ABSTRACT.
Globally, 140 million children under 5 years of age are estimated to be stunted. Previous studies have found an association between stunting and poor cognitive outcomes. However, there is limited evidence of this association in sub-Saharan African settings, such as the Democratic Republic of the Congo (DRC). This prospective cohort study of 286 children under 5 years was conducted in rural DRC to investigate the association between diarrhea prevalence, child growth, and child cognitive developmental outcomes. Developmental outcomes were assessed by communication, fine motor, gross motor, personal social, problem-solving, and combined developmental scores measured by the Extended Ages and Stages Questionnaire (EASQ) at a 6-month follow-up visit. Height and weight were measured at baseline and a 6-month follow-up. Diarrhea prevalence was assessed through surveillance visits. Diarrhea prevalence was not associated with follow-up combined EASQ Z-scores at the 6-month follow-up (coefficient: −0.06 [95% CI: −0.29, 0.17]). Each additional standard deviation (SD) increase in height-for-age Z-scores from baseline to the 6-month follow-up increased combined EASQ Z-scores by 0.22 (95%: 0.14, −0.31) SDs. Each additional SD increase in weight-for-age Z-scores from baseline to the 6-month follow-up increased combined EASQ Z-scores by 0.21 (95%: 0.10, −0.32) SDs. Linear growth faltering and reduced weight gain were associated with reduced cognitive developmental outcomes among children residing in rural DRC. Interventions are urgently needed for this susceptible pediatric population to improve child growth and cognitive developmental outcomes.
INTRODUCTION
In 2020, 144 million children under 5 years of age were estimated to be stunted—nearly a quarter of all children under 5 years of age, globally.1 Previous studies have found an association between stunting and poor cognitive outcomes.2–4 In Peru, severe stunting was associated with reduced cognition.2 In Jamaica, stunting in early life was associated with poorer behavioral and emotional outcomes in adolescent years.3 In Bangladesh, stunting was associated with lower cognitive scores.4 However, there are no studies, to our knowledge, of this association in sub-Saharan African settings, such as the Democratic Republic of the Congo (DRC).
Diarrheal disease during early life has been shown to be associated with subsequent malnutrition and impaired growth in young children.5–10 Enteric infections can reduce a child’s ability to absorb nutrients, resulting in malnutrition and impaired growth.11 The first 2 years of life represent a critical window for child development; this is a time when adequate nutrient intake is essential because the brain is rapidly developing.12 During this period, poor child cognitive developmental outcomes can occur if energetic demands are not met because of enteric infections.2,3,12 Previous studies in Brazil, Peru, and India found that enteric infections were associated with lower cognitive function in children.13–15
In this prospective cohort study, we sought to expand on this evidence base in a sub-Saharan African setting by investigating the association between child growth and child cognitive developmental outcomes in rural DRC. We hypothesized that diarrhea prevalence and impaired growth among young children would result in adverse cognitive development outcomes.
METHODS
Ethical approval.
Informed consent was obtained from a parent or guardian of all study participants. Study procedures were approved by the research ethical review committees of the University of Kinshasa (Protocol 043-2017) and the Johns Hopkins Bloomberg School of Public Health (Protocol 8057).
Study design.
The objective of the Reducing Enteropathy, Undernutrition, and Contamination in the Environment (REDUCE) program is to identify exposure pathways to fecal pathogens that are significant contributors to morbidity for young children in the DRC, and to develop and evaluate scalable interventions to reduce exposure to fecal pathogens from these pathways. This prospective cohort study of 286 children under 5 years of age was conducted in rural Walungu Territory of South Kivu in the DRC as part of the REDUCE program. The study was part of a larger USAID/Bureau for Humanitarian Assistance-funded Development Food Security Activities (DFSA) award with the goal of improving food and nutrition security and economic well-being of vulnerable households in South Kivu and Tanganyika provinces of DRC. Participants were enrolled between June 2018 and January 2019. A 6-month follow-up was conducted in households between December 2018 and August 2019. The sample size was based on the number of study participants with child developmental outcome data and baseline and 6-month follow-up child growth data available. All children with at least 5 months of surveillance data from baseline to follow-up that were younger than 5 years of age at follow-up were included in the analysis. Caregivers were administered a clinical surveillance questionnaire at baseline on whether their child had diarrhea (three or more loose stools over a 24-hour period in the past 2 weeks). Diarrhea prevalence at baseline was calculated using this clinical surveillance questionnaire.
Child growth measurements.
Research assistants with training in standardized anthropometry measured the child’s weight once and height/length three times at baseline and the 6-month follow-up. Length was measured for children 0–23 months and height for children 24–59 months. These measurements were used to calculate Z-scores according to the WHO child growth standards.16 Height-for-age Z-scores (HAZ), weight-for-age Z-scores (WAZ), and weight-for-height/length Z-scores (WHLZ) were calculated.
Child developmental outcomes.
Communication, gross motor, fine motor, problem-solving, and personal social skills were assessed for children under 5 years using the Extended Ages and Stages Questionnaire (EASQ) at the 6-month follow-up. This questionnaire is a combination of direct tests and parental reports, which was adapted for use in low- and middle-income countries (LMICs).17,18 Direct tests included drawings, naming items in a picture book, stacking blocks, and kicking a ball. The domains for the tests were in 2-month age bands up until 24 months, then in 3-month age bands from 25 to 36 months, and 6-month age bands thereafter. Respondents could respond “yes,” “sometimes,” or “no” for items. The EASQ was reviewed by the study psychologist, translated and back-translated, and piloted according to previously published methods.19 Eighteen testers (university graduates) received a 10-day extensive hands-on training on how to administer the EASQ. We arranged refresher trainings every 3 months. The standardized Z-scores were constructed for each domain and all domains combined based on the mean and standard deviation (SD) in each age band.
Statistical analysis.
The primary objective was to determine whether diarrhea prevalence and child growth were associated with subsequent child developmental outcomes. To assess the association between diarrhea prevalence, child growth, and child developmental outcomes, linear regression models were fit using generalized estimating equations to account for clustering at the household level and to approximate 95% CIs. Child developmental outcomes (combined, communication, fine motor, gross motor, problem-solving, and personal social Z-scores) were modeled separately as continuous outcomes and diarrhea prevalence and child growth (both the change in growth and baseline growth measures) as predictors. Models were adjusted for caregiver formal education (household education), number of individuals in the household (household size), and household wall type (housing type). Analyses were performed in SAS software (version 9.4, North Carolina).
RESULTS
Two hundred eighty-six children from 176 households had anthropometric measurements from baseline and follow-up, and EASQ data available. The median baseline age was 2 years ± 1.1 (0.6–5.0) (median ± SD [SD], [range]) (Table 1). Fifty percent of children (143/286) were female. Forty-eight percent of children (134/281) were stunted (HAZ < −2) at baseline, 5% (13/284) were wasted (WHLZ < −2), and 15% (43/285) were underweight (WAZ < −2). The mean change in HAZ from baseline to the 6-month follow-up was −0.52, −0.24 for the change in WAZ, and 0.09 for the change in WHLZ. For children under 2 years, the mean change in HAZ from baseline to the 6-month follow-up was −1.01, −0.29 for the change in WAZ, and 0.28 for the change in WHLZ. The diarrhea prevalence at baseline (three or more loose stools over a 24-hour period in the past 2 weeks) was 30% (83/274). The median household size was six individuals ±2.4 (2–17). Seventy-four percent of children (209/283) resided in households with at least one household member with any level of formal education. Sixty-two percent of children (171/278) resided in households with mud walls, 8% (21/278) wood walls, 6% (18/278) concrete walls, 6% (16/278) wood and mud walls, 4% (12/278) biomass walls, 5% (14/278) brick walls, and 3% (8/278) wood and concrete walls.
Table 1.
Baseline demographic characteristics among children under 5 years in rural Democratic Republic of the Congo
| % | n | N | |
|---|---|---|---|
| Children < 5 years of age | – | – | 286 |
| Baseline age (Years) | |||
| Median ± SD (Min–Max) | 2.1 ± 1.1 (0.6–5.0) | 286 | |
| Gender | |||
| Female | 50 | 143 | 286 |
| Household wall type | |||
| Mud walls | 62 | 171 | 278 |
| Wood walls | 8 | 21 | 278 |
| Concrete walls | 6 | 18 | 278 |
| Wood and mud walls | 6 | 16 | 278 |
| Biomass walls | 4 | 12 | 278 |
| Brick walls | 5 | 14 | 278 |
| Wood and concrete walls | 3 | 8 | 278 |
| Other | 6 | 18 | 278 |
| Household member with any formal education | 74 | 209 | 283 |
| Household size | |||
| Median ± SD (Min–Max) | 6.0 ± 2.4 (2–17) | 278 | |
| Baseline diarrhea prevalence | 30 | 83 | 274 |
| Baseline growth measurements | |||
| Stunted (HAZ < −2) | 48 | 134 | 281 |
| Wasted (WHLZ < −2) | 5 | 13 | 284 |
| Underweight (WAZ < −2) | 15 | 43 | 285 |
| Mean HAZ | −1.80 | – | 281 |
| Mean WHLZ | 0.42 | – | 284 |
| Mean WAZ | −0.68 | – | 285 |
n represents the number of children with the individual or household level characteristic. HAZ = height-for-age Z-score; WHLZ = weight-for-height/length Z-scores; WAZ = weight-for-age Z-score. Diarrhea prevalence: three or more loose stools over a 24-hour period in the past 2 weeks.
All regression models were adjusted for wall type, number of household members, and household education level. Regression models were also adjusted for baseline anthropometric Z-score when the predictor was a follow-up anthropometric measure.
Diarrhea prevalence was not associated with follow-up combined EASQ Z-scores at the 6-month follow-up (coefficient: −0.06 [95% CI: −0.29, 0.17]) (Table 2). Each additional SD increase in HAZ from baseline to the 6-month follow-up increased combined EASQ Z-scores by 0.22 (95%: 0.14, −0.31) SDs as well as increased communication EASQ Z-scores (0.17 [95% CI: 0.09, 0.26]), gross motor EASQ Z-scores (0.15 [95% CI: 0.06, 0.25]), fine motor EASQ Z-scores (0.20 [95% CI: 0.11, 0.29]), problem-solving EASQ Z-scores (0.14 [95% CI: 0.05, 0.22]), and personal social EASQ Z-scores (0.20 [95% CI: 0.10, 0.30]). Each additional SD increase in WAZ from baseline to the 6 month follow-up increased EASQ Z-scores by 0.21 (95%: 0.10, −0.32) SDs as well communication EASQ Z-scores (0.15 [95% CI: 0.02, 0.28]), fine motor EASQ Z-scores (0.15 [95% CI: 0.02, 0.27]), problem-solving EASQ Z-scores (0.18 [95% CI: 0.05, 0.31]), and personal social EASQ Z-scores (0.20 [95% CI: 0.08, 0.32]). Underweight status at baseline decreased EASQ Z-scores by −0.45 (95% CI: −0.72, −0.18) SDs as well as gross motor EASQ Z-scores (−0.69 [95% CI: −1.00, −0.37]), fine motor EASQ Z-scores (−0.45 [95% CI: −0.70, −0.20]), and problem-solving EASQ Z-scores (−0.40 [95% CI: −0.70, −0.10]). Similar results were observed for children under 2 years of age.
Table 2.
Association between change in child growth and diarrhea and Extended Ages and Stages Questionnaire Z-scores in a Cohort Study in the Democratic Republic of the Congo
| Risk factor | Combined Z-score | Communication Z-score | Gross motor Z-score | Fine motor Z-score | Problem-solving Z-score | Personal social Z-score | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Coefficient (95% CI) | Coefficient (95% CI) | Coefficient (95% CI) | Coefficient (95% CI) | Coefficient (95% CI) | Coefficient (95% CI) | |||||||||||||
| Children under 5 years (N = 286) | ||||||||||||||||||
| Change in height-for-age Z-score | 0.22 | 0.14 | 0.31 | 0.17 | 0.09 | 0.26 | 0.15 | 0.06 | 0.25 | 0.20 | 0.11 | 0.29 | 0.14 | 0.05 | 0.22 | 0.20 | 0.10 | 0.30 |
| Change in weight-for-age Z-score | 0.21 | 0.10 | 0.32 | 0.15 | 0.02 | 0.28 | 0.11 | −0.02 | 0.25 | 0.15 | 0.02 | 0.27 | 0.18 | 0.05 | 0.31 | 0.20 | 0.08 | 0.32 |
| Change in· weight-for-height/ | 0.03 | −0.06 | 0.12 | −0.001 | −0.10 | 0.10 | 0.01 | −0.10 | 0.11 | −0.01 | −0.12 | 0.10 | 0.08 | −0.02 | 0.19 | 0.03 | −0.07 | 0.14 |
| length Z-score | ||||||||||||||||||
| Baseline stunting | −0.003 | −0.22 | 0.21 | 0.02 | −0.19 | 0.22 | −0.16 | −0.40 | 0.07 | −0.06 | −0.29 | 0.17 | −0.01 | −0.24 | 0.22 | 0.06 | −0.17 | 0.28 |
| Baseline underweight | −0.45 | −0.72 | −0.18 | −0.27 | −0.59 | 0.06 | −0.69 | −1.00 | −0.37 | −0.45 | −0.70 | -0.20 | −0.40 | −0.70 | −0.10 | −0.17 | −0.46 | 0.12 |
| Baseline wasting | −0.26 | −0.74 | 0.21 | −0.21 | −0.70 | 0.28 | −0.36 | −0.90 | 0.19 | −0.27 | −0.73 | 0.20 | −0.07 | −0.54 | 0.40 | −0.22 | −0.81 | 0.38 |
| Baseline diarrhea prevalence | −0.06 | −0.29 | 0.17 | −0.09 | −0.31 | 0.13 | −0.01 | −0.27 | 0.26 | −0.15 | −0.40 | 0.10 | −0.03 | −0.24 | 0.18 | −0.13 | −0.37 | 0.11 |
| Children under 2 years (N = 123) | ||||||||||||||||||
| Change in height-for-age Z-score | 0.26 | 0.13 | 0.40 | 0.22 | 0.09 | 0.35 | 0.15 | 0.03 | 0.28 | 0.19 | 0.04 | 0.35 | 0.13 | −0.01 | 0.26 | 0.28 | 0.14 | 0.41 |
| Change in weight-for-age Z-score | 0.22 | 0.05 | 0.38 | 0.21 | 0.04 | 0.38 | 0.11 | −0.04 | 0.26 | 0.08 | −0.10 | 0.26 | 0.17 | 0.001 | 0.35 | 0.20 | 0.02 | 0.38 |
| Change in weight-for-height/ | ||||||||||||||||||
| length Z-score | 0.002 | −0.14 | 0.14 | 0.001 | −0.14 | 0.14 | 0.01 | −0.13 | 0.15 | −0.07 | −0.22 | 0.08 | 0.09 | −0.05 | 0.24 | −0.04 | −0.19 | 0.11 |
| Baseline stunting | 0.06 | −0.26 | 0.38 | 0.20 | −0.13 | 0.53 | −0.10 | −0.38 | 0.18 | 0.02 | −0.32 | 0.36 | 0.07 | −0.23 | 0.38 | −0.06 | −0.42 | 0.30 |
| Baseline underweight | −0.14 | −0.47 | 0.18 | 0.34 | −0.20 | 0.89 | −0.51 | −0.89 | −0.13 | 0.01 | −0.41 | 0.42 | −0.36 | −0.73 | 0.01 | 0.04 | −0.45 | 0.53 |
| Baseline wasting | 0.01 | −0.57 | 0.59 | 0.33 | −0.20 | 0.86 | −0.35 | −1.17 | 0.46 | −0.22 | −0.91 | 0.47 | 0.20 | −0.37 | 0.77 | 0.14 | −0.58 | 0.87 |
| Baseline diarrhea prevalence | −0.20 | −0.52 | 0.13 | −0.17 | −0.51 | 0.16 | −0.15 | −0.42 | 0.12 | −0.07 | −0.43 | 0.29 | −0.12 | −0.43 | 0.20 | −0.27 | −0.60 | 0.06 |
Models are adjusted for wall type, number of household members, household educational level, and baseline anthropometric Z-score (where the predictor was a follow-up anthropometric measure). Diarrhea prevalence is reporting three or more loose stools in the past 2 weeks at baseline.
Boldface indicates significant (P < 0.05).
DISCUSSION
In this prospective cohort study among young children in rural DRC, we investigated the association between diarrhea, child growth, and child cognitive developmental outcomes. We found that linear growth faltering was associated with reduced child cognitive developmental outcomes. Reductions in WAZ and underweight status at baseline were also associated with decreased child developmental outcomes among this pediatric cohort. These findings further demonstrate the close relationship between impaired child growth and adverse child cognitive developmental outcomes, and provide evidence of this association in a sub-Saharan African setting.
Our study findings are consistent with a meta-analysis by Walker et al., which included studies from Guatemala, Peru, Philippines, and Brazil.20 Our study found no significant association between diarrhea and cognition, which was in contrast to our study hypothesis that diarrhea prevalence would be associated with reduced cognition among young children. One potential explanation for our finding is that we only measured diarrhea at a single time point and therefore did not have a robust measure of diarrhea prevalence to investigate an association with cognitive development. A second potential explanation is that cognitive impairment might be explained by reduced HAZ and WAZ independent of the child’s diarrhea prevalence such as chronic asymptomatic enteric infections. A third explanation is that socioeconomic (SES) status may have confounded the relationship between diarrhea and reduced cognition, because lower SES households often have higher rates of diarrhea among young children.21,22 Future studies with a larger sample size are needed to investigate this association with diarrhea surveillance conducted at multiple time points.
In our cohort study, we found that linear growth faltering and decreases in WAZ were associated with impaired child cognitive developmental outcomes. This finding is consistent with previous studies conducted in Peru, Bangladesh, Philippines, Brazil, and Guatemala.2,4,20,21 Impaired growth among young children measured using HAZ, WAZ, and WHLZ are indices of malnutrition.23 Malnutrition is a result of several factors including inadequate food intake, lack of dietary diversity, and malabsorption of nutrients.24 The first few years of life represent a critical period for brain development.12 Nutrient deficiencies during this period can negatively impact brain development and result in cognitive deficits later in life.23,24 Our observed association between linear growth faltering and decreased WAZ and child developmental outcomes is likely reflective of poor childhood nutrient intake and absorption through food insecurity and chronic infections resulting in malnutrition and subsequent impaired child growth and reduced cognitive outcomes.9 Future studies are needed that assess food insecurity and the micronutrient status of study children to further elucidate the association between child nutrition and child cognitive developmental outcomes.
Linear growth faltering rather than baseline stunting was associated with lower cognitive development outcomes. The likely explanation for this findings is that linear growth faltering (measured using the change in HAZ) provides a more robust measure of the growth trajectory of the child and better reflects their nutritional status compared with a single growth measurement at baseline. For the lack an association between change in WHLZ, wasting, and child cognitive outcomes, the change in WHLZ for our study children was small (mean: 0.08) and wasting was low at 5%. The low variability in these indices is a likely explanation for the lack of an association with child cognitive outcomes. Future studies are needed in sub-Saharan African settings to investigate these associations further.
This study has some limitations. First, our cohort was of children under 5 years of age, therefore we cannot determine the longer-term impacts of child growth on child cognitive developmental outcomes. Second, we administered the EASQ tool to children of a wide age range, and because of our small sample size we could not evaluate the impact of growth faltering for children in different age strata. Third, we only included diarrhea prevalence at baseline rather than at multiple time points over the study period. Future studies should conduct diarrhea surveillance frequently over the study period. Finally, we relied on EASQ outcomes from a single point, and therefore cannot determine trends over time. Future studies should collect EASQ outcomes at multiple time points over the study period.
This study has strengths. First, we collected anthropometric data at baseline and the 6-month follow-up, which allowed us to assess liner growth faltering. Second, we collected EASQ data at the 6-month follow-up, building upon previous cross-sectional studies and allowing us to investigate the impact of growth faltering on subsequent child developmental outcomes. Finally, we conducted multiple direct and indirect tests to evaluate child cognitive developmental outcomes using a tool that was previously adapted to LMICs.18
The results from this prospective cohort study have shown that linear growth faltering and decreased WAZ are associated with reduced child cognitive developmental outcomes among children residing in rural DRC. These findings indicate the need for effective interventions for this susceptible pediatric population to improve child growth and subsequent cognitive developmental outcomes.
ACKNOWLEDGMENTS
We thank USAID/Bureau for Humanitarian Assistance and Phil Moses and Amagana Togo at Food for the Hungry for their support. We also thank all the study participants and the following research supervisors and assistants who were crucial to the successful implementation of this study: Willy Mapendano, Eric-Yves Iragi, Pascal Tezangi, Blessing Muderhwa, Manu Kabiyo, Fraterne Luhiriri, Wivine Ntumba, Julienne Rushago, Pacifique Kitumaini, Freddy Endelea, Claudia Bazilerhe, Jean Claude Lunye Lunye, Adolophine F. Rugusha, Gisele N. Kasanzike, Brigitte Munyerenkana, Jessy T. Mukulikire, Dieudonné Cibinda, Jean Basimage, and Siloé Barhuze. These individuals were supported by funding from the USAID and declare no conflicts of interest. This material is based in part upon work supported by the USAID Bureau for Humanitarian Assistance (BHA), under a Development Food Security Activity (DFSA), led by Food for the Hungry in the Sud Kivu and Tanganyika provinces of DRC (Cooperative Agreement AID-FFP-A-16-00010). Any opinion, findings, and conclusions or recommendations expressed in this material are those of the author and do not necessarily reflect the views of partner organizations or the U.S. Government.
REFERENCES
- 1. World Health Organization , 2020. UNICEF/WHO/The World Bank Group Joint Child Malnutrition Estimates: Levels and Trends in Child Malnutrition: Key Findings of the 2020 Edition. Geneva, Switzerland: WHO. [Google Scholar]
- 2.Berkman DS, Lescano AG, Gilman RH, Lopez SL, Black MM, 2002. Effects of stunting, diarrhoeal disease, and parasitic infection during infancy on cognition in late childhood: a follow-up study. Lancet 359: 564–571. [DOI] [PubMed] [Google Scholar]
- 3.Walker SP, Chang SM, Powell CA, Simonoff E, Grantham-McGregor SM, 2007. Early childhood stunting is associated with poor psychological functioning in late adolescence and effects are reduced by psychosocial stimulation. J Nutr 137: 2464–2469. [DOI] [PubMed] [Google Scholar]
- 4.Tarleton JL, Haque R, Mondal D, Shu J, Farr BM, Petri WA, Jr, 2006. Cognitive effects of diarrhea, malnutrition, and Entamoeba histolytica infection on school age children in Dhaka, Bangladesh. Am J Trop Med Hyg 74: 475–481. [PubMed] [Google Scholar]
- 5.Checkley W. et al. , 1997. Asymptomatic and symptomatic cryptosporidiosis: their acute effect on weight gain in Peruvian children. Am J Epidemiol 145: 156–163. [DOI] [PubMed] [Google Scholar]
- 6.Lee G. et al. , 2013. Symptomatic and asymptomatic Campylobacter infections associated with reduced growth in peruvian children. PLoS Negl Trop Dis 7: e2036. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Lee G. et al. , 2014. Effects of Shigella-, Campylobacter- and ETEC-associated diarrhea on childhood growth. Pediatr Infect Dis J 33: 1004–1009. [DOI] [PubMed] [Google Scholar]
- 8.George CM. et al. , 2018. Enteric infections in young children are associated with environmental enteropathy and impaired growth. Trop Med Int Health 23: 26–33. [DOI] [PubMed] [Google Scholar]
- 9.Guerrant RL, Oriá RB, Moore SR, Oriá MO, Lima AA, 2008. Malnutrition as an enteric infectious disease with long-term effects on child development. Nutr Rev 66: 487–505. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. GBD-Collaborators , 2017. Estimates of global, regional, and national morbidity, mortality, and aetiologies of diarrhoeal diseases: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Infect Dis 17: 909–948. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.MacIntyre J, McTaggart J, Guerrant RL, Goldfarb DM, 2014. Early childhood diarrhoeal diseases and cognition: are we missing the rest of the iceberg? Paediatr Int Child Health 34: 295–307. [DOI] [PubMed] [Google Scholar]
- 12.Prado EL, Dewey KG, 2014. Nutrition and brain development in early life. Nutr Rev 72: 267–284. [DOI] [PubMed] [Google Scholar]
- 13.Ajjampur SS. et al. , 2011. Effect of cryptosporidial and giardial diarrhoea on social maturity, intelligence and physical growth in children in a semi-urban slum in south India. Ann Trop Paediatr 31: 205–212. [DOI] [PubMed] [Google Scholar]
- 14.Guerrant DI, Moore SR, Lima AA, Patrick PD, Schorling JB, Guerrant RL, 1999. Association of early childhood diarrhea and cryptosporidiosis with impaired physical fitness and cognitive function four-seven years later in a poor urban community in northeast Brazil. Am J Trop Med Hyg 61: 707–713. [DOI] [PubMed] [Google Scholar]
- 15.Pinkerton R. et al. , 2016. Early childhood diarrhea predicts cognitive delays in later childhood independently of malnutrition. Am J Trop Med Hyg 95: 1004–1010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.de Onis M, Onyango AW, 2008. WHO child growth standards. Lancet 371: 204. [DOI] [PubMed] [Google Scholar]
- 17.Fernald LC, Kariger P, Hidrobo M, Gertler PJ, 2012. Socioeconomic gradients in child development in very young children: evidence from India, Indonesia, Peru, and Senegal. Proc Natl Acad Sci USA 109 ( Suppl 2 ): 17273–17280. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Tofail F. et al. , 2018. Effect of water quality, sanitation, hand washing, and nutritional interventions on child development in rural Bangladesh (WASH Benefits Bangladesh): a cluster-randomised controlled trial. Lancet Child Adolesc Health 2: 255–268. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Fernald LC, Kariger P, Engle P, Raikes A, 2009. Examining Early Child Development in Low-Income Countries: A Toolkit for the Assessment of Children in the First Five Years of Life. Washington, DC: World Bank. [Google Scholar]
- 20.Fischer Walker CL. et al. , 2012. Does childhood diarrhea influence cognition beyond the diarrhea-stunting pathway? PLoS One 7: e47908. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Sigman M, McDonald MA, Neumann C, Bwibo N, 1991. Prediction of cognitive competence in Kenyan children from toddler nutrition, family characteristics and abilities. J Child Psychol Psychiatry 32: 307–320. [DOI] [PubMed] [Google Scholar]
- 22.Galler JR, Ramsey F, Solimano G, Lowell WE, 1983. The influence of early malnutrition on subsequent behavioral development. II. Classroom behavior. J Am Acad Child Psychiatry 22: 16–22. [DOI] [PubMed] [Google Scholar]
- 23.De Onis M, Onyango AW, Borghi E, Garza C, Yang H, Group WMGRS, 2006. Comparison of the World Health Organization (WHO) child growth standards and the national center for health statistics/WHO international growth reference: implications for child health programmes. Public Health Nutr 9: 942–947. [DOI] [PubMed] [Google Scholar]
- 24.de Onis M, Blössner M, World Health Organization, 1997. WHO Global Database on Child Growth and Malnutrition. Geneva, Switzerland: WHO. [DOI] [PubMed] [Google Scholar]