Perinatally Accessible Biomarkers of Complex Gastroschisis: Systematic Review and Individual Patient Data Meta‐Analysis

OBJECTIVE: To systematically review perinatally accessible body fluid biomarkers of gastroschisis and those associated with disease severity or postnatal morbidities. METHODS: PubMed, Embase, Web of Science, Scopus, Cochrane CENTRAL, ClinicalTrials.gov, and the International Clinical Trials Registry Platform were searched for studies reporting body fluid biomarkers obtained from women carrying a fetus or neonates with gastroschisis. The primary aim was to identify biomarkers indicating gastroschisis; secondary aims included identifying biomarkers associated with disease severity (simple vs. complex) or postnatal morbidity. RESULTS: Twenty-two studies were included, showing substantial heterogeneity in sampling timing, fluid type, and biomarkers assessed. Among 13 studies reporting prenatal biomarkers, amniotic fluid total protein, IL-8, and ferritin differentiated fetuses with gastroschisis from normal fetuses. Total protein correlated with disease severity. Bile acid findings were inconsistent. Increased cord blood IL-8 at delivery was associated with the presence of gastroschisis and prolonged parenteral nutrition. Neonatal urinary intestinal fatty acid-binding protein indicated the presence and severity of gastroschisis. An individual patient data meta-analysis of three studies identified four inflammatory cord blood biomarkers (IL-8, CXCL10, IL-4, and CX3CL1) associated with prolonged parenteral nutrition. CONCLUSIONS: Several perinatally accessible biomarkers are associated with gastroschisis, and some further correlate with severity or postnatal morbidity.