Authors
ten Tusscher, GW., Steerenberg, PA., van Loveren, H., Vos, JG., vondem Borne, AEGK., Westra, M., vander Slikke, JW., Olie, K., Pluim, H., Koppe, JG.

Title
Persistent hematological and immunological disturbances in Dutch eight-year-old children associated with perinatal dioxin exposure.

Journal
Environmental Health Perspectives, Online 14 May 2003.

Summary
Dioxins are a family of compounds that are primarily produced through the combustion of natural material, such as fossil fuels and wood, and through municipal and industrial incineration processes. Because dioxins are persistent and tend to accumulate in fatty tissues, most human exposures occur through meat, dairy products and fish. Animal studies have shown that dioxins have the ability to cause a broad range of immunotoxic effects including the suppression of humoral and cell-mediated immune responses and reducing the resistance to infections. In 1994, Pluim et al. found decreased thrombocyte and granulocyte counts in relation to perinatal dioxin exposure in a cohort of 11 week old Dutch infants. Eight years after Pluim's study, ten Tusscher et al. hypothesized that there would be a persistent suppression in immune function among children in this cohort who had higher dioxin exposure levels during the perinatal period.

In this ongoing study, 27 mother baby pairs were successfully recruited. The children were born to well-nourished Caucasian women (average age 29.2 years) intending to breastfeed at least 2 months. Dioxin levels were previously measured by Pluim et al. (1994). The concentration of dioxin in the mother's breast milk shortly after giving birth was taken as the prenatal dioxin exposure level. Postnatal cumulative dioxin exposure was established by multiplying the dioxin concentration in breast milk times the amount of breast milk ingested during the breastfeeding period. Each mother also kept a diary throughout her breastfeeding period, which was later used to validate the accuracy of the data. For the current study, a complete medical history was taken on each child at 8 years of age and various hematological and immune parameters were measured including: hemoglobin, red blood cell count, white blood cell count and platelets. As well, documentation of possible clinical effects such as infections or allergies was noted. Other factors affecting immune function were considered in the analysis including urinary mercury and blood lead levels, and maternal smoking during pregnancy.

The data suggested that children with higher prenatal (p=0.023) or postnatal (p=0.030) dioxin exposure were less likely to have allergies. All the allergies reported were from female children. When analyzing females only, again a significant decrease in allergies was seen for dioxin exposure in the prenatal (p=0.008) and postnatal (p=0.006) periods. No relationship was found between dioxin levels and any of the other clinical outcomes such as ear infections, pneumonia, or chickenpox.

The hematological findings showed a significant decrease in platelets in relation to increasing exposure to dioxin in the postnatal period (p=0.04). This finding is similar to that found by Pluim et al. in 1994, in the same group of children at just 11 weeks of age. As well, a significant increase was observed for thrombopoietin (a hormone that regulates the production of platelets) in relation to cumulative postnatal dioxin exposure (p=0.03). With reference to the immunological parameters, a significant increase in CD4 positive (T-helper) cells (p=0.006) and CD45RA count (p=0.019) was seen with increasing postnatal dioxin exposure.

There is limited human research on the immunotoxic effects of environmental compounds making this study an important contribution to the literature. The decrease in allergies and increase in CD4 helper cells observed in this study may indicate an interference of dioxin with the immune system. However, other factors such as the small sample size, other current exposures, and lifestyle factors may have influenced the findings. The results also suggest that dioxins may negatively influence the production of platelets, necessitating an increase in thrombopoietin production. However, all the platelet counts were still within an acceptable clinical range. Nevertheless, the persistent effect of perinatal dioxin exposures on platelet levels in children at both 11 weeks and 8 years of age is intriguing and warrants follow-up later in life.