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Abstract Background Cardiac anomalies are the most prevalent congenital malformations among live births in the world. In Brazil, it is estimated that nearly 25,757 new cases occur each year, and the Southeast region presents the highest prevalence, with 10 new cases/1,000 live births. Objective The aim of this study is to evaluate the epidemiology of congenital heart disease (CHD) in the state of São Paulo. Methods This is a cross-sectional and time-series observational study with data from the Brazilian Information System on Live Births. Heart-related cardiac malformation cases — International Classification of Diseases (ICD) 10th revision Q20.0 to Q24.9 — were selected from January 2010 to December 2018, in the state of São Paulo, Brazil. This study analyzed rates of malformations per year and investigated associated factors, using single and multiple logistic regression models. The significance level adopted in this study was 5%. Results The highest cardiac malformation rate was in the São Paulo metropolitan region (2.84:1000), while the lowest was found in the region of Franca (0.3:1000). The most frequent defect was interatrial communication (38.2%). The main associated factors observed in this study were prematurity of 22 to 27 weeks (OR=4,401 95% CI: 3,796-5,104) — CI: Confidence Interval; OR: Odds ratio —, mother’s age between 35 and 49 years of age (OR=1,602 95% CI: 1,525-1,682), yellow race (OR=1,481 95% CI: 1,235-1,775), triple or more pregnancy (OR=1,438 95% CI: 1,004-2,060), and history of a dead child (OR=1,213 95% CI: 1,152-1,277). Conclusion The main factors associated with this outcome, which are part of the obstetric history of mothers, should be addressed and considered when pregnancy is a planned event. world Brazil 25757 25 757 25,75 prevalence 1 cases1000 000 cases/1,00 CHD (CHD crosssectional cross sectional timeseries time series Births Heartrelated Heart related ICD (ICD th Q200 Q Q20 0 Q20. Q249 Q24 9 Q24. 201 2018 models 5 5% 2.841000, 2841000 2.84 1000 , 2 84 (2.84:1000) 0.31000. 031000 0.3 . 3 (0.3:1000) 38.2%. 382 38.2% 38 (38.2%) OR=4,401 OR4401 OR 4 401 (OR=4,40 95 CI 3,7965,104 37965104 3,796 5,104 796 104 3,796-5,104 Interval mothers mother s OR=1,602 OR1602 602 (OR=1,60 1,5251,682, 15251682 1,525 1,682 525 682 1,525-1,682) OR=1,481 OR1481 481 (OR=1,48 1,2351,775, 12351775 1,235 1,775 235 775 1,235-1,775) OR=1,438 OR1438 438 (OR=1,43 1,0042,060, 10042060 1,004 2,060 004 060 1,004-2,060) OR=1,213 OR1213 213 (OR=1,21 1,1521,277. 11521277 1,152 1,277 152 277 1,152-1,277) outcome event 2575 75 25,7 cases100 00 cases/1,0 Q2 20 841000 2.841000 284100 284 2.8 100 8 (2.84:1000 31000 0.31000 03100 03 0. (0.3:1000 38.2 (38.2% OR=4,40 OR440 40 (OR=4,4 7965 3,7965,10 3796510 3796 3,79 5104 5,10 79 3,796-5,10 OR=1,60 OR160 60 (OR=1,6 5251 1,5251,682 1525168 1525 1,52 1682 1,68 52 68 1,525-1,682 OR=1,48 OR148 48 (OR=1,4 2351 1,2351,775 1235177 1235 1,23 1775 1,77 23 77 1,235-1,775 OR=1,43 OR143 43 0042 1,0042,060 1004206 1004 1,00 2060 2,06 06 1,004-2,060 OR=1,21 OR121 21 (OR=1,2 1521 1,1521,277 1152127 1152 1,15 1277 1,27 15 1,152-1,277 257 7 25, cases10 cases/1, 84100 2.84100 28410 28 2. (2.84:100 3100 0.3100 0310 (0.3:100 38. (38.2 OR=4,4 OR44 (OR=4, 3,7965,1 379651 379 3,7 510 5,1 3,796-5,1 OR=1,6 OR16 6 (OR=1, 1,5251,68 152516 1,5 168 1,6 1,525-1,68 OR=1,4 OR14 1,2351,77 123517 123 1,2 177 1,7 1,235-1,77 1,0042,06 100420 1,0 206 2,0 1,004-2,06 OR=1,2 OR12 1,1521,27 115212 115 1,1 127 1,152-1,27 cases1 cases/1 8410 2.8410 2841 (2.84:10 310 0.310 031 (0.3:10 (38. OR=4, OR4 (OR=4 3,7965, 37965 37 3, 51 5, 3,796-5, OR=1, OR1 (OR=1 1,5251,6 15251 1, 16 1,525-1,6 1,2351,7 12351 12 17 1,235-1,7 1,0042,0 10042 2, 1,004-2,0 1,1521,2 11521 11 1,152-1,2 cases/ 841 2.841 (2.84:1 31 0.31 (0.3:1 (38 OR=4 (OR= 3,7965 3,796-5 OR=1 1,5251, 1,525-1, 1,2351, 1,235-1, 1,0042, 1,004-2, 1,1521, 1,152-1, (2.84: (0.3: (3 OR= (OR 3,796- 1,5251 1,525-1 1,2351 1,235-1 1,0042 1,004-2 1,1521 1,152-1 (2.84 (0.3 ( 1,525- 1,235- 1,004- 1,152- (2.8 (0. (2. (0 (2