Table 2.
Case-control studies examining hypospadias and environmental endocrine-disrupting chemicals (EDCs) during pregnancy
| Author, citation number (year) | Country Subjects (cases) | EDCs Data source (relation to pregnancy) | Covariates | Significant findings |
|---|---|---|---|---|
| Phthalates/phthalate metabolites | ||||
| Chevrier, [25] (2012) | France 63 (21 cases) |
Low MWP, ΣDEHP metabolites, high MWP Maternal urine (after birth) |
Cases and controls matched for residence area, gestational age at urine sample collection, and date and day of collection (Sunday–Monday vs. other) | • MEP, MBP, and MiBP at intermediate concentrations (OR 0.15; 95% CI 0.02–0.9) |
| Jensen, [26•] (2015) | Denmark 300 (75 cases) |
Metabolites of DEHP, DiNP Amniotic fluid (second trimester) |
No confounders described. Amniocentesis indication was generally maternal age > 35 but there were some cases with identified congenital abnormalities | • No association with DiNP metabolites (OR 1.69; 95% CI 0.78–3.67) or DEHP metabolites. |
| Persistent organic pollutants | ||||
| Carmichael, [27] (2010) | USA 48 (28 cases) |
5 PBDE and 4 PCB congeners Maternal serum (second trimester) |
Foreign-born Hispanic race-ethnicity, time elapsed between blood collections, and AFP analysis | • No notable association found for PBDE 28, 47, 99, 100, 153 or for PCB 52, 99, 153, 180. |
| Giordano, [28] (2010) | USA 58 (21 cases) |
DDE, HCB, and 4 PCB congeners Maternal serum (third trimester) |
Lipid (%), maternal age, and breastfeeding duration | • Serum HCB concentration above the median of all subjects (OR 5.50; 95% CI 1.24-24.31) • HCB as a continuous variable (OR 1.26; 95% CI 1.04–1.52) • PCB118 (OR 1.40; 95% CI 0.99–1.97). |
| McGlynn, [29] (2009) | USA 794 (201 cases) |
11 PCB congeners Maternal serum (third trimester) |
Serum triglycerides, cholesterol, DDE levels | • No notable associations |
| Rignell-Hydbom, [30] (2012) | Sweden 472 (237 cases) |
PBC-153, p,p′-DDE, HCB Maternal serum (week 14 of gestation) |
Controls matched for maternal age, birth year, parity and maternal smoking habits in early pregnancy | • p,p’-DDE levels above the median (OR 1.69; 95% CI 0.97–2.93) • p,p’-DDE highest quartile (OR 1.65; 95% CI 1.02–2.69) |
| Toft, [31] (2016) | Denmark 375 (75 cases) |
Perfluorooctane Sulfonate Amniotic fluid (after 15 weeks gestation from amniocentesis) |
Gestational age of amniocentesis, year of amniocentesis, maternal age, gestational age at delivery, birth weight, and maternal cotinine (smoking) | • No notable association |
| Pesticides | ||||
| Agopian, [32] (2013) | USA 16,433 (9647 cases) |
Atrazine Estimated concentration in maternal water supply based on US Geological Survey data (Water levels at birth and at delivery) |
Season of conception, birth year, and maternal age, race-ethnicity, education, history of previous live births, birthplace, and smoking | • Medium-low (OR 1.11; 95% CI 1.04–1.18) and medium levels (OR 1.22; 95% CI 1.12–1.33) of atrazine associated with all hypospadias. • Medium-low (OR 1.52; 95% CI 1.25–1.85) and medium levels (OR 1.44; 95% CI 1.11–1.85) of atrazine associated with midshaft and proximal hypospadias. • High levels protective (OR 0.82; 95% CI 0.74–0.91) |
| Bhatia, [33] (2005) | USA 353 (70 cases) |
DDT and DDE Maternal serum (latest possible serum from pregnancy, otherwise earliest postpartum serum) |
Triglyceride level, cholesterol level, maternal age, pre-pregnancy BMI, parity, maternal ethnicity, maternal place of birth, maternal occupation before pregnancy, birth weight, gestational age, date of blood draw, and season of birth | • No notable effect of DDT or DDE |
| Dugas, [34] (2010) | England 961 (471 cases) |
Biocides and insect repellants Maternal questionnaire and tallying of insect repellant exposure and “biocide score” exposure index (first trimester of pregnancy |
Maternal smoking, maternal age, parental income, birth weight, previous stillbirth, folate intake during first 3 months of pregnancy) | • Use of insect repellent (OR 1.81; 95% CI 1.06–3.11). • High biocide scores (score 3; OR 1.73; 95% CI 1.02–2.94; scores 4 and 5 combined: OR 2.98; 95% CI 1.01–8.78) |
| Flores-Luévano, [35] (2003) | Mexico 69 (41 cases) |
DDT and DDE Maternal Serum |
Age of the mother, age of the father, lactation and employment during the pregnancy | • No notable effect |
| Longnecker, [36] (2002) | USA 751 (199 cases) |
DDE Maternal serum (during the first and third trimesters) |
Race, triglyceride levels, cholesterol levels | • No notable effect |
| Trabert, [37] (2012) | USA 754 (197 cases) |
Chlordanes: trans-nonachlor and oxychlordane Maternal serum (third trimester of pregnancy) |
Serum p,p′-DDE (5 categories), total PCBs (four categories), serum triglycerides, serum cholesterol, socioeconomic index | • Trans-nonachlor concentrations (ORs 0.84–1.08; 95% CI all including 1.0). • Oxychlordane concentrations (ORs 1.06–1.24; 95% CI all including 1.0) |
| Winston, [38] (2016) | USA 1765 (343 cases) |
Atrazine Estimated concentration in maternal water supply based on US Geological Survey data (Gestation weeks 6–16) |
Private well use, residential use of water filtration, state of residence, maternal age, maternal race-ethnicity, multiple or singleton birth, previous pregnancies, maternal education, maternal diabetes, maternal hypertension, maternal BMI, choline use, and use of artificial reproductive technology. | • No notable effect |
Abbreviations: DDE, dichlorodiphenyldichloroethylene; DEHP, bis(2-ethylhexyl) phthalate; DiNP, diisononyl phthalate; HCB, hexachlorobenzene; MBP, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene; MiBP, monoisobutyl phthalate; MWP, molecular weight pthalate; p,p′-DDE, 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene; PBDE, polybrominated diphenyl ethers; PCB, polychlorinated biphenyl