"Dutch girls and boys: response from Vreugdenhil et al. (Correspondence).

Cicchetti's comments about our article "Effects of Prenatal Exposure to PCBs and Dioxins on Play Behavior in Children at School Age" (Vreugdenhil et al. 2002) are based on a multitude of misinterpretations and misunderstandings.

Cicchetti correctly noted that our data show that on the Pre-School Activities Inventory (PSAI) boys score significantly higher on the masculine scale than girls, and correspondingly, girls score significantly higher on the feminine scale than boys. The composite scores for boys also indicate an overall masculine score and, correspondingly, the composite scores for girls indicate an overall feminine score. He also correctly noted that mean cord PCB levels are virtually the same in boys and girls; however, this does not rule out the possibility of a difference in effect of cord PCB levels on a PSAI scale between boys and girls. Cicchetti mistakenly concludes that our major outcome,

   that a higher prenatal exposure to PCBs was associated
   with less masculinized play behavior in boys
   and with more masculinized play behavior in girls,

is not at all what we report. The interaction sex x exposure represents the difference in effect of, for example, ln[SIGMA]PC[B.sub.cord] (the log-normal concentration of the sum of PCBs in cord plasma) on a PSAI scale between girls and boys; it represents the effect among girls minus the effect among boys, which is shown in Tables 2 and 3 of our paper (Vreugdenhil et al. 2002). The estimate of this difference is based on the assumptions that the other explanatory variables have the same effects in boys and girls and that the variance of the residual term is the same in boys and girls. There is no suspicion that these assumptions would not hold true for our data.

Cicchetti also has problems with our Figure 1 (Vreugdenhil et al. 2002). This figure includes two ordinary partial regression plots of the residuals of the masculine scale and ln[SIGMA]PC[B.sub.cord], when both these variables are regressed upon the other independent (confounding) variables. The slopes of these regression lines coincide with the regression coefficients given in our Table 2 (Vreugdenhil et al. 2002). The null hypothesis of these regression coefficients being zero coincides with the partial correlations in Figure 1 being equal to zero, so that the p-values coincide. In order for a multiple linear regression analysis to be valid, it is not necessary to make assumptions on the distribution of the independent variables (e.g., lnPC[B.sub.cord]). Also, it is well known that, in a multiple regression analysis, the percentage of explained variability is a different concept than validity of the estimated regression coefficients. A small percentage explained by a fitted model does not necessarily invalidate the estimated coefficients of that model.

Cicchetti claims that we performed 39 (and likely many more) regressions. This is again obviously due to a misunderstanding or misinterpretation of our paper (Vreugdenhil et al. 2002). For the effect in boys, the effect in girls, and the difference in effect between boys and girls, we used only one regression model. Moreover, the composite score is the difference between the feminine score and the masculine score. Hence, the regression results of the composite score can be essentially derived from the regressions of the feminine and masculine score, up to one parameter (the correlation of the residuals of the feminine score and the masculine score). The multiplicity correction suggested by Cicchetti for the significance level per test is based on mutual independence of the statistical tests and is therefore known to be rather conservative. This holds more strongly for the results of our exploratory study. Because of the nature of our study, we presented the p-values as calculated to three decimal places and we did not propose a multiplicity correction for the significance level per test. Control for chance finding (or actually lack of control) is, in our opinion, an improper criterion to disregard the results of a study or even to leave them unpublished. This is because it is based on a rather arbitrarily and externally (to the study) chosen method to lower the already arbitrarily chosen threshold for the p-value. Moreover, strictly applying this criterion as proposed by Cicchetti would prevent science from storing and building up evidence. Certainly it does not make sense to divide the overall significance level by the spurious number 39 as he proposed for the reasons given above.

Cicchetti proposes that our findings should be dismissed from the scientific community because not all of our p-values are smaller than his proposed spurious multiplicity correction for the significance level per test. We think however, that the scientific community itself is perfectly able to judge the merits of our results by its own means.

The authors declare they have no conflict of interest.

REFERENCES

Vreugdenhil HJI, Slijper FME, Mulder PGH, Weisglas-Kuperus N. 2002. Effects of perinatal exposure to PCBs and dioxins on play behavior in Dutch children at school age. Environ Health Perspect 110:A593-A598.

Hestien J.I. Vreugdenhil

Erasmus University Rotterdam

and Sophia Children's Hospital

Rotterdam, the Netherlands

Paul G.H. Mulder

Erasmus University Rotterdam

Rotterdam, the Netherlands

Nynke Weisglas-Kuperus

Erasmus University Rotterdam

and Sophia Children's Hospital

Rotterdam, the Netherlands

E-mail: [e-mail]