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Neural tube defect (NTD) is a public health burden caused by folic acid deficiency, hereditary, lifestyle, environmental factors, chromosomal abnormalities, among others. However, prevalence and causes at the Kumasi Metropolis of Ghana is not documented. This study therefore assessed the prevalence and risk factors of NTD at the Komfo Anokye Teaching Hospital (KATH), Kumasi. Secondary data was obtained from the medical records of the babies with NTD while primary data was collected through interviews with 65 mothers of live babies with and 65 without NTD born between the period of January 2012 to December 2016. From the study, prevalence of NTD at KATH was 2.63 per 1,000 births with the commonest diagnoses been meningocele. Also, NTD was significantly inversely proportional to the age of mothers. Mothers in urban centres and were less likely to have babies with NTD than mothers in rural communities. Single mothers had higher chance of having babies with NTD than married mothers. Folic acid intake before pregnancy (at least a year) reduced the likelihood of having babies with NTD. Mothers in case group were mainly diagnosed of anaemia and eclampsia more than of control group while gestational diabetic mothers exposed to smoke as well as anaemic mothers living in dusty environment had significantly higher likelihood of giving birth to babies with NTD. Nutrition and healthy lifestyle education should be given to pregnant women during antennal visit. Pregnant women should also be made aware of their risk factors to help know how to interact with the environment to prevent the occurrence of NTDs. Ministry of Health should further embark on massive folic acid intake education to help reduce the occurrence of NTDs. [ABSTRACT FROM AUTHOR]