How Placental Inflammation Shapes Infant Body Fat Accumulation?

Histologic chorioamnionitis (HCA), an inflammation of the membranes surrounding the fetus, is a well-known risk factor for preterm birth and adverse neonatal outcomes. But could this in-utero insult also shape how very preterm infants grow after birth—particularly in terms of fat mass?

Our recent study of 375 mother–infant pairs born before 32 weeks of gestation explored this question by combining detailed placental pathology with body composition measurements at term-equivalent age. Using air displacement plethysmography, we examined how the severity of maternal (MIR) and fetal (FIR) inflammatory responses related to infant fat mass (FM).

What we found

Dose-response relationship: Each stage of HCA severity was linked to increases in infant fat mass. Infants with severe MIR had higher body fat percentages (18%) compared to those with mild inflammation (14%).

Gestational age only partial explanation: While preterm birth mediated about half of this relationship, HCA itself directly contributed to greater fat accumulation.

Other growth measures unchanged: Length, head circumference, and weight trajectories were not significantly affected.

Why it matters

These findings highlight an important dilemma: traditional growth charts may not fully capture how preterm infants grow. Fat mass, rather than just weight or length, offers a deeper view into nutritional and metabolic health. The results also raise questions about whether the increased fat accumulation observed is an adaptive response—or an early marker of future metabolic risk.

What’s next

The long-term significance of this early fat gain remains uncertain. Prior evidence suggests preterm infants often “catch up” metabolically to their term-born peers, but inflammation-driven fat distribution could alter this trajectory. Future studies should track these infants into childhood, integrating placental pathology with body composition and metabolic biomarkers to better understand risks and resilience.

Takeaway:
This study is the first to show a direct, dose-dependent link between chorioamnionitis severity and fat mass in very preterm infants. By looking beyond weight and length, it reminds us that early-life inflammation may leave metabolic imprints that deserve careful monitoring.

Gunawan, E., Jain, V.G., Hardy, S., Irvin, M.R., Salas, A.A. Histologic chorioamnionitis and fat mass accretion in infants born preterm. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04413-2