Exposure assessment methodology development in support of a pilot study of the long-term neuropsychological impacts of methemoglobinemia and high nitrate exposure in infants of Transylvania, Romania with an added case/control study of methemoglobinemia ri

摘要

An exposure assessment was developed in support of an international, epidemiological pilot study conducted in the Transylvania Region of Romania. This region has an incidence rate of methemoglobinemia, MHG in the several hundreds per 100,000 population. The exposure assessment supports a retrospective, pilot-cohort study examining whether cases, exposed controls, or controls would exhibit different performance abilities on a number of Romanian-adapted, standardized tests of neuropsychological developmental ability.;Information from the pilot, retrospective cohort study was used to develop an additional, nested case-control study to examine risk factors related to MHG. This study provided an opportunity to examine the risk factors for MHG. The presence of readily available, risk related information on clearly delineated cohorts and current controversies surrounding the risk factors for MHG provided the impetus to examine exposures, environmental conditions, diarrheal conditions, breast feeding, water sources, boiling practices, and use of vitamin supplements as they related to MHG.;Exposures were well differentiated into three tertiles based on a point estimate of average daily intake of nitrite in mg/kg/day. Analysis of tertile means indicated significant difference between the groups (ANOVA, one way, <0.0001). Individual exposures were multivariately analyzed using canonical analysis and the generation of centroid values. The most significant contributors of nitrate enrichment in the diet included chi (tea) and powdered formula (both due to dietary water) at 2 mos. of age and beets and formula feedings (dietary water) at 6 mos. of life.;Univariate and multi-factorial analysis of risk factors for MHG indicate that MHG is strongly associated with nitrate exposure through the dietary route (water) and that breast feeding is protective for infants under six months of age. The presence or absence of diarrheal conditions was somewhat predicative of the presence or absence of infantile MHG. When intensity/frequency of diarrheal episodes is considered, the association was no longer significantly predictive of infantile MHG.