Are maternal thyroid autoantibodies generated by PCBs the missing link to impaired development of the brain?

In her interesting review addressing endocrine disruption and the developing brain, Colborn (2004) asked rightly for special attention to the role of a disruption of thyroid hormones and thyroid hormone metabolism, which negatively influence early development of the fetal brain. As mechanisms of action, chemicals such as polychlorinated biphenyls (PCBs) were discussed in a dose-related way; the higher the exposure level of the mother, the more problems of brain development will be found in the baby (Colborn 2004). However, this is not always true. Patandin et al. (1999) found a four-point decline in IQ at 4 years of age in relation to maternal PCB levels in the Netherlands. In a follow-up study of Faroese children at 7 years of age, Grandjean et al. (1997) found no relation of PCBs with cognitive impairment; the levels of PCBs were almost 4 times higher in the Faroese population than in the Dutch population (Longnecker et al. 2003).

One explanation of the missing link might be that effects of PCBs are not directly toxic but instead are toxic through immuno-modulatory mechanisms in the mother. In a comment on the impact of maternal PCB and dioxin exposure on the neonate's thyroid hormone status, Vulsma (2000) noted that PCBs affect the generation of autoantibodies against thyroid tissue [e.g., thyroid peroxidase antibodies (TPO-Ab)]. In a study in Slovakia, Langer et al. (1998) described an increase in TPO-Ab in relation to PCB exposure. These antibodies do pass through the placenta.

An important risk factor for impaired infant development is a low free thyroxine (f[T.sub.4]) concentration in early pregnancy; particularly at risk are the mothers with low f[T.sub.4] and high TPO-Ab titers. These antibodies are found in 10% of (euthyroid) women at 12 weeks' gestation in the Netherlands (Pop et al. 1995, 1999). To my knowledge, none of the studies on effects of PCBs in human pregnancy have reported data on maternal TPO-Ab titers.

If the findings reported by Colborn (2004) can be explained by autoimmune processes that cause low f[T.sub.4] in the mother and negatively affect her developing baby, then it seems more logical that prenatal PCB exposure is related to developmental impairment instead of the amount of PCBs transferred by breast milk after birth.

I agree with Colborn (2004) that all women who plan to become pregnant should be evaluated for thyroid hormone status.

The author declares she has no competing financial interests.

Janna G. Koppe

ECOBABY Society

Amsterdam, the Netherlands

E-mail: [e-mail]

REFERENCES

Colborn T. 2004. Neurodevelopment and endocrine disruption. Environ Health Perspect 112:944-949.

Grandjean P, Weihe P, White RF, Debes F, Araki S, Yokoyama K, et al. 1997. Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury. Neurotoxicol Teratol 19:417-428.

Langer P, Tajtakova M, Forodr G, Kocan A, Bohov P, Michalek J, et al. 1998. Increased thyroid volume and prevalence of thyroid disorders in an area heavily polluted by polychlorinated biphenyls. Eur J Endocrinol 139:402-409.

Longnecker MP, Wolff MS, Gladen BC, Brock JW, Grandjean P, Jacobson JL, et al. 2003. Comparison of polychlorinated biphenyl levels across studies of human neurodevelopment. Environ Health Perspect 111:65-70.

Patandin S, Lanting CI, Mulder PG, Boersma ER, Sauer PJ, Weisgla-Kuperus N. 1999. Effects of environmental exposure to polychlorinated biphenyls and dioxins on cognitive abilities in Dutch children at 42 months of age. J Pediatr 134:33-41.

Pop VJ, de Vries E, van Baar AL, Waelkens JJ, de Rooy HA, Horsten M, et al. 1995. Maternal thyroid peroxidase antibodies during pregnancy: a marker of impaired child development? J Clin Endocrinol Metab 80:3561-3566.

Pop VJ, Kuijpens JL, van Baar AL, Verkerk G, van Son MM, de Vijlder JJ, et al. 1999. Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy. Clin Endocrinol 50:149-155.

Vulsma T. 2000. Impact of exposure to maternal PCBs and dioxins on the neonate's thyroid hormone status. Epidemiology 11:239-241.

Maternal Thyroid Autoantibodies: Colborn's Response

I thank Koppe for raising the question of the significance of the presence of increased thyroid peroxidase antibodies (TPO-Ab) during neurodevelopment or even later in life. I have wondered for years why medical practitioners and laboratories do not routinely quantify TPO-Ab in blood screening for thyroid disorders. High priority should be given to learning more about the relationship between the combination of high TPO-Ab and low free thyroxine (f[T.sub.4]), and impaired IQ and psychomotor development and the possible role of foreign substances such as polychlorinated biphenyls (PCBs) in these changes. Although the value of routine antithyroglobin antibody (TG-Ab) testing is being questioned, in future epidemiologic studies looking at the role of PCBs in neurodevelopment perhaps TG-Ab should be included in the design as well. It might prove enlightening to also routinely test for TG-Ab at several research/medical institutions to continue to explore this immune connection with the thyroid economy. Also, perhaps it is time to explore the nutritional state (protein consumption, quality and quantity of serum proteins) of the mother and her unborn child during gestation, which might contribute to the conflicting findings among the various cohort studies about the role of PCBs in neurodevelopment. In the meantime, until more is understood about neurodevelopmental impairment, I would like to take this opportunity in reinforce the need to routinely test all pregnant women and those planning to become pregnant for f[T.sub.4], free triiodothyronine, thyroid-stimulating hormone, and TPO-Ab. Information such as this would allow for intervention, if needed, to prevent irreversible brain damage.

The author declares she has no competing financial interests.

Theo Colborn

The Endocrine Disruption Exchange

Paonia, Colorado

E-mail: [e-mail]