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Data were obtained from the population-based Birth Defects Surveillance System in Hunan Province, China (2010\u20132020). The surveillance population included all live births, stillbirths, infant deaths, and legal terminations of pregnancy from 28\u00a0weeks of gestation to 42\u00a0days after birth between 2010 and 2020 when the mother resided in the surveillance area (Liuyang County and Shifeng District, Hunan Province). The prevalence of birth defects is the number of birth defects per 1000 infants (\u2030). The death rate of birth defects is the number of deaths attributable to birth defects per 100 birth defects (%). The prevalence and death rate with 95% confidence intervals (CI) were calculated by the log-binomial method. Crude odds ratios (ORs) were calculated to examine the association of each demographic characteristic with birth defects. Our study included 228,444 infants, and 4453 birth defects were identified, with a prevalence of 19.49\u2030 (95%CI 18.92\u201320.07). Congenital heart defects were the most common specific defects (5.29\u2030), followed by limb defects (4.01\u2030). Birth defects were more common in males than females (22.34\u2030 vs. 16.26\u2030, OR\u2009=\u20091.38, 95%CI 1.30\u20131.47), in premature birth than not (91.82\u2030 vs. 16.14\u2030, OR\u2009=\u20096.16, 95%CI 5.72\u20136.65), in birth weight\u2009&lt;\u20092500\u00a0g (98.26\u2030 vs. 16.22\u2030, OR\u2009=\u20096.61, 95%CI 6.11\u20137.15) or\u2009&gt;\u20094000\u00a0g (19.48\u2030 vs. 16.22\u2030, OR\u2009=\u20091.21, 95%CI 1.03\u20131.42) than birth weight 2500\u20134000\u00a0g, in hospitalized deliveries than other institutions (22.16\u2030 vs. 11.74\u2030, OR\u2009=\u20091.91, 95%CI 1.76\u20132.07), in multiple births than singletons (28.50\u2030 vs. 19.28\u2030, OR\u2009=\u20091.49, 95%CI 1.27\u20131.76), in maternal age\u2009&lt;\u200920\u00a0years (26.33\u2030 vs. 18.69\u2030, OR\u2009=\u20091.42, 95%CI 1.15\u20131.76) or\u2009&gt;\u2009\u2009=\u200935\u00a0years (24.31\u2030 vs. 18.69\u2030, OR\u2009=\u20091.31, 95%CI 1.18\u20131.45) than maternal age 25\u201329\u00a0years, and in number of pregnancies\u2009&gt;\u2009\u2009=\u20094 (22.91\u2030 vs. 18.92\u2030, OR\u2009=\u20091.22, 95%CI 1.10\u20131.35) than the first pregnancy. A total of 747 deaths attributable to birth defects were identified, including 603 (80.72%) stillbirths, 75 (10.04%) deaths within 7\u00a0days after birth, 46 (6.16%) deaths in 7\u201327\u00a0days after birth, 23 (3.08%) deaths in 28\u201342\u00a0days after birth. The death rate of birth defects was 16.78% (95%CI 15.57\u201317.98). Deaths attributable to birth defects accounted for 51.09% (747\/1462) of all deaths. Central nervous system defects had the highest death rate (90.27%), and neonatal genetic metabolic defects had the lowest death rate (0.39%). In summary, we have described the prevalence and epidemiology of birth defects from population-based surveillance in Hunan Province, China, 2010\u20132020. 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