Article Text

Factors associated with head circumference and indices of cognitive development in early childhood
  1. Laura Nicolaou1,2,
  2. Tahmeed Ahmed3,
  3. Zulfiqar Ahmed Bhutta4,
  4. Pascal Bessong5,
  5. Margaret Kosek6,
  6. Aldo A M Lima7,
  7. Sanjaya Shrestha8,
  8. Ram Chandyo9,
  9. Estomih R Mduma10,
  10. Laura Murray-Kolb11,
  11. Brooks Morgan1,2,
  12. Matthew R Grigsby1,2,
  13. William Checkley1,2
  14. on behalf of the MALED Network Investigators
  1. 1Division of Pulmonary and Critical Care, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
  2. 2Center for Global Non-Communicable Diseases Research and Training, Johns Hopkins University, Baltimore, United States
  3. 3Division of Nutrition and Food Security, International Centre for Diarrhoeal Disease Research, Matlab, Bangladesh
  4. 4Centre for Global Child Health, The Hospital for Sick Children, Toronto, Ontario, Canada
  5. 5HIV/AIDS and Global Health Research Programme, University of Venda, Thohoyandou, Limpopo, South Africa
  6. 6Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA
  7. 7Clinical Research Unit and Institute of Biomedicine, Faculty of Medicine, Univ Fed Ceara, Fortaleza, Ceará, Brazil
  8. 8Walter Reed Armed Forces Research Institute of Medical Sciences (AFRIMS) Research Unit, Kathmandu, Nepal
  9. 9Department of Community Medicine, Kathmandu Medical College, Sinamangal, Kathmandu, Nepal
  10. 10Haydom Lutheran Hospital, Haydom, United Republic of Tanzania
  11. 11Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, University Park, Pennsylvania, USA
  1. Correspondence to Dr William Checkley; wcheckl1{at}


Background While head circumference (HC) has been related to intracranial volume and brain size, its association with cognitive function remains unclear. We sought to understand the relationship among various biological and socioeconomic risk factors, HC and cognitive development.

Methods We analysed data across resource-poor settings in Bangladesh, India, Nepal, Peru, South Africa and Tanzania from the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development longitudinal birth cohort study. Participating children were enrolled and followed up between 2009 and 2014. A final sample of 1210 children aged 0–24 months were included in the analyses. The main outcomes were HC for age Z-score and cognitive, gross motor and language scores from Bayley Scales of Infant Development-III tests. Length, weight and HC were measured monthly, and cognitive tests were administered at 6, 15 and 24 months of age. To disentangle the associations between risk factors and HC from linear growth and to distinguish the direct and indirect effects of these risk factors on cognitive function, we conducted mediation analysis using longitudinal models to account for all data measured during follow-up.

Results Average HC-for-age Z-score (HCAZ) was −0.54 (95% CI −0.47 to −0.62) near birth and −1.01 (95% CI −0.94 to −1.08) at 24 months. Children with higher enrolment weight (p<0.0001), higher socioeconomic score (p=0.00037) and taller mothers (p=0.00084) had higher HCAZ at all ages, while enteropathogen infection (p=0.013) and more febrile episodes (p=0.013) were associated with lower HCAZ. The associations between HCAZ and enrolment weight-for-age, maternal height, socioeconomic status or pathogen burden were partly mediated through their associations with length-for-age. HCAZ showed no association with cognitive, gross motor or language skills at 6, 15 and 24 months of age.

Conclusions The main risk factors associated with HC are similar to those associated with body length, and HC is not related to cognitive function.

  • child health
  • epidemiology
  • paediatrics

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  • Handling editor Seye Abimbola

  • Correction notice This article has been corrected since it published online to fix the figures size.

  • Contributors LN and WC conducted statistical analyses and wrote the first draft of the manuscript. BM and MRG contributed to the literature search and data analysis. TA, ZAB, PB, MK, AAML, SS, RC, ERM and LM-K contributed to data interpretation and reviewed and contributed to the manuscript content.

  • Funding The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) is carried out as a collaborative project supported by the Bill & Melinda Gates Foundation (#OPP47075), the Foundation for the NIH and the National Institutes of Health/Fogarty International Center.

  • Disclaimer The Bill & Melinda Gates Foundation did not play any role in the writing of the manuscript nor did the funders of the study have any role in the study design, data collection, data analysis or interpretation of study results. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Ethics approval was obtained from the Institutional Review Boards at participating institutions (online supplemental etable 1).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available in a public, open access repository. Data for this study are available to others in the scientific community at

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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