# Anthropometric and neurocognitive consequences of Campylobacter, enterotoxigenic Escherichia coli, and norovirus: A systematic review

## TL;DR

This review examines the long-term effects of three common diarrhea-causing pathogens on child growth and brain development, finding modest evidence of growth impacts but limited data on neurodevelopment.

## Contribution

The study systematically reviews the long-term anthropometric and neurocognitive consequences of three enteric pathogens in children under five.

## Key findings

- Modest evidence links all three pathogens to linear growth detriments in children.
- Campylobacter was associated with limited weight gain, but no significant impact on wasting or neurodevelopment was found.
- Variability in study design and reporting hinders meta-analysis and highlights the need for standardized reporting.

## Abstract

Synthesizing the evidence of the longer-term consequences of enteric pathogens, such as stunted growth and suboptimal neurodevelopment, is a key step to articulating the value of, and generating demand for, vaccines.

We conducted a systematic review of published literature documenting associations of three leading causes of diarrhea (enterotoxigenic Escherichia coli [ETEC], norovirus, and Campylobacter species [sp.]) with prospective anthropometric and neurocognitive outcomes in children under five years (PROSPERO CRD42024600676).

Thirty publications were included, including several reporting on data from the same underlying cohort; 16 publications included outcomes associated with Campylobacter, 12 ETEC, and 7 norovirus. There was large variation in how studies reported outcomes, exposure groups, and timeframes of association. There was modest evidence of linear growth detriments associated with all three pathogens, modest evidence of Campylobacter limiting weight gain, and no evidence of detrimental impacts of these pathogens on wasting or neurodevelopment, albeit these two outcomes were rarely reported.

Differences in outcome definitions, comparison groups, and timeframes prohibited meta-analysis and emphasize the need for more standardization of reporting anthropometric and neurocognitive outcomes following enteric pathogen infection. Randomized controlled trials of efficacious pathogen-specific interventions may help to address challenges with confounding and reverse causality in observational studies.

We reviewed previously conducted research studies to see if infections with common diarrhea-causing infections have long lasting effects on growth and brain development in young children. We specifically looked at published studies that tested for norovirus, Campylobacter, and enterotoxigenic E.coli in stool samples and followed children over time to evaluate changes in weight, height, and neurodevelopmental outcomes. Thirty studies met our inclusion criteria, some from the same study group, and studies varied widely in terms of how they assessed these associations and the duration of follow-up. There was modest evidence that each pathogen was associated with slower height growth and some evidence that Campylobacter was associated with restricted weight gain following infection. Although we did not find evidence that these infections led to measurable delays in neurocognitive development, these outcomes were rarely assessed, possibly because they require long follow-up to assess. We recommend standardized reporting of comparison groups and timeframes to enable synthesizing data on these complex relationships. Conducting pathogen-specific intervention trials, controlling for differences between those with and without the intervention, will clarify the extent to which these infections impact child growth and development, and help inform policy decisions around priorities for such interventions.