Sex Difference in Celiac Disease in Undiagnosed Populations: A Systematic Review and Meta-analysis

BACKGROUND & AIMS: A higher proportion of female vs male patients receive a diagnosis of celiac disease. Little is known about sex-based differences in the prevalence of celiac disease in undiagnosed populations. We aimed to address this knowledge gap with a systematic review and meta-analysis. METHODS: We searched MEDLINE, Embase, Cochrane, and Scopus databases through 2017 for studies of screen-detected or undiagnosed celiac disease. Our final analysis included studies that included screening and confirmatory tests (either second serologic analysis or a small intestine biopsy) and provided information on the sex of participants. Studies were excluded if they were performed with specific, high-risk, or referral populations. The primary outcome was the percentage of undetected celiac disease among female and male patients. RESULTS: We identified 4070 articles and analyzed data from 87. Our meta-analysis comprised data from 291,969 study participants. The pooled prevalence of undetected celiac disease in female participants was 0.589% (95% CI, 0.549%-0.629%) and in male participants was 0.415% (95% CI, 0.343%-0.487%). The risk of undetected celiac disease was higher among female than male participants (relative risk [RR], 1.42; 95% CI, 1.27-1.57; P < .00001). The I-2 was 5% (low heterogeneity among studies). In subgroup analyses, the RR of celiac disease for girls vs boys was 1.79 (95% CI, 1.44-2.22; P < .00001; I-2 = 18%), the RR for female vs male blood donors was 1.13 (95% CI, 0.76-1.69; P = .54; I-2 = 0), and the RR for women vs men with villous atrophy was 1.38 (95% CI, 1.07-1.79; P = .01; I-2 = 0). CONCLUSIONS: In a systematic review and meta-analysis, we found a higher risk for celiac disease in women than men in an undiagnosed populations (identified through general population screening). The increased risk for celiac disease among girls and women should be considered for screening, diagnosis, and management strategies.