Zonulin levels in complicated pregnancy: a systematic review and meta-analysis.

Zonulin is a novel biomarker of intestinal permeability. The existing data suggest that upregulation of zonulin might be linked to systemic inflammation and pregnancy complications. A systematic search was performed in medical electronic databases to identify eligible studies that reported circulating zonulin levels in complicated pregnancies compared to controls. Eight studies with 1196 serum samples of pregnant women were included in the systematic review. Meta-analysis on four studies revealed a significant increase in serum zonulin in women with Gestational diabetes mellitus (GDM) compared to healthy controls (Cohen's d = 2.06; 95% Confidence Interval (CI): 0.15, 3.98). By pooling four studies that investigated zonulin levels in Hypertensive disorders of pregnancy (HDP), higher zonulin concentrations were found in cases, while the difference was not significant (Cohen's d = 0.86; 95% CI: -0.04, 1.75). Current evidence suggests that higher levels of zonulin during pregnancy seem to be associated with inflammation-related complications, including GDM and HDP.Impact StatementWhat is already known on this subject? Increased zonulin levels are considered as a marker of intestinal hyper-permeability. Upregulation of zonulin and concurrent systemic inflammation, are known to be associated with some pregnancy complications.What do the results of this study add? We performed a meta-analysis to evaluate changes in serum zonulin levels in pregnancies complicated with Gestational diabetes mellitus (GDM), Hypertensive disorders of pregnancy (HDP), and Intrahepatic cholestasis of pregnancy (ICP). According to our results, zonulin levels were significantly higher in complicated pregnancies than in normal pregnancies, particularly for GDM.What are the implications of these findings for clinical practice and/or further research? Our findings revealed a probable association between increased zonulin levels and inflammation-related complications during pregnancy. Moreover, zonulin could serve as a reliable diagnostic clinical biomarker to identify (or predict) complications during pregnancy. Further studies are needed to examine the clinical accuracy of zonulin for detecting pregnancy-related complications.