Project description:BackgroundGrowth 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. Identification of effective interventions remains a challenge.MethodsWe analysed the effect 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 defined growth faltering as fall in Z score between 3 months and 21 months of age.FindingsWe 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).InterpretationA combination of nutrition-sensitive and nutrition-specific 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.FundingUK Medical Research Council, UK Department for International Development.
Project description:Background:Cryptosporidiosis is a major cause of childhood diarrhea in low- and middle-income countries and has been linked to impairment of child growth. This study investigated the burden of cryptosporidiosis and its impact on child growth in both a rural and an urban site in Bangladesh. Methods:Pregnant women in the second trimester were identified at 2 sites in Bangladesh, 1 urban and 1 rural. Their offspring were enrolled at birth into the study (urban, n = 250; rural, n = 258). For 2 years, the children were actively monitored for diarrhea and anthropometric measurements were obtained every 3 months. Stool samples were collected monthly and during diarrheal episodes with Cryptosporidium infection and causative species determined by quantitative polymerase chain reaction assays. Results:Cryptosporidium infections were common at both sites and mostly subclinical. In the urban site, 161 (64%) children were infected and 65 (26%) had ?2 infections. In the rural site, 114 (44%) were infected and 24 (9%) had multiple infections. Adjusted for potential confounders, cryptosporidiosis was associated with a significantly greater drop in the length-for-age z score (LAZ) at 24 months from LAZ at enrollment (?-LAZ), an effect greatest in the children with multiple episodes of cryptosporidiosis. The most common species in Mirpur was Cryptosporidium hominis, whereas Cryptosporidium meleagridis predominated in Mirzapur. Conclusions:Cryptosporidiosis is common in early childhood and associated with early growth faltering in Bangladeshi children. Predominant Cryptosporidium species differed between the 2 sites, suggesting different exposures or modes of transmission but similar consequences for child growth. Clinical Trials Registration:NCT02764918.
Project description:BackgroundChild growth faltering persists in sub-Saharan Africa despite the scale-up of nutrition, water, and sanitation interventions over the past 2 decades. High temperatures have been hypothesised to contribute to child growth faltering via an adaptive response to heat, reduced appetite, and the energetic cost of thermoregulation. We did a cross-sectional study to assess whether child growth faltering is related to environmental temperature in sub-Saharan Africa.MethodsData were extracted from 52 Demographic and Heath Surveys, dating from 2003 to 2016, that recorded anthropometric data in children aged 0-5 years, and were linked with remotely sensed monthly mean daytime land surface temperature for 2000-16. The odds of stunting (low height-for-age), wasting (low weight-for-height), and underweight (low weight-for-age) relative to monthly mean daytime land surface temperature were determined using multivariable logistic regression.FindingsThe study population comprised 656 107 children resident in 373 012 households. Monthly mean daytime land surface temperature above 35°C was associated with increases in the odds of wasting (odds ratio 1·27, 95% CI 1·16-1·38; p<0·0001), underweight (1·09, 1·02-1·16; p=0·0073), and concurrent stunting with wasting (1·23, 1·07-1·41; p=0·0037), but a reduction in stunting (0·90, 0·85-0·96; p=0·00047) compared with a monthly mean daytime land surface temperature of less than 30°C.InterpretationChildren living in hotter parts of sub-Saharan Africa are more likely to be wasted, underweight, and concurrently stunted and wasted, but less likely to be stunted, than in cooler areas. Studies are needed to further investigate the relationship between temperature and child growth, including whether there is a direct effect not mediated by food security, regional wealth, and other environmental variables. Rising temperature, linked to anthropogenic climate change, might increase child growth faltering in sub-Saharan Africa.FundingUK Medical Research Council and UK Global Challenges Research Fund.
Project description:BACKGROUND:HIV-exposed uninfected (HEU) children experience increased mortality compared with their HIV-unexposed uninfected (HUU) peers. It is unclear whether HEU children are also at increased risk for undernutrition, a modifiable risk factor for mortality. METHODS:We conducted a cross-sectional, population-based survey of children <5 years of age in 5 health districts in Botswana. Linear mixed-effects models were used to assess continuous outcomes, and generalized estimating equations were used to estimate relative risks of stunting, wasting, and underweight between HEU (n = 396) and HUU (n = 1109) children. Secondary analyses examined potential mediation by low birth weight. RESULTS:The association between maternal HIV exposure and child stunting varied significantly by child age (P < 0.01). HEU children <1 and ?2 years of age had 1.85 [95% confidence interval (CI): 1.03 to 3.31; P = 0.04] and 1.41 (95% CI: 1.06 to 1.88; P = 0.02) times the risk of stunting compared with HUU children after multivariate adjustment, respectively. During the period of 1-2 years of age, when breastfeeding cessation occurred among HUU children, HUU children had increased risk of stunting compared with HEU children who were predominantly formula fed (relative risk: 1.56; 95% CI: 1.05 to 2.32; P = 0.03). A mediation analysis estimated that 67% of the excess risk of stunting among HEU children ?2 years was attributable to low birth weight (P = 0.02). There was no difference in risk of wasting or underweight. CONCLUSION:HEU children are at increased risk of stunting compared with their HUU peers; however, interventions to increase birth weight may significantly ameliorate this excess risk. Interventions to support optimal growth during weaning are needed for all breast-fed children.
Project description:BackgroundInfants with atopic eczema have an increased risk of impaired growth, but the origin of this impairment is unclear. The aim of this study was to examine fetal and infant growth in relation to infantile atopic eczema.MethodsWithin the UK Southampton Women's Survey, 1,759 infants with known maternal menstrual data had anthropometric measurements at 11, 19, and 34 weeks' gestation, birth, and ages 6 and 12 months, enabling derivation of growth velocity SD scores. Infantile atopic eczema at ages 6 and/or 12 months was ascertained using modified UK Working Party diagnostic criteria.ResultsExpressed per SD increase, higher femur length and abdominal circumference at 34 weeks' gestation were associated with decreased risks of atopic eczema (eczema OR/SD increase 0.81 [95% CI 0.69-0.96], P=0.017 and 0.78 [95% CI 0.65-0.93], P=0.006, respectively), while every SD increase in head to abdominal circumference ratio (indicating disproportionate growth) was associated with an increase in risk of atopic eczema (1.37 [1.15-1.63], P=0.001). Lower velocities of linear growth from 11 weeks' gestation to birth and birth to age 6 months were associated with atopic eczema (atopic eczema OR/SD increase 0.80 [0.65-0.98], P=0.034 and 0.8 [1 0.66-1.00], P=0.051, respectively). Infants with atopic eczema at age 12 months had a larger head circumference in early gestation and faltering of abdominal growth velocity from 19 to 34 weeks' gestation (atopic eczema OR/SD increase 0.67 [0.51-0.88], P=0.003).ConclusionInfants with atopic eczema demonstrate altered patterns of fetal growth, including faltering of linear growth in utero, prior to the clinical onset of atopic eczema. These findings suggest growth falters prior to the start of clinical atopic eczema and its treatment.
Project description:BackgroundCerebral malaria (CM) is a severe neurological complication of Plasmodium falciparum infection. A number of pathological findings have been correlated with pediatric CM including sequestration, platelet accumulation, petechial haemorrhage and retinopathy. However, the molecular mechanisms leading to death in CM are not yet fully understood.MethodsA shotgun plasma proteomic study was conducted using samples form 52 Gambian children with CM admitted to hospital. Based on clinical outcome, children were assigned to two groups: reversible and fatal CM. Label-free liquid chromatography-tandem mass spectrometry was used to identify and compare plasma proteins that were differentially regulated in children who recovered from CM and those who died. Candidate biomarkers were validated using enzyme immunoassays.ResultsThe plasma proteomic signature of children with CM identified 266 proteins differentially regulated in children with fatal CM. Proteins from the coagulation cascade were consistently decreased in fatal CM, whereas the plasma proteomic signature associated with fatal CM underscored the importance of endothelial activation, tissue damage, inflammation, haemolysis and glucose metabolism. The concentration of circulating proteasomes or PSMB9 in plasma was not significantly different in fatal CM when compared with survivors. Plasma PSMB9 concentration was higher in patients who presented with seizures and was significantly correlated with the number of seizures observed in patients with CM during admission.ConclusionsThe results indicate that increased tissue damage and hypercoagulability may play an important role in fatal CM. The diagnostic value of this molecular signature to identify children at high risk of dying to optimize patient referral practices should be validated prospectively.
Project description:ObjectiveWe hypothesise that exposure to aflatoxins and fumonisins, measured in serum, alters protein synthesis, reducing serum protein and insulin-like growth factor 1 (IGF-1), increasing inflammation and infection, leading to child's linear growth failure.DesignChildren 6-35 months, stratified by baseline stunting, were subsampled from an intervention trial on quality protein maize consumption and evaluated at two time-points.SettingBlood samples and anthropometric data were collected in the pre-harvest (August-September 2015) and post-harvest (February 2016) seasons in rural Ethiopia.Participants102 children (50 stunted and 52 non-stunted).ResultsProportions of children exposed to aflatoxin G1, aflatoxin G2 and aflatoxin M1 were higher in the pre-harvest (8, 33 and 7, respectively) compared to post-harvest season (4, 28 and 4, respectively). The proportion of children exposed to any aflatoxin was higher in the pre-harvest than post-harvest season (51 % v. 41 %). Fumonisin exposure ranged from 0 % to 11 %. In joint statistical tests, aflatoxin exposure was associated with serum biomarkers of inflammation (C-reactive protein, α-1-glycoprotein) and protein status (transthyretin, lysine, tryptophan), IGF-1 and linear growth (all P < 0·01). However, exposure to specific aflatoxins was not significantly associated with any biomarkers or outcomes (all P > 0·05).ConclusionsAflatoxin exposure among rural Ethiopian children was high, with large variation between seasons and individual aflatoxins. Fumonisin exposure was low. There was no clear association between aflatoxin exposure and protein status, inflammation or linear growth. A larger study may be needed to examine the potential biological interactions, and the assessment of aflatoxins in food is needed to determine sources of high exposure.
Project description:BackgroundVascular risk factors have been proposed as important targets for the prevention of dementia. As lipid fractions represent easily modifiable targets, we examined the longitudinal relationship of baseline lipid fractions with 13-y incident dementia and its subtypes (Alzheimer disease [AD] and mixed or vascular dementia) in older community-dwelling persons.Methods and findingsNon-institutionalized persons aged 65+ y (n = 9,294) were recruited for the Three-City Study (3C Study), a population-based cohort study from the electoral rolls of the cities of Dijon, Bordeaux, and Montpellier, France, between March 1999 and March 2001. Follow-up examinations were performed every 2 y after the baseline assessment. The final study sample comprised 7,470 participants from the 3C Study (mean age ± standard deviation [SD] 73.8 ± 5.3 y, 61.0% women) who were prospectively followed up for up to 13 y. Fasting lipid fractions (triglycerides [TGs], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC]) were studied as continuous variables, and results are reported per SD increase of each lipid fraction. Incident dementia and its subtypes were studied as censored variables using Cox models with age as time scale. Analyses were adjusted for sex, study center, and educational level, as well as vascular risk factors and apolipoprotein E (APOE) ε4 genotype. We corrected for multiple testing, yielding a significance threshold of 0.0169. p-Values above the significance threshold but less than 0.05 were considered nominally significant. During a mean (± SD) follow-up period of 7.9 ± 3.6 y, 779 participants developed incident dementia (n = 532 AD and n = 154 mixed or vascular dementia). Higher LDL-C and TC concentrations at baseline were associated with an increased risk of AD (hazard ratio [HR] per SD increase = 1.13 [95% CI 1.04-1.22], p = 0.0045, and HR = 1.12 [1.03-1.22], p = 0.0072, respectively). These associations were largely unchanged after adjustment for vascular risk factors and were attenuated after adjustment for APOEε4 (HR per SD increase = 1.12 [1.03-1.23], p = 0.0110, and HR = 1.12 [1.02-1.23], p = 0.0171, respectively). Higher TG concentrations at baseline were associated with an increased risk of all dementia (HR per SD increase = 1.11 [1.03-1.19], p = 0.0044) and mixed or vascular dementia (HR = 1.21 [1.04-1.41], p = 0.0163). However, these associations disappeared after adjusting for vascular risk factors (HR = 1.07 [0.98-1.17], p = 0.1374, and HR = 1.17 [0.96-1.42], p = 0.1206, respectively). Main limitations of the study include interval censoring of incident dementia cases, potential selective survival bias, and the fact that variation in lipid concentrations during follow-up could not be accounted for in the analyses.ConclusionsIn a large population-based sample of older community-dwelling persons with up to 13 y of follow-up, we observed that higher LDL-C and TC concentrations were associated with an increased risk of AD. This result was independent of vascular risk factors and was attenuated after adjustment for APOEε4 carrier status. TG and HDL-C concentrations were not associated with risk of incident dementia or its subtypes after accounting for vascular risk factors.
Project description:Early life exposures are important predictors of adult disease risk. Although the underlying mechanisms are largely unknown, telomere maintenance may be involved. This study investigated the relationship between seasonal differences in parental exposures at time of conception and leukocyte telomere length (LTL) in their offspring. LTL was measured in two cohorts of children aged 2 yrs (N = 487) and 7-9 yrs (N = 218). The association between date of conception and LTL was examined using Fourier regression models, adjusted for age, sex, leukocyte cell composition, and other potential confounders. We observed an effect of season in the older children in all models [likelihood ratio test (LRT) χ²2 = 7.1, p = 0.03; fully adjusted model]. LTL was greatest in children conceived in September (in the rainy season), and smallest in those conceived in March (in the dry season), with an effect size (LTL peak-nadir) of 0.60 z-scores. No effect of season was evident in the younger children (LRT χ²2 = 0.87, p = 0.65). The different results obtained for the two cohorts may reflect a delayed effect of season of conception on postnatal telomere maintenance. Alternatively, they may be explained by unmeasured differences in early life exposures, or the increased telomere attrition rate during infancy.
Project description:The associations between enteric pathogenic parasites and growth in infants in São Tomé were explored using a refined anthropometric approach to recognize early growth faltering. A birth cohort study was conducted with follow-up to 24 months of age. Microscopic examination for protozoa and soil-transmitted helminths was performed. Anthropometric assessments included: z-scores for weight-for-length (WLZ), length-for-age (LAZ), weight (WAVZ) and length velocities (LAVZ), length-for-age difference (LAD), and wasting and stunting risk (?-1 SD). Generalized additive mixed effects regression models were used to explore the associations between anthropometric parameters and enteric parasitic infections and cofactors. A total of 475 infants were enrolled, and 282 completed the study. The great majority of infants were asymptomatic. Giardia lamblia was detected in 35.1% of infants in at least one stool sample, helminths in 30.4%, and Cryptosporidium spp. in 14.7%. Giardia lamblia and helminth infections were significantly associated with mean decreases of 0.10 in LAZ and 0.32 in LAD, and of 0.16 in LAZ and 0.48 in LAD, respectively. Cryptosporidium spp. infection was significantly associated with a mean decrease of 0.43 in WAVZ and 0.55 in LAVZ. The underestimated association between subclinical parasitic enteric infections and mild growth faltering in infants should be addressed in public health policies.