Background: Intestinal damage and malabsorption caused by chronic environmental enteropathy are associated with growth faltering seen in infants in less-developed countries. Evidence has suggested ...that supplementary omega-3 (n−3) long-chain PUFAs (LC-PUFAs) might ameliorate this damage by reducing gastrointestinal inflammation. LC-PUFA supplementation may also benefit cognitive development.Objective: We tested whether early n−3 LC-PUFA supplementation improves infant intestinal integrity, growth, and cognitive function.Design: A randomized, double-blind, controlled trial 200 mg DHA and 300 mg EPA or 2 mL olive oil/d for 6 mo was conducted in a population of 172 rural Gambian infants aged 3–9 mo. The primary endpoints were anthropometric measures and gut integrity assessed by using urinary lactulose:mannitol ratios (LMRs). Plasma fatty acid status, intestinal mucosal inflammation (fecal calprotectin), daily morbidity, and cognitive development (2-step means-end test and an attention assessment) were secondary endpoints.Results: PUFA supplementation resulted in a significant increase in plasma n−3 LC-PUFA concentrations (P < 0.001 for both DHA and EPA) and midupper arm circumference (MUAC) (effect size: 0.31 z scores; 95% CI: 0.06, 0.56; P = 0.017) at 9 mo of age. At 12 mo, MUAC remained greater in the intervention group, and we observed significant increases in skinfold thicknesses (P ≤ 0.022 for all). No other significant differences between treatment groups were detected for growth or LMRs at 9 mo or for secondary outcomes.Conclusions: Fish-oil supplementation successfully increased plasma n−3 fatty acid status. However, in young, breastfed Gambian infants, the intervention failed to improve linear growth, intestinal integrity, morbidity, or selected measures of cognitive development. The trial was registered at www.isrctn.org as ISRCTN66645725.
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CMK, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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.
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.
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.
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.
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CEKLJ, DOBA, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
•First investigation of validity of longitudinal infant channel-space fNIRS analysis.•Novel image reconstruction analysis conducted.•Variability in array position is dominant factor driving different ...inferences.•Channel-space fNIRS analyses robust to implicit assumptions at group-level.•Hope to encourage more widespread use of image reconstruction in infant analyses.
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Human milk oligosaccharides (HMOs) play an important role in the health of an infant as substrate for beneficial gut bacteria. Little is known about the effects of HMO composition and its changes on ...the morbidity and growth outcomes of infants living in areas with high infection rates. Mother's HMO composition and infant gut microbiota from 33 Gambian mother/infant pairs at 4, 16, and 20 weeks postpartum were analyzed for relationships between HMOs, microbiota, and infant morbidity and growth. The data indicate that lacto-N-fucopentaose I was associated with decreased infant morbidity, and 3'-sialyllactose was found to be a good indicator of infant weight-for-age. Because HMOs, gut microbiota, and infant health are interrelated, the relationship between infant health and their microbiome were analyzed. While bifidobacteria were the dominant genus in the infant gut overall, Dialister and Prevotella were negatively correlated with morbidity, and Bacteroides was increased in infants with abnormal calprotectin. Mothers nursing in the wet season (July to October) produced significantly less oligosaccharides compared to those nursing in the dry season (November to June). These results suggest that specific types and structures of HMOs are sensitive to environmental conditions, protective of morbidity, predictive of growth, and correlated with specific microbiota.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Human milk provides a very wide range of nutrients and bioactive components, including immune factors, human milk oligosaccharides, and a commensal microbiota. These factors are essential for ...interconnected processes including immunity programming and the development of a normal infant gastrointestinal microbiome. Newborn immune protection mostly relies on maternal immune factors provided through milk. However, studies dealing with an in-depth profiling of the different immune compounds present in human milk and with the assessment of their natural variation in healthy women from different populations are scarce. In this context, the objective of this work was the detection and quantification of a wide array of immune compounds, including innate immunity factors (IL1β, IL6, IL12, INFγ, TNFα), acquired immunity factors (IL2, IL4, IL10, IL13, IL17), chemokines (IL8, Groα, MCP1, MIP1β), growth factors IL5, IL7, epidermal growth factor (EGF), granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, TGFβ2, and immunoglobulins (IgA, IgG, IgM), in milk produced by healthy women of different ethnicities living in different geographic, dietary, socioeconomic, and environmental settings. Among the analyzed factors, IgA, IgG, IgM, EGF, TGFβ2, IL7, IL8, Groα, and MIP1β were detected in all or most of the samples collected in each population and, therefore, this specific set of compounds might be considered as the "core" soluble immune factors in milk produced by healthy women worldwide. This approach may help define which immune factors are (or are not) common in milk produced by women living in various conditions, and to identify host, lifestyle, and environmental factors that affect the immunological composition of this complex biological fluid.
www.ClinicalTrials.gov, identifier NCT02670278.
Exposure to aflatoxin, a mycotoxin produced by fungi that commonly contaminates cereal crops across sub-Saharan Africa, has been associated with impaired child growth. We investigated the impact of ...aflatoxin exposure on the growth of Gambian infants from birth to two years of age, and the impact on insulin-like growth factor (IGF)-axis proteins.
A subsample (N = 374) of infants from the Early Nutrition and Immune Development (ENID) trial (ISRCTN49285450) were included in this study. Aflatoxin-albumin adducts (AF-alb) were measured in blood collected from infants at 6, 12 and 18 months of age. IGF-1 and IGFBP-3 were measured in blood collected at 12 and 18 months. Anthropometric measurements taken at 6, 12, 18 and 24 months of age were converted to z-scores against the WHO reference. The relationship between aflatoxin exposure and growth was analysed using multi-level modelling.
Inverse relationships were observed between lnAF-alb and length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) z-scores from 6 to 18 months of age (β = - 0·04, P = 0·015; β = - 0·05, P = 0.003; β = - 0·06, P = 0·007; respectively). There was an inverse relationship between lnAF-alb at 6 months and change in WLZ between 6 and 12 months (β = - 0·01; P = 0·013). LnAF-alb at 12 months was associated with changes in LAZ and infant length between 12 and 18 months of age (β = - 0·01, P = 0·003; β = - 0·003, P = 0·02; respectively). LnAF-alb at 6 months was associated with IGFBP-3 at 12 months (r = - 0·12; P = 0·043).
This study found a small but significant effect of aflatoxin exposure on the growth of Gambian infants. This relationship is not apparently explained by aflatoxin induced changes in the IGF-axis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Microbial communities in human milk and those in feces from breastfed infants vary within and across populations. However, few researchers have conducted cross-cultural comparisons between ...populations, and little is known about whether certain "core" taxa occur normally within or between populations and whether variation in milk microbiome is related to variation in infant fecal microbiome. The purpose of this study was to describe microbiomes of milk produced by relatively healthy women living at diverse international sites and compare these to the fecal microbiomes of their relatively healthy infants.
We analyzed milk (
= 394) and infant feces (
= 377) collected from mother/infant dyads living in 11 international sites (2 each in Ethiopia, The Gambia, and the US; 1 each in Ghana, Kenya, Peru, Spain, and Sweden). The V1-V3 region of the bacterial 16S rRNA gene was sequenced to characterize and compare microbial communities within and among cohorts.
Core genera in feces were
, and
, and in milk were
and
, although substantial variability existed within and across cohorts. For instance, relative abundance of
was highest in feces from rural Ethiopia and The Gambia, and lowest in feces from Peru, Spain, Sweden, and the US;
was relatively more abundant in milk produced by women in rural Ethiopia than all other cohorts. Bacterial diversity also varied among cohorts. For example, Shannon diversity was higher in feces from Kenya than Ghana and US-California, and higher in rural Ethiopian than Ghana, Peru, Spain, Sweden, and US-California. There were limited associations between individual genera in milk and feces, but community-level analyses suggest strong, positive associations between the complex communities in these sample types.
Our data provide additional evidence of within- and among-population differences in milk and infant fecal bacterial community membership and diversity and support for a relationship between the bacterial communities in milk and those of the recipient infant's feces. Additional research is needed to understand environmental, behavioral, and genetic factors driving this variation and association, as well as its significance for acute and chronic maternal and infant health.
Prompt access to primary healthcare before onset of severe illness is vital to improve morbidity and mortality rates. The Gambia has high rates of child mortality and research is needed to ...investigate contributing factors further. This study aimed to identify factors affecting access to primary healthcare for children <5 years (y) in rural Gambia focusing on delayed presentation and severe illness at presentation as indicators in a setting where primary healthcare is delivered free of charge.
Data were extracted from an electronic medical records system at a rural primary healthcare clinic in The Gambia for children (0-5y) between 2009 and 2012. First clinic attendances with malaria, lower respiratory tract infections (LRTI) and diarrhoeal disease, the main contributors to mortality in this setting, were identified and categorized as delayed/non-delayed and severe/non-severe representing our two main outcome measures. Potential explanatory variables, identified through a comprehensive literature review were obtained from an ongoing demographic surveillance system for this population. Variables associated with either delayed/non-delayed and/or with severe/non-severe presentations identified by univariate analysis (p<0.1) were assessed in multivariate models using logistic regression (p<0.05).
Out of 6554 clinic attendances, 571 relevant attendances were identified. Delayed presentation was common (45% of all presentations) and there was a significantly reduced risk associated with being from villages with free regular access to transport (OR 0.502, 95%CI0.310, 0.814, p = 0.005). Children from villages with free regular transport were also less likely to present with severe illness (OR 0.557, 95%CI0.325, 0.954, p = 0.033).
Transport availability rather than distance to health clinic is an important barrier to accessing healthcare for children in The Gambia, and public health interventions should aim to reduce this barrier.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sex-specific effects of pregnancy calcium carbonate supplementation have been reported in 8–12 year old Gambian children, indicating faster growth in boys but slower growth in girls born to ...calcium-supplemented mothers.
To determine whether the pregnancy supplement resulted in sex-specific effects on offspring IGF1 and other growth-related indices in mid-childhood.
Analysis of archived data obtained in mid-childhood from the children of rural Gambian mothers who had been randomised to 1500 mgCa/d (Ca) or placebo (P) from 20 weeks pregnancy to delivery (ISRCTN96502494).
Of the 526 children born and followed in infancy, 290 had early-morning, fasting plasma assayed for IGF1, IGFBP3, leptin, insulin and calcium-related indices and had anthropometry performed at age 7.5 (SD1.2) years (N/group: Males(M)-Ca = 64, Females(F)-Ca = 77; M-P = 76, F-P = 73). Sex-specific effects of maternal supplementation were considered using regression with sexes separated and together to test for sex ∗ supplement interactions.
Boys had lower IGF1, IGFBP3, leptin and insulin than girls (P ≤ 0.004). IGF1 was higher in M-Ca than M-P (+14.2 (SE7.7)%, P = 0.05) but lower in F-Ca than F-P (−17.8 (SE7.4)%, P = 0.01); sex ∗ supplement interaction P = 0.001. IGF1 concentrations (ng/ml, geometric mean −1SE,+1SE) were M-Ca = 78.14.3,4.5, M-P = 67.83.4,3.6; F-Ca = 99.54.8,5.1, F-P = 118.96.4,6.8. Similar sex ∗ supplement interactions were seen for IGFBP3 and IGF1-adjusted-for-IGFBP3 but group differences were smaller. There were no significant supplement effects on the other biochemical indices.
Calcium carbonate supplementation of pregnant Gambian mothers resulted in higher IGF1 in boys and lower IGF1 in girls during mid-childhood, consistent with the reported maternal supplement effects on growth of the offspring in later childhood.
•Pregnancy calcium supplementation of Gambian mothers resulted in faster childhood growth in boys, slower growth in girls.•At mean age 7.5 years, plasma IGF1 of offspring was altered in a sex-specific manner before growth effects were evident.•Plasma IGF1 was higher in girls than boys.•Plasma IGF1 was higher in boys of calcium-supplemented mothers than those of mothers who consumed placebo.•Plasma IGF1 was lower in girls of calcium-supplemented mothers than those of mothers who consumed placebo.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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