Background: Periconception interactions between maternal conditions and environmental and genetic factors are involved in the pathogenesis and prevention of neural tube defects (NTD), such as spina bifida. These factors have in common that they can impair the oxidative pathway, resulting in excessive (chronic) oxidative stress and inflammation. Methods: Review of the literature concerning underlying mechanisms and biomarkers of aging particularly during reproduction. A number of molecular markers for biological aging have been identified, including telomere length (TL). Excessive telomere shortening is an index of senescence, causes genomic instability and is associated with a higher risk of age-related diseases. Furthermore, TL shortening is associated with the similar environmental and lifestyle exposures associated with NTD risk. Results: Embryonic mice deficient in the telomerase gene show shorter TL and failure of closure of the neural tube as the main defect, suggesting that this developmental process is among the most sensitive to telomere loss and chromosomal instability. Conclusions: From this background, we hypothesize that preconceptional long term exposure to harmful environmental and lifestyle risk factors accelerates a woman's aging process, which can be measured by TL, and thereby her underlying risk of NTD offspring. Alternatively, it might be that women with an increased NTD risk already exhibit a more advanced biological age before the onset of pregnancy compared to women of identical calendar age.

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Keywords aging, folic acid, lifestyle, neural tube defects, nutrition, oxidative stress, telomere length
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Journal Birth Defects Research
Aoulad Fares, D. (Damiat), Schalekamp-Timmermans, S, Nawrot, T.S. (Tim S.), & Steegers-Theunissen, R.P.M. (Régine P. M.). (2020). Preconception telomere length as a novel maternal biomarker to assess the risk of spina bifida in the offspring. Birth Defects Research. doi:10.1002/bdr2.1682