Pesticide-Induced Diseases: Birth/Fetal Effects

In 2005, the births of three babies born in Florida with severe birth defects to mothers who all worked for Ag-Mart Produce, a company that produces chemically-treated tomatoes and other agricultural products, brought the connection between birth defects and pesticide exposure into the public consciousness. Birth defects are structural or functional abnormalities present at birth that cause physical or mental disabilities, ranging from mild to fatal. Researchers have identified thousands of different types of birth defects. Currently, birth defects are the leading cause of death for infants during the first year of life.

• Association of selected persistent organic pollutants in the placenta with the risk of neural tube defects
  Placental concentrations of polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides, polychlorinated biphenyls, and polybrominated diphenyl ethers were analyzed in 80 fetuses or newborns with neural tube defects (NTDs). A dose–response relationship was observed between PAH levels and the risk of NTDs.
  [Ren, A. et al. 2011. PNAS. 108 (31) 12770-12775]
  
• Urinary Biomarkers of Prenatal Atrazine Exposure and Adverse Birth Outcomes in the PELAGIE Birth Cohort
  This study, a case-cohort design nested in a prospective birth cohort conducted in the Brittany region from 2002 through 2006, collected maternal urine samples to examine pesticide exposure biomarkers before the 19th week of gestation. Quantifiable levels of atrazine were found in urine samples from 5.5% of 579 pregnant women, and various metabolites were identified in 20-40% of samples. The presence versus absence of quantifiable levels of atrazine or a specific atrazine metabolite was associated with fetal growth restriction and small head circumference. Head circumference was also inversely associated with the presence of the herbicide metolachlor. Daily News
  [Chevrier C, Limon G, Monfort C, Rouget F, Garlantézec R, Petit C, et al. 2011.. Environ Health Perspect. doi:10.1289/ehp.1002775]
• PESTICIDES: Examining DDT’s Urogenital Effects
  Review of reserach documenting a variety of urogenital malformations in male babies born to women living in an area of South Africa where the potentially endocrine-disrupting pesticide DDT is still used.
  [Lubick, N. 2010. Environ Health Perspect. 118(1): A18]
• Agricultural-related chemical exposures, season of conception, and risk of gastroschisis in Washington State
  Reserchers conducted a retrospective, case-controlled study using Washington State Birth Certificate and US Geological Survey databases. Cases included all live-born singleton infants with gastroschisis. Distance between a woman's residence and site of elevated exposure to agrichemicals was calculated. Gastroschisis occurred more frequently among those who resided <25 km from a site of high atrazine concentration (odds ratio, 1.6). Risk was related inversely to the distance between the maternal residence and the closest toxic atrazine site.
  [Waller, S.A., Paul, K., Peterson, S.E. andHitti, J.E. . 2010. Am J Obst Gyn. 202(3): 241.e1–241.e6.]
  
• Parental occupational exposure to potential endocrine disrupting chemicals and risk of hypospadias in infants
  The aim of this study was to investigate the association between both maternal and paternal occupational exposures to endocrine disrupting chemcials (EDCs) and hypospadias. Analysis showed a strong association with potential maternal occupational exposure to heavy metals with an over twofold increased risk of hypospadias and women exposed to phthalates were more likely to have an affected son. The risks of moderate–severe hypospadias or multiple defects were increased up to two- and fivefold, respectively, with maternal exposure to most types of EDCs. Paternal occupational exposures to polychlorinated organic and bi-phenolic compounds were also possible risk factors.
  [Nassar, N. et al. 2010. Occup Environ Med 2010;67:585-589]
  
• Maternal Pesticide Exposure and Neural Tube Defects in Mexican Americans
  The relation between maternal pesticide exposures and neural tube defects (NTDs) in offspring was evaluated in 184 Mexican American case-women and 225 comparison women. women who reported using pesticides in their homes or yards were two times more likely to have NTD-affected pregnancies than women without these reported exposures. Case-women were also more likely to report living within 0.25 mile of cultivated fields than control-women. As sources of pesticide exposure opportunities increased, risk of NTDs also increased.
  [Brender, JD., et al. 2010. Ann Epidemiol. 20(1):16-22]
• Correlation Between Pesticide Use in Agriculture and Adverse Birth Outcomes in Brazil: An Ecological Study
  This ecological study analyzed the association between pesticide use and prematurity, low weight and congenital abnormality at birth, infant death by congenital abnormality, and fetal death in Brazil in 2001. The association between pesticide use and low birth weight and, congenital abnormality and infant death rate by congenital abnormality remained after the adjustment made by the proportion of pregnant women with a low number of prenatal care visits.
  [de Siqueira, MT et al. 2010. Bull Environ Contam Toxicol. 84(6):647-51]
• Impact on fetal growth of prenatal exposure to pesticides due to agricultural activities: a prospective cohort study in Brittany, France
  Pregnant women living in a municipality where peas or potatoes were grown had an increased risk of giving birth to an infant with a small head circumference. Head circumference also tended to be lower where wheat was grown, but not to statistically significant degree. The study found no association between head circumference and proximity to other crops. The study’s authors suggest that pesticides, specifically organophosphates, are a possible cause. OPs were applied to most of the area devoted to pea and potato crops, but used less frequently in areas growing corn and wheat.
  [Petit, C., et al. 2010. Environmental Health, 9(71).]
• Glyphosate Formulations Induce Apoptosis and Necrosis in Human Umbilical, Embryonic, and Placental Cells
  One study found that the so-called "inert" ingredient in Roundup amplified the effects of the active, toxic ingredient, glyphosate by causing cell membranes to become more permeable and accelerating the rate of apoptosis and necrosis.
  [Benachour, N., et al. 2009. Chemical Research in Toxicology, 22(1)]
• Risk of limb birth defects and mother's home proximity to cornfields
  Authors studied birth defects in relation to the area of corn or soybeans within 500 m of the mother's residence. Results found that limb birth defects increased in relation to cornfields. None of the birth defect types studied was associated with soybeans.
  [Ochoa-Acuña, H. and Carbajo. C. 2009. Sci Total Environ. 407(15):4447-51]
  
• Agrichemicals in surface water and birth defects in the United States
  Researchers compiled data for monthly concentrations of pesticides/nitrates and birth defect rates between 1996 and 2002, and found that the months (April-July) with the highest rates of pesticides conincided with the months with the highest rates of birth defects.
  [Winchester, P., et al. 2009. Acta Paediatrica, 98(4).]
• Pesticides and hypospadias: A meta-analysis
  Study used meta-analytic techniques to synthesize the findings of the current body of published literature regarding the risk of hypospadias resulting from parental exposure to pesticides. Elevated but marginally significant risks of hypospadias were associated with maternal occupational exposure and paternal occupational exposure. Exposure assessment using a job-exposure matrix resulted in slightly higher estimated risk than agricultural occupation in fathers; but this effect was reversed in mothers, suggesting the importance of indirect and residential pesticide exposures in this group.
  [Rocheleau CM, Romitti PA, Dennis LK. 2009. J Pediatr Urol. 5(1):17-24]
• Use of biocides and insect repellents and risk of hypospadias
  Study found an association between the use of insect repellent and total biocide score and risk of hypospadias. The use of insect repellent during the first trimester of pregnancy was associated with an 81% increased risk of hypospadias.
  [Dugas J., et al. 2009. Occupational and Environmental Medicine, doi:10.1136/oem.2009.047373]
  
• Cryptorchidism at birth in Nice area (France) is associated with higher prenatal exposure to PCBs and DDE, as assessed by colostrum concentrations
  A 2008 study finds a link between total chemical contamination in the bodies of pregnant women and the risk of cryptorchidism in their male babies. Mothers whose babies were born with the defect had the highest concentrations of persistent organic pollutants (POPs), mostly organochlorines like PCB and DDE, in their breast milk. The study compares prebirth exposure to chemicals, as measured through their mother’s milk, and the risk of undescended testicles or cryptorchidism, during a three-year period. While all subjects in the study had detectable levels of these chemicals in either their blood or breast milk, the researchers found that mothers in the highest exposure group for PCBs and DDE in breast milk had two-fold greater odds of giving birth to a boy baby with cryptorchidism, as compared to moms with low to medium exposure. The occurrence of cryptorchidism indicates that testosterone production and/or hormone signaling conditions in the womb have gone awry. Both of these conditions are related to sperm production and the risk of testicular cancer later in life. Cryptorchidism is seen in about 3% of male full-term births, 30% of premature births and is one cause of male infertility.
  [Brucker-Davis F., et al. 2008. Human Reproduction, 23(8).]
• Mammary Gland Development as a Sensitive End Point after Acute Prenatal Exposure to an Atrazine Metabolite Mixture in Female Long-Evans Rats.
  Exposure of rats late in pregnancy to amixture of metabolites of atrazine also leads to persistent changes in mammary gland development in the pups that were exposed during gestation. These abnormalities in prenatally exposed rats persist into adulthood.
  [Enoch R.R., et al. 2006. Environmental Health Perspectives, 115(4).]
• Differential Effects of Glyphosate and Roundup on Human Placental Cells and Aromatase
  A 2005 study finds damaging endocrine effects of glyphosate (Roundup) to fetal growth at levels 10 times lower than used in agriculture. The product formulation Roundup was shown to be at least twice as toxic as the active ingredient alone. According to the researchers, the study demonstrates that Roundup acts as a disruptor of aromatase activity (, a mammalian enzyme crucial for sex steroid hormone synthesis and physiologic functions, including female and male reproduction, sex differentiation, and bone growth.) from concentrations 100 times lower than the recommended use in agriculture. The effect they report is noticeable on human placental cells after only 18 hours.
  [Richard S., et al. 2005. Environmental Health Perspectives, 113(6).]
• Pesticides and children
  This study examines how children are at risk for other effects of organophosphates and synthetic pyrethroids, including physical and mental retardation, alterations of the cardiovascular system and musculoskeletal defects, alterations of the menstrual cycle, obesity, and failure to develop secondary sex characteristics.
  [Garry, V.F., 2004. Toxicology and Applied Pharmacology, 198(2): p. 152-163.]
• Low-Dose Agrochemicals and Lawn-Care Pesticides Induce Developmental Toxicity in Murine Preimplantation Embryos.
  Lawn pesticide products containing herbicides and fertilizers (such as “weed and feed” products) tested on mice show increased risk of infertility, miscarriage and birth defects at very low dosages.
  [Greenlee, A., et al. 2004. Environmental Health Perspectives, 112(6): 703-709.]
• Birth Malformations and Other Adverse Perinatal Outcomes in Four U.S. Wheat-Producing States.
  A 2003 EPA study suggests an association between rates of birth malformations and indirect measures of human exposure to chlorophenoxy herbicides, such as 2,4-D and MCPA, common weed killers sold commercially and used in agriculture. Combined circulatory and respiratory malformations increased by more than two-fold, and musculoskeletal malformations increased by 50%; Death rates from birth malformations among male infants were more than double; and, compared with births conceived during other months of the year, an increased chance of circulatory and respiratory (excluding heart) malformations for infants conceived from April to June, a time that more than 85% of the acreage treated with chlorophenoxy herbicides is applied on durum wheat in the states studied.
  [Schreinemachers, D. 2003. Environmental Health Perspectives, 111(9).]
• Effects of Transplacental Exposure to Environmental Pollutants on Birth Outcomes in a Multiethnic Population.
  A 2003 study finds that prenatal exposure to the pesticide chlorpyrifos adversely affects fetal development. The researchers examined 250 non-smoking African American and Dominican women in the New York City area for prenatal exposure to chlorpyrifos by measuring levels of the pesticide in the umbilical cord of the newborn. The results associated chlorpyrifos presence with decreased birth weight and birth length.
  [Perera, F. et al. Feb. 2003. Environmental Health Perspectives, 111(2).]
• Developmental neurotoxicity of chlorpyrifos modeled in vitro: Comparative effects of metabolites and other cholinesterase inhibitors on DNA synthesis in PC12 and C6 cells.
  A 2001 published study finds that organophosphate pesticides and their major metabolites can affect a fetus or newborn at concentrations that are nontoxic to adults. The study compared the effects of these pesticides in two in vitro models, using neuronotypic and gliotypic cells.
  [Qiao, D. et al. 2001. Environmental Health Perspectives, 109(9):909-913.]
• Chlorpyrifos (Dursban)-associated birth defects: report of four cases.
  A 1996 study of children exposed to chlorpyrifos in utero found that extensive and unusual patterns of birth defects, including brain, nervous system, eyes, ears, palate, teeth, heart, feet, nipples, and genitalia. Published literature and EPA documents contain reports that identify similarities in defects found in test animals and children exposed to chlorpyrifos.
  [Sherman, J.D. 1996. Environmental Health Perspectives, 51(1).]
• Pesticide appliers, biocides, and birth defects in rural Minnesota.
  A study of live births in Minnesota farming communities links the use of 2,4-D and other penoxy-acetic acid-derived herbicides to significantly higher rates of central nervous system, urogenital, circulatory/respiratory, or musculoskeletal anomalies in the children of pesticide applicators versus the average population.
  [Garry, V., et al. 1996. Environmental Health Perspectives 104(4):394-399.]