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Background In-home iron fortification for infants in developing countries is recommended for control of anaemia, but low absorption typically results in >80% of the iron passing into the colon. Iron is essential for growth and virulence of many pathogenic enterobacteria. We determined the effect of high and low dose in-home iron fortification on the infant gut microbiome and intestinal inflammation. Methods We performed two double-blind randomised controlled trials in 6-month-old Kenyan infants (n=115) consuming home-fortified maize porridge daily for 4 months. In the first, infants received a micronutrient powder (MNP) containing 2.5 mg iron as NaFeEDTA or the MNP without iron. In the second, they received a different MNP containing 12.5 mg iron as ferrous fumarate or the MNP without the iron. The primary outcome was gut microbiome composition analysed by 16S pyrosequencing and targeted real-time PCR (qPCR). Secondary outcomes included faecal calprotectin (marker of intestinal inflammation) and incidence of diarrhoea. We analysed the trials separately and combined. Results At baseline, 63% of the total microbial 16S rRNA could be assigned to Bifidobacteriaceae but there were high prevalences of pathogens, including Salmonella Clostridium difficile, Clostridium perfringens, and pathogenic Escherichia coli. Using pyrosequencing, +FeMNPs increased enterobacteria, particularly Escherichia/Shigella (p=0.048), the enterobacteria/bifidobacteria ratio (p=0.020), and Clostridium (p=0.030). Most of these effects were confirmed using qPCR; for example, +FeMNPs increased pathogenic E. coli strains (p=0.029). +FeMNPs also increased faecal calprotectin (p=0.002). During the trial, 27.3% of infants in +12.5 mgFeMNP required treatment for diarrhoea versus 8.3% in −12.5 mgFeMNP (p=0.092). There were no study-related serious adverse events in either group. Conclusions In this setting, provision of iron-containing MNPs to weaning infants adversely affects the gut microbiome, increasing pathogen abundance and causing intestinal inflammation. Trial registration number NCT01111864.

Hepcidin regulation by competing stimuli such as infection and iron deficiency has not been studied in infants and it's yet unknown whether hepcidin regulatory pathways are fully functional in infants. In this cross-sectional study including 339 Kenyan infants aged 6.0±1.1 months (mean±SD), we assessed serum hepcidin-25, biomarkers of iron status and inflammation, and fecal calprotectin. Prevalence of inflammation, anemia, and iron deficiency was 31%, 71%, 26%, respectively. Geometric mean (±SD) serum hepcidin was 6.0 (±3.4) ng/mL, and was significantly lower in males than females. Inflammation (C-reactive protein and interleukin-6) and iron status (serum ferritin, zinc protoporphyrin and soluble transferrin receptor) were significant predictors of serum hepcidin, explaining nearly 60% of its variance. There were small, but significant differences in serum hepcidin comparing iron deficient anemic (IDA) infants without inflammation to iron-deficient anemic infants with inflammation (1.2 (±4.9) vs. 3.4 (±4.9) ng/mL; P<0.001). Fecal calprotectin correlated with blood/mucus in the stool but not with hepcidin. Similarly, the gut-linked cytokines IL-12 and IL-17 did not correlate with hepcidin. We conclude that hepcidin regulatory pathways are already functional in infancy, but serum hepcidin alone may not clearly discriminate between iron-deficient anemic infants with and without infection. We propose gender-specific reference values for serum hepcidin in iron-replete infants without inflammation.

ObjectivesWe sought to understand the influence of recurrent assessments on the behaviour of children and caregivers in a 2-year study of an agricultural livelihood intervention.DesignThis study used qualitative exit interviews from caregivers in the control arm of a large, cluster-randomised control trial, Shamba Maisha.SettingThe study was conducted in Western Kenya and involved 12 health facilities between 2016 and 2019.ParticipantsParticipants were 99 caregivers in the control arm who had a child that was 6–36 months in age at the start of the study.InterventionsIntervention participants within Shamba Maisha received an irrigation pump, farming lessons and a microloan. Control participants received no intervention but were offered the intervention after completing the 2-year study.ResultsDespite receiving no formal benefits, control caregivers reported improved mental health and enhanced knowledge of their child’s health compared with the beginning of the study and reported changes in the child’s play and diet that they attributed to participation in study assessments. Caregivers in the control arm attributed their changed behaviour to recurrent questioning, instrumental support, interactions with study staff and increased health knowledge.ConclusionsRecurrent assessments altered participant behaviour, which may have made inference of the intervention’s impact more difficult. In designing future, such studies with intervention and control arms, a trade-off between the gains in statistical power provided by recurrent visits and the avoidance of alterations in participants’ behaviour that could affect responses to assessments must be considered when deciding on the number of visits for assessment.Trial registration numbersNCT03170986; NCT02815579.

The beneficial effects from exclusive breastfeeding (EBF) have been widely acknowledged. We assessed the effect of exclusive breastfeeding promotion by peer counsellors in Uganda and Burkina Faso, on cognitive abilities, social emotional development, school performance and linear growth among 5-8 years old children. Children in the PROMISE EBF trial (2006-2008) were re-enrolled in the follow-up PROMISE Saving Brains (SB) study (2013-2015). Caretaker interviews captured sociodemographic characteristics and social emotional development using the parent version of the Strengths and Difficulties Questionnaire (SDQ). Overall cognition and working memory were assessed using the Kaufman Assessment Battery for Children, second edition (KABC2), cognitive flexibility was measured with the Child Category Test (CCT), and attention with the Test of Variables of Attention (T.O.V.A), while school performance was measured by a standardized test on arithmetic and reading. Country-pooled, age adjusted z-scores from each of the above outcomes were entered into a linear regression model controlling for confounders. The number of children re-enrolled in the intervention and control arms were: 274/396 (69.2%) and 256/369 (69.4%) in Uganda and 265/392 (67.6%) and 288/402 (71.6%) in Burkina Faso. Assessment of cognitive ability showed small and no significant differences, of which general cognition (z-scores, 95% CI) showed the largest mean difference: -0.17 (-0.40; 0.05). Social emotional symptoms were similar across arms. There were no differences in school performance or linear growth for age detected. Peer promotion for exclusive breastfeeding in Burkina Faso and Uganda was not associated with differences at 5-8 years of age in a range of measures of child development: cognitive abilities, emotion-behaviour-social symptoms or linear growth. This study from sub Saharan Africa did not reconfirm findings elsewhere that have shown an association between exclusive breastfeeding and cognitive performance. This might be due to a number of methodological limitations inherent in the current study. For example since the majority of the children were breastfed, the benefits of the intervention could have been diluted. Other factors such as the mental and HIV status of the mothers (which were not assessed in the current study) could have affected our results. Hence regarding the effect of exclusive breastfeeding on measures of child neurocognitive development in sub Saharan Africa, the jury is still out. ClinicalTrials.gov NCT01882335.

We aimed to study the effects of schooling on aspects of attention using the Test of Variables of Attention (TOVA) among children in rural Burkina Faso. We re-enrolled children of a previously community-based cluster randomized exclusive breastfeeding trial in rural Burkina Faso. A total of 534 children (280 boys and 254 girls) aged 6 to 8 years were assessed using the TOVA. We examined the effect size difference using Cohen's d, ANOVA and conducted regression analyses. Forty nine percent of the children were in school. Children not in school performed poorly with a small effect size difference for 'Response Time', 'Errors of omission', and 'Errors of commission' compared to children in school. The effect size difference was moderate for 'Response Time Variability', and 'D prime score'. Schooling affects different aspects of attention in rural Burkina Faso. In settings where literacy and schooling rate is low, public sensitizations of the benefits of schooling need to be reinforced and advice on sending children to school need to be provided continuously.

Background In Burkina Faso, stunting affects children and is a public health problem. We studied the association between stunting and child’s neuro-psychological outcomes at 6–8 years of age in rural Burkina Faso using the Kaufman Assessment Battery for Children, 2nd edition (KABC-II), the Children’s Category Test 1 (CCT-1) and the Test of Variable of Attention (TOVA). Methods We re-enrolled children of a previously community-based Exclusive breastfeeding trial in Burkina Faso. We assessed a total of 532 children aged 6–8 years using KABC-II for memory (Atlantis and Number Recall subtests), spatial abilities (Conceptual Thinking, Face Recognition and Triangle subtests), reasoning (Block Counting subtest), general cognition and CCT-1 for cognitive flexibility. A total 513 children were assessed using the TOVA to measure attention and inhibition. We calculated the Cohen’s d to examine the effect size and conducted a linear regression to examine the association. Results The proportion of stunting was 15.6% (83/532). Stunted children performed significantly poorer for memory (Atlantis and Number Recall), spatial abilities (Conceptual Thinking, Face Recognition and Triangle), general cognition and attention with a small effect size compared to non-stunted children. Children who were exposed scored significantly higher errors for cognitive flexibility and inhibition with a small effect size compared to unexposed children. At standardized and unstandardized multivariable regression analysis, stunted children performed significantly poorer for Atlantis (p = 0.001), Number Recall (p = 0.02), Conceptual Thinking (p = 0.01), Triangle (p = 0.001), general cognition (p ≤ 0.0001) and attention (p = 0.04) compared to non-stunted children. Children who were exposed scored significantly higher errors for cognitive flexibility (p = 0.02) and for inhibition (p = 0.02) compared to unexposed children. We adjusted all the results for age, schooling, sex, playing, father education, mother employment and promotion of previous exclusive breastfeeding. Conclusion Stunting is associated with poorer neuro-psychological outcomes among children in rural Burkina Faso. Initiatives related to prevention need to be established and advice on nutrition need to be provided.

In Burkina Faso, it is not uncommon for mothers to drink alcohol, even during pregnancy. We aimed to study the association between maternal alcohol consumption during pregnancy and the child's cognitive performance using the Kaufman Assessment Battery for Children, 2nd edition (KABC-II) and the Children's Category Test Level 1 (CCT-1) in rural Burkina Faso. We conducted a follow-up study of a community cluster-randomised Exclusive breastfeeding trial, and re-enrolled the children in rural Burkina Faso. A total of 518 children (268 boys and 250 girls) aged 6-8 years were assessed using the KABC-II and the CCT-1. We examined the effect size difference using Cohen's d and conducted a linear regression analysis to examine the association. Self-reported alcohol consumption during pregnancy was 18.5% (96/518). Children whose mothers reported alcohol consumption during pregnancy performed significantly poorly for memory and spatial abilities tests from small effect size difference for 'Atlantis' (0.27) and 'Triangle' (0.29) to moderate effect size difference for 'Number recall' (0.72) compared to children whose mothers did not consume alcohol during pregnancy; the exposed children scored significantly higher errors with a small effect size (0.37) at problem solving (CCT-1) test compared to unexposed children. At unstandardized and standardized multivariable analysis, children whose mothers reported alcohol consumption during pregnancy performed significantly poorer for memory-'Atlantis' (  = 0.03) and 'Number recall' (  = 0.0001), and spatial ability tests-'Triangle' (  = 0.03); they scored significantly higher errors at problem solving CCT-1 test (  = 0.002); all the results were adjusted for age, sex, schooling, stunting, father's education, mother's employment and the promotion of exclusive breastfeeding. No statistical association was found for visual abilities-'Conceptual Thinking', 'Face recognition', 'Story completion', and reasoning tests-'Rover', 'Block counting', and 'Pattern Reasoning'. Maternal alcohol consumption during pregnancy is associated with poorer cognitive performance for memory, spatial ability, and problem solving tests in the offspring in rural Burkina Faso. Futures studies needs to assess in more detail the maternal alcohol consumption patterns in Burkina Faso and possible preventive strategies.

The study examines the relationship between orphanhood status and nutritional status and food security among children living in the rapidly growing and uniquely vulnerable slum settlements in Nairobi, Kenya. The study was conducted between January and June 2007 among children aged 6–14 years, living in informal settlements of Nairobi, Kenya. Anthropometric measurements were taken using standard procedures and z scores generated using the NCHS/WHO reference. Data on food security were collected through separate interviews with children and their caregivers, and used to generate a composite food security score. Multiple regression analysis was done to determine factors related to vulnerability with regards to food security and nutritional outcomes. The results show that orphans were more vulnerable to food insecurity than non-orphans and that paternal orphans were the most vulnerable orphan group. However, these effects were not significant for nutritional status, which measures long-term food deficiencies. The results also show that the most vulnerable children are boys, those living in households with lowest socioeconomic status, with many dependants, and female-headed and headed by adults with low human capital (low education). This study provides useful insights to inform policies and practice to identify target groups and intervention programs to improve the welfare of orphans and vulnerable children living in urban poor communities.

Background Seizures are common in children admitted with severe falciparum malaria and are associated with neuro-cognitive impairments. Prolonged febrile seizures are associated with hippocampal damage and impaired memory. It was hypothesized that severe malaria causes impaired everyday memory which may be associated with hippocampal damage. Methods An everyday memory battery was administered on 152 children with cerebral malaria (CM) (mean age, 7 y 4 months [SD 13 months]; 77 males) 156 children (mean age, 7 y 4 months [SD, 14 months]; 72 males) with malaria plus complex seizures (MS) and 179 children (mean age, 7 y 6 months [SD, 13 months]; 93 males) unexposed to either condition. Results CM was associated with poorer everyday memory [95% CI, -2.46 to -0.36, p = 0.004] but not MS [95% CI, -0.91 to 1.16, p = 1.00] compared to unexposed children. Children with exposure to CM performed more poorly in recall [95% CI, -0.79 to -0.04, p = 0.024] and recognition subtests [95% CI, -0.90 to -0.17, p = 0.001] but not in prospective memory tests compared to controls. The health factors that predicted impaired everyday memory outcome in children with exposure to CM was profound coma [95% CI, 0.02 to 0.88, p = 0.037] and multiple episodes of hypoglycaemia [95% CI, 0.05 to 0.78, p = 0.020], but not seizures. Discussion The findings show that exposure to CM was associated with a specific impairment of everyday memory. Seizures commonly observed in severe malaria may not have a causal relationship with poor outcome, but rather be associated with profound coma and repeated metabolic insults (multi-hypoglycaemia) that are strongly associated with impaired everyday memory.

The ability to measure neuropsychological outcomes in a comparable manner in different cultural groups is important if studies conducted in geographically diverse regions are to advance knowledge of disease effects and moderating influences. The purpose of this study was to evaluate the application of neuropsychological test procedures developed for use in North America and Europe to children in a rural region of Kenya. Our specific aim was to determine if these methods could be adapted to a non-Western culture in a manner that would preserve test reliability and validity. Procedural modifications yielded reliable tests that were sensitive to both the sequelae of cerebral malaria and to children's social and school backgrounds. Results suggest that adaptations of existing tests can be made in such a way as to preserve their utility in measuring the cross-cultural sequelae of childhood neurological diseases. (JINS, 2004, 10, 246–260.)