Dichlorodiphenylethylene serum concentrations and effect on birthweight

Abstract

Matthew Longnecker and colleagues (July 14, 2001, p 110)1Longnecker MP Klebanoff MA Zhou H Brock JW Association between maternal serum concentration of the DDT metabolite DDE and preterm and small-for-gestational-age babies at birth.Lancet. 2001; 358: 110-114Summary Full Text Full Text PDF PubMed Scopus (350) Google Scholar note a positive association between maternal serum concentrations of the dichloro-diphenyltrichloroethane (DDT) metabolite, dichlorodiphenylethylene (DDE), and preterm and small-for-gestational-age babies at birth. They conclude that this effect is causal. They suggest several underlying mechanisms: DDE interfering in prostaglandin synthesis, or DDE acting as a placentar (neuro)toxin. I believe, however, that these mechanisms do not sufficiently address the issue of confounding. DDE is a hydrophobic compound, practically insoluble in water and completely soluble in organic solvents.2Budavari S Merck index: an encyclopedia of chemicals, drugs and biologicals. Merck, Rahway, NY, USA1989Google Scholar Longnecker and colleagues are aware of a binding of DDE to albumin, but reportedly too few samples were analysed to exclude albumin as a potential confounder.1Longnecker MP Klebanoff MA Zhou H Brock JW Association between maternal serum concentration of the DDT metabolite DDE and preterm and small-for-gestational-age babies at birth.Lancet. 2001; 358: 110-114Summary Full Text Full Text PDF PubMed Scopus (350) Google Scholar Next to albumin, DDE can also associate to lipoproteins.3Noren K Weistand C Karper F Distribution of PCB congeners, DDE, hexachlorobenzene, and methylsulfunyl metabolities of PCB and DDE among various fractions of human blood plasma.Arch Environ Contam Toxicol. 1999; 37: 408-414Crossref PubMed Scopus (67) Google Scholar With colleagues, I have studied distribution of lipophilic vitamins A and E over the lipoproteins, and noted that hydrophobicity of the vitamin and the lipoprotein mass concentration are strong determinants.4Demacker PNM Hectors MPC Stalenhoef AFH Chylomicron processing in familial dysbetalipoproteinemia and familial hyperlipidemia studied with vitamin A and E as markers: a new physiological concept.Atherosclerosis. 2000; 149: 169-180Summary Full Text Full Text PDF PubMed Scopus (10) Google Scholar Reportedly, 25% of serum DDE concentration is associated with lipoproteins.3Noren K Weistand C Karper F Distribution of PCB congeners, DDE, hexachlorobenzene, and methylsulfunyl metabolities of PCB and DDE among various fractions of human blood plasma.Arch Environ Contam Toxicol. 1999; 37: 408-414Crossref PubMed Scopus (67) Google Scholar Consequently, next to albumin, the serum lipoprotein concentrations could also be confounding factors to the above mentioned associations. Accordingly, multivariate analysis including adjustment for plasma lipids resulted in a lower odds ratio. Assessment of the individual plasma lipoprotein concentrations would confirm this positive association more strongly, but the long term storage at −20°C may induce lipoprotein denaturation, thus complicating DDE analysis. This remains an important question to answer. If true, lifestyle variables are important. The reported positive association between the socioeconomic index and smoking behaviour with the preterm and small-for-gestational-age index is suggestive.1Longnecker MP Klebanoff MA Zhou H Brock JW Association between maternal serum concentration of the DDT metabolite DDE and preterm and small-for-gestational-age babies at birth.Lancet. 2001; 358: 110-114Summary Full Text Full Text PDF PubMed Scopus (350) Google Scholar The principle of a hydrophobic ligand whose serum concentration under chronic intake is determined by the lipoprotein concentration, is examplified by the vitamin E status, which should always be considered in relation to the plasma cholesterol concentration. The same is probably true for other hydrophobic ligands such as nutrients, toxins, and drugs, in as much as their hydrophobicity mainly favours a binding to lipoproteins more than one to albumin.