Correspondence

Intellectual Function of Children Exposed to Polychlorinated Biphenyls in Utero

N Engl J Med 1997; 336:660-661February 27, 1997

Article

To the Editor:

Drs. Jacobson and Jacobson (Sept. 12 issue)1 reported that low-level exposure to polychlorinated biphenyls (PCBs) in utero is associated with lower IQ scores (by an average of 6.2 points) among school-age children. The results seem implausible given the fact that among Taiwanese children who were exposed prenatally to levels of PCBs that were 10 to 20 times higher and to levels of certain congeners of polychlorinated dibenzofurans that were 100,000 times higher than background levels, the IQ score was only 5 points lower than that in unexposed children.2

Several methodologic flaws cast doubt on the validity of the Jacobsons' findings. They studied only 212 children (47 percent) of the 452 mothers originally invited to participate. This group was a highly selected subgroup of the initial study population of 8482 women.3 The authors did not adequately explain these inconsistencies in sample size and did not provide the numbers of exposed and unexposed children for whom results were available. For example, descriptive statistics were presented for 212 children in Table 1 and IQ scores were given for 178 children according to PCB concentrations in maternal milk in Figure 1, yet PCBs were measured in only 113 samples of maternal milk. No data were presented to support the value of PCB concentrations in breast milk as an accurate measure of prenatal exposure.

Data on two important risk factors and potential confounders, alcohol ingestion and cigarette smoking, appear to be inconsistent. Although 37 percent of the mothers smoked before and 28 percent during pregnancy, virtually none drank during pregnancy (shown in Table 1 of the article). In contrast, data from the Behavioral Risk Factor Surveillance System suggested that a high proportion (14 to 21 percent) of women of childbearing age in Michigan consumed alcohol frequently.4 Furthermore, the method used to control for potential confounders may not be adequate. The authors stated that a variable's “association with either exposure or outcome can be used as the criterion for inclusion” in a model.1 However, standard epidemiologic analytic methods do not advocate the use of this method for model development.5

Given these methodologic issues, we think that this study provides little evidence that in utero exposure to low levels of PCBs affects intellectual function.

John P. Middaugh, M.D.
Grace M. Egeland, Ph.D.
Alaska Division of Public Health, Anchorage, AK 99524

5 References

1. 1

   Jacobson JL, Jacobson SW. Intellectual impairment in children exposed to polychlorinated biphenyls in utero. N Engl J Med 1996;335:783-789
   Full Text | Web of Science | Medline

2. 2

   Chen Y-CJ, Guo Y-L, Hsu C-C, Rogan WJ. Cognitive development of Yu-Cheng (`oil disease') children prenatally exposed to heat-degraded PCBs. JAMA 1992;268:3213-3218
   CrossRef | Web of Science | Medline

3. 3

   Jacobson JL, Jacobson SW, Humphrey HE. Effects of in utero exposure to polychlorinated biphenyls and related contaminants on cognitive functioning in young children. J Pediatr 1990;116:38-45
   CrossRef | Web of Science | Medline

4. 4

   Frequent alcohol consumption among women of childbearing age -- Behavioral Risk Factor Surveillance System, 1991MMWR Morb Mortal Wkly Rep 1994;43:328-9, 335
   Medline

5. 5

   Kleinbaum DG, Kupper LL, Morgenstern H. Epidemiologic research: principles and quantitative methods. New York: Van Nostrand Reinhold, 1982.
   

Author/Editor Response

The authors reply:

To the Editor: Drs. Middaugh and Egeland compare our Michigan data with data on more heavily exposed Taiwanese children. The validity of this type of comparison is uncertain, however, because the relative proportions of specific congeners of PCBs to which the two groups were exposed probably differed, and the relative neurotoxicity of the individual congeners is not known. Although we were not able to follow all the children recruited for the study, there was no difference between those we studied and those lost to follow-up on any of the cognitive-performance measures assessed during infancy and at four years of age. Moreover, there were no attrition-by-prenatal-exposure interactions for birth size or cognitive performance in infancy or at four years, indicating that there was no systematic bias in favor of retention in the study either of heavily exposed children who performed poorly or of children with low levels of exposure who performed well.

We assessed prenatal exposure to PCBs using a composite measure for the 178 children for whom one or more biologic measures of fetal exposure were available. Although PCBs were measured in only 113 samples of maternal milk, the composite measure, which was expressed as a z score, was converted to equivalent units of maternal-milk concentrations by multiplying it by the standard deviation in the sample for the PCB concentration in maternal milk and adding the sample mean. This conversion was done to enable us to report the data in units that would be meaningful to the reader and comparable to those used in other studies.

We collected detailed quantitative information regarding smoking and alcohol ingestion during pregnancy.1 Although a high proportion of Michigan women of childbearing age may consume alcohol frequently, such women were not represented in our sample. With respect to control for confounding, we reran the regression analyses for full-scale IQ and word-comprehension scores with all the control variables not included in the analyses reported in Table 3 of our article. The effect of prenatal exposure to PCBs on full-scale IQ and word-comprehension scores remained statistically significant.

Joseph L. Jacobson, Ph.D.
Sandra W. Jacobson, Ph.D.
Wayne State University, Detroit, MI 48202

1 References

1. 1

   Jacobson SW, Fein GG, Jacobson JL, Schwartz PM, Dowler JK. Neonatal correlates of prenatal exposure to smoking, caffeine, and alcohol. Infant Behav Dev 1984;7:253-265
   CrossRef | Web of Science

Citing Articles (3)

Citing Articles

1. 1

   Jack C. Clifton. (2007) Mercury Exposure and Public Health. Pediatric Clinics of North America 54:2, 237.e1-237.e45
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2. 2

   S.Allen Counter, Leo H Buchanan. (2004) Mercury exposure in children: a review. Toxicology and Applied Pharmacology 198:2, 209-230
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3. 3

   Harold Kalter. (2003) Teratology in the 20th century. Neurotoxicology and Teratology 25:2, 131-282
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