Comparative analysis of blood inflammatory profile and intestinal microbiota in late-fetal growth restriction vs. normal pregnancy

Abstract

To determine the association of blood inflammatory biomarkers and intestinal microbiota composition in women with late-onset fetal growth restriction. Fetal growth restriction (FGR) is a pathological condition in which fetus fails to achieve its genetically determined growth potential. FGR is associated with perinatal, childhood and long-term health consequences. FGR is typically classified into early-onset FGR (< 32 weeks) and late-onset FGR (≥ 32 weeks), based on the gestational age at diagnosis. The implication of blood inflammatory biomarkers and intestinal microbiota in mothers with late-onset FGR has been less studied. Pregnant women with late-onset FGR and controls were recruited during the third trimester and followed up until delivery. We employed Luminex and ELISA for blood inflammatory biomarkers and metagenomics (16S rRNA sequencing) for the intestinal microbiota to characterise late-onset FGR compared to normal pregnancies. Data were analysed using biostatistical methods, including both univariate and multivariate models. We identified a cluster of specific blood inflammatory biomarkers and intestinal microbiota microorganisms that, in our cohort, differentiated between women with late-onset FGR and women with normal pregnancy. This cluster is mainly characterised by lower lipopolysaccharide binding protein and increased levels of gamma interferon, interleukin 10, adiponectin and resistin, together with higher levels of Clostridium genus and a low abundance of the Parabacteroides , Ruminocooccaceae family, and Pseudomonas genus. This study provides insight into the main changes in inflammatory biomarkers and intestinal composition in mothers with late-onset FGR. Our findings showed that women with late-onset FGR, during the third trimester, harbour specific blood inflammatory biomarkers and intestinal microbiota composition that differ from those found in women with normal pregnancies. However, given the limited sample size and the absence of external validation, these findings should be considered hypothesis-generating. Future studies are encouraged to validate these findings clinically. NCT 04047966 (Registration date: 2019-08-07) https://clinicaltrials.gov/study/NCT04047966 .