Relation of Parity With Common Carotid Intima-Media Thickness Among Women of the Study of Health in Pomerania

To the Editor:

Wolff et al¹ report that both multiparity and nulliparity are associated with increased carotid artery intima-media thickening. I propose that folate deficiency may account, in part, for this result.

Folate deficiency is linked with hyperhomocystinemia,² which, in turn, is associated with accelerated progression of atherosclerosis³ and, thereby, carotid artery intima-media thickening. Pregnancy is potentially a cause of folate deficiency.⁴ Consequently, it is possible that multiparous women are at risk of prolonged folate deficiency; this may explain their susceptibility to the development of carotid artery intima-media thickening.

There may also be a link between folate deficiency and nulliparity. Folate is necessary for DNA and RNA synthesis, and folate deficiency may therefore theoretically lead to infertility. Moreover, there is an association between folate deficiency and spontaneous miscarriage.⁵ It is therefore possible that a high proportion of childless women may be folate deficient. If this assumption is correct, these women are also at risk of increased carotid artery intima-media thickening.

Wolff et al used a multivariate analysis to assess the significance of confounding variables. The causes of folate deficiency include chronic disease, such as Celiac or Crohn disease and poor diet, and these variables were not included as confounders. The possibility that a higher proportion of childless women included in this study suffer from an affliction leading to folate deficiency, compared with women with one or two children, cannot be ruled out.

If folate deficiency partially accounts for the results reported by Wolff et al then this may prompt further research into the benefits of folate supplementation to certain subgroups of patients to prevent progression of atherosclerosis.