Fertility patterns prior to testicular cancer diagnosis.

Although prenatal factors are associated with testicular cancer etiology, few studies have examined the reproductive profiles of men prior to diagnosis. This case--control study investigated fertility patterns prior to testicular cancer diagnosis by comparing pregnancies fathered by 201 men with testicular cancer and those fathered by 204 age- and neighborhood-matched controls. Regardless of histology, men with testicular cancer were less likely to have ever fathered a live-born infant (OR 0.67, 95% CI 0.42--1.06) and had fewer offspring than control men (means 1.8 and 2.1, respectively). Cases were more likely than controls to report having an infertility diagnosis (OR 9.47, 95% CI 1.19--75.2) or a low sperm count (OR 5.85, 95% CI 1.28--26.7) prior to cancer diagnosis. No differences were observed for pregnancy loss. These results indicate that men with testicular cancer may have impaired fecundity and fertility as evidenced by an infertility diagnosis or low sperm count and fewer live births. Further research is needed to determine the extent to which reproductive factors are involved in the etiology of testicular cancer.

Allergy and infectious disease histories and the risk of childhood acute lymphoblastic leukaemia.

Infectious disease histories were evaluated in a population-based case-control study of childhood acute lymphoblastic leukaemia (ALL) as it has been hypothesised that delays in early infections are associated with an increased risk of disease. Allergy histories were also assessed as part of a broader evaluation of the role of immune factors in ALL. Cases (n = 255) were diagnosed between 1980 and 1991 at one of four referral centres in a 31-county area of New York State; controls (n = 760) were a random sample of live births from the same region, frequency matched to cases by sex, race and birth year. Data were collected by mailed questionnaire, completed by case and control parents in 1995. Allergy and infectious histories before the age at leukaemia diagnosis for cases and an equivalent age for controls were evaluated. The adjusted odds ratio and 95% confidence interval [CI] associated with a positive history of any allergy was 0.58 [95% CI 0.38, 0.88] compared with a negative allergy history. The occurrence of several common childhood illnesses before 25 months of age and ALL were assessed, with both weak positive and weak inverse associations observed. Overall, these analyses provide little support for the hypothesis that infection delay in early life is associated with an increased risk of ALL. Children with positive allergy histories reported significantly more infections than those with negative histories; however, effect modification of the infection-ALL associations by child allergy history was not observed. Nonetheless, these observations suggest the importance of assessing both allergy and infectious histories and their possible interactions when evaluating the association between these immune factors and childhood ALL.

Birth defects risk associated with maternal sport fish consumption: potential effect modification by sex of offspring.

Contaminated sport fish consumption may result in exposure to various reproductive and developmental toxicants, including pesticides and other suspected endocrine disruptors. We investigated the relation between maternal sport fish meals and risk of major birth defects among infants born to members of the New York State (NYS) Angler Cohort between 1986 and 1991 (n=2237 births). Birth defects (n=125 cases) were ascertained from both newborn medical records and the NYS Congenital Malformations Registry. For sport fish meals eaten during pregnancy, the odds ratio (OR) for all major malformations combined was slightly elevated for < or =1 meal/month (OR=1.26, 95% confidence interval (CI): 0.84, 1.89) and > or =2 meals/month (OR=1.51, CI=0.74, 3.09), with no meals during pregnancy as the reference category. Higher ORs were consistently observed among male offspring compared with females. For > or =2 meals/month, the risk for males was significantly elevated (males: OR=3.01, CI: 1.2, 7.5; females: OR=0.73, CI: 0.2, 2.4). Exposure during pregnancy and effect modification by infants sex could be important considerations for future studies of birth outcomes associated with endocrine disruptors.

Relative concentrations of organochlorines in adipose tissue and serum among reproductive age women.

Much of the available literature focusing on organochlorine exposure and human health effects has relied upon serum for quantifying exposure despite adipose tissue being the purported "gold standard". The accuracy of exposure status is dependent upon serum being a valid and reliable proxy for adipose tissue regardless of compound under study and served as the impetus for study. Serum and omentum fat concentrations for 62 polychlorinated biphenyls (PCBs) and 7 organochlorine pesticides (OCPs) were determined using gas chromatography with electron capture and compared to assess their relative abundance and correlation among 15 women aged 18-40 years undergoing laparoscopy. The relation between concentration in serum and fat was determined by linear regression. Of the 20 organochlorines (OCs) (29%) present in both serum and fat samples, moderate linear correlations (r > 0.6) were observed between lipid-adjusted serum and fat concentrations for PCBs #138, 153, 180, 188, 194, 206, and DDE. Forty-nine OCs were present in adipose samples but measured below the LOD in serum samples. Our findings underscore the potential for discrepant human health results associated with OC exposure on the basis of medium used for quantification purposes, especially for less ubiquitous compounds or when study samples include individuals with relatively low exposures. These data support earlier findings and argue for concerted methodological work aimed at developing standardized laboratory methods for epidemiologic studies.

Are children born after assisted reproductive technology at increased risk for adverse health outcomes?

As assisted reproductive technologies (ARTs) are increasingly used to overcome infertility, there is concern about the health of the children conceived. The empirical evidence for associations with outcomes related to child health is variable and should be evaluated with consideration of methodological shortcomings. Currently, there is convincing evidence that ART treatment may increase the risk of a few outcomes. Experimental laboratory studies document that various constituents in culture media affect various embryo characteristics both positively and negatively. Multiple-gestation pregnancy and birth are increased with ART, both because of multiple embryo transfer and embryo splitting. There is evidence of an increase in chromosomal abnormalities among pregnancies conceived using intracytoplasmic sperm injection and low birth weight and preterm delivery among singletons conceived with all types of ART; however, there remains uncertainty about whether these risks stem from the treatment or the parental infertility. For some outcomes, data of an increased risk with ART are suggestive at best largely because of lack of purposeful study of sufficient size and scope. These include specific perinatal morbidities, birth defects, developmental disabilities, and retinoblastoma. The evidence for an association between ART and spontaneous abortion is inconsistent and weak. There is inconclusive evidence that ART may be associated with genetic imprinting disorders. For childhood cancer, chronic conditions, learning and behavioral disorders, and reproductive effects there is insufficient empirical research to date, but given the data for more proximal outcomes, these outcomes merit further study. Future research needs to address the unique methodological challenges underlying study in this area.

Our once-in-a-lifetime opportunity.

Longitudinal studies of the determinants of children's health are complex, costly, infrequent, and incredibly valuable. It has become clear in recent years that the periconceptional environment plays a surprisingly large role in the health of the resulting child. This short introduction to this mini-monograph briefly recaps the articles included herein and reminds us that adequate forethought and planning will result in a study that could shed new light on the earliest determinants of children's health and thereby fill critical data gaps.

Prospective pregnancy study designs for assessing reproductive and developmental toxicants.

The determinants of successful human reproduction and development may act as early as periconceptionally, underscoring the need to capture exposures during these critical windows when assessing potential toxicants. To identify such toxicants, couples must be studied longitudinally prior to conception without regard to a couple's ability to ascertain a clinically recognized pregnancy. We examined the utility and feasibility of prospective pregnancy study designs by conducting a systematic review of the literature to summarize relevant information regarding the planning, implementation, and success of previously published prospective pregnancy studies. Information concerning design elements and participation was abstracted from 15 eligible studies (from a total of 20 identified studies) using a standardized form. The primary author of each study was contacted to review our summary of their work and obtain missing information. Our findings confirm the ability to recruit women/couples from diverse populations using a variety of recruitment strategies. Among the studies we reviewed, 4-97% of eligible individuals were successfully contacted, with enrollment rates ranging from 42 to 100%. Length of follow-up varied from 3 to 12 months. A high percentage of women provided urine (57-98%) and blood (86-91%) specimens and most male partners (94-100%) provided semen samples. These data support the feasibility of this design.

The value of home-based collection of biospecimens in reproductive epidemiology.

Detection, quantification, and prognosis of environmental exposures in humans has been vastly enhanced by the ability of epidemiologists to collect biospecimens for toxicologic or other laboratory evaluation. Ease of collection and level of invasiveness are commonly cited reasons why study participants fail to provide biospecimens for research purposes. The use of methodologies for the collection of biospecimens in the home offers promise for improving the validity of health effects linked to environmental exposures while maximizing the number and type of specimens capable of being collected in a timely and cost-effective manner. In this review we examine biospecimens (urine and blood) that have been successfully collected from the home environment. Related issues such as storage and transportation will also be examined as well as promising new approaches for collecting less frequently studied biospecimens (including hair follicles, breast milk, semen, and others). Such biospecimens are useful in the monitoring of reproductive development and function.

Biomarkers for assessing reproductive development and health: Part 1--Pubertal development.

The proposed National Children's Study has helped raise awareness of the issues related to children's health and the importance of monitoring the growth and development of children from preconception through adulthood. Many genetic predispositions can adversely impact the normal development process, and various environmental exposures have been linked to adverse reproductive health in rodent models and a small number of accidental human exposures. To monitor reproductive health and identify adverse effects at the earliest possible juncture, investigators must develop a network of biomarkers covering all stages and aspects of reproductive development and function. Biomarkers are biological indicators that can be measured repeatedly and are informative on one or more aspects of biological development or function. They can range from the anatomical level down to the molecular level and may provide information on the nature of an exposure, the effect of an exposure, or the susceptibility of individuals or populations to the toxic effects of an exposure. In theory, biomarkers can be used to monitor a wide variety of conditions and responses ranging from abnormal development to early indicators of late-onset disease. The main stumbling block with this theory has been finding appropriate biomarkers for particular conditions and exposures. Such biomarkers must be easily accessible, robust, and sensitive. Ideally, they will be expressed across a large section of the population, and can be monitored quickly, easily, conveniently, and with minimal cost. In this review, we discuss some of the current and emerging biomarkers of human pubertal development.

Using commercial telephone directories to obtain a population-based sample for mail survey of women of reproductive age.

In the United States, sampling women of reproductive age from the general population for research purposes is a challenge. Even more difficult is conducting a population-based study of couples attempting pregnancy to assess fecundity and fertility or related impairments. To address the problem of obtaining representative samples from the population in order to study such health-related issues, a commercially and readily available CD-ROM telephone directory was used and tested as a sampling framework for studies aimed at enrolling gravid women aged 18-44 years. A self-administered questionnaire (SAQ) was mailed to a stratified random sample of 10 005 (3%) households in Erie County, NY, USA. Overall, 17% of the questionnaires were undeliverable despite updating all addresses with residential software before mailing. Thirteen per cent (n = 1089) of the households returned completed questionnaires, of which 35% (n = 377) were completed by women aged 18-44 years. Using 1990 census information for zip code, respondents were more likely to be white and to have higher median household incomes than non-respondents. Of the 377 women who completed the questionnaire, 79% had been pregnant at least once, 5% reported being unable to become pregnant, and 16% reporting never trying to become pregnant. Despite the overall low response to the SAQ, the sampling framework captured a diverse group of women of reproductive age who reported various fecundity and fertility outcomes. The use of low-cost commercially available software linked to census data for selecting samples of women or couples for reproductive and perinatal research may be possible; however, oversampling of households, use of incentives and follow-up of non-respondents is needed to ensure adequate sample sizes.

Maternal fish consumption and infant birth size and gestation: New York State Angler Cohort Study.

BACKGROUND: The scientific literature poses a perplexing dilemma for pregnant women with respect to the consumption of fish from natural bodies of water. On one hand, fish is a good source of protein, low in fat and a rich source of other nutrients all of which have presumably beneficial effects on developing embryos and fetuses. On the other hand, consumption of fish contaminated with environmental toxicants such as polychlorinated biphenyls (PCBs) has been associated with decrements in gestation and birth size. METHODS: 2,716 infants born between 1986-1991 to participants of the New York State Angler Cohort Study were studied with respect to duration of maternal consumption of contaminated fish from Lake Ontario and its tributaries and gestation and birth size. Hospital delivery records (maternal and newborn) were obtained for 92% of infants for the ascertainment of gestation (weeks), birth size (weight, length, chest, and head circumference) and other known determinants of fetal growth (i.e., maternal parity, history of placental infarction, uterine bleeding, pregnancy loss or cigarette smoking and infant's race, sex and presence of birth defect). Duration of maternal fish consumption prior to the index infant's birth was categorized as: none; 1-2, 3-7, 8+ years, while birth weight (in grams), birth length (in centimeters), and head and chest circumference (in centimeters) were left as continuous variables in multiple linear regression models. Birth size percentiles, ponderal indices and head to chest circumference ratios were computed to further assess proportionality and birth size in relation to gestational age. RESULTS: Analysis of variance failed to identify significant mean differences in gestation or any measure of birth size in relation to duration of maternal lifetime fish consumption. Multiple linear regressions identified gestational age, male sex, number of daily cigarettes, parity and placental infarction, as significant determinants of birth size. CONCLUSIONS: The results support the absence of an adverse relation between Lake Ontario fish consumption and reduced birth size as measured by weight, length and head circumference. Biological determinants and maternal cigarette smoking during pregnancy remain important determinants of birth size.

Blood lead levels and sexual maturation in U.S. girls: the Third National Health and Nutrition Examination Survey, 1988-1994.

Using data from the Third National Health and Nutrition Examination Survey, we assessed measures of puberty in U.S. girls in relation to blood lead levels to determine whether sexual maturation may be affected by current environmental lead exposure. The study sample included 1,706 girls 8-16 years old with pubic hair and breast development information; 1,235 girls 10-16 years old supplied information on menarche. Blood lead concentrations (range = 0.7-21.7 micro g/dL) were categorized into three levels: 0.7-2.0, 2.1-4.9, and 5.0-21.7 micro g/dL. Sexual maturation markers included self-reported attainment of menarche and physician determined Tanner stage 2 pubic hair and breast development. Girls who had not reached menarche or stage 2 pubic hair had higher blood lead levels than did girls who had. For example, among girls in the three levels of blood lead described above, the unweighted percentages of 10-year-olds who had attained Tanner stage 2 pubic hair were 60.0, 51.2, and 44.4%, respectively, and for girls 12 years old who reported reaching menarche, the values were 68.0, 44.3, and 38.5%, respectively. The negative relation of blood lead levels with attainment of menarche or stage 2 pubic hair remained significant in logistic regression even after adjustment for race/ethnicity, age, family size, residence in metropolitan area, poverty income ratio, and body mass index. In conclusion, higher blood lead levels were significantly associated with delayed attainment of menarche and pubic hair among U.S. girls, but not with breast development.

Ethnic differences in the presence of secondary sex characteristics and menarche among US girls: the Third National Health and Nutrition Examination Survey, 1988-1994.

OBJECTIVE: To assess measures of puberty-presence of pubic hair, breast development, and menarche-for 3 racial/ethnic groups of girls in the United States. METHODS: Using data from the Third National Health and Nutrition Examination Survey, this study sample was restricted to 1623 girls aged 8 to 16 years (466 non-Hispanic white, 589 non-Hispanic black, and 568 Mexican American) for whom information was available on Tanner stages of pubic hair and breast development. Subsequently, the sample was restricted to 1168 girls aged 10 to 16 years (330 non-Hispanic white, 419 non-Hispanic black, and 419 Mexican American) for whom menarche data were available. Tanner stage II or higher was used to define pubic hair and breast development; menarche status was self-reported. The percentage of girls who had pubic hair and breast development and had achieved menarche was computed by age and race/ethnicity. Probit and failure time models were applied to estimate mean ages at onset of pubic hair, breast development, and menarche. The racial/ethnic differences also were examined after adjustment for social and economic variables and current body mass index. RESULTS: Black and Mexican American girls had pubic hair and breast development and had achieved menarche at younger ages than white girls. For example, 49.4% of black girls aged 9 years had breast development compared with 24.5% of Mexican American girls and 15.8% of white girls. The mean age at onset of pubic hair, breast development, and menarche was 9.5, 9.5, and 12.1 year for black girls; 10.3, 9.8, and 12.2 years for Mexican American girls; and 10.5, 10.3, and 12.7 years for white girls. These ethnic differences remained even after adjustment for current body mass index and several social and economic variables. CONCLUSION: Black girls on average enter puberty first, followed by Mexican American and then white girls.

Methodologic considerations for population-based research on fetal deaths: overcoming data gaps.

Fetal deaths comprise a large component of perinatal mortality and remain an understudied pregnancy outcome, especially from a population perspective. Interpretation of the findings from clinical or community-based studies can be difficult without a clear understanding of fetal death at the population level. This article addresses the critical data gaps underlying population-based research on fetal deaths, including the magnitude and scope of the problem, the probability of occurrence, the populations at risk, and the importance of accounting for prior reproductive history. Suggestions are given for new avenues of population-based research such as prospective inquiry of couples attempting pregnancy and newer analytic and modeling strategies for assessing risk and for addressing the lack of independence in pregnancy outcomes.

PCB congeners and pesticides and female fecundity, New York State Angler Prospective Pregnancy Study.

Consumption of PCB-contaminated sport fish from Lake Ontario has been reported to be associated with diminished female fecundity. To identify Polychlorinated biphenyl (PCB) congeners and other pesticides that might be associated with reduced fecundity, we followed 102 women aged 20-34 years attempting pregnancy who completed daily diaries for 12 at risk menstrual cycles. Fecundity referred to time-to-pregnancy (TTP) or the number of at risk menstrual cycles required for pregnancy. Blood specimens were obtained for 88 (86%) women and were analyzed using gas chromatography and electron capture for 66 PCB congeners and seven pesticides. Laboratory values were recovery, background and fat corrected prior to natural log transformation. Using stepwise discriminant analysis, congeners IUPAC #205 and #206 and hexaclorobenzene were significantly and positively associated with increasing TTP when women were categorized as becoming pregnant in the first or first three at risk menstrual cycles, respectively. Congeners #205 and #206 are reported to have (anti) estrogenic structural activity.