**To :**  **Cc: Bcc:**  **Subject: Fw: clarification for 2003 Allergy paper - blood Pb and IgE** 

**From: Isabella Annesi-Maesano <isabella.annesi-maesano@inserm.fr>**  **To: Molini Patel/RTP/USEPA/US@EPA**  **Date: 05/20/2011 10:25 AM**  **Subject: Re: clarification for 2003 Allergy paper - blood Pb and IgE**  **Sent by: annesimaesano@gmail.com**  

### Dear Dr Patel, The units indicated in the paper are wrong. They should be microgram per liter. Best regards Isabella Annesi-Maesano

-- Dr Isabella Annesi-Maesano Directeur de Recherche INSERM Head: EPid Allergic Resp Dis Department ( www
. epar
. fr ) ADDRESS : EPAR UMR-S 707 INSERM & UPMC Paris6, Medi cal School Saint-Antoine Bureaux 803-4-6, 8ème étage 27, rue Chaligny 75571 Paris CEDEX 12 Tel: + 33 1 44738449 Fax: +33 1 44738454 Personal e-mail address: annesimaesano @ gmail

. com
2011/5/20 <Patel

. Molini @ epamail

. epa
. gov > Dear Dr. Annesi-Maesano, We are currently developing the Integrated Science Assessment for Lead and would like clarification for data presented in your 2003 Allergy paper: **Annesi-Maesano, I; Pollitt, R; King, G; Bousquet, J; Hellier, G; Sahuquillo, J; Huel, G (2003). In utero exposure to lead and cord blood total IgE. Is there a connection? Allergy 58(7):589-594.**  **Specifically, Table 2 (appended below and attached) indicates that the units for infant cord blood lead and maternal blood lead are micrograms per deciliter.**  **Mean +/-SD infant cord blood lead levels are presented as 67.37 +/- 47.77, 106.06 +/- 47.78, and 38.80 +/- 19.04 micrograms per deciliter in the Combined dataset, Study A, and Study B, respectively.**  **Mean +/-SD maternal blood lead levels are presented as 96.44 +/- 57.73, 133.02 +/- 59.69, and 61.61 +/- 25.11 micrograms per deciliter in the Combined dataset, Study A, and Study B, respectively.** 
**Please confirm whether these units are correct and if incorrect , please provide the correct units. Thank you for your assistance. Molini** 
**Molini M. Patel, PhD, MPH Epidemiologist**  **U.S. Environmental Protection Agency National Center for Environmental Assessment**  **Mail drop: B243-01 Research Triangle Park, NC 27711**  **Telephone: (919) 541-1492 Email:**  **patel**

**. molini**  **@ epa** 

**. go** **v**differ consistently in terms of birth weight, AGPAR,maternal allergic status, or passive smoking but significantly more male infants were born to respondents in study B (Table 1).
Baseline values of total IgE and lead Mean cord blood IgE levels did not vary significantly from one study to the other (Table 1). As expected, maternal and infant IgE were strongly correlated with each other in study B ( r 1⁄4 0.38, P < 0.001). In spite of the fact that total IgE has been related to ethnic group, no effect of ethnic group on cord blood IgE was found in our investigation and hence ethnic group was not considered as a confounder in the analysis. The mean lead levels for subjects in study A were considerably higher than those in study B for each lead variable measured (see Table 2). In study A, infant and maternal blood lead levels were highly correlated ( r 1⁄4 0.47, P < 0.0001) whereas infant and maternal hair lead levels were not. Furthermore, placental lead level was strongly correlated with both maternal blood lead ( r 1⁄4 0.37, P < 0.0001) and infant blood lead ( r 1⁄4 0.34, P < 0.0001). In study B, infant and maternal blood lead levels were also strongly correlated ( r 1⁄4 0.47, P < 0.0001), while maternal and infant hair lead levels were again unrelated.
Relationships between lead and cord blood total IgE levels There was a significant correlation in both samples between infant hair lead and cord blood log IgE levels (Table 2). No significant relationship of infant blood log IgE level to the other infant lead variables was found (in particular, placental lead in study A was unrelated to cord blood total IgE ( r 1⁄4 0.11, NS)). Combining the two data sets yielded an even more significant relationship ( P < 0.0001). This relationship was entirely confirmed by an analysis of variance between infant hair lead (four class variable) and mean log IgE levels (Table 3). The fraction of the total variation in cord blood total IgE accounted for by the fitted model was almost 10%. Furthermore, an association of borderline statistical significance (P < 0.10) was observed between mother blood lead and child cord blood Log(IgE) (Table 2).

Taking maternal allergic status into account showed that cord blood IgE level was significantly associated with infant hair lead overall in children of nonallergic mothers (Fig. 1). When considering the effects of passive smoking, Table 1. Characteristics of the study samples
Combined data n 1⁄4 374 Study A n 1⁄4 137 Study B n 1⁄4 237 Newborns

Sex ratio M/F 1.0 € 0.50 0.73 1.26 Birth weight (g), mean € SD 3331.32 € 438.17 3242.81 € 454.61 3383.14 € 420.66 AGPAR at 5 min, mean € SD 9.96 € 0.22 9.96 € 0.19 9.96 € 0.24 Cord blood IgE (IU/ml), GM, (95%CI) 0.29 (0.26, 0.33) 0.33 (0.02,.6.52) 0.27 (0.25, 0.30) Cord blood cotinine (ng/ml) – 10.49 € 34.26 – Mothers

Age (years), mean € SD 29.30 € 4.45 28.99 € 5.09 29.48 € 4.04 Allergic status (%) 33.0 35.1 33.2 Total IgE (IU/ml), GM, (95%CI) – – 34.89 (28.56, 42.61) Active smokers during pregnancy (%) 24.9 € 43.3 26.6 € 44 24.89 € 43 Maternal urine cotinine (CCR, ng/mg) – 58.14 € 172.18 – GM:geometric mean.

Table 2. Relationship between lead variables and infant cord blood Log(IgE) levels Combined data Study A Study B

Lead variable n mean € SD Spearman's correlation coefficient n mean € SD Spearman's correlation coefficient n mean € SD Spearman's correlation coefficient Infant cord blood ( l g/dl) 326 67.37 € 47.77

) 0.05 124 106.06 € 47.78 0.11 202 38.80 € 19.04

) 0.11 Maternal blood ( l g/dl) 332 96.44 € 57.73

) 0.09 135 133.02 € 59.69 0.07 197 61.61 € 25.11

) 0.11 Infant hair (ppm) 234 1.38 € 1.26 0.21** 45 1.74 € 0.65 0.32*** 189 1.29 € 1.37 0.19** Maternal hair (ppm) 360 5.16 € 6.08

) 0.04 129 6.79 € 5.91

) 0.01 231 4.05 € 5.96 0.02

** P < 0.01.

*** P 1⁄4 0.03. In utero exposure to lead and cord blood total IgE

591