Paternal arsenic exposure increases risk of myelomeningocele among offspring in a highly-exposed population

Abstract

Background: Neural tube defects, severe birth defects that occur when the neural plate fails to close in early gestation, continue to be a pressing public health concern, despite advances in prevention from folic acid-based strategies. Arsenic, a chemical naturally occurring in soils and drinking water, has been shown to induce neural tube defects in animal models and could contribute to neural tube defects in humans. We investigated the relationship between parental arsenic exposure and risk of myelomeningocele, a common and severe form of neural tube defect, in a case control study in Bangladesh. We also explored the interaction between arsenic levels and maternal serum folate. Methods: We analyzed arsenic in maternal and paternal toenail samples using inductively coupled plasma mass spectrometry. A total of 275 participants (153 cases and 122 controls) were included in the analysis. Results: On average, fathers of cases had higher levels of arsenic in toenails than fathers of controls. Maternal toenail arsenic levels were not significantly related to case status in the main effect model. In the paternal model, a 1-unit increase in the natural logarithm of toenail arsenic was significantly associated with 75% greater odds of being a case (adjusted odds ratios: 1.75) compared to being a control after adjusting for maternal serum folate level, parental age, child age, birth facility, and child sex. Results did not suggest an interaction between paternal arsenic and maternal serum folate. Conclusions: The findings from this study provide novel insight into the role of arsenic in neural tube defect risk in humans and add to the growing body of literature of the influence of paternal environmental factors on child health outcomes.