Abstract
Early-life interventions targeting maternal and child health, nutrition, and psychosocial care may influence infant growth and immune development by modulating systemic inflammation and growth factor pathways. However, causal evidence on comprehensive, integrated interventions initiated during early life remains limited. This study was nested in a factorial randomized controlled trial involving women aged 18-30 years. Participants were randomized to receive either a preconception intervention package or routine care until early childhood. The intervention included health care for growth-related conditions, nutrition, WASH (water, sanitation, and hygiene), and psychosocial care. The primary study demonstrated a substantial effect of the intervention on child growth and development. Blood samples from 381 infants (178 in intervention and 203 in control group) were analyzed at 3 and 6 months of age for inflammatory and growth-related biomarkers: C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), insulin-like growth factor 1 (IGF-1), and IGF binding protein 3 (IGFBP3). Generalized linear models were used to estimate mean differences and relative risks for the outcomes. The trial was registered at the Clinical Trials Registry-India: CTRI/2020/10/028770. Baseline maternal characteristics were similar between the two groups. At 3 and 6 months, the proportions of infants with CRP levels > 5 mg/L were similar in both groups. No significant differences were observed in AGP or IGF-1 concentrations at either time point. IGFBP3 was lower in the intervention group at 3 months [adjusted mean difference: [30.8(-55.3, -6.3)] ng/mL, but this effect was not sustained at 6 months. An integrated intervention delivered from preconception through pregnancy and early childhood did not reduce systemic inflammation markers or produce sustained improvements in growth factor profiles during the first six months of life. These findings highlight the complexity of early-life inflammatory processes and underscore the need for further research on long-term effects of early-life interventions in low-resource settings.