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<h4>Objective</h4>To describe the epidemiology of holoprosencephaly (HPE) in China with special reference to prevalence and associated anomalies.<h4>Methods</h4>Data were abstracted from the Chinese Birth Defects Monitoring Network for the period 2007-2014. Birth prevalence of HPE were assessed by birth year, fetal/infant sex, maternal age, and maternal residential area. Poisson regressions were used to calculate the crude and adjusted prevalence ratios (PR) and their 95% confidence intervals, and linear chi-square test was used to explore time trend for the prevalence of HPE.<h4>Results</h4>A total of 1222 HPE cases were identified in 13,284,142 births, yielding an overall prevalence of 0.92 per 10,000 births. The annual prevalence of HPE presented an upward trend (P<0.001), from 0.54 per 10,000 births in 2007 to 1.21 per 10,000 births in 2014. Higher prevalence was found in older maternal-age groups (30-34 years, adjusted PR: 1.19, 95% CI: 1.02-1.40; ≥35 years, adjusted PR: 1.53, 95% CI: 1.26-1.86) in comparison with the maternal-age group of 25 to 29 years. Higher prevalence was also found in infants born to mothers resided in urban areas (adjusted PR: 1.23, 95% CI: 1.08-1.39) and female infants (adjusted PR: 1.30, 95% CI: 1.15-1.47).<h4>Conclusions</h4>HPE is an important perinatal health issue because of its poor prognosis. This is the first study depicting a picture of epidemiological characteristics of HPE in China, which can provide useful references for future studies.