BACKGROUND: Meconium peritonitis (MP), a sterile chemical peritonitis caused by intrauterine bowel perforation, is a rare condition with high neonatal morbidity and mortality. The antenatal risk factors remain unknown. OBJECTIVES: This study aimed to explore the antenatal risk factors for MP. STUDY DESIGN: This was a retrospective case–control. The case group was enrolled upon diagnosis of MP by prenatal ultrasound screening, and the next four consecutive patients who matched all of the case-patient characteristics were included as controls. The maternal characteristics and fetal outcomes were collected from the medical record database. RESULTS: We included 92 MP cases and 368 controls. Multivariate logistic regression analyses showed that higher parity and male fetal sex were associated with higher risks of MP (odds ratio [OR]=1.36, 95% confidence interval [CI]: 1.09-1.70 and OR=1.76, 95% CI: 1.05-2.94, respectively). Mild ICP [total bile acid (TBA) 10-39µmol/L)] and severe ICP (TBA≥40 µmol/L) were associated with higher risks of MP, with ORs of 5.39 (95% CI: 2.65-10.98) and 10.55 (95% CI: 3.69-30.10), respectively, and the trend was significant. Pregnant women with mild anemia [hemoglobin (HGB) 90-109 g/L] also exhibited a higher risk of MP (OR=2.53, 95% CI: 1.35-4.72); however, there was no association between moderate anemia (HGB 60-89 g/L) and MP. CONCLUSION: Maternal ICP, mild anemia, higher parity and male fetal sex were independently associated with the risk of MP. Maternal serum TBA and fetal MP exhibited a dose-response relationship. These findings provide a novel insight into the pathogenesis underlying fetal bowel perforation.