CHAIN Publications

Childhood Acute Illness and Nutrition (CHAIN) Network: a protocol for a multi-site prospective cohort study to identify modifiable risk factors for mortality among acutely ill children in Africa and Asia

The Childhood Acute Illness and Nutrition Network

Introduction Children admitted to hospitals in resourcepoor settings remain at risk of both inpatient and postdischarge mortality. While known risk factors such as young age and nutritional status can identify children at risk, they do not provide clear mechanistic targets for intervention. The Childhood Acute Illness and Nutrition (CHAIN) cohort study aims to characterise the biomedical and social risk factors for mortality in acutely ill children in hospitals and after discharge to identify targeted interventions to reduce mortality.

Methods and analysis The CHAIN network is currently undertaking a multi-site, prospective, observational cohort study, enrolling children aged 1 week to 2 years at admission to hospitals at nine sites located in four African and two South Asian countries. The CHAIN Network supports the sites to provide care according to national and international guidelines. Enrolment is stratified by anthropometric status and children are followed throughout hospitalisation and for 6 months after discharge. Detailed clinical, demographic, anthropometric, laboratory and social exposures are assessed. Scheduled visits are conducted at 45, 90 and 180 days after discharge. Blood, stool and rectal swabs are collected at enrolment, hospital discharge and follow-up. The primary outcome is inpatient or post-discharge death. Secondary outcomes include readmission to hospital and nutritional status after discharge. Cohort analysis will identify modifiable risks, children with distinct phenotypes, relationships between factors and mechanisms underlying poor outcomes that may be targets for intervention. A nested case–control study examining infectious, immunological, metabolic, nutritional and other biological factors will be undertaken.

Ethics and dissemination This study protocol was reviewed and approved primarily by the Oxford Tropical Research Ethics Committee, and the institutional review boards of all partner sites. The study is being externally monitored. Results will be published in open access peerreviewed scientific journals and presented to academic and policy stakeholders.

Trial registration number NCT03208725.

Full article on:

The impact of malnutrition on childhood infections

Judd L. Walson and James A. Berkley


Purpose of review

Almost half of all childhood deaths worldwide occur in children with malnutrition, predominantly in sub- Saharan Africa and South Asia. This review summarizes the mechanisms by which malnutrition and serious infections interact with each other and with children’s environments.

Recent findings

It has become clear that whilst malnutrition results in increased incidence, severity and case fatality of
common infections, risks continue beyond acute episodes resulting in significant postdischarge mortality.
A well established concept of a ‘vicious-cycle’ between nutrition and infection has now evolving to
encompass dysbiosis and pathogen colonization as precursors to infection; enteric dysfunction constituting
malabsorption, dysregulation of nutrients and metabolism, inflammation and bacterial translocation. All of
these interact with a child’s diet and environment. Published trials aiming to break this cycle using
antimicrobial prophylaxis or water, sanitation and hygiene interventions have not demonstrated public
health benefit so far.

As further trials are planned, key gaps in knowledge can be filled by applying new tools to re-examine old questions relating to immune competence during and after infection events and changes in nutritional status; and how to characterize overt and subclinical infection, intestinal permeability to bacteria and the role of antimicrobial resistance using specific biomarkers.

clinical trial, children, colonization, dysbiosis, environmental, growth, malnutrition, mortality, survival,
susceptibility, undernutrition

Full article on:







Severe childhood malnutrition

AUTHORS: Zulfiqar A. Bhutta, James A. Berkley, Robert H. J. Bandsma, Marko Kerac, Indi Trehan and André Briend

Use the term ‘severe malnutrition’ to describe these conditions to better reflect the contributions of chronic poverty, poor living conditions with pervasive deficits in sanitation and hygiene, a high prevalence of infectious diseases and environmental insults, food insecurity, poor maternal and fetal nutritional status and suboptimal nutritional intake in infancy and early childhood.

The impact of rickets on growth and morbidity during recovery among children with complicated severe acute malnutrition in Kenya: A cohort study.

Investigated the associations of clinically diagnosed rickets with life-threatening events and anthropometric recovery during 1 year following inpatient treatment for complicated SAM. This was a secondary analysis of clinical trial data among non-human immunodeficiency virus-infected Kenyan children with complicated SAM (2-59 months) followed for 1 year posthospital discharge ( ID NCT00934492).


Severe malnutrition in infants aged <6 months-Outcomes and risk factors in Bangladesh: A prospective cohort study.

argue that severe acute malnutrition (SAM) affects ~4 million infants under 6 months (u6m) worldwide, but evidence underpinning their care is “very low” quality. To inform future research and policy, the objectives of our study were to identify risk factors for infant u6m SAM and describe the clinical and anthropometric outcomes of treatment with current management strategies. We conducted a prospective cohort study in infants u6m in Barisal district, Bangladesh. One group of 77 infants had SAM (weight-for-length Z-score [WLZ] <-3 and/or bipedal oedema); 77 others were “non-SAM” (WLZ ≥-2 to <+2, no oedema, mid-upper-arm circumference ≥125 mm). All were enrolled at 4-8 weeks of age and followed up at 6 months. Maternal education and satisfaction with breastfeeding were among factors associated with SAM. Duration of exclusive breastfeeding was shorter at enrolment (3·9 ± 2.1 vs. 5.7 ± 2.2 weeks, P < 0.0001) and at age 6 months (13.2 ± 8.9 vs. 17.4 ± 7.9 weeks; P = 0.003) among SAM infants. Despite referral, only 13 (17%) reported for inpatient care, and at 6 months, 18 (23%) infants with SAM still had SAM, and 3 (3.9%) died. In the non-SAM group, one child developed SAM, and none died. We conclude that current treatment strategies have limited practical effectiveness: poor uptake of inpatient referral being the main reason. World Health Organization recommendations and other intervention strategies of outpatient-focused care for malnourished but clinically stable infants u6m need to be tested. Breastfeeding support is likely central to future treatment strategies but may be insufficient alone. Better case definitions of nutritionally at-risk infants are also needed.



breastfeeding; infants under 6 months; moderate acute malnutrition; mortality; risk factors; severe acute malnutrition