Plasma homocysteine, folate and vitamin B(12) compared between rural Gambian and UK adults.

The disease risk indicator plasma total homocysteine (tHcy) is influenced by genetic and environmental factors, including folate and vitamin B(12) status. Little is known about the determinants of tHcy in rural West Africa. We explored the hypothesis that tHcy in rural Gambian adults might vary between the sexes and physiological groups, and/or with folate and vitamin B(12) status. Comparisons were made with a British national survey. Non-pregnant Gambian women (n 158) had tHcy concentrations (geometric mean 9.0 micromol/l) similar to those of non-pregnant UK women (n 449; 9.4 micromol/l), whereas pregnant Gambian women (n 12) had significantly lower values (6.2 micromol/l). Gambian men (n 22) had significantly higher values (14.7 micromol/l) than British men (n 354; 10.8 micromol/l). Gambian lactating women and British men and women exhibited significant inverse relationships between log(e)(tHcy) and folate status; however, only the British subjects exhibited significant inverse relationships between loge(tHcy) and vitamin B(12) status. In the British sample, and in Gambian lactating women, folate and vitamin B(12) status variations together accounted for 20-25 % of the variation in log(e)(tHcy). Within the UK, black-skinned adults had folate and tHcy levels similar to those of their white-skinned counterparts, but significantly higher vitamin B(12) values. We conclude that, whereas folate and vitamin B(12) status are similar between British and rural Gambian populations, tHcy is higher in Gambian men and lower in pregnant Gambian women, and that serum vitamin B(12) values appear to be higher in black-skinned than white-skinned British subjects. Possible reasons are discussed

Maternal protein-energy supplementation does not affect adolescent blood pressure in The Gambia.

BACKGROUND: Birthweight, and by inference maternal nutrition during pregnancy, is thought to be an important determinant of offspring blood pressure but the evidence base for this in humans is lacking data from randomized controlled trials. METHODS: The offspring from a maternal prenatal protein-energy supplementation trial were enrolled into a follow-up study of chronic disease risk factors including blood pressure. Subjects were 11-17 years of age and blood pressure was measured in triplicate using an automated monitor (Omron 705IT). One-thousand two-hundred sixty seven individuals (71% of potential participants) were included in the analysis. RESULTS: There was no difference in blood pressure between those whose mothers had consumed protein-energy biscuits during pregnancy and those whose mothers had consumed the same supplement post-partum. For systolic blood pressure the intention-to-treat regression coefficient was 0.46 (95% CI: -1.12, 2.04). Mean systolic blood pressure for control children was 110.2 (SD +/- 9.3) mmHg and for intervention children was 110.8 (SD +/- 8.8) mmHg. Mean diastolic blood pressure for control children was 64.7 (SD +/- 7.7) mmHg and for intervention children was 64.6 (SD +/- 7.6) mmHg. CONCLUSIONS: We have found no association between maternal prenatal protein-energy supplementation and offspring blood pressure in adolescence amongst rural Gambians. We found some evidence to suggest that offspring body composition may interact with the effect of maternal supplementation on blood pressure

Supplemental feeding during pregnancy compared with maternal supplementation during lactation does not affect schooling and cognitive development through late adolescence.

BACKGROUND: The long-term impact of early malnutrition on human capital outcomes remains unclear, and existing evidence has come largely from observational studies. OBJECTIVE: We compared the impact of a nutritional supplement given during pregnancy or lactation in rural Gambia on educational performance and cognitive ability in offspring at their maturity. DESIGN: This study was a follow-up of a randomized trial of prenatal high protein and energy supplementation conducted between 1989 and 1994. Subjects were 16-22 y of age at follow-up, and information was collected on schooling achievement and cognitive ability by using the Raven's progressive matrices test, Mill Hill vocabulary test, and forward and backward digit-span tests. RESULTS: A total of 1459 individuals were traced and interviewed and represented 71% of the original cohort and 81% of the surviving cohort. There was no difference in cognitive ability or educational attainment between treatment groups by using any of the methods of assessment. CONCLUSION: We have shown little evidence to support a long-term effect of prenatal protein-energy supplementation compared with supplementation during lactation on cognitive development in rural Gambians. This trial was registered at http://www.controlled-trials.com as ISRCTN72582014

Growth faltering in low-income countries.

Meta-analysis of growth data from over 50 low and low-middle income countries shows a consistent pattern of stunting and poor weight gain from about 3 months of age and persisting until at least 5 years. Children tend not to be wasted because their short stature offsets their underweight, leading to a rather adequately proportioned appearance. This frequently conceals the true levels of malnutrition in communities. At the macro-environmental level such growth faltering is due to the combined effects of poverty, food insecurity, low-dietary diversity, a highly infectious environment, poor washing facilities and poor understanding of the principles of nutrition and hygiene. These tend to be ameliorated as communities pass through the demographic transition with improved incomes and education. Because such changes will take generations to achieve, the global health community continues to search for effective interim solutions. Disappointingly, apart from intensive feeding programmes aimed at rehabilitating severely malnourished children, there are few examples of very successful nutrition interventions. This emphasizes the need for a better understanding of the etiology of growth failure. This paper uses anthropometric data collected over 6 decades in subsistence-farming communities from rural Gambia to illustrate the typical key features of growth faltering. Arising from this analysis, and from gaps in the published literature, the following issues are highlighted as still requiring a better resolution: (1) the pre-natal and inter-generational influences on growth failure; (2) the ontogeny of the infant immune system; (3) the exact nature of the precipitating insults that initiate gastroenteropathy; (4) the effects of both enteric and systemic infections on the hormonal regulation of growth; (5) interactions between macro- and micro-nutrient deficiencies and infections in causing growth failure, and (6) the role of the microbiome in modulating dietary influences on health and growth

Microbes and the malnourished child.

New research implicates a dysfunctional gut microbiome in the etiology of severe childhood malnutrition and confirms a role for antibiotics in its treatment

Effects of an iodine-containing prenatal multiple micronutrient on maternal and infant iodine status and thyroid function:a randomised trial in The Gambia

Background: Iodine supplementation is recommended to pregnant women in iodine-deficient populations, but the impact in moderate iodine deficiency is uncertain. We assessed the effect of an iodine-containing prenatal multiple micronutrient (MMN) supplement in a rural Gambian population at risk of moderate iodine deficiency. Materials and Methods: This study uses data and samples collected as a part of the randomized controlled trial Early Nutrition and Immune Development (ENID; ISRCTN49285450) conducted in Keneba, The Gambia. Pregnant women (<20 weeks gestation) were randomized to either a daily supplement of MMNs containing 300 μg of iodine or an iron and folic acid (FeFol) supplement. Randomization was double blinded (participants and investigators). The coprimary outcomes were maternal urinary iodine concentration (UIC) and serum thyroglobulin (Tg), assessed at baseline and at 30 weeks' gestation. Secondary outcomes were maternal serum thyrotropin (TSH), total triiodothyronine (TT3), total thyroxine (TT4) (assessed at baseline and at 30 weeks' gestation), breast milk iodine concentration (BMIC) (assessed at 8, 12, and 24 weeks postpartum), infant serum Tg (assessed at birth [cord], 12, and 24 weeks postpartum), and serum TSH (assessed at birth [cord]). The effect of supplementation was evaluated using mixed effects models. Results: A total of 875 pregnant women were enrolled between April 2010 and February 2015. In this secondary analysis, we included women from the MMN (n = 219) and FeFol (n = 219) arm of the ENID trial. At baseline, median (interquartile range or IQR) maternal UIC and Tg was 51 μg/L (33–82) and 22 μg/L (12–39), respectively, indicating moderate iodine deficiency. Maternal MMN supplement increased maternal UIC (p < 0.001), decreased maternal Tg (p < 0.001), and cord blood Tg (p < 0.001) compared with FeFol. Maternal thyroid function tests (TSH, TT3, TT4, and TT3/TT4 ratio) and BMIC did not differ according to maternal supplement group over the course of the study. Median (IQR) BMIC, maternal UIC, and infant Tg in the MMN group were 51 μg/L (35–72), 39 μg/L (25–64), and 87 μg/L (59–127), respectively, at 12 weeks postpartum, and did not differ between supplement groups. Conclusions: Supplementing moderately iodine-deficient women during pregnancy improved maternal iodine status and reduced Tg concentration. However, the effects were not attained postpartum and maternal and infant iodine nutrition remained inadequate during the first six months after birth. Consideration should be given to ensuring adequate maternal status through pregnancy and lactation in populations with moderate deficiency

Growth faltering in rural Gambian children after four decades of interventions: a retrospective cohort study

Background Growth faltering remains common in children in sub-Saharan Africa and is associated with substantial morbidity and mortality. Due to a very slow decline in the prevalence of stunting, the total number of children with stunting continues to rise in sub-Saharan Africa. Identifi cation of eff ective interventions remains a challenge. Methods We analysed the eff ect of 36 years of intensive health interventions on growth in infants and young children from three rural Gambian villages. Routine growth data from birth to age 2 years were available for 3659 children between 1976 and 2012. Z scores for weight-for-age, length-for-age, weight-for-length, mid-upper-arm circumference, and head circumference were calculated using the WHO 2006 growth standards. Seasonal patterns of mean Z scores were obtained by Fourier regression. We additionally defi ned growth faltering as fall in Z score between 3 months and 21 months of age. Findings We noted secular improvements in all postnatal growth parameters (except weight-for-length), accompanied by declines over time in seasonal variability. The proportion of children with underweight or stunting at 2 years of age halved during four decades of the study period, from 38·7% (95% CI 33·5–44·0) for underweight and 57·1% (51·9–62·4) for stunting. However, despite unprecedented levels of intervention, postnatal growth faltering persisted, leading to poor nutritional status at 24 months (length-for-age Z score –1·36, 95% CI –1·44 to –1·27, weight-for-age Z score –1·20, –1·28 to –1·11, and head circumference Z score –0·51, –0·59 to –0·43). The prevalence of stunting and underweight remained unacceptably high (30·0%, 95% CI 27·0–33·0, for stunting and 22·1%, 19·4 to 24·8, for underweight). Interpretation A combination of nutrition-sensitive and nutrition-specifi c interventions has achieved a halving of undernutrition rates, but despite these intensive interventions substantial growth faltering remains. We need to understand the missing contributors to growth faltering to guide development of new interventions

Preconceptional and gestational weight trajectories and risk of delivering a small-for-gestational-age baby in rural Gambia.

Background: Maternal nutritional status is a key determinant of small for gestational age (SGA), but some knowledge gaps remain, particularly regarding the role of the energy balance entering pregnancy.Objective: We investigated how preconceptional and gestational weight trajectories (summarized by individual-level traits) are associated with SGA risk in rural Gambia.Design: The sample comprised 670 women in a trial with serial weight data (7310 observations) that were available before and during pregnancy. Individual trajectories from 6 mo before conception to 30 wk of gestation were produced with the use of multilevel modeling. Summary traits were expressed as weight z scores [weight z score at 3 mo preconception (zwt-3 mo), weight z score at conception, weight z score at 3 mo postconception, weight z score at 7 mo postconception (zwt+7 mo), and conditional measures that represented the change from the preceding time] and were related to SGA risk with the use of Poisson regression with confounder adjustment; linear splines were used to account for nonlinearity.Results: Maternal weight at each time point had a consistent nonlinear relation with SGA risk. For example, the zwt-3 mo estimate was stronger in women with values ≤0.5 (RR: 0.736; 95% CI: 0.594, 0.910) than in women with values >0.5 (RR: 0.920; 95% CI: 0.682, 1.241). The former group had the highest observed SGA prevalence. Focusing on weight change, only conditional zwt+7 mo was associated with SGA and only in women with values >-0.5 (RR: 0.579; 95% CI: 0.463, 0.724).Conclusions: Protection against delivering an SGA neonate offered by greater preconceptional or gestational weight may be most pronounced in more undernourished and vulnerable women. Independent of this possibility, greater second- and third-trimester weight gain beyond a threshold may be protective. This trial was registered at http://www.isrctn.com/ as ISRCTN49285450

Thresholds of socio-economic and environmental conditions necessary to escape from childhood malnutrition: a natural experiment in rural Gambia.

BACKGROUND: Childhood malnutrition remains highly prevalent in low-income countries, and a 40% reduction in under-5 year stunting is WHO's top Global Target 2025. Disappointingly, meta-analyses of intensive nutrition interventions reveal that they generally have low efficacy at improving growth. Unhygienic environments also contribute to growth failure, but large WASH Benefits and SHINE trials of improved water, sanitation and hygiene (WASH) recently reported no benefits to child growth. METHODS: To explore the thresholds of socio-economic status (SES) and living standards associated with malnutrition, we exploited a natural experiment in which the location of our research centre within a remote rural village created a wide diversity of wealth, education and housing conditions within the same ecological setting and with free health services to all. A composite SES score was generated by grading occupation, education, income, water and sanitation, and housing and families were allocated to 5 groups (SES1 = highest). SES ranged from very poor subsistence-farming villagers to post graduate staff with overseas training. Nutritional status at 24 m was obtained from clinic records for 230 children and expressed relative to WHO Growth Standards. RESULTS: Height-for-age (HAZ) and weight-for-age (WAZ) Z-scores were strongly predicted by SES group. HAZ varied from - 0.67 to - 2.23 (P < 0.001) and WAZ varied from - 0.90 to - 1.64 (P < 0.001), from SES1 to SES5, respectively. Weight-for-height (WHZ) showed no gradient. Children in SES1 showed greater dispersion so were further divided in a post hoc analysis. Children resident in Western housing on the research compound (SES1A) had HAZ = + 0.68 and WAZ = + 0.36. The residual gradient between those in SES1B and SES5 spanned only 0.65 Z-score for HAZ (- 1.58 to - 2.23) and was not significant for WAZ or WHZ. CONCLUSIONS: The large difference in growth between children in SES1A living in Western-type housing and SES1B children living in the village, and the very shallow gradient between SES1B and SES5, implies a very high SES threshold before stunting and underweight will be eliminated. This may help to explain the lack of efficacy of the recent WASH interventions and points to the need for what is termed 'Transformative WASH'. Good quality housing, with piped water into the home, may be key to eliminating malnutrition

Birth season and environmental influences on blood leucocyte and lymphocyte subpopulations in rural Gambian infants

BACKGROUND: In rural Gambia, birth season predicts infection-related adult mortality, providing evidence that seasonal factors in early life may programme immune development. This study tested whether lymphocyte subpopulations assessed by automated full blood count and flow cytometry in cord blood and at 8, 16 and 52 weeks in rural Gambian infants (N = 138) are affected by birth season (DRY = Jan-Jun, harvest season, few infections; WET = Jul-Dec, hungry season, many infections), birth size or micronutrient status. RESULTS: Geometric mean cord and postnatal counts were higher in births occurring in the WET season with both season of birth and season of sampling effects. Absolute CD3+, CD8+, and CD56+ counts, were higher in WET season births, but absolute CD4+ counts were unaffected and percentage CD4+ counts were therefore lower. CD19+ counts showed no association with birth season but were associated with concurrent plasma zinc status. There were no other associations between subpopulation counts and micronutrient or anthropometric status. CONCLUSION: These results demonstrate a seasonal influence on cell counts with a disproportionate effect on CD8+ and CD56+ relative to CD4+ cells. This seasonal difference was seen in cord blood (indicating an effect in utero) and subsequent samples, and is not explained by nutritional status. These findings are consistent with the hypothesis than an early environmental exposure can programme human immune development