Infections and systemic inflammation are associated with lower plasma concentration of insulin-like growth factor I among Malawian children

Kenneth Maleta, Yue Mei Fan, Juho Luoma, Ulla Ashorn, Jaden Bendabenda, Kathryn G. Dewey, Heikki Hyöty, Mikael Knip, Emma Kortekangas, Kirsi Maarit Lehto, Andrew Matchado, Minyanga Nkhoma, Noora Nurminen, Seppo Parkkila, Sami Purmonen, Riitta Veijola, Sami Oikarinen, Per Ashorn

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BACKGROUND: Insulin-like growth factor I (IGF-I) is the most important hormonal promoter of linear growth in infants and young children. OBJECTIVES: The objectives of this study were to compare plasma IGF-I concentration in a low- compared with a high-income country and characterize biological pathways leading to reduced IGF-I concentration in children in a low-income setting. METHODS: We analyzed plasma IGF-I concentration from 716 Malawian and 80 Finnish children at 6-36 mo of age. In the Malawian children, we studied the association between IGF-I concentration and their environmental exposures; nutritional status; systemic and intestinal inflammation; malaria parasitemia and viral, bacterial, and parasitic enteric infections; as well as growth at 18 mo of age. We then conducted a pathway analysis to identify direct and indirect associations between these predictors and IGF-I concentration. RESULTS: The mean IGF-I concentrations were similar in Malawi and Finland among 6-mo-old infants. At age 18 mo, the mean ± SD concentration was almost double among the Finns compared with the Malawians [24.2 ± 11.3 compared with 12.5 ± 7.7 ng/mL, age- and sex-adjusted difference in mean (95% CI): 11.8 (9.9, 13.7) ng/mL; P < 0.01]. Among 18-mo-old Malawians, plasma IGF-I concentration was inversely associated with systemic inflammation, malaria parasitemia, and intestinal Shigella, Campylobacter, and enterovirus infection and positively associated with the children's weight-for-length z score (WLZ), female sex, maternal height, mother's education, and dry season. Seasonally, mean plasma IGF-I concentration was highest in June and July and lowest in December and January, coinciding with changes in children's length gain and preceded by ∼2 mo by the changes in their WLZ. CONCLUSIONS: The mean plasma IGF-I concentrations are similar in Malawi and Finland among 6-mo-old infants. Thereafter, mean concentrations rise markedly in Finland but not in Malawi. Systemic inflammation and clinically nonapparent infections are strongly associated with lower plasma IGF-I concentrations in Malawi through direct and indirect pathways.

Original languageEnglish
Pages (from-to)380-390
Number of pages11
JournalThe American journal of clinical nutrition
Issue number2
Publication statusPublished - 2021
Publication typeA1 Journal article-refereed


  • childhood growth faltering
  • hormonal regulation
  • infection
  • pathway analysis
  • stunting
  • systemic inflammation

Publication forum classification

  • Publication forum level 3

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


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