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Van Der Merwe L.F.,London School of Hygiene and Tropical Medicine | Moore S.E.,London School of Hygiene and Tropical Medicine | Fulford A.J.,London School of Hygiene and Tropical Medicine | Halliday K.E.,London School of Hygiene and Tropical Medicine | And 3 more authors.
American Journal of Clinical Nutrition | Year: 2013

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. © 2013 American Society for Nutrition. Source


Olausson H.,MRC Human Nutrition Research | Olausson H.,Gothenburg University | Goldberg G.R.,MRC Human Nutrition Research | Ann Laskey M.,MRC Human Nutrition Research | And 3 more authors.
Nutrition Research Reviews | Year: 2012

Pregnancy and lactation are times of additional demand for Ca. Ca is transferred across the placenta for fetal skeletal mineralisation, and supplied to the mammary gland for secretion into breast milk. In theory, these additional maternal requirements could be met through mobilisation of Ca from the skeleton, increased intestinal Ca absorption efficiency, enhanced renal Ca retention or greater dietary Ca intake. The extent to which any or all of these apply, the underpinning biological mechanisms and the possible consequences for maternal and infant bone health in the short and long term are the focus of the present review. The complexities in the methodological aspects of interpreting the literature in this area are highlighted and the inter-individual variation in the response to pregnancy and lactation is reviewed. In summary, human pregnancy and lactation are associated with changes in Ca and bone metabolism that support the transfer of Ca between mother and child. The changes generally appear to be independent of maternal Ca supply in populations where Ca intakes are close to current recommendations. Evidence suggests that the processes are physiological in humans and that they provide sufficient Ca for fetal growth and breast-milk production, without relying on an increase in dietary Ca intake or compromising long-term maternal bone health. Further research is needed to determine the limitations of the maternal response to the Ca demands of pregnancy and lactation, especially among mothers with marginal and low dietary Ca intake, and to define vitamin D adequacy for reproductive women. © 2012 The Author. Source


Prentice S.,MRC Human Nutrition Research | Fulford A.J.,London School of Hygiene and Tropical Medicine | Jarjou L.M.A.,MRC Keneba | Goldberg G.R.,MRC Human Nutrition Research | Prentice A.,MRC Human Nutrition Research
Annals of Human Biology | Year: 2010

Menarcheal age is a key indicator of female maturity and development. Studies in many countries have reported a downward secular trend in age of menarche over the past century. This study presents data gained using the 'status quo' method and interval regression to estimate median menarcheal age of girls in a rural Gambian community. Cross-sectional studies carried out in 1989, 2000 and 2008 revealed a median menarcheal age of 16.06 (95% CI 15.6716.45), 15.03 (95% CI 14.7615.30) and 14.90 (95% CI 14.5215.28), respectively. The average rate of decline of median age of menarche was amongst the most rapid yet reported, at 0.65 years of age per decade (p < 0.00001). There was no evidence for a change in the rate of decline over the two decades studied. These results probably reflect ongoing socio-economic development within the region. © 2010 Informa UK, Ltd. Source


Braithwaite V.,Medical Research Council MRC Human Nutrition Research | Jarjou L.M.A.,MRC Keneba | Goldberg G.R.,Medical Research Council MRC Human Nutrition Research | Prentice A.,Medical Research Council MRC Human Nutrition Research
Bone | Year: 2012

A relationship between iron and fibroblast growth factor-23 (FGF23) metabolic pathways has been proposed. Iron deficiency anaemia is prevalent in The Gambia and concentrations of fibroblast growth factor-23 FGF23 are elevated in a large percentage of Gambian children with rickets-like bone deformity.We speculate that low iron status may be involved in the aetiology of Gambian rickets. The aim of this study was to determine if there was a relationship between haemoglobin, as a marker of iron status, and FGF23 in samples from children with and without a history of rickets-like bone deformities in The Gambia. We conducted a retrospective analysis of studies carried out from 2006 to 2008 in children from a rural community in The Gambia where iron deficiency anaemia is endemic and where elevated circulating concentrations of FGF23 have been found. To investigate the relationship between circulating FGF23 and haemoglobin concentrations we used an age-adjusted linear regression model on data from children < 18. y of age with a family or personal history of rickets-like bone deformity (BD) (n= 108) and from the local community (LC) (n= 382).We found that circulating concentration of FGF23 was inversely correlated with haemoglobin concentration. This effect was more pronounced in BD children compared with LC children (interaction: P≤0.0001). Anaemia and elevated FGF23 were more prevalent in BD children compared to LC children (P=0.0003 and P=0.0001 respectively).In conclusion, there is a stronger relationship between FGF23 and haemoglobin in Gambian children with a history of rickets compared to local community children. This study provides support for the contention that iron may be involved in FGF23 metabolic pathways. © 2012 Elsevier Inc. Source


Braithwaite V.,MRC Human Nutrition Research | Jarjou L.M.A.,MRC Keneba | Goldberg G.R.,MRC Human Nutrition Research | Goldberg G.R.,University of Witwatersrand | And 3 more authors.
Bone | Year: 2012

We have previously reported on a case-series of children (n = 46) with suspected calcium-deficiency rickets who presented in The Gambia with rickets-like bone deformities. Biochemical analyses discounted vitamin D-deficiency as an aetiological factor but indicated a perturbation of Ca-P metabolism involving low plasma phosphate and high circulating fibroblast growth factor-23 (FGF23) concentrations.A follow-up study was conducted 5. years after presentation to investigate possible associated factors and characterise recovery. 35 children were investigated at follow-up (RFU). Clinical assessment of bone deformities, overnight fasted 2. h urine and blood samples, 2-day weighed dietary records and 24. h urine collections were obtained. Age- and season-matched data from children from the local community (LC) were used to calculate standard deviation scores (SDS) for RFU children.None of the RFU children had radiological signs of active rickets. However, over half had residual leg deformities consistent with rickets. Dietary Ca intake (SDS-Ca=-0.52 (0.98) p=0.04), dietary Ca/P ratio (SDS-Ca/P=-0.80 (0.82) p=0.0008) and TmP:GFR (SDS-TmP:GFR=-0.48 (0.81) p=0.04) were significantly lower in RFU children compared with LC children and circulating FGF23 concentration was elevated in 19% of RFU children. Furthermore an inverse relationship was seen between haemoglobin and FGF23 (R2=25.8, p=0.004).This study has shown differences in biochemical and dietary profiles between Gambian children with a history of rickets-like bone deformities and children from the local community. This study provided evidence in support of the calcium deficiency hypothesis leading to urinary phosphate wasting and rickets and identified glomerular filtration rate and iron status as possible modulators of FGF23 metabolic pathways. © 2011 Elsevier Inc. Source

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