Background: Neural tube defects (NTDs) are serious brain and spine birth defects. Although NTDs are primarily pregnancy complications, such as abortion and stillbirth, they also contribute to under-five morbidity and mortality, as well as long-term disability and psychological impact. Despite these negative outcomes, the determinants of NTDs are not widely studied in Ethiopia, particularly in the country's east. As a result, we sought to identify the risk factors for NTDs in neonates born in public referral hospitals in eastern Ethiopia.

Methods: A facility-based unmatched case-control study was carried out at Hiwot Fana Comprehensive Specialized Hospital and Sheik Hassen Yabare Jigjiga University Referral Hospital in Eastern Ethiopia. We included 59 cases identified in the selected facilities between September 10, 2021, and February 5, 2022, and 118 control neonates, with a case-to-control ratio of 1:2. Data were gathered through the use of interviewer-administered questionnaires and medical record review. To identify determinant factors of NTDs, a multivariable logistic regression model was used, which included all predictor variables from the bivariable analysis. The results were reported using an Adjusted Odds Ratio (AOR) with a 95% confidence interval. A p-value of < 0.05 was considered statistically significant.

Results: In total, 59 cases of NTDs were identified out of 2915 live birth total births registered in the two hospitals, making the incidence of NTDs 202.4/10,000 births. In the final model analysis, determinant factors such as gender of newborn [AOR = 2.97; 95%CI(1.27, 6.92)], having no history of antenatal care[AOR = 4.45;95%CI(1.30,15.20)], having a poor food consumption score (AOR = 3.38;95% CI;1.06,10.72), having history of monotonous diet consumption (AOR = 4.80; 95%CI: 1.09, 9.08; P = 0.038), and coffee consumption of three or more cups per day during pregnancy (AOR = 3.84:95% CI: 1.23, 11.97) were statistically associated with NTDs.

Conclusion: Modifiable and non-modifiable determinants were identified as major contributors of neural tube defect in this study. Early screening, dietary intervention counseling to increase consumption of a healthy diet, coffee consumption reduction, and pre-pregnancy supplementation programs should be developed to reduce NTDs in Ethiopia.