Organochlorines, including pesticides (such as DDT), are ubiquitous in the environment. All humans are exposed to low levels of these compounds. Exposure begins before birth, since the compounds cross the placenta, and continues throughout life. Evaluation of potential health effects of that exposure is essential to understanding what dangers, if any, these compounds may pose to humans. Several studies of health effects of the DDT family of compounds are underway. These include examinations of the relationship of prenatal exposure to anogenital distance (a sensitive measure of prenatal hormone exposure) in newborn boys, to childhood growth, and to adolescent growth and pubertal devlopment. They also include studies of adult exposure to both duration of lactation and timing of menopause. (1) We are studying the relationship of prenatal DDE exposure to anogenital distance (AGD) in newborn boys in southern Mexico. In animals, AGD is a sensitive measure of prenatal hormone exposure. DDE, the most persistent DDT metabolite, has anti-androgenic properties, and exposure to DDE reduces AGD in male rats. AGD has rarely been studied in humans, so our study includes development of a standard protocol and assessment of reliability of the measurements. We will examine basic determinants of AGD, including measures of overall body size such as birthweight. We will also examine the relationship of DDT to AGD; chemical analysis of maternal samples is ongoing. (2) Prenatal exposure to DDT compounds can impact birthweight and may have continuing effects as children age. We are using a subset of data from the Collaborative Perinatal Project (CPP), a longitudinal study from birth to 7 years of children born in the early 1960s. Archived blood samples obtained by the CPP from the mothers during pregnancy have been analyzed for DDE. We are examining the relationship of prenatal exposure to height and weight at 1, 4, and 7 years of age. Height is lower in those with the highest exposures, but weight is unaffected. (3) Our previous work had shown that boys with higher prenatal exposures to DDE were taller and heavier than other boys in their teenage years. This was an unexpected finding, and we are attempting to replicate it. Some of the children in the CPP were followed through adolescence in the Philadelphia Blood Pressure Project (PBPP). We have obtained anthropometric and pubertal data from the PBPP and analyzed archived blood samples for DDE and DDT. No relationship of DDE or DDT to any of the outcome measures was seen. (4) Our previous work had shown that DDT can adversely affect lactation, shortening the duration, although the evidence on this point is still inconclusive. We are studying this question in the Mexican population being examined for AGD. Followup visits to the mothers to ask about the progress of lactation are underway. (5) Previous work had shown a relationship of timing of menopause and DDE exposure. That study used postmenopausal samples to measure DDE; this is not optimal timing for measuring exposure. A new study has been done in mothers of a cohort of children we previously studied. Samples obtained from the mother around the time of childbirth were analyzed for DDE in the previous study. A questionnaire to assess menopausal status has been administered. Field work is recently completed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES040012-05
Application #
7007138
Study Section
(BB)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2004
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Kamel, F; Engel, L S; Gladen, B C et al. (2007) Neurologic symptoms in licensed pesticide applicators in the Agricultural Health Study. Hum Exp Toxicol 26:243-50
Romano-Riquer, S Patricia; Hernandez-Avila, Mauricio; Gladen, Beth C et al. (2007) Reliability and determinants of anogenital distance and penis dimensions in male newborns from Chiapas, Mexico. Paediatr Perinat Epidemiol 21:219-28
Gladen, Beth (2006) Questions regarding the basis of the analyses in study of the relationship of maternal concentrations of dichlorodiphenyl dichloroethylene (DDE) and initiation and duration of breast feeding: extrapolations of organochlorine levels for estimating exposure Paediatr Perinat Epidemiol 20:360-1; author reply 362-4
Ribas-Fito, Nuria; Gladen, Beth C; Brock, John W et al. (2006) Prenatal exposure to 1,1-dichloro-2,2-bis (p-chlorophenyl)ethylene (p,p'-DDE) in relation to child growth. Int J Epidemiol 35:853-8
Gladen, Beth C; Klebanoff, Mark A; Hediger, Mary L et al. (2004) Prenatal DDT exposure in relation to anthropometric and pubertal measures in adolescent males. Environ Health Perspect 112:1761-7
Longnecker, Matthew P; Wolff, Mary S; Gladen, Beth C et al. (2003) Comparison of polychlorinated biphenyl levels across studies of human neurodevelopment. Environ Health Perspect 111:65-70
Gladen, Beth C; Shkiryak-Nyzhnyk, Zoreslava A; Chyslovska, Nataliya et al. (2003) Persistent organochlorine compounds and birth weight. Ann Epidemiol 13:151-7
Gladen, Beth C; Doucet, Josee; Hansen, Larry G (2003) Assessing human polychlorinated biphenyl contamination for epidemiologic studies: lessons from patterns of congener concentrations in Canadians in 1992. Environ Health Perspect 111:437-43
Gladen, B C; Ragan, N B; Rogan, W J (2000) Pubertal growth and development and prenatal and lactational exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene. J Pediatr 136:490-6
Longnecker, M P; Gladen, B C; Patterson Jr, D G et al. (2000) Polychlorinated biphenyl (PCB) exposure in relation to thyroid hormone levels in neonates. Epidemiology 11:249-54

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