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.
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.
Multiple micronutrients (MMN) are commonly prescribed in pediatric primary healthcare in sub-Saharan Africa to improve nutritional status and appetite without evidence for their effectiveness or ...international clinical guidelines. Community-wide MMN supplementation has shown limited and heterogeneous impact on growth and morbidity. Short-term ready-to-use therapeutic foods in acutely sick children in a hospital setting also had limited efficacy regarding subsequent growth. The effectiveness of MMN in improving morbidity or growth in sick children presenting for primary care has not been assessed.
We undertook a double-blind randomised controlled trial of small-quantity lipid-based nutrient supplements (SQ-LNS) fortified with 23 micronutrients in children aged 6 months (mo) to 5 years (y) presenting with an illness at a rural primary healthcare centre in The Gambia. Primary outcomes were repeat clinic presentations and growth over 24 wk. Participants were randomly assigned to receive 1 of 3 interventions: (1) supplementation with micronutrient-fortified SQ-LNS for 12 wk (MMN-12), (2) supplementation with micronutrient-fortified SQ-LNS for 6 wk followed by unfortified SQ-LNS for 6 wk (MMN-6), or (3) supplementation with unfortified SQ-LNS for 12 wk (MMN-0) to be consumed in daily portions. Treatment masking used 16 letters per 6-wk block in the randomisation process. Blinded intention-to-treat analysis based on a prespecified statistical analysis plan included all participants eligible and correctly enrolled. Between December 2009 and June 2011, 1,101 children (age 6-60 mo, mean 25.5 mo) were enrolled, and 1,085 were assessed (MMN-0 = 361, MMN-6 = 362, MMN-12 = 362). MMN supplementation was associated with a small increase in height-for-age z-scores 24 wk after recruitment (effect size for MMN groups combined: 0.084 SD/24 wk, 95% CI: 0.005, 0.168; p = 0.037; equivalent to 2-5 mm depending on age). No significant difference in frequency of morbidity measured by the number of visits to the clinic within 24 wk follow-up was detected with 0.09 presentations per wk for all groups (MMN-0 versus MMN-6: adjusted incidence rate ratio IRR 1.03, 95% CI: 0.92, 1.16; MMN-0 versus MMN-12: 1.05, 95% CI: 0.93, 1.18). In post hoc analysis, clinic visits significantly increased by 43% over the first 3 wk of fortified versus unfortified SQ-LNS (adjusted IRR 1.43; 95% CI: 1.07, 1.92; p = 0.016), with respiratory presentations increasing by 52% with fortified SQ-LNS (adjusted IRR 1.52; 95% CI: 1.01, 2.30; p = 0.046). The number of severe adverse events during supplementation were similar between groups (MMN-0 = 20 1 death; MMN-6 = 21 1 death; MMN-12 = 20 0 death). No participant withdrew due to adverse effects. Study limitations included the lack of supervision of daily supplementation.
Prescribing micronutrient-fortified SQ-LNS to ill children presenting for primary care in rural Gambia had a very small effect on linear growth and did not reduce morbidity compared to unfortified SQ-LNS. An early increase in repeat visits indicates a need for the establishment of evidence-based guidelines and caution with systematic prescribing of MMN. Future research should be directed at understanding the mechanisms behind the lack of effect of MMN supplementation on morbidity measures and limited effect on growth.
ISRCTN 73571031.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Karlberg model of human growth describes the infancy, childhood, and puberty (ICP) stages as continuous and overlapping, and defined by transitions driven by sequential additional effects of ...several endocrine factors that shape the growth trajectory and resultant adult size. Previous research has suggested that a delayed transition from the infancy to the childhood growth stage contributes to sub-optimal growth outcomes. A new method developed to analyze the structure of centile crossing in early life has emerged as a potential tool for identifying the infancy-childhood transition (ICT), through quantifying patterns of adjacent monthly weight-for-age z-score (WAZ) deviation correlations. Using this method, the infancy-childhood transition was identified as taking place at around 12 months of age in two cohorts of UK infants. Here, we apply this method to data collected as part of a longitudinal growth study in rural Gambia the Hormonal and Epigenetic Regulators of Growth, or HERO-G study,
= 212 (F = 99, M = 113), in order to identify the ICT and assess whether timing of this transition differs across groups based on sex or birth seasonality. We calculated Pearson correlation coefficients for adjacent monthly WAZ score deviations. Based on the patterns of change in the correlation structure over time, our results suggest that the infancy-childhood transition occurs at around 9 months of age in rural Gambian infants. This points to an accelerated ICT compared to UK infants, rather than a delayed ICT. A comparatively later transition, seen in UK infants, allows maximal extension of the high rates of growth during the infancy stage; an earlier transition as seen in Gambian infants cuts short this period of rapid growth, potentially impacting on growth outcomes in childhood while diverting energy into other processes critical to responses to acute infectious challenges. Growth in later developmental stages in this population offers an extended window for catch-up.
Low birthweight and reduced height gain during infancy (stunting) may arise at least in part from adverse early life environments that trigger epigenetic reprogramming that may favor survival. We ...examined differential DNA methylation patterns using targeted methyl sequencing of regions regulating gene activity in groups of rural Gambian infants: (a) low and high birthweight (DNA from cord blood (n = 16 and n = 20, respectively), from placental trophoblast tissue (n = 21 and n = 20, respectively), and DNA from peripheral blood collected from infants at 12 months of age (n = 23 and n = 17, respectively)), and, (b) the top 10% showing rapid postnatal length gain (high, n = 20) and the bottom 10% showing slow postnatal length gain (low, n = 20) based on z score change between birth and 12 months of age (LAZ) (DNA from peripheral blood collected from infants at 12 months of age). Using BiSeq analysis to identify significant methylation marks, for birthweight, four differentially methylated regions (DMRs) were identified in trophoblast DNA, compared to 68 DMRs in cord blood DNA, and 54 DMRs in 12‐month peripheral blood DNA. Twenty‐five DMRs were observed to be associated with high and low length for age (LAZ) at 12 months. With the exception of five loci (associated with two different genes), there was no overlap between these groups of methylation marks. Of the 194 CpG methylation marks contained within DMRs, 106 were located to defined gene regulatory elements (promoters, CTCF‐binding sites, transcription factor‐binding sites, and enhancers), 58 to gene bodies (introns or exons), and 30 to intergenic DNA. Distinct methylation patterns associated with birthweight between comparison groups were observed in DNA collected at birth (at the end of intrauterine growth window) compared to those established by 12 months (near the infancy/childhood growth transition). The longitudinal differences in methylation patterns may arise from methylation adjustments, changes in cellular composition of blood or both that continue during the critical postnatal growth period, and in response to early nutritional and infectious environmental exposures with impacts on growth and longer‐term health outcomes.
The first 1,000 days of life are a critical window of vulnerability to exposure to socioeconomic and health challenges (i.e. poverty/undernutrition). The Brain Imaging for Global Health (BRIGHT) ...project has been established to deliver longitudinal measures of brain development from 0 to 24 months in UK and Gambian infants and to assess the impact of early adversity. Here results from the Habituation‐Novelty Detection (HaND) functional near‐infrared spectroscopy (fNIRS) task at 5 and 8 months are presented (N = 62 UK; N = 115 Gambia). In the UK cohort distinct patterns of habituation and recovery of response to novelty are seen, becoming more robust from 5 to 8 months of age. In The Gambia, an attenuated habituation response is evident: a larger number of trials are required before the response sufficiently suppresses relative to the response during the first presented trials. Furthermore, recovery of response to novelty is not evident at 5 or 8 months of age. As this longitudinal study continues in The Gambia, the parallel collection of socioeconomic, caregiving, health and nutrition data will allow us to stratify how individual trajectories of habituation and recovery of response to novelty associate with different risk factors and adaptive mechanisms in greater depth. Given the increasing interest in the use of neuroimaging methods within global neurocognitive developmental studies, this study provides a novel cross‐culturally appropriate paradigm for the study of brain responses associated with attention and learning mechanisms across early development.
The Brain Imaging for Global Health (BRIGHT) project has been established to deliver longitudinal measures of brain development from 0‐24 months in UK and Gambian infants. A novel cross‐culturally appropriate functional near infrared spectroscopy (fNIRS) paradigm demonstrated habituation and novelty detection brain responses in 5 and 8 month old infants in the UK. In the Gambia, habituation brain responses were attenuated, and a recovery of response to novelty absent, at the group level, at 5‐8 months of age.
Infants in low‐resource settings are at heightened risk for compromised cognitive development due to a multitude of environmental insults in their surroundings. However, the onset of adverse outcomes ...and trajectory of cognitive development in these settings is not well understood. The aims of the present study were to adapt the Mullen Scales of Early Learning (MSEL) for use with infants in a rural area of The Gambia, to examine cognitive development in the first 24‐months of life and to assess the association between cognitive performance and physical growth. In Phase 1 of this study, the adapted MSEL was tested on 52 infants aged 9‐ to 24‐months (some of whom were tested longitudinally at two time points). Further optimization and training were undertaken and Phase 2 of the study was conducted, where the original measures were administered to 119 newly recruited infants aged 5‐ to 24‐months. Infant length, weight and head circumference were measured concurrently in both phases. Participants from both phases were split into age categories of 5–9 m (N = 32), 10–14 m (N = 92), 15–19 m (N = 53) and 20–24 m (N = 43) and performance was compared across age groups. From the ages of 10–14 m, Gambian infants obtained lower MSEL scores than US norms. Performance decreased with age and was lowest in the 20–24 m old group. Differential onsets of reduced performance were observed in the individual MSEL domains, with declines in visual perception and motor performance detected as early as at 10–14 months, while reduced language scores became evident after 15–19 months of age. Performance on the MSEL was significantly associated with measures of growth.
The Mullen Scales of Early Learning were adapted to assess cognitive development among infants aged 5‐ to 25‐ months in a rural area of The Gambia. From the age of 10‐14 months, Gambian infants had lower scores compared to US norms and the discrepancy in scores increased with age. Cognitive performance was also associated with the infants' height and weight.
Background:
Although breastfeeding is common in The Gambia, high rates of undernutrition in children under five highlight the importance of understanding drivers of particular feeding patterns in ...this environment, especially early introduction of non-breast milk foods (NBMFs). The country’s marked seasonality, which is associated with annual food insecurity and heavy maternal workload, may influence breastfeeding patterns; however, longitudinal assessments of infant diet in relationship to such factors are limited. We aimed to characterize infant breastfeeding patterns and timing of introduction of local complementary foods in a rural Gambian population across the first twelve months of life. Potential environmental and sociodemographic predictors of exclusive breastfeeding (EBF) duration were explored in order to identify factors that may influence infant feeding decisions in this population.
Methods:
Data from dietary questionnaires (administered every ten days until 12 months of age) collected as a part of the Hormonal and Epigenetic Regulators of Growth study (2013-2018) were used to calculate EBF duration in a subsample of 194 mother-infant pairs. Socioeconomic questionnaires and Principal Component Analysis were used to calculate household sociodemographic position (SEP). Multiple linear regression analyses were used to investigate potential predictors of EBF duration, including seasonality, SEP, and maternal and infant factors.
Results:
Mean age at introduction of food or liquid other than maternal milk was five months (±1.5). At twelve months, 98.7% of infants continue to receive some maternal milk. Being born in May significantly predicted shorter EBF duration by -1.68 months (95% CIs: -2.52, -0.84mo; P<.0001). SEP, maternal parity, and infant sex were non-significant predictors of EBF duration.
Conclusions:
Maternal milk is a vital component of infant diet across the first twelve months of life in this population. Earlier introduction of NBMFs coincides with the annual period where maternal agricultural workload intensifies in this region, though additional investigation is warranted.
Abstract only
The goal of our project is to establish assessments to evaluate the efficacy of nutritional interventions during the first 1000 days of life. Here we examine behavioral performance on a ...standardised developmental assessment scale (Mullen Scales of Early Learning; MSEL) and anthropometric growth indices in infants at a research station in West Africa.
The MSEL is a developmental assessment battery for use from birth to five years of age. We adapted the MSEL for use in The Gambia. A committee of native, dual‐language speakers and trained MSEL administrators reviewed and adapted the measure where appropriate (i.e. linguistic translation of the item‐by‐item verbal prompts, as well as the substitution of stimuli that were deemed culturally inappropriate). 225 infants ranging from 6 – 24 months of age were assessed and their MSEL scores compared with an age‐matched group of infants tested in the UK.
Relative to the U.K infants, scores of cognitive development declined over the first two years of life, particularly for the language subscales of the MSEL. An analysis of the relationship between growth and cognitive development revealed that height for age z‐scores correlated with scores on the MSEL. In particular for infants in their second year of life lower scores of cognitive development (MSEL) were related to lower height for age scores.
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.
We tested whether early n−3 LC-PUFA supplementation improves infant intestinal integrity, growth, and cognitive function.
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.
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.
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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