Reply: Maternal Lead Exposure, Secondary Sex Ratio and Dose-Exposure Fallacy

Details

• Personal Author:
  Hernandez-Avila M ; Hu H ; Jarrell J ; Tellez-Rojo MM ; Weisskopf MG ; Weuve J
• Description:
  Sir, 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 (mg/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 ¼ 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. [Description provided by NIOSH]
• Subjects:
  Biomarkers Endocrine System Environmental Exposure Lead Occupational Health Risk Assessment Risk Factors Safety Urogenital System Women
• Keywords:
  Blood Lead Levels Children Endocrine Disruptors Exposure Levels Humans Lead Compounds Reproduction Risk Factors Statistical Analysis
• ISSN:
  0268-1161
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; Michigan ; OSHA Region 1 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  22
• Issue:
  10
• NIOSHTIC Number:
  nn:20059859
• Citation:
  Hum Reprod 2007 Oct; 22(10):2792-2793
• Contact Point Address:
  Marc G. Weisskopf, Environmental and Occupational Medicine and Epidemiology Program, Harvard School of Public Health, Landmark Center, 401 Park Dr, PO Box 15697, Boston, MA 02215
• Email:
  mweissko@hsph.harvard.edu
• CAS Registry Number:
  Lead (CAS RN 7439-92-1)
• Federal Fiscal Year:
  2008
• Performing Organization:
  Harvard School of Public Health
• Peer Reviewed:
  False
• Start Date:
  20050701
• Source Full Name:
  Human Reproduction
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:13008a5b23576b0bc35a840f761594b88d49a5df562f31aeb871cd128989e7c5c8692b0e027c3898ddd209ae76bf0ffefa67a4d6fc82f9b70df11be534587a7f
• Download URL:
  https://stacks.cdc.gov/view/cdc/223923/cdc_223923_DS1.pdf
• File Type:
  [PDF - 79.28 KB ]