• Early childhood cognitive development is affected by interactions among illness, diet, enteropathogens and the home environment: Findings from the MAL-ED birth cohort study

      Murray-Kolb, LE; Acosta, AM; De Burga, RR; Chavez, CB; Flores, JT; Olotegui, MP; Pinedo, SR; Salas, MS; Trigoso, DR; Vasquez, AO; Ahmed, I; Alam, D; Ali, A; Bhutta, ZA; Qureshi, S; Rasheed, M; Soofi, S; Turab, A; Zaidi, AKM; Bodhidatta, L; Mason, CJ; Babji, S; Bose, A; George, AT; Hariraju, D; Jennifer, MS; John, S; Kaki, S; Kang, G; Karunakaran, P; Koshy, B; Lazarus, RP; Muliyil, J; Raghava, MV; Raju, S; Ramachandran, A; Ramadas, R; Ramanujam, K; Bose, A; Roshan, R; Sharma, SL; Sundaram, SE; Thomas, RJ; Pan, WK; Ambikapathi, R; Carreon, JD; Charu, V; Doan, V; Graham, J; Hoest, C; Knobler, S; Lang, DR; McCormick, BJJ; McGrath, M; Miller, MA; Mohale, A; Nayyar, G; Psaki, S; Rasmussen, Z; Richard, SA; Seidman, JC; Wang, V; Blank, R; Gottlieb, M; Tountas, KH; Amour, C; Bayyo, E; Mduma, ER; Mvungi, R; Nshama, R; Pascal, J; Swema, BM; Yarrot, L; Ahmed, T; Ahmed, AMS; Haque, R; Hossain, I; Islam, M; Mahfuz, M; Mondal, D; Tofail, F; Chandyo, RK; Shrestha, PS; Shrestha, R; Ulak, M; Bauck, A; Black, RE; Caulfield, LE; Checkley, W; Kosek, MN; Lee, G; Schulze, K; Yori, PP; Murray-Kolb, LE; Catharine Ross, A; Schaefer, B; Simons, S; Pendergast, L; Abreu, CB; Costa, H (2018-07-01)
      © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. background Millions of children in low-income and middle-income countries (LMICs) are at risk of not reaching their full cognitive potential. Malnutrition and enteric infections in early life are implicated as risk factors; however, most studies on these risks and their associations with cognitive development have failed to adequately account for confounding factors or the accumulation of putative insults. Here, we examine the interaction between infections and illness on cognitive development in LMIC community settings. Methods As part of the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) longitudinal birth cohort study, children from eight LMICs were followed from birth to 24 months to understand the influence of repeated enteric infections on child growth and development. Here, data from six sites were employed to evaluate associations between infection, illness, the home environment, micronutrient intake and status, maternal reasoning, and cognitive development at 24 months. results Higher rates of enteropathogen detection and days with illness were associated with lower haemoglobin concentrations, which in turn were associated with lower cognitive scores at 24 months. Children with lower environmental health/safety scores and lower intakes of vitamin B 6 and folate had more enteropathogen detections and illness. Strength of associations varied by weight-for-age in the first 17 days of life; lower weight infants were more susceptible to the negative effects of enteropathogens and illness. Conclusions Enteropathogens were negatively related to child cognitive development. However, other factors were more strongly associated with child cognition. Targeting of interventions to improve cognitive development should include a focus on reducing frequency of illness, improving the safety and healthfulness of the child's environment, and improving dietary intake.
    • Early Life Child Micronutrient Status, Maternal Reasoning, and a Nurturing Household Environment have Persistent Influences on Child Cognitive Development at Age 5 years: Results from MAL-ED

      McCormick, BJJ; Richard, SA; Caulfield, LE; Pendergast, LL; Seidman, JC; Koshy, B; Roshan, R; Shrestha, R; Svensen, E; Blacy, L; Rasmussen, Z; Maphula, A; Scharf, R; Nahar, B; Haque, S; Rasheed, M; Oria, R; Rogawski, ET; Murray-Kolb, LE; Acosta, AM; De Burga, RR; Chavez, CB; Flores, JT; Olotegui, MP; Pinedo, SR; Salas, MS; Trigoso, DR; Vasquez, AO; Ahmed, I; Alam, D; Ali, A; Bhutta, ZA; Qureshi, S; Soofi, S; Turab, A; Zaidi, AKM; Bodhidatta, L; Mason, CJ; Babji, S; Bose, A; George, AT; Hariraju, D; Jennifer, MS; John, S; Kaki, S; Kang, G; Karunakaran, P; Lazarus, RP; Muliyil, J; Raghava, MV; Raju, S; Ramachandran, A; Ramadas, R; Ramanujam, K; Sharma, SL; Sundaram, SE; Thomas, RJ; Pan, WK; Ambikapathi, R; Carreon, JD; Charu, V; Doan, V; Graham, J; Hoest, C; Knobler, S; Lang, DR; McGrath, M; Miller, MA; Mohale, A; Nayyar, G; Psaki, S; Wang, V; Blank, R; Gottlieb, M; Tountas, KH; Amour, C; Bayyo, E; Mduma, ER; Mvungi, R; Nshama, R; Pascal, J; Swema, BM; Yarrot, L; Ahmed, T; Ahmed, AMS; Haque, R; Hossain, I; Islam, M; Mahfuz, M; Mondal, D; Tofail, F; Chandyo, RK; Shrestha, PS; Ulak, M; Bauck, A; Black, RE; Checkley, W; Kosek, MN; Lee, G; Schulze, K (2019-08-01)
      © Copyright American Society for Nutrition 2019. Background: Child cognitive development is influenced by early-life insults and protective factors. To what extent these factors have a long-term legacy on child development and hence fulfillment of cognitive potential is unknown. Objective: The aim of this study was to examine the relation between early-life factors (birth to 2 y) and cognitive development at 5 y. Methods: Observational follow-up visits were made of children at 5 y, previously enrolled in the community-based MAL-ED longitudinal cohort. The burden of enteropathogens, prevalence of illness, complementary diet intake, micronutrient status, and household and maternal factors from birth to 2 y were extensively measured and their relation with the Wechsler Preschool Primary Scales of Intelligence at 5 y was examined through use of linear regression. Results: Cognitive T-scores from 813 of 1198 (68%) children were examined and 5 variables had significant associations in multivariable models: mean child plasma transferrin receptor concentration (β: -1.81, 95% CI: -2.75, -0.86), number of years of maternal education (β: 0.27, 95% CI: 0.08, 0.45), maternal cognitive reasoning score (β: 0.09, 95% CI: 0.03, 0.15), household assets score (β: 0.64, 95% CI: 0.24, 1.04), and HOME child cleanliness factor (β: 0.60, 95% CI: 0.05, 1.15). In multivariable models, the mean rate of enteropathogen detections, burden of illness, and complementary food intakes between birth and 2 y were not significantly related to 5-y cognition. Conclusions: A nurturing home context in terms of a healthy/clean environment and household wealth, provision of adequate micronutrients, maternal education, and cognitive reasoning have a strong and persistent influence on child cognitive development. Efforts addressing aspects of poverty around micronutrient status, nurturing caregiving, and enabling home environments are likely to have lasting positive impacts on child cognitive development.
    • Norovirus infection and acquired immunity in 8 countries: Results from the MAL-ED study

      Rouhani, S; Peñataro Yori, P; Paredes Olortegui, M; Siguas Salas, M; Rengifo Trigoso, D; Mondal, D; Bodhidatta, L; Platts-Mills, J; Samie, A; Kabir, F; Lima, AAM; Babji, S; Mason, CJ; Kalam, A; Bessong, P; Ahmed, T; Mduma, E; Bhutta, ZA; Lima, I; Ramdass, R; Lang, D; George, A; Zaidi, AKM; Kang, G; Houpt, E; Kosek, MN; Brett, N; Acosta, AM; De Burga, RR; Chavez, CB; Flores, JT; Olotegui, MP; Pinedo, SR; Salas, MS; Trigoso, DR; Vasquez, AO; Ahmed, I; Alam, D; Ali, A; Qureshi, S; Rasheed, M; Soofi, S; Turab, A; Bose, A; Hariraju, D; Jennifer, MS; John, S; Kaki, S; Karunakaran, P; Koshy, B; Lazarus, RP; Muliyil, J; Raghava, MV; Raju, S; Ramachandran, A; Ramadas, R; Ramanujam, K; Roshan, R; Sharma, SL; Shanmuga Sundaram, E; Thomas, RJ; Pan, WK; Ambikapathi, R; Carreon, JD; Charu, V; Doan, V; Graham, J; Hoest, C; Knobler, S; McCormick, BJJ; McGrath, M; Miller, MA; Mohale, A; Nayyar, G; Psaki, S; Rasmussen, Z; Richard, SA; Seidman, JC; Wang, V; Blank, R; Gottlieb, M; Tountas, KH; Amour, C; Bayyo, E; Mvungi, R; Nshama, R; Pascal, J; Swema, BM; Yarrot, L; Ahmed, AS; Haque, R; Hossain, I; Islam, M; Mahfuz, M; Tofail, F; Chandyo, RK; Shrestha, PS; Shrestha, R; Ulak, M; Bauck, A (2016-05-15)
      © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. Background. Norovirus is an important cause of childhood diarrhea. We present data from a longitudinal, multicountry study describing norovirus epidemiology during the first 2 years of life. Methods. A birth cohort of 1457 children across 8 countries contributed 7077 diarrheal stools for norovirus testing. A subset of 199 children contributed additional asymptomatic samples (2307) and diarrheal stools (770), which were used to derive incidence rates and evaluate evidence for acquired immunity. Results. Across sites, 89% of children experienced at least 1 norovirus infection before 24 months, and 22.7% of all diarrheal stools were norovirus positive. Severity of norovirus-positive diarrhea was comparable to other enteropathogens, with the exception of rotavirus. Incidence of genogroup II (GII) infection was higher than genogroup I and peaked at 6-11 months across sites. Undernutrition was a risk factor for symptomatic norovirus infection, with an increase in 1 standard deviation of length-for-age z score associated with a 17% reduction (odds ratio, 0.83 [95% confidence interval,. 72-.97]; P =. 011) in the odds of experiencing diarrhea when norovirus was present, after accounting for genogroup, rotavirus vaccine, and age. Evidence of acquired immunity was observed among GII infections only: Children with prior GII infection were found to have a 27% reduction in the hazard of subsequent infection (hazard ratio, 0.727; P =. 010). Conclusions. The high prevalence of norovirus across 8 sites in highly variable epidemiologic settings and demonstration of protective immunity for GII infections provide support for investment in vaccine development.
    • Relationship between growth and illness, enteropathogens and dietary intakes in the first 2 years of life: Findings from the MAL-ED birth cohort study

      Acosta, AM; De Burga, RR; Chavez, CB; Flores, JT; Olotegui, MP; Pinedo, SR; Salas, MS; Trigoso, DR; Vasquez, AO; Ahmed, I; Alam, D; Ali, A; Bhutta, ZA; Qureshi, S; Rasheed, M; Soofi, S; Turab, A; Zaidi, AKM; Bodhidatta, L; Mason, CJ; Babji, S; Bose, A; George, AT; Hariraju, D; Steffi Jennifer, M; John, S; Kaki, S; Kang, G; Karunakaran, P; Koshy, B; Lazarus, RP; Muliyil, J; Raghava, MV; Raju, S; Ramachandran, A; Ramadas, R; Ramanujam, K; Bose, A; Roshan, R; Sharma, SL; Shanmuga Sundaram, E; Thomas, RJ; Pan, WK; Ambikapathi, R; Daniel Carreon, J; Charu, V; Doan, V; Graham, J; Hoest, C; Knobler, S; Lang, DR; McCormick, BJJ; McGrath, M; Miller, MA; Mohale, A; Nayyar, G; Psaki, S; Rasmussen, Z; Richard, SA; Seidman, JC; Wang, V; Blank, R; Gottlieb, M; Tountas, KH; Amour, C; Bayyo, E; Mduma, ER; Mvungi, R; Nshama, R; Pascal, J; Swema, BM; Yarrot, L; Ahmed, T; Shamsir Ahmed, AM; Haque, R; Hossain, I; Islam, M; Mahfuz, M; Mondal, D; Tofail, F; Chandyo, RK; Shrestha, PS; Shrestha, R; Ulak, M; Bauck, A; Black, RE; Caulfield, LE; Checkley, W; Kosek, MN; Lee, G; Schulze, K; Yori, PP; Murray-Kolb, LE; Catharine Ross, A; Schaefer, B; Simons, S; Pendergast, L; Abreu, CB; Costa, H; Di Moura, A (2017-01-01)
      © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. Background Dietary and illness factors affect risk of growth faltering; the role of enteropathogens is less clear. As part of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study, we quantify the effects of enteropathogen infection, diarrhoea and diet on child growth. Methods Newborns were enrolled and followed until 24 months. Length and weight were assessed monthly. Illnesses and breastfeeding practices were documented biweekly; from 9 to 24 months, non-breast milk intakes were quantified monthly. Routinely collected non-diarrhoeal stools were analysed for a broad array of enteropathogens. A linear piecewise spline model was used to quantify associations of each factor with growth velocity in seven of eight MAL-ED sites; cumulative effects on attained size at 24 months were estimated for mean, low (10th percentile) and high (90th percentile) exposure levels. Additionally, the six most prevalent enteropathogens were evaluated for their effects on growth. results Diarrhoea did not have a statistically significant effect on growth. Children with high enteropathogen exposure were estimated to be 1.21±0.33 cm (p<0.001; 0.39 length for age (LAZ)) shorter and 0.08±0.15 kg (p=0.60; 0.08 weight-for-age (WAZ)) lighter at 24 months, on average, than children with low exposure. Campylobacter and enteroaggregativeEscherichia coli detections were associated with deficits of 0.83±0.33 and 0.85±0.31 cm in length (p=0.011 and 0.001) and 0.22±0.15 and 0.09±0.14 kg in weight (p=0.14 and 0.52), respectively. Children with low energy intakes and protein density were estimated to be 1.39±0.33 cm (p<0.001; 0.42 LAZ) shorter and 0.81±0.15 kg (p<0.001; 0.65 WAZ) lighter at 24 months than those with high intakes. conclusions Reducing enteropathogen burden and improving energy and protein density of complementary foods could reduce stunting.