Comparative epidemiology of selected midline congenital abnormalities.

We present comparative epidemiologic characteristics of five congenital abnormalities that have been suggested to result from midline abnormal developmental disturbances: esophageal atresia with or without tracheoesophageal fistula (EA/TEF), imperforate anus with or without fistula (IA/F), omphalocele (OM), bladder exstrophy (BE), and diaphragmatic hernia (DH). The purpose was to assess the extent of epidemiologic similarities among these five defects. Data were collected as part of a population-based case-control study of infants with these defects born to mothers residing in Maryland, Washington, D.C., or Northern Virginia from 1980 through 1987. The estimated annual birth prevalences (per 10,000 live births) and 95% confidence intervals (CI) of these five defects were 0.40 (0.26-0.61) for BE, 1.34 (1.08-1.67) for OM, 1.59 (1.29-1.95) for DH, 2.11 (1.76-2.53) for EA/TEF, and 2.97 (2.55-3.46) for IA/F. The birth prevalence of IA/F and DH increased between 1980 and 1987. In contrast to the other four defects, DH showed a significant male preponderance (rate ratio 1.57, 95% CI 1.03-2.47), a significant white excess (rate ratio white:other, 1.56, 95% CI 1.00-2.48), and a lower proportion of multiple associated defects (30% vs. 46-61%). We concluded from this study that the descriptive epidemiology of diaphragmatic hernia is different from that of the other four defects. This finding may imply differences in etiologic and pathogenetic mechanisms underlying DH.

Genetic-epidemiologic study of omphalocele and gastroschisis: evidence for heterogeneity.

On the basis of clinical manifestations, epidemiologic characteristics, and the presence of additional malformations, omphalocele (OM) and gastroschisis (GA) are considered casually and pathogenetically distinct abdominal wall defects. More than 50% of infants with OM have additional defects, but only about 15% of those with GA do. To evaluate whether there is heterogeneity between isolated and multiply affected cases of OM and GA, we analyzed epidemiologic characteristics and familial risks of major defects for 82 OM and 81 GA cases drawn from a population-based study in the Maryland-Washington, DC-Northern Virginia area and born from 1980 through June 1987. We examined year of birth, sex, race, and maternal age distributions after stratifying the infants into isolated and multiple defect groups. We found significant differences in maternal age between cases with isolated OM and GA, but not between cases with GA or OM who had other defects. Using regressive logistic models, we analyzed familial aggregation of birth defects among relatives of infants with OM and GA. An autosomal recessive model of inheritance was found to be the most parsimonious explanation for the families of infants with isolated OM or GA. However, for families of infants with multiple defects, a sporadic or nongenetic model fit best. These findings are not only useful for estimating familial risk of major birth defects, but they also suggest further heterogeneity of infants with OM and GA according to the presence of other malformations.

Ethical and professional issues in the changing practice of epidemiology.

New ethical and professional issues are affecting epidemiology today as a result of the changing social and scientific context in which epidemiology is practiced. These issues arise in interpreting the findings of epidemiologic studies, dealing with potential conflicts of interest, fulfilling obligations to the people studied, publishing study results and providing others access to the data after studies have been completed. The epidemiologist is also faced with new challenges including the need to communicate new information on health risks to non-epidemiologists, and to apply her epidemiologic expertise and study findings to the development of public policy.

Evaluating the evidence for the effectiveness of prevention.

This report reviews a number of issues that should be considered in evaluating the evidence for the effectiveness of primary and secondary prevention. In evaluating primary prevention, changes in disease incidence are the ideal index but mortality may also be a useful surrogate in certain cases. Both relative risk and attributable risk are valuable concepts in evaluating the benefits of primary prevention. In evaluating screening, the most notable approach to secondary prevention, certain potential biases should be taken into account. These include selection biases due to referral or length-biased sampling, lead time bias, and overdiagnosis bias. An understanding of the methodologic issues involved in evaluating prevention will help ensure the validity of any conclusions drawn regarding the effectiveness of preventive measures and programs.

Consumption of methylxanthine-containing beverages and risk of pancreatic cancer.

This paper reviews published studies of a possible relationship of consumption of methylxanthine-containing beverages, primarily coffee, to risk of pancreatic cancer (PC). Certain ecologic studies suggested a possible relation of pancreatic cancer mortality and coffee consumption by country. The findings from case-control studies are not entirely consistent; in general, no significant increased risk with a clear dose-response relationship is reported, but some of the studies suggest the possibility of some increase in risk. The prospective studies reported generally agree that there is no significant association of coffee consumption with increased risk of PC. The few data available on tea consumption do not suggest an increased risk of PC. It seems reasonable to conclude that current epidemiologic evidence does not suggest any significant increased risk of PC with coffee consumption. Further research might clarify whether the divergent results reported for coffee consumption might be a result of confounding or other methodologic problems or might reflect some small but real increase in risk of PC associated with coffee consumption.

Morbidity among breech infants according to method of delivery.

To determine whether vaginally born breech infants are at increased risk for morbid events as compared with breech infants delivered by cesarean, we studied 1240 singleton breech infants without congenital anomalies delivered in Northern California Kaiser Permanente Medical Care Program hospitals during 1976-1977. Medical record review provided information on indications for method of delivery, delivery complications and injuries, neonatal complications, and neurologic sequelae up to 4 years of age. The relative risk estimates for asphyxia (1.0; 95% confidence interval 0.7, 1.4), head trauma (1.6; 95% confidence interval 0.2, 17.0), neonatal seizures (0.8; 95% confidence interval 0.1, 7.1), cerebral palsy (1.6; 95% confidence interval 0.2, 17.4), and developmental delay (2.0; 95% confidence interval 0.9, 4.4) for vaginally born compared with cesarean-delivered infants indicated that vaginally born infants were not at increased risk for these outcomes. We used multiple logistic regression to control for confounding variables. The adjusted relative risk estimate for the combined-outcome category of head trauma, neonatal seizures, cerebral palsy, mental retardation, or spasticity was 0.5 in vaginally delivered infants (95% confidence interval 0.1, 3.2). When all morbid outcomes were considered in combination, the adjusted relative risk estimate was 0.9 for vaginally delivered infants (95% confidence interval 0.6, 1.4).

Geographic and environmental factors in pediatric cancer.

It is important to determine the relative contributions of genetic and environmental factors to the etiology of childhood cancer in order to elucidate the pathogenic mechanisms involved and to develop effective means of primary prevention. Geographic differences in cancer incidence as well as changes in incidence over calendar time have long been used to generate clues to possible etiologic agents. The important role of genetic factors in childhood cancer is clear, and is exemplified by the observations in retinoblastoma. The importance of the contributions of environmental factors in general and of specific factors in particular, to the etiology of cancers in children, has proven more difficult to determine. A variety of environmental factors have been implicated to varying degrees in the etiology of different childhood cancers. These factors include physical agents such as radiation, chemical agents such as nitrosamines, and organic solvents, and infectious agents such as the Epstein-Barr virus. The observations that certain compounds may act as teratogens when a prenatal exposure occurs early in pregnancy and as carcinogens when the exposure occurs late in pregnancy, suggests that there may be a continuum of teratogenesis and carcinogenesis. This finding has major implications for the possible biologic mechanisms that could be involved in childhood cancers and for the design of future research of their etiology and prevention. The etiology of childhood cancer should be viewed as an interaction of environmental factors to which the child or his parent were exposed together with varying degrees of genetically determined susceptibility of the child to the carcinogenic effects of these factors.

Diet and other risk factors for cancer of the pancreas.

The findings of a case - control study of cancer of the pancreas, which was conducted in the Baltimore metropolitan area, are reported. Two hundred one patients with pancreatic cancer were matched on age (+/- 5 years), race, and sex to hospital and non-hospital controls, the latter selected by random-digit-dialing (RDD). All subjects were interviewed regarding diet, beverage consumption, occupational and environmental exposures, and medical and surgical history. Significantly decreased risks were associated with consumption of raw fruits and vegetables and diet soda, and significantly increased risks were associated with consumption of white bread when cases were compared with hospital and RDD controls. A significantly reduced risk was associated with consumption of wine when cases were compared to RDD controls. Risk ratios for consumption of coffee were not significantly different from one, although there appeared to be a dose - response relationship in women. A moderate but statistically nonsignificant increase in relative odds was found for cigarette smoking, and cessation of smoking was associated with a marked reduction in risk. No significant associations were found with particular occupational exposures. Tonsillectomy was associated with a significantly reduced risk, a finding that has been observed for other cancers as well. The current evidence indicates that pancreatic cancer is likely to result from a complex interaction of factors and suggests that the study of its etiology requires a multidisciplinary approach involving both laboratory and epidemiologic components.

General concepts for use of markers in clinical trials.

Both indirect and direct methods have been widely employed for measuring medication compliance. Indirect methods include therapeutic or preventive outcome, assessment by the physician, interview with the patient, whether or not the prescription was filled, and a count of remaining pills. In many situations, direct methods may be feasible, including measurement of blood or serum levels or testing urine for excretion of the medication itself, a metabolic by-product, or a marker or tracer that has been added to the medication for detection purposes. For example, detection of penicillin or of salicylates can be used in measuring compliance, while in other circumstances, it may be necessary to add a detectable label to the medication. Ideally, such a marker should be nontoxic and pharmacologically and chemically inert [Porter AM: Br Med J 1:218-222, 1969]. The marker should be unaffected by physical and chemical properties of the urine, such as pH and temperature, quickly and freely excreted, and noncumulative. A simple, sensitive, and specific detection method should be available, and the marker should be such that the patient is unaware that it has been added. In direct measures of compliance, it is necessary to consider pharmacokinetic variations among individuals in absorption, distribution, metabolism, and excretion of drugs. In addition, temporal aspects of the sampling scheme assume great importance. Finally, the definition of compliance and noncompliance for a given study in relation to the specific question being tested in the investigation, as well as in regard to use of the marker itself, is an important issue for consideration.(ABSTRACT TRUNCATED AT 250 WORDS)

Estrogen use and myocardial infarction risk: a case-control study.

A case-control study was conducted to examine the relationship of estrogen use to myocardial infarction in postmenopausal white women. After exclusion of proxy responses and of controls with discharge diagnoses of gynecologic or gallbladder diseases, there remained 39 matched sets (33 pairs and 6 triplets). The unadjusted relative odds ratio (RO) for past estrogen use was found to be 0.83. However, after simultaneous adjustment for cardiovascular diseases, smoking, education, and type of menopause, the net RO was 0.61. Type of menopause was found to interact with estrogen use, in that the protective effect was seen mainly in surgical menopause women, in whom the net RO for estrogen use was 0.37. Although none of the results reached statistical significance, they are consistent with recent results indicating a protective effect for estrogen therapy in regard to coronary heart disease, mainly among women undergoing surgical menopause.