Relation of obesity and body fat distribution to endometrial cancer in Shanghai, China.

In a case-control study involving 268 cases of endometrial cancer and an equal number of population controls, we assessed the relationship of risk to body weight and fat distribution, examining weight at various ages and current anthropometric measurements. Weight gain during later adulthood and resultant high body masses were important risk predictors, indicating that obesity is an important risk factor, even in an area where the prevalence of obesity and incidence of endometrial cancer are low. Certain fat distribution patterns were related to risk of endometrial cancer independent of general obesity. In particular, fat deposits on the trunk were associated with elevated risks, with the odds ratio for the highest versus lowest quartile of subscapular skinfolds remaining significant even after adjustment for body mass index (odds ratio = 2.9; 95% confidence interval, 1.1-7.3). Central versus peripheral obesity, as measured by the subscapular:triceps ratio, also was related to increased risk, although the association failed to remain significant after adjustment for body mass (highest to lowest quartile, odds ratio = 1.7). In contrast, upper body obesity, as assessed by the waist:thigh ratio, was unrelated to risk. These results support the need for future studies assessing the relationship of hormonal and other biological parameters of fat distribution to assist in identifying causal mechanisms for this tumor.

Dietary factors and the risk of pancreatic cancer: a case-control study in Shanghai China.

In Shanghai, China, age-adjusted incidence rates for pancreatic cancer have increased steadily, beginning in the early 1970s. To examine the effects of diet on this cancer, a population-based case-control study was conduct. Cases (n = 451) were permanent residents of Shanghai, 30-74 years of age, newly diagnosed with pancreatic cancer between October 1, 1990 and June 30, 1993. Decreased cases (19%) were excluded from the study. Controls (n = 1552) were selected among Shanghai residents, frequency matched to cases by gender and age. Information on usual adult dietary intake was obtained by trained interviewers in person, using a food frequency questionnaire. Dietary associations were measured by odds ratios and 95% confidence intervals. Risks of pancreatic cancer were inversely associated with consumption of vegetables (P for trend among men = 0.03; among women = 0.15) and fruits (P among men = 0.02; among women = 0.08). Reductions in risk were related also to intake of dietary fiber and micronutrients abundant in plant sources, such as vitamins C and E and carotene. There was also an inverse association with egg consumption (P for trend among men = 0.08; among women = 0.001). No consistent positive associations were observed with intake of other food groups, including preserved animal foods, fresh red meat, organ meat, poultry, and staple foods. On the other hand, risks increased with frequency of consumption of preserved vegetables and foods that were deep fried, grilled, cured, or smoked, providing clues to the possible role of nitrosamines, polycyclic aromatic hydrocarbons, and heterocyclic aromatic amines. The inverse associations observed with intake of dietary fat and protein in our study were unexpected, although these findings were based on consumptions well below the average intake in Western countries, where most previous studies on pancreatic cancer were conducted. Our results suggest that dietary variations have contributed little to the rising trends of pancreatic cancer in Shanghai. However, given the improving food availability and changing dietary patterns in China, further study of dietary and nutritional risk factors for pancreatic cancer appears warranted.

Centers needed to study women's environmental health.

The view of women as primarily fecund beings goes back to prehistory, where it is expressed in the well-known series of Venuses--stone figures of women with enlarged breasts, who are often represented as pregnant. Although the Venus figures date from the late Paleolithic era, this view of women did not change much in the next 20,000 years. With the approaching millennium, however, the field of health research has begun to consider women apart from their children or prospective progeny. Reflecting this shift in viewpoint, funds for research on the environmental health of women have now become available. However, no coordinated program has been launched on the scale of the newly established Centers for Children's Environmental Health and Disease Prevention Research (1). Should women, like children, be the focus of a concerted research effort?

Using reproductive effect markers to observe subclinical events, reduce misclassification, and explore mechanism.

Biological markers of effect, in general less widely available than exposure markers, do exist in the field of reproduction and increasingly are being used in epidemiological studies. Several such markers, including semen quality, menstrual hormones, early pregnancy loss, and placental abnormalities, are cited as examples. We argue the value of effect markers for detecting subclinical events that are critical for reproductive performance. Such studies can extend knowledge of the true frequency and determinates of reproductive disorders. A second portion of the paper deals with the role of effect markers in reducing disease misclassification. With a hypothetical early pregnancy study as a case in point, we illustrate the degree and direction of bias associated with several different protocols and encourage epidemiologists to weigh these quantitative considerations in deciding on study design. Finally, we discuss uses of biological markers to explore mechanisms, drawing on experience in an ongoing reproductive study that is testing a hypothetical pathway from maternal psychosocial stress to reduced fetal growth using urine catecholamine levels as a physiological marker of exposure and placental vascular abnormalities as a marker of effect.

Reproductive and developmental effects of disinfection by-products in drinking water.

Recent epidemiologic studies have reported associations between the consumption of chlorinated drinking water and reproductive and developmental effects. Here we review the available epidemiologic data, assess the hazard potential posed by exposure to disinfection by-products, identify critical data gaps, and offer recommendations for further research. The epidemiologic evidence supporting associations between exposure to water disinfection by-products (DBPs) and adverse pregnancy outcomes is sparse, and positive findings should be interpreted cautiously. The methods used during the early stages of research in this area have been diverse. Variability in exposure assessment and endpoints makes it difficult to synthesize or combine the available data. Exposure misclassification and unmeasured confounding may have lead to bias in risk estimation. Future studies of reproductive outcome and exposure to chlorinated water should use improved methods for exposure assessment to 1) assure selection of appropriate exposure markers, 2) assess seasonal and annual fluctuations in DBPs, 3) assess variability within the distribution system, and 4) assess exposure through multiple routes such as bathing and showering, as well as consumption. Population-based studies should be conducted to evaluate male and female fertility, conception delay, growth retardation, and specific birth defects. The reproductive and developmental effects of exposure to DBPs could be efficiently explored in ongoing investigations by incorporating valid exposure markers and relevant questionnaire information. Future studies should make use of naturally occurring variability in the concentrations of DBPs and may incorporate biomarkers of exposure and effect in their design. Epidemiologic investigations should be conducted in parallel with laboratory-based and animal studies in a coordinated, multidisciplinary approach.

Early ultrasound dating of pregnancy: selection and measurement biases.

Can using early ultrasound examinations to date pregnancy introduce information bias in perinatal research? Our purpose was to identify determinants of early ultrasound examinations and to compare early ultrasound to menstrual history dating. Between January 1987 and June 1989, 1159 white, largely middle class, prenatal patients were contacted for a prospective observational study. 876 (76%) agreed to participate. Of these 764 (87%) met the eligibility criteria for this analysis, namely singleton pregnancy, delivered after 20 weeks (spontaneous or induced, vaginal or c-section), with prenatal chart abstracted. Selection factors for early ultrasound identified in multivariate analysis were: bleeding in early pregnancy, OR = 1.9 (1.0, 3.5), attendance at health maintenance organization OR = 7.2 (3.4, 15), no insurance or Medicaid only OR = 0.3 (0.1, 0.6), and increasing time from last menstrual period to first prenatal visit in weeks OR = 0.89 (0.85, 0.93). In conformity with previous results, ultrasound dating of pregnancy led to a higher estimate of preterm delivery (10 vs 7.6%), a higher estimate of term delivery (87.2 vs 82.7%) and a lower estimate of postterm delivery (2.8 vs 9.7%) than dating by menstrual history, p < 0.001. Selection factors and measurement issues, such as those described here, could introduce bias and should be carefully considered in the design, analysis and interpretation of perinatal research.

Continuous labor support from labor attendant for primiparous women: a meta-analysis.

OBJECTIVE: To evaluate the available literature on the effects of continuous labor support among primiparous women. DATA SOURCES: We did a Medline search using the keywords "labor support," "doula," and "monitrice." Papers published in English from 1965 to May 1995 were eligible for this review. We also cross-checked all the references in the selected reports. METHODS OF STUDY SELECTION: We identified seven randomized clinical trials published during that period; four of these were eligible for our meta-analysis. DATA EXTRACTION AND SYNTHESIS: Meta-analysis of four studies conducted among young, low-income, primiparous women who gave birth on a busy labor floor in the absence of a companion suggested that continuous labor support by a labor attendant shortens the duration of labor by 2.8 hours (95% confidence interval [CI] 2.2-3.4), doubles spontaneous vaginal birth (relative risk [RR] 2.01, 95% CI 1.5-2.7) and halves the frequency of oxytocin use (RR 0.44, 95% CI 0.4-0.7), forceps use (RR 0.46, 95% CI 0.3-0.7), and cesarean delivery rate (RR 0.54, 95% CI 0.4-0.7). Women with labor support also reported higher satisfaction and a better postpartum course. CONCLUSION: Labor support may have important positive effects on obstetric outcomes among young, disadvantaged women. Further studies on benefit relative to cost are needed before a broad-scale program is advocated.

Depressive symptomatology during pregnancy: evidence for an association with decreased fetal growth in pregnancies of lower social class women.

The relationship between depressive symptom scores on the Center for Epidemiological Studies Depression Scale (CES-D; L. S. Radloff, 1977) at each trimester of pregnancy and a decrement in either fetal growth or gestational duration was evaluated among 666 pregnant women. There was no association overall, but among 222 women from lower occupational status households, each unit increase on the CES-D at 28 weeks gestation was associated with a reduction of 9.1 g (95% confidence interval [CI] = -16.0, -2.3) in gestational-age-adjusted birth weight. When missing data were multiply imputed, the estimate was -4.6 g (95% CI = - 10.7, 1.5). CES-D score was unrelated to fetal growth or gestational duration in analyses among other potentially high-risk subgroups: smokers, women with a history of adverse outcome, and women with social vulnerabilities. These results raise the possibility that among lower status women, depressive mood may be associated with restricted fetal growth.

Lack of effect of psychosocial stress on maternal corticotropin-releasing factor and catecholamine levels at 28 weeks' gestation.

OBJECTIVE: Corticotropin-releasing factor (CRF) and catecholamines are among the major hormones activated during the adaptive response to stressful stimuli. In pregnant women, serum CRF and catecholamines levels increase during labor and preterm delivery. The aim of the present study was to evaluate whether psychosocial stress measures are correlated with serum CRF or urinary catecholamine [ie, epinephrine, norepinephrine (NE), dopamine (DA)] levels in healthy midtrimester pregnant women. METHODS: A large group of white pregnant women (n = 382) participated in the present study. The Work Conditions Questionnaire and the Psychiatric Epidemiology Research Interview were administered to measure job stress and general life stress, respectively. Urine and blood specimens were collected at 28 weeks of gestation at the time of psychosocial evaluation. Epinephrine, NE, and DA were quantified in the urine by a highly sensitive method based on an amperometric detector. Serum CRF and cortisol levels were measured in blood specimens by using specific radioimmunoassays. RESULTS: Serum CRF and cortisol levels did not vary between patients with high and low scores on psychological tests, and no correlation was found between CRF and cortisol levels. One job stress measure, low job latitude, was significantly associated with a mild increase in NE and DA levels in the afternoon and night (P < .05, analysis of variance). Serum cortisol levels were inversely correlated with NE in the morning (r = -0.447; P =.002) and night segments (r = -0.391; P = .007) and with DA in the night period (r = -0.367; P = .013). CONCLUSION: The absence of a significant relationship between CRF/cortisol and psychosocial stress measures in pregnant women suggests that the hypothalamic-pituitary-adrenal response to psychosocial stress may be masked at midtrimester by the constantly high levels of placental CRF, whose control is beyond the influence of environmental stressors.

Assessing female fertility.

A concern exists that infertility is on the rise among American couples. While secular trends do not support this, there is reason to believe that deferral of child bearing is associated with a delay in conception. This paper reviews the data on factors that interfere with fertility and fecundity, such as maternal age and occupational exposures. Also discussed are epidemiological tools and strategies for evaluating the various components of female fertility and for identifying adverse influences.

Assessment of reproductive disorders and birth defects in communities near hazardous chemical sites. II. Female reproductive disorders.

Members of the workgroup on female reproductive disorders discussed methods to evaluate five principal functions: menstrual dysfunction, infertility, pregnancy loss, lactation disorders, and pregnancy complications. To test each function, a nested strategy was considered, based on progressive levels of effort available to conduct field investigations. This strategy was analogous to the three-tier classification of biomarkers used by other workshops. The lowest level of effort, corresponding to Tier 1, consists only of questionnaires, diaries, and reviews of maternal and infant medical records. The medium level of effort (Tier 2) collects data from questionnaires and diaries, and some biologic specimens. Suggested laboratory analyses included measurement of progesterone in saliva and several glycoprotein hormones in urine that evaluate menstrual dysfunction, infertility, and pregnancy loss. The highest level of effort (Tier 3) involves prospective collection of diary information and simultaneous collection of biological specimens.

Work stress and menstrual patterns among American and Italian nurses.

OBJECTIVES: This study assessed whether job stress alters menstrual patterns among nurses working in 2 different settings: a tertiary care hospital in New York (99 nurses) and a university hospital in Rome (25 nurses). METHODS: Data on menstrual patterns were collected by a daily diary in which the nurses recorded their basal body temperature (BBT) and their menstrual bleeding status for a 3-month period. The BBT curves were used to classify cycles as biphasic or monophasic, and as adequate or inadequate with respect to the luteal phase. Job stress was evaluated by both objective (environmental and work characteristics) and subjective (perceived stress) criteria. RESULTS: The American nurses, especially those assigned to high stress units, had an increased risk for long and monophasic cycles [relative risk (RR) 4.3, 95% confidence interval (95% CI) 1.1-16.2 and RR 5.5, 95% CI 1.2-25.5, respectively]. Among those who perceived their stress at work to be high or reported strenuous work activity, the risk for longer cycles was also raised (RR 2.3, 95% CI 0.6-8.0 and RR 1.6, 95% CI 0.7-4.2, respectively). Luteal phase inadequacy followed the same pattern. Similar trends were observed in the Italian data. In addition, the rotating shiftwork pattern prevalent in the Italian group was possibly associated with higher rates of short cycles and inadequate luteal phases when compared with those of nurses working fixed shifts either day or night. CONCLUSIONS: Menstrual function may be affected by stressful work conditions.

Psychosocial work stress and pregnancy-induced hypertension.

We examined the association between work during pregnancy and pregnancy-induced hypertension in a prospective cohort study of 717 women. We classified cases, whom we identified by uniform review of blood pressures and proteinuria in prenatal records, into two categories: gestational hypertension (N = 16, 2.5%) and preeclampsia (N = 11, 1.7%). All cases of pregnancy-induced hypertension occurred among the 575 subjects who worked during the first trimester of pregnancy. The association with employment was not explained by primiparity or other known risk factors, or by physical work demands, long work hours, or total hours of paid work, housework, and child care. Stressful job characteristics, however, did show associations with pregnancy-induced hypertension. In particular, gestational hypertension was associated with low decision latitude and low job complexity among women in lower-status jobs [standardized odds ratio (SOR) = 2.4 for low latitude, 95% confidence interval (CI) = 1.1-5.2; SOR = 2.1 for low complexity, 95% CI = 1.0-4.6]. Among women in higher-status jobs, gestational hypertension was associated with job pressures/low control (SOR = 3.6, 95% CI = 0.9-15.1). Psychosocial job stressors, not studied previously, might explain earlier reports of a raised risk of pregnancy-induced hypertension among pregnant workers.

Stress, social support and pregnancy outcome: a reassessment based on recent research.

We present an assessment of studies published in the last decade that consider the relationship of stress and social support to preterm delivery or fetal growth retardation. Included in the review are all reports on the direct effects of stressors or psychological distress; the indirect effects of stressors or distress through health behaviours such as smoking; and the direct and buffering effects of social support. Although an important stimulus for recent stress research has been the attempt to explain racial and social class differences in birth outcome, the recent data show that stressful life events during pregnancy, though more common in disadvantaged groups, do not increase the risk of preterm birth. In contrast, intimate social support from a partner or family member appears to improve fetal growth, even for women with little life stress. Questions unanswered by the research to date are whether elevated levels of depressive symptoms affect pregnancy outcome, either directly or by encouraging negative health behaviours, and whether chronic (vs. acute) stressors are harmful. Additional research is also needed to determine whether psychosocial factors interact with specific clinical conditions to promote adverse pregnancy outcomes. Focusing on intimate support and how it benefits pregnancy outcome could lead to the design of more effective interventions.

Polycyclic aromatic hydrocarbon-DNA adducts in spontaneously aborted fetal tissue.

Fetal tissue and placentas from 15 human spontaneous abortions were evaluated for DNA adducts of polycyclic aromatic hydrocarbons (PAHs), using a competitive enzyme-linked immunosorbent assay (ELISA) with fluorescent end-point detection. PAH-derived adducts were found in 43% of placentas, 27% of fetal liver samples and 42% of fetal lung specimens, thus confirming that the human fetus is a target for DNA damage. As there was only 60% concordance between placenta and fetal lung or liver on the presence or absence of detectable PAH adducts, the placenta was not a good surrogate for adduct formation in other fetal organs. PAH-derived adducts in fetal liver and lung presumably form as a result of transplacental exposure to environmental stimuli. Since none of the positive fetal samples were from women who reported smoking during pregnancy, cigarette smoke is, in this case, an unlikely candidate and the adducts detected must be due to some other common source(s) of hydrocarbon exposure. The high frequency of positive samples in our small series casts some doubt on whether fetal PAH-DNA adducts identify a population at increased risk for transplacental carcinogenesis.

Working during pregnancy: physical and psychosocial strain.

The article concerns more general aspects of stress during pregnancy in connection with employment. Various existing studies are reviewed, mainly related to pre-term delivery and birth weight.

Stress and preterm delivery: a conceptual framework.

Numerous epidemiological studies of various kinds of stress and preterm delivery have produced either negative or weakly positive results. Those inconclusive findings could be either because of the absence of an association or because of recognised methodological problems that may have masked an association. The biological plausibility of the stress hypothesis provides one rationale for continuing stress research, using better study designs. To further this agenda, we propose an epidemiological model, based on the classic "host, environment, agent" triangle of epidemiological causality. The host is the individual woman, more or less susceptible to stressor-induced pathology. The environment includes the social and cultural conditions that are ongoing stressors as well as social and cultural modifiers of stress e.g. those factors that may influence how a particular stressor is experienced or what the physical response to it may be. The agent is the immediate emotional or physical stressor requiring her response. We draw from recent literature, published principally since 1990, to illustrate this model. This epidemiological model posits that whether the individual is overwhelmed by stressors depends not only on the strength of the agents but also upon host susceptibility to stress, as well as the background level of acute, environmental and contextual stressors, and the moderating influence of host, environmental and contextual resources for handling stress. Future research needs to be based on stress hypotheses that include all sides of the triangle, data collection instruments that adequately capture relevant stressors and stress responses, and analytical techniques capable of handling complex, multilevel relationships.

Epidemiology of pregnancy-induced hypertension.

Mounting evidence clearly indicates an immunologic basis for PIH, parity being the most convincing factor. Genetic susceptibility, physiologic change, and environmental influence may also modulate an individual's risk of developing PIH. Pathologic and follow-up studies further suggests further suggest that currently diagnosed PIH may actually be a heterogeneous entity comprising several disorders of different etiologies (150), such as chronic renal disease, borderline chronic hypertension, genetic susceptibility to hypertension, and genuine PIH. For many diseases, etiologic research and clinical management often go hand in hand. Unfortunately, in the case of PIH, etiologic research may have followed clinical steps too closely and have been misled. For clinical management, genuine preeclampsia and preeclampsia superimposed on chronic hypertension are treated as virtually the same: The ultimate goal is to prevent eclampsia. Because a sizable portion of PIH is probably due to chronic renal disease or latent chronic hypertension (33), and late-onset gestational hypertension is of less concern than preeclampsia, one could argue that it may not be clinically important to separate the subtypes of PIH. In etiologic research, however, by focusing on a heterogeneous outcome we have confused ourselves and hampered our progress. On the other hand, one should also realize that currently available techniques are unlikely to substantially improve our proficiency in differential diagnosis. Besides renal biopsy, which is impractical, especially in epidemiologic research, there are virtually no measures available that can distinguish genuine PIH from hypertension due to latent renal disorder, chronic hypertension, or genetic susceptibility. Until noninvasive measures with acceptable-sensitivity and specificity are available for differential diagnosis, frustration in etiologic research on PIH is likely to continue. One clue that may potentially advance our knowledge of the pathogenesis and future prevention of PIH is the finding that smoking reduces risk of PIH. Epidemiologists should transfer this knowledge to laboratory scientists.