Introduction Neural tube defects affect the brain and the spinal cord of the developing embryo. The defects occur due to incomplete or failure of closure of the neural tube. The condition eventually causes death and lifelong disability. Worldwide, more than 300,000 babies are born with neural tube defects each year. The highest burden is in low- and middle-income countries. Therefore, this study aims to identify the risk factors associated with neural tube defects among mothers who gave birth in North Shoa Zone Hospitals. Methods A hospital based unmatched case-control study was conducted among 243 (81 cases and 162 controls) study participants in North Shoa Zone Hospitals. The hospitals were selected using simple random sampling and all cases and randomly selected controls in the selected hospitals were included in the study. The data were collected by using pre-tested structured questionnaire. Results Different factors were identified to have association with neural tube defect. Family annual cash income less than 24000ETB (AOR: 3.73, 95%CI: 1.35, 10.26), history of still birth (AOR: 3.63, 95%CI: 1.03, 12.2), history of abortion (AOR: 6.15, 95%CI: 2.63, 18.56), preconception tea use (AOR: 2.36, 95%CI: 1.15, 4.86) and pesticides/chemical exposure (AOR: 5.34, 95%CI: 1.77, 16.05) were positively associated factors. In contrast, preconception care (AOR: 0.14, 95%CI: 0.05, 0.39) and taking iron/folic acid/multivitamin during the current pregnancy (AOR: 0.16, 95%CI: 0.07, 0.33) showed a protective effect. Conclusion Family annual income less than 24000ETB, history of still birth, history of abortion, preconception tea uses and pesticides/chemical exposure were associated factors of neural tube defects. Preconception counseling and screening should be recommended for women who plan for pregnancy.
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