Associations of suboptimal growth with all-cause and cause-specific mortality in children under five years: a pooled analysis of ten prospective studies

Ibironke Olofin, Christine M McDonald, Majid Ezzati, Seth Flaxman, Robert E Black, Wafaie W Fawzi, Laura E Caulfield, Goodarz Danaei, Nutrition Impact Model Study (anthropometry cohort pooling), Linda Adair, Shams Arifeen, Nita Bhandari, Michel Garenne, Betty Kirkwood, Kåre Mølbak, Joanne Katz, Alfred Sommer, Keith P West Jr, Mary E Penny, Ibironke Olofin, Christine M McDonald, Majid Ezzati, Seth Flaxman, Robert E Black, Wafaie W Fawzi, Laura E Caulfield, Goodarz Danaei, Nutrition Impact Model Study (anthropometry cohort pooling), Linda Adair, Shams Arifeen, Nita Bhandari, Michel Garenne, Betty Kirkwood, Kåre Mølbak, Joanne Katz, Alfred Sommer, Keith P West Jr, Mary E Penny

Abstract

Background: Child undernutrition affects millions of children globally. We investigated associations between suboptimal growth and mortality by pooling large studies.

Methods: Pooled analysis involving children 1 week to 59 months old in 10 prospective studies in Africa, Asia and South America. Utilizing most recent measurements, we calculated weight-for-age, height/length-for-age and weight-for-height/length Z scores, applying 2006 WHO Standards and the 1977 NCHS/WHO Reference. We estimated all-cause and cause-specific mortality hazard ratios (HR) using proportional hazards models comparing children with mild (-2≤Z<-1), moderate (-3≤Z<-2), or severe (Z<-3) anthropometric deficits with the reference category (Z≥-1).

Results: 53 809 children were eligible for this re-analysis and contributed a total of 55 359 person-years, during which 1315 deaths were observed. All degrees of underweight, stunting and wasting were associated with significantly higher mortality. The strength of association increased monotonically as Z scores decreased. Pooled mortality HR was 1.52 (95% Confidence Interval 1.28, 1.81) for mild underweight; 2.63 (2.20, 3.14) for moderate underweight; and 9.40 (8.02, 11.03) for severe underweight. Wasting was a stronger determinant of mortality than stunting or underweight. Mortality HR for severe wasting was 11.63 (9.84, 13.76) compared with 5.48 (4.62, 6.50) for severe stunting. Using older NCHS standards resulted in larger HRs compared with WHO standards. In cause-specific analyses, all degrees of anthropometric deficits increased the hazards of dying from respiratory tract infections and diarrheal diseases. The study had insufficient power to precisely estimate effects of undernutrition on malaria mortality.

Conclusions: All degrees of anthropometric deficits are associated with increased risk of under-five mortality using the 2006 WHO Standards. Even mild deficits substantially increase mortality, especially from infectious diseases.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Associations of anthropometric measures (in…
Figure 1. Associations of anthropometric measures (in increments of 0.5 Z scores) with all-cause mortality, WHO 2006 child growth standards.
(A) Weight-for-age; (B) Height/length-for-age; (C) Weight-for-Height/Length.

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