Infectious disease and inflammation in the first 24 months of life and emerging risk factors for metabolic syndrome in Peruvian Infants

Preventable risk exposures related to undernutrition, infectious disease and inflammation in early life are known to contribute to pathophysiological processes leading to later chronic disease. However, the majority of studies that attempt to understand these processes have been conducted in developed nations, where levels of overnutrition are high, undernutrition is uncommon and individuals are exposed to relatively few infectious pathogens. We investigated the association between childhood illness, inflammation, and nutritional status in infancy and risk factors for metabolic syndrome (MetS) at 3–5 years of age among children living in the Peruvian Amazon by conducting a nested study of children participating in the Peruvian cohort of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL‐ED) study, who had previously been well‐characterized in terms of enteric and nutritional exposures over the first 24 months of life. Out of 301 children ever enrolled, 156 children were followed up, of whom 146 completed surveillance from 0–24 months of age. The mean age at follow up was 48.4 months (SD=7.6) Mean fasting glucose was 83.7 mg/dL, and the mean homeostatic model assessment (HOMA) was 0.89. Mean lipid levels for males and females were, respectively, 138.3 mg/dL and 145.5 mg/dL for total cholesterol (TC), 80.4 mg/dL and 88.0 mg/dL for low‐density lipoprotein cholesterol (LDL‐C), 44.0 mg/dL and 45.3 mg/dL for high‐density lipoprotein cholesterol (HDL‐C, geometric mean), and 82.6 mg/dL and 91.4 mg/dL for triglycerides (TG, geometric mean). The mean arterial pressure (MAP) was 64.0 mmHg. Two percent (2.0%) of children had a systolic blood pressure, and 18.0% had a diastolic blood pressure above the 90 th percentile for their age and gender. Birth weight, birth length, and early growth, as classified using a group‐based trajectory model to classify length‐for‐age trajectories from 0–24 months of age, was unassociated with any risk factors for MetS in our population, as was maternally reported fever and diarrheal days from 0–24 months. Greater weight‐for‐height at the time of follow‐up was associated with higher blood pressure and greater waist circumference. Higher AGP and CRP at 7 months, but not 15 or 24 months, were both statistically significantly associated with higher MAP, and with having a blood pressure above the 90 th percentile for age and sex. This association was related to diastolic, rather than systolic, blood pressure, and remained significant after adjusting for weight‐for‐height. Higher AGP/CRP at 7 months was not associated with elevated TG, lowered HDL, or waist circumference. Our results suggest that inflammation at 7 months of age, but not later in infancy, is associated with elevated blood pressure among children living in rural Peru. Support or Funding Information This project was supported as an Early Career Award to Gwenyth Lee by the Thrasher Foundation. 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, the Foundation for the National Institutes of Health, and the National Institutes of Health, Fogarty International Center.