Letters to the Editor |
Reply: Maternal lead exposure, secondary sex ratio and dose-exposure fallacy
1 Environmental and Occupational Medicine and Epidemiology Program, Harvard School of Public Health, Landmark Center, 401 Park Dr, PO Box 15697, Boston, MA 02215, USA 2 University of Calgary, Canada 3 School of Public Health, University of Michigan, Ann Arbor, USA 4 Instituto Nacional de Salud Publica, Mexico City, Mexico
5 Correspondence address: Tel: +617-384-8872; Fax: +617- 384-8994; E-mail: mweissko{at}hsph.harvard.edu
We appreciate the comments and suggestions of Dr Jongbloet who points out that the increase in the sex ratio among children of those mothers in the third quintile of blood lead measurements in our data (Jarrell et al., 2006
) may represent changes predicted by the overripeness ovopathy concept (Jongbloet, 2004). We had noted this increased sex ratio, but had concluded, in light of the data with respect to our other biomarkers of lead, that overall there did not appear to be any consistent association between any of the lead biomarkers and the sex ratio.
We have undertaken a secondary analysis to determine if there is evidence of an increase in the sex ratio over the first three quintiles (n = 507) when using the blood lead measurements as a continuous variable. In this re-analysis, we found a significant increase in the adjusted odds ratio (OR) for male birth per unit (µg/dl) increase in blood lead [OR: 1.14; 95% confidence interval (CI): 1.02–1.28; P = 0.03]. There was not a significant change in the sex ratio from the third to fifth quintiles (n = 476). For each unit increase in maternal blood lead over the last three quintiles the OR for a male was 0.98 (95% CI: 0.93–1.03, P = 0.43).
The fact that the other biomarkers of lead did not show similar patterns, however, should be considered. With respect to other birth outcomes—such as birth weight, infant weight gain, head circumference, birth length and scores on the Bayley scales of mental development at age 2 years—maternal bone lead biomarkers have proven to be better predictors of adverse outcomes than blood lead (Gonzalez-Cossio et al., 1997; Gomaa et al., 2002; Hernandez-Avila et al., 2002).
The mechanism of the overripeness ovopathy concept that might account for the predicted initial increase in sex ratio as a result of lead exposure would imply that circulating lead levels at the time of conception would be most relevant for any effect. The maternal blood lead in our study was taken at the time of delivery and the bone lead measurements at one month post-partum. The half-life of lead in blood is 
30 days, while that of patella lead is several years. The question is which is a better indicator of circulating lead at conception? In our cohort, we have very little data on this. However, in the few mothers for whom we do have this data, we find a higher correlation of pre-pregnancy blood lead with maternal blood lead at delivery (0.67; P = 0.0002; n = 26) than with cord blood at delivery (0.53; P = 0.08; n = 12), patella bone (0.33; P = 0.10; n = 26) or tibia bone (0.21; P = 0.33; n = 24) at one month post-partum (all correlations are Spearman). We do not have the relevant data for the assessment of spontaneous abortion that Dr Jongbloet recommends to do.
These results do appear to at least be in part consistent with Dr Jongbloet's overripeness ovopathy concept. It should be noted, however, that we have been unable to identify reports that indicate lead might act as a reproductive endocrine disruptor or that lead is associated with either altered cervical mucous production or altered ovulation patterns—factors usually invoked to explain the overripeness ovopathy concept.
References
Jarrell JF, Weisskopf MG, Weuve J, Téllez-rojo MM, Hu H, Hernàndez-Avila M. Maternal lead exposure and the secondary sex ratio. Hum Reprod (2006) 21:1901–1906.
Jongbloet PH. Over-ripeness ovopathy—a challenging hypothesis for sex ratio modulation. Hum Reprod (2004) 19:769–774. 1036–1038.
Gonzalez-Cossio T, Peterson KE, Sanin LH, Fishbein E, Palazuelos E, Aro A, Hernandez-Avila M, Hu H. Decrease in birth weight in relation to maternal bone-lead burden. Pediatrics (1997) 100:856–862.
Gomaa A, Hu H, Bellinger D, Schwartz J, Tsaih SW, Gonzalez-Cossio T, Schnaas L, Peterson K, Aro A, Hernandez-Avila M. Maternal bone lead as an independent risk factor for fetal neurotoxicity: a prospective study. Pediatrics (2002) 110:110–118.
Hernandez-Avila M, Peterson KE, Gonzalez-Cossio T, Sanin LH, Aro A, Schnaas L, Hu H. Effect of maternal bone lead on length and head circumference of newborns and 1-month-old infants. Arch Environ Health (2002) 57:482–488.[Web of Science][Medline]
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