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Objective To investigate the influence factors of birth defects. Methods The congenital malformational fetuses born from 13 week of gestation to 7 days after birth were selected as the study group between April 1st, 2009 and March 31st, 2010. The health born fetuses were set as control in the same period. Case-control and the three-level of monitor network of birth defects were used in the study in the participating 75 hospitals (Qingdao Women and Children's Medical Center, Affiliated Hospital of Medical College Qingdao University, Qingdao Municipal Hospital, etc.) . The study and control group's parents were interviewed by an uniformed questionnaire which was designed specially with influence factors of birth defects. Results (1) There are 466 congenital malformational fetuses in the total of 77 231 fetuses collected in 75 hospitals. The congenital malformational rate accounts for about 6. 034‰. The top six defect diseases were congenital heart disease (112 cases) , total harelip (cleft lip; cleft lip with palate; 85 cases) ,polydactyly (53 cases) , neural tube defects (38 cases) , congenital hydrocephalus (37 cases) and limb reduction defect (27 cases) in turn, which amounts to 353 cases (54.48% , 353/648). (2) Their mother education level in the birth-defect group (25. 6%) were significantly lower than that in control group (30. 0% , P < 0. 05). (3) The rate of passive smoking, drinking, raising pets of the parents in birth-defect group were significantly higher than that in control group (P < 0. 05). (4) The rate of exposure to harmful chemical and physical factors of mothers in birth defects group (13.9% and 20. 5% , respectively) was higher than that in control group (1.1% and 11.7% , respectively) , the difference between which were significant (P < 0. 01) . The rate of disease (34. 3%) , fever (13. 1%) , taking drugs (33. 8%) in pregnancy period in birth defect group were higher than that in control group (13. 5% , 1.5% and 9. 9% ,respectively) , the difference between which were significant (P <0. 01). The rate of bad moral irritation to the mother in pregnancy in birth defect group (11. 3%) was significantly higher than that in control group (1.4% , P<0.01). (5) There were 19 cases (2.9% , 19/648) with family heredity medical history in birth defect group, but there were none in the control group, the difference between which were significant (P<0. 01). There were 89 cases (13.7% , 89/648) with unusual birth history of their mothers in birth defect group, but there were 31 cases (4. 8% , 31/650) in control group, the difference between which were significant (P<0. 01). (6) Conditional Logistic Regression model was used for univalent and multivariate analysis. The results showed that main influence factors were identified as having important effect on birth defects, including mothers' exposure to harmful chemical factors (OR=13. 46) , disease (OR=3. 37) ,taking drugs (OR=2. 20) , exposure to bad moral irritation (OR=5. 44) , food-choosy (OR=1. 90) ,anemia (OR=1. 52) in gestational period, polyembryony (OR=4. 40) , father drinking (OR=1. 55) .While it was protective factors to supplement microelements such as the calcium iron and nutrient, etc. in pregnancy period (OR=0. 45). Conclusions First, the main birth defects were congenital heart disease, total harelip (cleft lip; cleft lip with palate) , polydactyly, neural tube defects, congenital hydrocephalus and limb reduction defect in turn. Second, the main influence factors identified as having important effect on birth defects were mothers' exposure to harmful chemical factors, ill, taking drugs, exposure to bad moral irritation, food-choosy, anemia in gestational period, polyembryony, father drinking. But it is protective factors to supplement microelements such as the calcium iron and nutrient, etc. in pregnancy period. Finally, it is the important part to prevent the birth defects by reducing and controlling dangerous factors in pregnancy period.