Menstrual and reproductive characteristics of women whose mothers were exposed in utero to diethylstilbestrol (DES)

BACKGROUND: In women, prenatal exposure to diethylstilbestrol (DES) is associated with adult reproductive dysfunction. The mouse model, which replicates many DES outcomes, suggests DES causes epigenetic alterations, which are transmissable to daughters of prenatally exposed animals. We report menstrual and reproductive characteristics in a unique cohort comprising daughters of women exposed prenatally to DES. METHODS: Menstrual and reproductive outcomes and baseline characteristics were assessed by mailed questionnaire in 793 women whose mothers had documented information regarding in utero DES exposure. RESULTS: Mean age at menarche was 12.6 years in both groups, but daughters of the exposed women attained menstrual regularization later (mean age of 16.2 years vs. 15.8 years; P = 0.05), and were more likely to report irregular menstrual periods, odds ratio (OR) = 1.54 [95% confidence interval (95% CI 1.02-2.32)]. A possible association between mothers' DES exposure and daughters' infertility was compatible with chance, age, and cohort adjusted OR = 2.19 (95% CI 0.95-5.07). We found limited evidence that daughters of the exposed had more adverse reproductive outcomes, but daughters of exposed women had fewer live births (1.6) than the unexposed (1.9) (P = 0.005). CONCLUSIONS: The high risk of reproductive dysfunction seen in women exposed to DES in utero was not observed in their daughters, but most women in our cohort have not yet attempted to start their families, and further follow-up is needed to assess their reproductive health. Our findings of menstrual irregularity and possible infertility in third-generation women are preliminary but compatible with speculation regarding transgenerational transmission of DES-related epigenetic alterations in humans.     

Offspring of women exposed in utero to diethylstilbestrol (DES): a preliminary report of benign and malignant pathology in the third generation

BACKGROUND: Animal studies suggest that prenatal exposure to the synthetic estrogen diethylstilbestrol (DES) causes epigenetic changes that may be transmitted to the next generation. Specifically, these studies show an elevated incidence of reproductive tumors in the female offspring of prenatally-exposed mice. METHODS: We assessed cancer and benign pathology diagnoses occurring in the offspring of women whose prenatal exposure to DES (or lack of exposure) was verified by medical record. Our data arose from 2 sources: the mothers' reports of cancers occurring in 8216 sons and daughters, and pathology-confirmed cancers and benign diagnoses self-reported by a subset of 793 daughters. RESULTS: Although statistical power is limited, our data are consistent with no overall increase of cancer in the sons or daughters of women exposed in utero to DES. Based on pathology-confirmed diagnoses reported by the daughters, we saw no association between DES and risk of benign breast disease or reproductive tract conditions. Based on 3 cases, the incidence of ovarian cancer was higher than expected in the daughters of women exposed prenatally to DES. CONCLUSIONS: Our data do not support an overall increase of cancer risk in the sons or daughters of women exposed prenatally to DES, but the number of ovarian cancer cases was greater than expected. While preliminary, this finding supports continued monitoring of these daughters.     

DES exposure and the aging woman: mothers and daughters

Diethylstilbestrol (DES), the first orally active artificial estrogen ever developed, was prescribed to several million pregnant women during the 1940s through the 1960s in the mistaken belief that it reduced the risk of miscarriage. In 1971, the US Food and Drug Administration contraindicated its use in pregnancy when DES was associated with the development of vaginal clear cell adenocarcinoma (CCA) in daughters exposed in utero. In daughters whose mothers took DES during pregnancy, the drug has been associated with congenital malformations of the reproductive tract, fertility problems, a possible increased risk of cervical carcinoma in situ, and a presumed lifetime risk of vaginal and cervical CCA. DES mothers have an increased risk of breast cancer (RR = 1.3). DES sons have an increased prevalence of urogenital anomalies, and a possible increased risk of testicular cancer.     

Secondary sex ratio among women exposed to diethylstilbestrol in utero

BACKGROUND: Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the mid-1900s, is a potent endocrine disruptor. Previous studies have suggested an association between endocrine-disrupting compounds and secondary sex ratio. METHODS: Data were provided by women participating in the National Cancer Institute (NCI) DES Combined Cohort Study. We used generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relation of in utero DES exposure to sex ratio (proportion of male births). Models were adjusted for maternal age, child's birth year, parity, and cohort, and accounted for clustering among women with multiple pregnancies. RESULTS: The OR for having a male birth comparing DES-exposed to unexposed women was 1.05 (95% CI, 0.95-1.17). For exposed women with complete data on cumulative DES dose and timing (33%), those first exposed to DES earlier in gestation and to higher doses had the highest odds of having a male birth. The ORs were 0.91 (95% C, 0.65-1.27) for first exposure at > or = 13 weeks gestation to < 5 g DES; 0.95 (95% CI, 0.71-1.27) for first exposure at > or = 13 weeks to > or = 5 g; 1.16 (95% CI, 0.96-1.41) for first exposure at < 13 weeks to < 5 g; and 1.24 (95% CI, 1.04-1.48) for first exposure at < 13 weeks to > or = 5 g compared with no exposure. Results did not vary appreciably by maternal age, parity, cohort, or infertility history. CONCLUSIONS: Overall, no association was observed between in utero DES exposure and secondary sex ratio, but a significant increase in the proportion of male births was found among women first exposed to DES earlier in gestation and to a higher cumulative dose.     

Randomised trial of high doses of stilboestrol and ethisterone therapy in pregnancy: long-term follow-up of the children.

The 27-year follow-up is reported of 136 children whose mothers were involved in a randomised trial of high doses of stilboestrol and ethisterone therapy during pregnancy. The children were not contacted directly. Information about them was obtained from hospitals, general practitioners, and other official sources; and the persons who responded to our inquiries were unaware of who had been exposed to hormones in utero and whose mothers had received an inactive tablet. All children were traced. Urogenital anomalies were reported more frequently in the hormone-exposed than the unexposed children (14% and 9% respectively). The earlier in pregnancy the therapy began, the higher the prevalence rate of abnormalities (X2 for trend, p less than 0.02). No malignant tumours were reported. For males, the proportion reported to be married or living as married was lower in the exposed than in the unexposed group (32% and 62% respectively). The proportion was lower the earlier in pregnancy hormonal exposure occurred and the higher the total hormone dose to which they were exposed (X2 for trend, p less than 0.02). These findings suggest that some interference with sexual function may not be uncommon in males exposed to high doses of stilboestrol and ethisterone while in utero.     

Incidence of squamous neoplasia of the cervix and vagina in des-exposed daughters

PURPOSE: Women exposed to diethylstibestrol (DES) in utero are known to have an excess risk of clear cell adenocarcinoma of the vagina and cervix, in addition to vaginal epithelial changes, but the effect on the incidence of squamous neoplasia is uncertain. This study evaluated the long-term risk of developing high-grade squamous neoplasia of the genital tract among women exposed prenatally to diethylstilbestrol.METHODS: A cohort comprising 3899 DES-exposed and 1374 unexposed daughters was followed for thirteen years (1982-1995) for pathology-confirmed diagnoses of high-grade squamous neoplasia. A pathologist blinded to exposure status reviewed seventy-seven percent of cases. Poisson regression analysis was used to compute relative risks (RR) and 95% confidence intervals (CI) controlling for age, calendar year, screening history and other covariates.RESULTS: The RR (95% CI) among DES-exposed versus unexposed, based on 111 cases of high-grade disease, was 2.12 (1.19-3.77). Adjustment for screening history had little effect, but when the analysis was restricted to a group highly screened before 1982, the risk was reduced. Risk estimates were higher among women exposed earlier in gestation; the RR (95% CI) for exposure within 7 weeks of the last menstrual period was 2.82 (1.43-5.53).CONCLUSIONS: The findings support an association between in utero DES exposure and high-grade squamous neoplasia, although a role for more intensive screening among DES-exposed women in the production of this excess could not be completely ruled out.     

Maternal Exposure to a Brominated Flame Retardant and Genitourinary Conditions in Male Offspring

Background

The upward trend in industrial nations in the incidence of male genitourinary (GU) conditions may be attributed to increased exposure to endocrine disruptors. Polybrominated biphenyl (PBB), a brominated flame retardant, is one such suspected endocrine disruptor.

Objective

We investigated the relationship between maternal serum levels of PBBs and GU conditions among male offspring exposed in utero.

Methods

In this cohort study of sons born to women accidentally exposed to PBBs during 1973–1974, we examined self-reported data on GU conditions among male offspring in relation to maternal serum PBB levels. We used generalized estimating equations to calculate odds ratios (ORs), controlling for gestational age at birth.

Results

Of 464 sons, 33 reported any GU condition (13 hernias, 10 hydroceles, 9 cryptorchidism, 5 hypospadias, and 1 varicocele). Four reported both hernia and hydrocele, and one both hernia and cryptorchidism. After adjustment for gestational age at birth, sons of highly exposed women (> 5 ppb) were twice as likely to report any GU condition compared with sons of the least exposed women [≤1 ppb; OR = 2.0; 95% confidence interval (CI), 0.8–5.1]. This risk was increased when we excluded sons born after the exposure but before the mother’s serum PBB measurement (OR = 3.1; 95% CI, 1.0–9.1). We found evidence of a 3-fold increase in reported hernia or hydrocele among sons with higher PBB exposure (test of trend p-value = 0.04). Neither hypospadias nor cryptorchidism was individually associated with PBB exposure.

Conclusions

Although cryptorchidism and hypospadias were not associated with in utero PBB exposure, this study suggests that other GU conditions may be associated with exposure to endocrine-disrupting chemicals during development.     

A case-control study of testicular cancer using Connecticut tumour registry data

This case-control study was designed to determine whether males who were exposed to diethylstilboestrol (DES) in utero are at increased risk of testicular cancer. Questionnaires were completed for 79 residents of Connecticut, who were diagnosed with primary cancer of the testes between 1945 and approximately six months into 1980. An equal number of matched controls drawn from birth certificate records available from the Connecticut State Department of Health Services also submitted questionnaires. Information included data on past medical conditions of subjects and obstetrical history of mothers. The major finding of this study was a statistically significant elevated risk for premature birth for the testicular cancer cases. The study failed to show that DES increased the risk for testicular cancer. However, in view of the findings from previous human and animal studies of such abnormalities as undescended and hypoplastic testes as well as the consideration that only the earliest exposed birth cohort has reached the age of substantial cancer risk, it would seem prudent for any male who has been prenatally exposed to DES to seek medical follow-up.     

Maternal and gestational risk factors for hypospadias

BACKGROUND: An increase in the prevalence of hypospadias has been reported, but the environmental causes remain virtually unknown. OBJECTIVES: Our goal was to assess the association between risk of hypospadias and indicators of placental function and endogenous hormone levels, exposure to exogenous hormones, maternal diet during pregnancy, and other environmental factors. METHODS: We conducted a case-control study in Sweden and Denmark from 2000 through 2005 using self-administered questionnaires completed by mothers of hypospadias cases and matched controls. The response rate was 88% and 81% among mothers of cases and controls, respectively. The analyses included 292 cases and 427 controls. RESULTS: A diet during pregnancy lacking both fish and meat was associated with a more than 4-fold increased risk of hypospadias [odds ratio (OR) = 4.6; 95% confidence interval (CI), 1.6-13.3]. Boys born to obese [body mass index (BMI) > or = 30] women had a more than 2-fold increased risk of hypospadias (OR = 2.6; 95% CI, 1.2-5.7) compared with boys born to mothers with a normal weight (BMI = 20-24). Maternal hypertension during pregnancy and absence of maternal nausea increased a boy's risk of hypospadias 2.0-fold (95% CI, 1.1-3.7) and 1.8-fold (95% CI, 1.2-2.8), respectively. Nausea in late pregnancy also appeared to be positively associated with hypospadias risk (OR = 7.6; 95% CI, 1.1-53). CONCLUSIONS: A pregnancy diet lacking meat and fish appears to increase the risk of hypospadias in the offspring. Other risk associations were compatible with a role for placental insufficiency in the etiology of hypospadias.     

Breast cancer incidence in women prenatally exposed to maternal cigarette smoke

BACKGROUND: Clinical studies show that maternal cigarette smoking reduces pregnancy estrogen levels. Women prenatally exposed to maternal cigarette smoke may, therefore, have a lower breast cancer risk because the fetal mammary gland's exposure to maternal estrogen is decreased. Associations between prenatal maternal cigarette smoke exposure and breast cancer, however, have not been observed in previous case-control studies that relied on exposure assessment after the onset of cancer. At the start of this study, cigarette smoking history was obtained directly from the mother. METHODS: The National Cooperative DES Adenosis project was a follow-up study of health outcomes in women prenatally exposed to diethylstilbestrol (DES). At the start of the study, women's mothers provided information about cigarette smoking habits during the time they were pregnant with the study participant. In the current study, the breast cancer rates are compared among 4031 women who were or were not prenatally exposed to maternal cigarette smoke. The resultant relative rate (RR) is adjusted for potential confounding by other breast cancer risk factors using Poisson regression modeling. RESULTS: Fetal exposure to maternal cigarette smoke appeared to be inversely associated with breast cancer incidence (RR = 0.49; 95% confidence interval [CI] = 0.24-1.03). The inverse association was more apparent among women whose mothers smoked 15 cigarettes or fewer per day than among daughters of heavier smokers. There were, however, too few cases to precisely estimate a possible dose-response relationship. CONCLUSION: These results support the hypothesis that in utero exposure to maternal cigarette smoke reduces breast cancer incidence.     

Endocrine disruptor compounds and their role in the developmental programming of the reproductive axis

Different perturbations during fetal and postnatal development unleash endocrine adaptations that permanently alter metabolism, increasing the susceptibility to develop later disease, process known as "developmental programming." Endocrine disruptor compounds (EDC) are widely spread in the environment and display estrogenic, anti-estrogenic or anti-androgenic activity; they are lipophilic and stored for long periods in the adipose tissue. Maternal exposure to EDC during pregnancy and lactation produces the exposure of the fetus and neonate through placenta and breast milk. Epidemiological and experimental studies have demonstrated reproductive alterations as a consequence of intrauterine and/or neonatal exposure to EDC. Diethystilbestrol (DES) is the best documented compound, this synthetic estrogen was administered to pregnant women in the 1950s and 1960s to prevent miscarriage. It was implicated in urogenital abnormalities in children exposed in utero and was withdrawn from the market. The "DES daughters" are women with high incidence of vaginal hypoplasia, spontaneous abortion, premature delivery, uterine malformation, menstrual abnormalities and low fertility. The "DES sons" show testicular dysgenesis syndrome, which is characterized by hypospadias, cryptorchidism and low semen quality. This entity is also associated wtih fetal exposure to anti-androgens as flutamide. The effects on the reproductive axis depend on the stage of development and the window of exposure, as well as the dose and the compound. The wide distribution of EDC into the environment affects both human health and ecosystems in general, the study of their mechanisms of action is extremely important currently.     

Cryptorchidism and hypospadias in sons of gardeners and farmers.

Cryptorchidism and hypospadias have been related to prenatal estrogen exposure in animal models. Some chemicals used in farming and gardening have been shown to possess estrogenic and other hormone-disrupting effects. Earlier studies have indicated increased risks of urogenital malformations in the sons of pesticide appliers. In the present study, parental occupation in the farming and gardening industry among 6,177 cases of cryptorchidism, 1,345 cases of hypospadias, and 23,273 controls, born live from 1983 to 1992 in Denmark, was investigated in a register-based case-control study. A significantly increased risk of cryptorchidism but not hypospadias was found in sons of women working in gardening (adjusted odds ratio = 1.67; 95% confidence interval, 1.14-2.47). The risks were not increased in sons of men working in farming or gardening. The increased risk of cryptorchidism among sons of female gardeners could suggest an association with prenatal exposure to occupationally related chemicals.     

Administration of diethylstilbestrol during pregnancy, a public health problem

The analysis of the health risks associated with the administration of diethylstilbestrol (DES) during pregnancy (for the prevention or treatment of threatened abortions) has been largely published. Concerning mothers, a relationship between DES exposure during pregnancy and risk of cancer is unproved. However, existing studies are sufficient cause for serious concern over drug's carcinogenic potential, and further follow-up studies are required. Concerning daughters, a clear association between in utero exposure to DES and clear cell adenocarcinoma of the vagina or cervix is established (incidence between 0.14 and 1.4 per 1000 through age 24). The risk for squamous cell cancer of the vagina and cervix does not seem to be increased. Cervico-vaginal adenosis is frequent (20% to 60% of exposed subjects). This is not a pre-cancerous lesion, its spontaneous evolution is towards regression. No treatment is prescribed. Morphological changes of the genital tract have been described, their consequences on fertility and pregnancy are not clear. Concerning sons, an excess of genital abnormalities (especially of the epididymis and undescended testis) has been reported, but information on the fertility implications of these findings is not available. There is no evidence of an increased risk of testicular cancer. The analysis of all these informations should allow to bring up a policy to take into account these risks in the population.     

A retrospective cohort study of stroke onset: implications for characterizing short term effects from ambient air pollution

Background

Androgens are crucial for normal testicular descent. Studies show that some pesticides have estrogenic or antiandrogenic effects, and that female workers exposed to pesticides have increased risk of having a boy with cryptorchidism. The main objective of the present study was to investigate whether pregnant women exposed to pesticides due to their work in horticulture experience excess risk of having sons with cryptorchidism.

Methods

We conducted a cohort study of pregnant women working in horticulture using four cohorts including one cohort established with data from the departments of occupational medicine in Jutland and Funen and three existing mother-child cohorts (n = 1,468). A reference group was established from the entire Danish population of boys born in the period of 1986-2007 (n = 783,817). Nationwide Danish health registers provided information on birth outcome, cryptorchidism diagnosis and orchiopexy. The level of occupational exposure to pesticides was assessed by expert judgment blinded towards outcome status. Risk of cryptorchidism among exposed horticulture workers compared to the background population and to unexposed horticulture workers was assessed by Cox regression models.

Results

Pesticide exposed women employed in horticulture had a hazard ratio (HR) of having cryptorchid sons of 1.39 (95% CI 0.84; 2.31) and a HR of orchiopexy of 1.34 (0.72; 2.49) compared to the background population. Analysis divided into separate cohorts revealed a significantly increased risk of cryptorchidism in cohort 2: HR 2.58 (1.07;6.20) and increased risk of orchiopexy in cohort 4: HR 2.76 (1.03;7.35), but no significant associations in the other cohorts. Compared to unexposed women working in horticulture, pesticide exposed women had a risk of having sons with cryptorchidism of 1.34 (0.30; 5.96) and of orchiopexy of 1.93 (0.24;15.4).

Conclusions

The data are compatible with a slightly increased risk of cryptorchidism in sons of women exposed to pesticides by working in horticulture.     

Maternal pregnancy levels of trans-nonachlor and oxychlordane and prevalence of cryptorchidism and hypospadias in boys

Background: The etiologies of the male urogenital anomalies—cryptorchidism and hypospadias—are poorly understood. Given positive associations between chlordane isomers and testicular germ cell tumors, it is reasonable to assume that chlordanes might also be associated with other testicular dysgenesis syndrome disorders, namely cryptorchidism and hypospadias.Objective: To examine whether exposure to in utero chlordane is related to cryptorchidism and hypospadias, we evaluated levels of chlordane derivatives, trans-nonachlor and oxychlordane, among pregnant women enrolled in the Collaborative Perinatal Project (CPP).Methods: From 1959 to 1965, the CPP enrolled pregnant women at 12 U.S. medical centers. We analyzed serum trans-nonachlor and oxychlordane levels measured in third-trimester serum from the mothers of 217 sons with cryptorchidism, 197 sons with hypospadias, and 557 sons with neither condition. Adjusted odds ratios (ORs) and 95% confidence intervals were calculated using conditional logistic regression.Results: The quartile-specific ORs for cryptorchidism or hypospadias show no notable associations with trans-nonachlor or oxychlordane. Further, there were no significant trends with increasing quartile of maternal trans-nonachlor or oxychlordane level in either cryptorchidism or hypospadias (p-trend all > 0.45).Conclusions: The results do not support an association between chlordane levels and cryptorchidism or hypospadias. It is unlikely that current chlordane exposure is related to the development of either anomaly, given that serum chlordane levels at the time of sample collection, the early 1960s, were considerably higher than levels at present.     

Evaluation of an association between loratadine and hypospadias--United States, 1997-2001

Hypospadias is a birth defect that affects approximately seven in 1,000 male infants in the United States. In affected infants, the urethral opening is located along the underside of the penis, scrotum, or perineum; the condition usually is corrected by surgery. Hypospadias is classified in order of increasing severity as first, second, or third degree. In 2002, a study in Sweden noted that among male infants born to women who while pregnant had taken loratadine (Claritin), a nonsedating antihistamine commonly used for seasonal allergies, hypospadias prevalence was twice that of the general population. However, insufficient data were available to determine the severity of the hypospadias cases, and the study did not control for confounding variables (e.g., family history of hypospadias or maternal age). In 2003, a prospective study using data from four countries indicated that five of 142 pregnancies in women exposed to loratadine resulted in infants with major malformations, a prevalence consistent with that of the general population; none had hypospadias. To further assess any potential association between loratadine and hypospadias, CDC analyzed data from the National Birth Defects Prevention Study (NBDPS). This report summarizes the results of that analysis, which determined that no increased risk for second- or third-degree hypospadias existed among women who used loratadine in early pregnancy. These results might be useful for women and health-care providers to address concerns about loratadine use and hypospadias.     

Maternal factors and breast cancer risk among young women

The results from previous studies have provided evidence to support the hypothesised association between intrauterine oestrogen exposure and subsequent risk of breast cancer. Information has not been available to study this relationship for several perinatal factors thought to be related to pregnancy oestrogen levels. Data collected from the mothers of women in two population-based case–control studies of breast cancer in women under the age of 45 years (510 case mothers, 436 control mothers) who were diagnosed between 1983 and 1992 in three western Washington counties were used to investigate further the relationship between intrauterine oestrogen exposure and risk of breast cancer. A pregnancy weight gain of 25–34 pounds was associated with breast cancer risk (odds ratio [OR] = 1.5; 95% confidence interval [CI] 1.1, 2.0); however, women whose mothers gained 35 pounds or more were not at increased risk. Use of antiemetic medication in women with any nausea and vomiting (OR = 2.9; 95% CI 1.1, 8.1) and use of diethylstilboestrol (DES) (OR = 2.3; 95% CI 0.8, 6.4) appeared to be positively associated with breast cancer risk. The results from this study provide limited support for the hypothesis that in utero oestrogen exposure may be related to subsequent breast cancer risk among young women.     

The Prevalence of Socioeconomic and Behavioral Characteristics and their Impact on Very Low Birth Weight in Black and White Infants in Georgia

Objectives: We examined possible reasons for the disparity in the rate of very low birth weight (VLBW) delivery (<1500 g) in the United States between black women and white women. Methods: Using data from a population-based, case–control study of very low birth weight infants, we compared the prevalence of sociodemographic and behavioral characteristics between black and white mothers of normal birth weight infants; the difference in these characteristics between case and control mothers; and, using logistic regression, calculated odds ratios for VLBW for black versus white infants, adjusting for these characteristics. Results: Although black women were disadvantaged on every variable examined, they did not report more behavioral risk factors. Among white women, several traditional risk factors were associated with VLBW, while among black women, only marital status, cigarette smoking, and vitamin nonuse were associated with VLBW delivery. Controlling for the socioeconomic and behavioral factors reduced the odds ratio for VLBW delivery among black mothers from 3.7 to 3.3. Conclusions: Racial disparity in socioeconomic status may be greater than our current ability to adjust for it in epidemiologic studies. The fact that traditional risk factors were not associated with VLBW delivery in black women may be due to the very high prevalence of these risk factors among black women or to different or additional risks or stresses experienced by black women.     

Infertility among women exposed prenatally to diethylstilbestrol

Although it is well established that women exposed to diethylstilbestrol in utero have an increased risk of spontaneous abortion, ectopic pregnancy, and preterm delivery, it is not known whether they also have an increased risk of infertility. The authors assessed this question in data from a collaborative follow-up study of the offspring of women who took diethylstilbestrol during pregnancy. In 1994, 1,753 diethylstilbestrol-exposed and 1,050 unexposed women from an ongoing cohort study (National Cooperative Diethylstilbestrol Adenosis Study and Dieckmann cohorts) provided data on difficulties in conceiving and reasons for the difficulty. Age-adjusted relative risks were computed for the association of diethylstilbestrol exposure with specific types of infertility. A greater proportion of exposed than unexposed women were nulligravid (relative risk (RR) = 1.3, 95% confidence interval (CI): 1.1, 1.5), and a greater proportion had tried to become pregnant for at least 12 months without success (RR = 1.8, 95% CI: 1.6, 2.1). Diethylstilbestrol exposure was significantly associated with infertility due to uterine and tubal problems, with relative risks of 7.7 (95% CI: 2.3, 25) and 2.4 (95% CI: 1.2, 4.6), respectively. The present findings indicate that diethylstilbestrol-exposed women have a higher risk of infertility than do unexposed women and that the increased risk of infertility is primarily due to uterine or tubal problems.     

Household pesticides and the risk of Wilms tumor

BACKGROUND: Previous epidemiologic studies have suggested that exposure to pesticides in utero and during early childhood may increase the risk for development of childhood cancer, including Wilms tumor, a childhood kidney tumor. OBJECTIVES: In this analysis we evaluated the role of residential pesticide exposure in relation to the risk of Wilms tumor in children using data from a North American case-control study. METHODS: The National Wilms Tumor Study Group (NWTSG) collected information on exposure to residential pesticides from the month before pregnancy through the diagnosis reference date using detailed phone interviews from 523 case mothers and 517 controls frequency matched on child's age and geographic region and identified by list-assisted random digit dialing. Pesticides were grouped according to type of pesticide and where they were used. RESULTS: A slightly increased risk of Wilms tumor was found among children of mothers who reported insecticide use [odds ratio (OR) = 1.4, 95% confidence interval (CI), 1.0-1.8; adjusted for education, income, and the matching variables]. Results from all other categories of pesticides were generally close to the null. CONCLUSIONS: This study is the largest case-control study of Wilms tumor to date. We were unable to confirm earlier reports of an increased risk for Wilms tumor among those exposed to residential pesticides during pregnancy through early childhood.