Impact of an integrated intervention package during preconception, pregnancy, and early childhood on inflammation, IGF-1, IGFBP3 during the first 6 months of life: Findings from the WINGS randomized controlled trial

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. 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. 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 was
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. 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.