Bibliography Tag: birth defects

Landrigan, 2018

Philip J. Landrigan, “Pesticides and Human Reproduction,” JAMA Internal Medicine, 2018, 178:1, DOI:10.1001/jamainternmed.2017.5092


Invited commentary by Managing Weeds for Healthy Kids science team member Dr. Landrigan reports that herbicide use has increased sharply, with glyphosate use up 250-fold from 1974 to 2014.  And, “measurable levels of multiple pesticides are found in the bodies of nearly all Americans…and pesticides are capable of causing a wide range of asymptomatic effects at levels of exposure too low to produce overt signs and symptoms.”  New theories suggest that long term exposure to pesticides cause this kind of subclinical toxicity.  Dr. Landrigan reviews the known linkages, including in utero chlorpyrifos exposure leading to neurodevelopmental deficits, and reproductive injury including adverse birth outcomes and birth defects. He recommends: “We need to overcome the strident objections of the pesticide manufacturing industry, recognize the hidden costs of deregulation, and strengthen requirements for both premarket testing of new pesticides, as well as postmarketing surveillance of exposed populations— exactly as we do for another class of potent, biologically active molecules—drugs.”  FULL TEXT

Winston et al., 2016

Jennifer J. Winston, Michael Emch, Robert E. Meyer, Peter Langlois, Peter Weyer, Bridget Mosley, Andrew F. Olshan, Lawrence E. Band, Thomas J. Luben and the National Birth Defects Prevention Study, “Hypospadias and maternal exposure to atrazine via drinking water in the National Birth Defects Prevention study,” Environmental Health, 15:76, DOI: 10.1186/s12940-016-0161-9


BACKGROUND: Hypospadias is a relatively common birth defect affecting the male urinary tract. It has been suggested that exposure to endocrine disrupting chemicals might increase the risk of hypospadias by interrupting normal urethral development.

METHODS: Using data from the National Birth Defects Prevention Study, a population-based case-control study, we considered the role of maternal exposure to atrazine, a widely used herbicide and potential endocrine disruptor, via drinking water in the etiology of 2nd and 3rd degree hypospadias. We used data on 343 hypospadias cases and 1,422 male controls in North Carolina, Arkansas, Iowa, and Texas from 1998–2005. Using catchment level stream and groundwater contaminant models from the US Geological Survey, we estimated atrazine concentrations in public water supplies and in private wells. We assigned case and control mothers to public water supplies based on geocoded maternal address during the critical window of exposure for hypospadias (i.e., gestational weeks 6–16). Using maternal questionnaire data about water consumption and drinking water, we estimated a surrogate for total maternal consumption of atrazine via drinking water. We then included additional maternal covariates, including age, race/ethnicity, parity, and plurality, in logistic regression analyses to consider an association between atrazine and hypospadias.

RESULTS: When controlling for maternal characteristics, any association between hypospadias and daily maternal atrazine exposure during the critical window of genitourinary development was found to be weak or null (odds ratio for atrazine in drinking water = 1. 00, 95 % CI = 0.97 to 1.03 per 0.04 μg/day increase; odds ratio for maternal consumption = 1.02, 95 % CI = 0.99 to 1.05; per 0.05 μg/day increase).

CONCLUSIONS: While the association that we observed was weak, our results suggest that additional research into a possible association between atrazine and hypospadias occurrence, using a more sensitive exposure metric, would be useful.  FULL TEXT

Agopian et al., 2013a

A.J. Agopian, PhD, Yi Cai, MS, Peter H. Langlois, PhD, Mark A. Canfield, PhD, and Philip J. Lupo, PhD, “Maternal Residential Atrazine Exposure and Risk for Choanal Atresia and Stenosis in Offspring,” Journal of Pediatrics 2013, 162:3, DOI: 10.1016/j.jpeds.2012.08.012


OBJECTIVE: To assess the relationship between estimated residential maternal exposure to atrazine during pregnancy and the risk for choanal atresia or stenosis in offspring.

STUDY DESIGN: Data for 280 nonsyndromic cases and randomly selected, population-based controls delivered between 1999 and 2008 were obtained from the Texas Birth Defects Registry. County-level estimates of atrazine levels obtained from the US Geological Survey were assigned to cases and controls based on maternal county of residence at delivery. Unconditional logistic regression was used to assess the relationship between maternal residential atrazine exposure and the risk for choanal atresia or stenosis in offspring.

RESULTS: Compared with offspring of mothers with low levels of estimated residential atrazine exposure, those with high levels had nearly a 2-fold increase in risk for choanal atresia or stenosis (aOR, 1.79; 95% CI, 1.17-2.74). A significant linear trend was also observed with increasing levels of atrazine exposure (adjusted P = .002).

CONCLUSION: A link between maternal exposure to endocrine disruptors, such as atrazine, and the risk of choanal atresia is plausible based on previous findings. Our results lend further support to this hypothesis.  FULL TEXT

Avila-Vazquez et al., 2018

Avila-Vazquez, M., Difilippo, F.S., Lean, B.M., Maturano, E. and Etchegoyen, A., “Environmental Exposure to Glyphosate and Reproductive Health Impacts in Agricultural Population of Argentina,” Journal of Environmental Protection, 2018, 9, DOI: 10.4236/jep.2018.93016.


Argentina annually utilizes 240,000 tones of glyphosate in industrial agriculture and a change in the profile of morbidity is perceived for physicians of agricultural areas; now reproductive disorders seem to prevail. The objective of this study is to determine concurrence of glyphosate exposure and  reproductive disorders in a typical argentine agricultural town (Monte Maíz). An ecological study was developed with an environmental analysis of pollution sources including measurements of glyphosate and other pesticides and a cross-sectional study of spontaneous abortions and congenital abnormalities prevalence. Glyphosate was detected in soil and grain dust and was found to be at an even higher concentration in the village soil than in the rural area; 650 tonnes of glyphosate are used annually in the region and manipulated inner town contaminating the soil and dust in suspension of the town creating an burden of environmental exposure to glyphosate of 79 kg per person per year. We do not find other relevant sources of pollution. The spontaneous abortion and congenital abnormalities rates are three and two times higher than the national average reported by the national health (10% vs. 3% and 3% – 4.3% vs 1.4% respectively). Our study verified high environmental exposure to glyphosate in association with increased frequencies of reproductive disorders  (spontaneous abortion and congenital abnormalities) in argentine agricultural village, but is unable to make assertions cause-effect. Further studies are required with designs for such purposes. FULL TEXT

Di Renzo et al., 2015

Gian Carlo Di Renzo, Jeanne A. Conry, Jennifer Blake, Mark S. DeFrancesco, Nathaniel DeNicola, James N. Martin Jr., Kelly A. McCue, David Richmond, Abid Shah, Patrice Sutton, Tracey J. Woodruff, Sheryl Ziemin van der Poel, Linda C. Giudice, “International Federation of Gynecology and Obstetrics opinion on reproductive health impacts of exposure to toxic environmental chemicals,” International Journal of Gynecology and Obstetrics, 2015, 131, DOI: 10.1016/j.ijgo.2015.09.002


Exposure to toxic environmental chemicals during pregnancy and breastfeeding is ubiquitous and is a threat to healthy human reproduction. There are tens of thousands of chemicals in global commerce, and even small exposures to toxic chemicals during pregnancy can trigger adverse health consequences. Exposure to toxic environmental chemicals and related health outcomes are inequitably distributed within and between countries; universally, the consequences of exposure are disproportionately borne by people with low incomes. Discrimination, other social factors, economic factors, and occupation impact risk of exposure and harm. Documented links between prenatal exposure to environmental chemicals and adverse health outcomes span the life course and include impacts on fertility and pregnancy, neurodevelopment, and cancer. The global health and economic burden related to toxic environmental chemicals is in excess of millions of deaths and billions of dollars every year. On the basis of accumulating robust evidence of exposures and adverse health impacts related to toxic environmental chemicals, the International Federation of Gynecology and Obstetrics (FIGO) joins other leading reproductive health professional societies in calling for timely action to prevent harm. FIGO recommends that reproductive and other health professionals advocate for policies to prevent exposure to toxic environmental chemicals, work to ensure a healthy food system for all, make environmental health part of health care, and champion environmental justice. FULL TEXT

Romano et al., 2011

Romano MA, Romano RM, Santos LD, Wisniewski P, Campos DA, de Souza PB, Viau P, Bernardi MM, Nunes MT, de Oliveira CA, “Glyphosate impairs male offspring reproductive development by disrupting gonadotropin expression.,” Archives in Toxicology, 2012, 86:4, DOI: 10.1007/s00204-011-0788-9.


Sexual differentiation in the brain takes place from late gestation to the early postnatal days. This is dependent on the conversion of circulating testosterone into estradiol by the enzyme aromatase. The glyphosate was shown to alter aromatase activity and decrease serum testosterone concentrations. Thus, the aim of this study was to investigate the effect of gestational maternal glyphosate exposure (50 mg/kg, NOAEL for reproductive toxicity) on the reproductive development of male offspring. Sixty-day-old male rat offspring were evaluated for sexual behavior and partner preference; serum testosterone concentrations, estradiol, FSH and LH; the mRNA and protein content of LH and FSH; sperm production and the morphology of the seminiferous epithelium; and the weight of the testes, epididymis and seminal vesicles. The growth, the weight and age at puberty of the animals were also recorded to evaluate the effect of the treatment. The most important findings were increases in sexual partner preference scores and the latency time to the first mount; testosterone and estradiol serum concentrations; the mRNA expression and protein content in the pituitary gland and the serum concentration of LH; sperm production and reserves; and the height of the germinal epithelium of seminiferous tubules. We also observed an early onset of puberty but no effect on the body growth in these animals. These results suggest that maternal exposure to glyphosate disturbed the masculinization process and promoted behavioral changes and histological and endocrine problems in reproductive parameters. These changes associated with the hypersecretion of androgens increased gonadal activity and sperm production.

Mostafalou and Abdollahi, 2017

Sara Mostafalou and Mohammad Abdollahi, “Pesticides: an update of human exposure and toxicity,” Archives of Toxicology, February 2017, 91:2, DOI: 10.1007/s00204-016-1849-x.


Pesticides are a family of compounds which have brought many benefits to mankind in the agricultural, industrial, and health areas, but their toxicities in both humans and animals have always been a concern. Regardless of acute poisonings which are common for some classes of pesticides like organophosphoruses, the association of chronic and sub-lethal exposure to pesticides with a prevalence of some persistent diseases is going to be a phenomenon to which global attention has been attracted. In this review, incidence of various malignant, neurodegenerative, respiratory, reproductive, developmental, and metabolic diseases in relation to different routes of human exposure to pesticides such as occupational, environmental, residential, parental, maternal, and paternal has been systematically criticized in different categories of pesticide toxicities like carcinogenicity, neurotoxicity, pulmonotoxicity, reproductive toxicity, developmental toxicity, and metabolic toxicity. A huge body of evidence exists on the possible role of pesticide exposures in the elevated incidence of human diseases such as cancers, Alzheimer, Parkinson, amyotrophic lateral sclerosis, asthma, bronchitis, infertility, birth defects, attention deficit hyperactivity disorder, autism, diabetes, and obesity. Most of the disorders are induced by insecticides and herbicides most notably organophosphorus, organochlorines, phenoxyacetic acids, and triazine compounds.

Weselak et al., 2007

Weselak M, Arbuckle TE, Foster W., “Pesticide exposures and developmental outcomes: the epidemiological evidence.,” Journal of Toxicology and Environmental Health, Part B, Critical Reviews, 1-2, 2007,  DOI: 10.1080/10937400601034571


Since the advent of DDT as an insecticide in the late 1930s, billions of kilograms of pesticide active ingredient have been sold in North America and around the world. In recent years, there has been a heightened public awareness of pesticides and child health and a number of epidemiologic studies linked pre- and postnatal exposures to pesticides to a number of adverse developmental outcomes, including fetal death, intrauterine growth restriction, preterm birth, and birth defects. Given this, it was felt prudent to critically appraise the evidence for periconceptual pesticide exposures and developmental outcomes. The epidemiological evidence for specific pesticide classes, families, and active ingredients were examined and summarized and recommendations were made for how to improve future studies in order to address the current pitfalls and gaps in the studies in this area. Many of the studies suffered from poor exposure estimation, relying on job title only and/or the exposure category “any pesticide” as a measure of exposure, and there was limited or inadequate evidence to support causality for all associations examined.

Rull et al., 2006

Rudolph P. Rull Beate Ritz Gary M. Shaw, “Neural Tube Defects and Maternal Residential Proximity to Agricultural Pesticide Applications,” American Journal of Epidemiology, 163:8, 15 April 2006, DOI: 10.1093/aje/kwj101


Residential proximity to applications of agricultural pesticides may be an important source of exposure to agents that have been classified as developmental toxins. Data on two case-control study populations of infants with neural tube defects (NTDs) and nonmalformed controls delivered in California between 1987 and 1991 were pooled to investigate whether maternal residential proximity to applications of specific pesticides or physicochemical groups of pesticides during early gestation increases the risk of these malformations. Maternal residential proximity within 1,000 m of pesticide applications was ascertained by linking mothers’ addresses with agricultural pesticide use reports and crop maps. Odds ratios were computed by using conventional single- and multiplepesticide and hierarchical multiple-pesticide logistic regression. In single-pesticide models, several pesticides were associated with NTDs after adjustment for study population, maternal ethnicity, educational level, cigarette smoking, and vitamin use. In a hierarchical multiple-pesticide model, effect estimates for only benomyl and methomyl suggested a possible association. Elevated risks of NTDs and anencephaly or spina bifida subtypes were also  associated with exposures to chemicals classified as amide, benzimidazole, methyl carbamate, or organophosphorus pesticides and with increasing numbers of pesticides. These results suggest that ambient exposure to certain categories of agricultural pesticides may increase the risk of NTDs.  FULL TEXT

Benachour et al., 2007

N. Benachour, H. Sipahutar, S. Moslemi, C. Gasnier, C. Travert, G. E. Séralini, “Time- and Dose-Dependent Effects of Roundup on Human Embryonic and Placental Cells,” Archives of Environmental Contamination and Toxicology, 53:1, July 2007, DOI:


Roundup® is the major herbicide used worldwide, in particular on genetically modified plants that have been designed to tolerate it. We have tested the toxicity and endocrine disruption potential of Roundup (Bioforce®) on human embryonic 293 and placental-derived JEG3 cells, but also on normal human placenta and equine testis. The cell lines have proven to be suitable to estimate hormonal activity and toxicity of pollutants. The median lethal dose (LD50) of Roundup with embryonic cells is 0.3% within 1 h in serum-free medium, and it decreases to reach 0.06% (containing among other compounds 1.27 mM glyphosate) after 72 h in the presence of serum. In these conditions, the embryonic cells appear to be 2–4 times more sensitive than the placental ones. In all instances, Roundup (generally used in agriculture at 1–2%, i.e., with 21–42 mM glyphosate) is more efficient than its active ingredient, glyphosate, suggesting a synergistic effect provoked by the adjuvants present in Roundup. We demonstrated that serum-free cultures, even on a short-term basis (1 h), reveal the xenobiotic impacts that are visible 1–2 days later in serum. We also document at lower non-overtly toxic doses, from 0.01% (with 210 μM glyphosate) in 24 h, that Roundup is an aromatase disruptor. The direct inhibition is temperature-dependent and is confirmed in different tissues and species (cell lines from placenta or embryonic kidney, equine testicular, or human fresh placental extracts). Furthermore, glyphosate acts directly as a partial inactivator on microsomal aromatase, independently of its acidity, and in a dose-dependent manner. The cytotoxic, and potentially endocrine-disrupting effects of Roundup are thus amplified with time. Taken together, these data suggest that Roundup exposure may affect human reproduction and fetal development in case of contamination. Chemical mixtures in formulations appear to be underestimated regarding their toxic or hormonal impact. FULL TEXT