Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)


Healthcare Genetics

Committee Chair/Advisor

Dr. Jane DeLuca

Committee Member

Dr. Stephanie Davis

Committee Member

Dr. Sara Sarasua

Committee Member

Dr. Natallia Sianko

Committee Member

Dr. Roger Stevenson


Neural tube defects (NTDs) are congenital anomalies that affect both the morbidity and mortality of infants worldwide. Inadequate levels of the vitamin folate in women during early pregnancy have been shown to be a risk factor for NTDs. Recent efforts to ensure adequate folate intake in mothers have been helpful in reducing but not eliminating NTDs. This dissertation examines additional risk factors for NTDs as possible focus areas for decreasing NTD occurrence.

Chapter Two and Chapter Three are literature reviews conducted to explore select factors associated with an increased risk of NTDs and how these factors may affect folate availability for mothers. The seven risk factors implicated in NTD development include maternal obesity, hyperthermia, pregestational diabetes, MTHFR C677T variant, Hispanic race/ethnicity, twin pregnancy, and drugs affecting folate metabolism. In both literature reviews, these risk factors were evaluated using historical literature and three databases for the years 2016–2021. In the first review, evidence from meta-analyses, systematic reviews, and large studies linked these risk factors to NTDs, although some studies countered these findings. The second literature review evaluated whether these risk factors could affect folate levels in mothers. Lower serum or RBC folate levels were observed in women who were homozygous for the MTHFR C77T variant, and those with obesity, and women exposed to antiepileptic drugs (AEDs).

Chapter Four is a research study of NTD cases occurring in South Carolina over a 28-year period (1992–2019). Using data from the South Carolina NTD Surveillance and Prevention Program, this study examined the occurrence of each of the seven risk factors in 515 isolated NTDs during the study period. Distribution of the risk factors in the three common NTD types (spina bifida, anencephaly, and encephalocele) and between the periods of pre-fortification and post-fortification were explored. Of the 515 isolated NTD cases, 57% had one or more of the seven risk factors studied. Continued research and focus on NTD risk factors may offer opportunities for NTD prevention.

Available for download on Saturday, August 31, 2024

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