Stunting Status and Exposure to Infection and Inflammation in Early Life Shape Antibacterial Immune Cell Function Among Zimbabwean Children

Abstract

BackgroundChildren who are stunted (length-for-age Z-score<-2) are at greater risk of infectious morbidity and mortality. Previous studies suggest that stunted children have elevated inflammatory biomarkers, but no studies have characterised their capacity to respond to new infections (i.e., their immune function). We hypothesised that antibacterial immune function would differ between stunted and non-stunted children and relate to their health and environment during early life.MethodsWe enrolled a cross-sectional cohort of 113 HIV-negative children nested within a longitudinal cluster-randomised controlled trial of household-level infant and young child feeding (IYCF) and water, sanitation and hygiene (WASH) interventions in rural Zimbabwe (SHINE; Clinical trials registration: NCT01824940). Venous blood was collected at 18 months of age and cultured for 24 h without antigen or with bacterial antigens: heat-killed Salmonella typhimurium (HKST) or Escherichia coli lipopolysaccharide (LPS). TNFα, IL-6, IL-8, IL-12p70, hepcidin, soluble (s)CD163, myeloperoxidase (MPO) and IFNβ were quantified in culture supernatants by ELISA to determine antigen-specific immune function. The effect of stunting status and early-life exposures (anthropometry, inflammation at 18 months, maternal health during pregnancy, household WASH) on immune function was tested in logit and censored log-normal (tobit) regression models.ResultsChildren who were stunted (n = 44) had higher proportions (86.4% vs. 65.2%; 88.6% vs. 73.4%) and concentrations of LPS-specific IL-6 (geometric mean difference (95% CI): 3.46 pg/mL (1.09, 10.80), p = 0.035) and IL-8 (3.52 pg/mL (1.20, 10.38), p = 0.022) than non-stunted children (n = 69). Bacterial antigen-specific pro-inflammatory cytokine concentrations were associated with biomarkers of child enteropathy at 18 months and biomarkers of systemic inflammation and enteropathy in their mothers during pregnancy. Children exposed to the WASH intervention (n = 33) produced higher LPS- (GMD (95% CI): 10.48 pg/mL (1.84, 60.31), p = 0.008) and HKST-specific MPO (5.10 pg/mL (1.77, 14.88), p = 0.003) than children in the no WASH group (n = 80). There was no difference in antigen-specific immune function between the IYCF (n = 55) and no IYCF groups (n = 58).ConclusionsAntibacterial immune function among 18-month-old children in a low-income setting was shaped by their stunting status and prior exposure to maternal inflammation and household WASH. Heterogeneity in immune function due to adverse exposures in early life could plausibly contribute to infection susceptibility.

Severe acute malnutrition promotes bacterial binding over proinflammatory cytokine secretion by circulating innate immune cells

“…Fourth, although our study is the largest of its kind, powered for our primary comparison between the SAM and healthy groups, it is increasingly apparent from clinical studies, including our own ( 6 , 9 , 53 ), that specific comorbidities contribute to subconditions within current SAM diagnostic criteria (e.g., HIV-SAM, cerebral palsy–SAM, and edematous/non-edematous SAM); a larger or comorbidity-focused sample size would be required to conclusively evaluate the impact of these variables on immune function. Because some of these comorbidities are shared by hospitalized children without SAM and recent studies suggest that these children have distinct antibacterial proinflammatory mediator responses relative to healthy controls to those we observe in SAM ( 39 , 62 ), it would be desirable to include such children as an additional comparison group in future studies.…”

The interlink between chrono-nutrition and stunting: current insights and future perspectives

“…Stunting, the chronic and severe form of undernutrition characterized by impaired growth and development in children due to inadequate nutrition, has a range of short-term adverse effects. Children affected by stunting often suffer from weakened immune systems, making them more susceptible to infections and illnesses ( 23 ). These health issues can lead to frequent bouts of diarrhea and respiratory infections, causing discomfort and distress.…”

Ketahanan Rumah Tangga Balita Stunting di Daerah Stunting, Kelurahan Bakung, Kota Makassar: Laporan Data

“…Penetapan standar ambang kategori stunting adalah di bawah minus dua (-2) standar deviasi menurut Peraturan Menteri Kesehatan Nomor 2 Tahun 2020 tentang Standar Antropomentri Anak. Konsekuensi jangka panjang masalah stunting tidak hanya berkaitan dengan kondisi fisik anak, namun juga meliputi fungsi kognitif yang buruk dan risiko performa pendidikan yang rendah, penghasilan yang rendah di usia dewasa, produktivitas yang menurun, dan peningkatan risiko terkena penyakit kronis yang berhubungan dengan nutrisi di usia dewasa jika disertai dengan peningkatan berat badan yang berlebihan pada masa anak-anak (Mutasa et al, 2022;Soliman et al, 2021).…”

“…Faktor risiko stunting dapat dibagi sebagai faktor langsung dan tidak langsung yang memengaruhi status gizi anak. Faktor langsung termasuk makanan, penyakit menular, dan karakteristik anak seperti jenis kelamin laki-laki, berat lahir rendah, dan konsumsi makanan (Akhmad et al, 2016;Anggryni et al, 2021;Mutasa et al, 2022) Sementara itu, faktor tidak langsung meliputi pemberian ASI tidak eksklusif, layanan kesehatan, dan karakteristik keluarga seperti pekerjaan, pendidikan, dan status ekonomi orang tua (Mulyaningsih et al, 2021;Reyes et al, 2004;Utami et al, 2019). Secara khusus dalam menentukan faktor rumah tangga sebagai salah satu determinan utama penyebab stunting, Organisasi Kesehatan Dunia melalui kerangka konseptual memetakan faktor rumah tangga dan keluarga, pemberian makanan pendamping yang tidak memadai, pemberian ASI, dan infeksi.…”