Infant methemoglobinemia: Fewtrell responds.In her letter, Zeman seems to be objecting to three points relating my article (Fewtrell 2004): that the role of cofactors is not new, that her articles were not cited, and that exposure-response data are available. First, in my article (Fewtrell 2004) I did not suggest that the role of cofactors was a novel discovery, as evidenced by the selection of articles I cited noting such factors. Rather, I noted the fact that the role of cofactors often seems to be overlooked in some of the literature. Second, as stated in the conclusion (Fewtrell 2004), "the study did not set out to review the role of nitrates in the causation causation Relation that holds between two temporally simultaneous or successive events when the first event (the cause) brings about the other (the effect). According to David Hume, when we say of two types of object or event that “X causes Y” (e.g. of methemoglobinemia Methemoglobinemia Definition When excessive hemoglobin in the blood is converted to another chemical that cannot deliver oxygen to tissues, called methemoglobin. " nor, by extension, the role of cofactors; thus the literature citation was selective. Finally, I assessed the article by Zeman et al. (2002) in the literature review for my study (Fewtrell 2004), but I felt it did not provide useful drinking water drinking water supply of water available to animals for drinking supplied via nipples, in troughs, dams, ponds and larger natural water sources; an insufficient supply leads to dehydration; it can be the source of infection, e.g. leptospirosis, salmonellosis, or of poisoning, e.g. (i.e., exposure) data related to the level of methemoglobinemia in infants (i.e., response data); therefore, the article by Zeman et al. (2002) was not cited (although I do consider the new data presented in Zeman's letter to be of interest). Three points that influenced my decision not to cite the article by Zeman et al. (2002) are worth noting. First, Zeman et al.'s Figure 2 shows an apparent relationship between nitrate nitrate, chemical compound containing the nitrate (NO3) radical. Nitrates are salts or esters of nitric acid, HNO3, formed by replacing the hydrogen with a metal (e.g., sodium or potassium) or a radical (e.g., ammonium or ethyl). level in wells (parts per million parts per million mg/kg or ml/l; see ppm. ) and "nitrate" (this is presumably pre·sum·a·ble adj. That can be presumed or taken for granted; reasonable as a supposition: presumable causes of the disaster. nitrite nitrite Any salt or ester of nitrous acid (HNO2). The salts are inorganic compounds with ionic bonds, containing the nitrite ion (NO2−) and any cation. , as described in the figure legend and Zeman's letter) exposure in milligrams per kilogram kilogram, abbr. kg, fundamental unit of mass in the metric system, defined as the mass of the International Prototype Kilogram, a platinum-iridium cylinder kept at Sèvres, France, near Paris. per day. This was reported to have a correlation of 0.71, presumably resulting in a coefficient of determination Coefficient of determination A measure of the goodness of fit of the relationship between the dependent and independent variables in a regression analysis; for instance, the percentage of variation in the return of an asset explained by the market portfolio return. Also known as R-square. of 0.50. However, some reported concentrations are remarkably high, exceeding 1,000 ppm nitrate. The reported relationship appears, visually, to be dependent on a few very high value(s) for the claimed correlation, making inference--or application of the functional relationship--within more usual exposure levels inappropriate. The data points within more "usual" elevated exposure ranges (say < 500 ppm) do not appear to exhibit a clear correlation between nitrate concentration (parts per million) in well water and calculated nitrite intake in milligrams per kilogram per day. Second, this figure simply claims a correlation between a concentration (i.e., nitrate in water, parts per million) and a precurser of the outcome condition (i.e., calculated nitrite intake, milligrams per kilogram per day), not the "outcome" of interest I discussed (Fewtrell 2004). It is unclear how the boiling of water (which may lead to an increase in nitrate concentrations) is accounted for in the relationship presented by Zeman et al. (2002). The relationship is also likely to be location specific, being dependent upon local feeding habits [e.g., level of formula, tea (chi), vegetables, etc., given to the infant]. Third, Zeman et al. (2002) did not provide a detailed explanation of how the dependent variable numerical values in their Figure 2 were derived, making it difficult to assess the quality of this information. The selection of appropriate studies to include in any global assessment is difficult and will always be contentious. I hope that these observations explain my decision not to cite the article by Zeman et al. (2002). The author declares she has no competing financial interests. REFERENCES Fewtrell L. 2004. Drinking-water nitrate, methemoglobinemia, and global burden of disease: a discussion. Environ Health Perspect 112:1371-1374. Zemen CL, Kross B, Vlad M. 2002. A nested case-control study A nested case-control study is a type of study design where new case controls are applied into cohorts which were defined before the study begins. Compared with case-control study, nested case-control study can reduce 'recall bias' and temporal ambiguity, and compared with of methemoglobinemia risk factors in children of Transylvania, Romania. Environ Health Perspect 110:817-822. Lorna Fewtrell Centre for Research into Environment and Health Crewe, Cheshire, United Kingdom E-mail: lorna@creh.demon.co.uk |
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