Background 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 of comprehensive, integrated interventions initiated during early life is limited.

Methods The study was nested in a factorial randomized controlled trial (RCT) in women aged 18–30 years. Participants included in this study 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 growth and development. Blood samples from 381 (178 from the intervention group and 203 from the control group) infants 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 the mean differences and relative risks of inflammatory markers and growth-related biomarkers between the intervention and routine care groups. This trial was registered at Clinical Trials Registry–India: CTRI/2020/10/028770.

Results Baseline maternal characteristics were similar between the two study groups. At 3 and 6 months, the proportion of infants with CRP levels greater than 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 ng/mL; 95% CI: –55.3, –6.3), but this effect was not sustained at 6 months.

Conclusions An integrated intervention delivered from preconception through pregnancy and early childhood did not result in reductions in markers of systemic inflammation or 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 the long-term and synergistic effects of early interventions in low-resource settings.

The authors have declared no competing interest.

Clinical Trial Registry of India under the identifier: CTRI/2020/10/028770

· Specific grant numbers: grant IA/CPHI/20/1/505247 · Initials of authors who received each award: RC · Full names of funding agency: DBT and Wellcome India Alliance DBT - Department of Biotechnology, Government of India · Initials of authors who received salary or other funding from commercial companies: NA · URLs to sponsors’ websites: https://www.indiaalliance.org/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Ethical clearance for this study was granted by the Ethics Review Committee of the Society for Applied Studies in New Delhi, India. This study was registered with the Clinical Trial Registry of India under the identifier CTRI/2020/10/028770. Written informed consent was secured primarily from mothers before their inclusion in the study.

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