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Editor,—I read the article by Bound et al on the involvement of deprivation and environmental lead in neural tube defects (NTDs) in the journal with great interest.1
The authors suggested that lead is a possible cause of NTDs, especially anencephaly, either by direct action on rapidly developing nervous tissue or could act indirectly by causing zinc deficiency with secondary folate deficiency. Lead reduces the bioavailability of zinc from food and the folate uptake is reduced by secondary zinc deficiency. They pointed out that further investigation is needed to study the role of zinc deficiency in the aetiology of NTDs.1
Severe first pointed out, from epidemiological evidence, a possible relationship between zinc deficiency and central nervous system malformation.2 In fact, the essential role of zinc in embryonic development and a relationship between maternal zinc deficiency and NTDs have been the subject of several studies.3-5
Furthermore, in a genetic zinc deficiency disorder, acrodermatitis enteropathica, there is severe intestinal mucosal atrophy that can be reversed by effective oral zinc supplementation. In seven pregnancies in patients with acrodermatitis enteropathica, there was one spontaneous abortion and two major congenital malformations.6 Conversely, pregnancy outcome was good when a patient with acrodermatitis enteropathica was given supplemental zinc throughout her pregnancy.7
A case of a nutritionally zinc deficient young Turkish woman was reported who had previously delivered two anencephalic stillborn infants. After zinc supplementation she delivered a normal full term child.8
Our recent report concerning maternal plasma zinc concentrations after an oral zinc tolerance test in pregnancies associated with NTDs in Turkey showed that some of the affected women had defective zinc absorption due to chronic zinc deficiency, which returned to normal after zinc supplementa- tion.9 Four affected women gave birth to normal infants; only one infant had closed spina bifida.10
Previous data and findings in human studies are evidence for the possible role of zinc metabolism at least in some of the mothers of babies with NTDs.
Dr Bound comments:
I would like to thank Dr Akar for his interesting letter. We knew of some of the references associating NTDs with zinc deficiency, but were not aware if recent work had shown it to act directly or by causing folate deficiency.
Our statement that further investigation was needed referred primarily to the need to assess by reliable methods the zinc and folate status of mothers of future cases.
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