.isrctn.com as ISRCTN49285450.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Natural killer (NK) cells differentiate and mature during the human life course; human cytomegalovirus (HCMV) infection is a known driver of this process. We have explored human NK cell phenotypic ...and functional maturation in a rural African (Gambian) population with a high prevalence of HCMV. The effect of age on the frequency, absolute number, phenotype, and functional capacity of NK cells was monitored in 191 individuals aged from 1 to 49 years. Increasing frequencies of NK cells with age were associated with increased proportions of CD56dim cells expressing the differentiation marker CD57 and expansion of the NKG2C+ subset. Frequencies of NK cells responding to exogenous cytokines declined with age in line with a decreased proportion of CD57− cells. These changes coincided with a highly significant drop in anti-HCMV IgG titers by the age of 10 years, suggesting that HCMV infection is brought under control as NK cells differentiate (or vice versa). Deletion at the NKG2C locus was associated with a gene dose-dependent reduction in proportions of CD94+ and CD57+ NK cells. Importantly, anti-HCMV IgG titers were significantly elevated in NKG2C−/− children, suggesting that lack of expression of NKG2C may be associated with altered control of HCMV in childhood.
•HCMV infection in early life is associated with rapid phenotypic and functional differentiation of NK cells.•Emergence of CD57+ NK cells is attenuated in children lacking NKG2C.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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
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.
Tweetable
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.
Linked article: This article is commented on by Fields et al., pp. 1844 in this issue. To view this minicommentary visit https://doi.org/10.1111/1471‐0528.17236.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Innate lymphoid cell (ILC) lineages mirror those of CD4+ T helper cell subsets, producing type 1, 2 and 3 cytokines respectively. Studies in adult human populations have shown contributions of ...non-cytotoxic ILC to immune regulation or pathogenesis in a wide range of diseases and have prompted investigations of potential functional redundancy between ILC and T helper cell compartments in neonates and children. To investigate the potential for ILC to contribute to immune responses across the human lifespan, we examined the numbers and frequencies of peripheral blood ILC subsets in a cohort of Gambians aged between 5 and 73 years of age. ILC2 were the most abundant peripheral blood ILC subset in this Gambian cohort, while ILC1 were the rarest at all ages. Moreover, the frequency of ILC1s (as a proportion of all lymphocytes) was remarkably stable over the life course whereas ILC3 cell frequencies and absolute numbers declined steadily across the life course and ILC2 frequencies and absolute numbers declined from childhood until the age of approx. 30 years of age. Age-related reductions in ILC2 cell numbers appeared to be partially offset by increasing numbers of total and GATA3+ central memory (CD45RA-CCR7+) CD4+ T cells, although there was also a gradual decline in numbers of total and GATA3+ effector memory (CD45RA-CCR7-) CD4+ T cells. Despite reduced overall abundance of ILC2 cells, we observed a coincident increase in the proportion of CD117+ ILC2, indicating potential for age-related adaptation of these cells in childhood and early adulthood. While both CD117+ and CD117- ILC2 cells produced IL-13, these responses occurred predominantly within CD117- cells. Furthermore, comparison of ILC frequencies between aged-matched Gambian and UK young adults (25-29 years) revealed an overall higher proportion of ILC1 and ILC2, but not ILC3 in Gambians. Thus, these data indicate ongoing age-related changes in ILC2 cells throughout life, which retain the capacity to differentiate into potent type 2 cytokine producing cells, consistent with an ongoing role in immune modulation.
Exposures during early life are increasingly being recognised as factors that play an important role in the aetiology of chronic non-communicable diseases (NCDs). The "Developmental Origins of Health ...and Disease" (DOHaD) hypothesis asserts that adverse early-life exposures - most notably unbalanced nutrition - leads to an increased risk for a range of NCDs and that disease risk is highest when there is a "mismatch" between the early- and later-life environments. Thus, the DOHaD hypothesis would predict highest risk in settings undergoing a rapid nutrition transition.
We investigated the link between early-life nutritional exposures and long-term health in rural Gambia, West Africa. Using demographic data dating back to the 1940s, the follow-up of randomised controlled trials of nutritional supplementation in pregnancy, and the "experiment of nature" that seasonality in this region provides, we investigated the DOHaD hypothesis in a population with high rates of maternal and infant under-nutrition, a high burden from infectious disease, and an emerging risk of NCDs. Key Messages: Our work in rural Gambia suggests that in populations with high rates of under-nutrition in early life, the immune system may be sensitive to nutritional deficiencies early in life, resulting in a greater susceptibility to infection-related morbidity and mortality.
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BFBNIB, NMLJ, NUK, PNG, UL, UM, UPUK
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