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Biomedical subjects

L E Sever

Publications and source records attributed to L E Sever.

At least 37 records · Page 2Linked to original sources

Acute myelocytic leukemia and prior allergies.

The relationship between prior allergies and adult acute myelocytic leukemia was investigated in a population-based case-control study. Based on data from personal interviews of 98 cases and 133 controls, a history of any type of allergy was associated with a significantly decreased risk of acute myelocytic leukemia (OR = 0.35, 95% CI = 0.20-0.60). Risk declined with the total number of specific allergies reported (p less than 0.001), and was reduced in relation to a history of prior asthma, eczema and hives. The implications of these findings in relation to natural immune surveillance against developing neoplasms are discussed.

Adult↗

Intrauterine growth retardation and risk of sudden infant death syndrome (SIDS)

The purpose of this study was to assess whether intrauterine growth retardation was associated with an increased risk of sudden infant death syndrome (SIDS). A total of 148 SIDS cases were identified from the Upstate New York (exclusive of New York City) live birth cohort for 1974 (n = 132,948). Dead controls represented all other sudden deaths (n = 114). Live controls were randomly selected and matched to cases on mother's age, race, parity, and residence and infant's birth date (n = 355). Data were collected from vital certificates (response, 97%), medical records (89%), and autopsy reports (100%). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with the use of logistic regression techniques to control for confounding. With live controls, significant risks were observed for gestations less than 37 weeks (OR = 2.2, CI 1.2-4.1), birth weights less than 2,500 g (OR = 2.5, CI 1.3-5.0) and birth lengths less than or equal to 47.0 cm (OR = 3.4, CI 1.8-6.4). Birth length less than or equal to 47.0 cm was the only significant risk factor observed when dead controls were used (OR = 2.9, CI 1.3-6.8). Risk decreased with increasing gestation and birth size. Postterm infants (greater than or equal to 42 weeks) were at lowest risk (live controls OR = 0.9, CI 0.5-1.6; dead controls OR = 0.6, CI 0.3-1.1). When gestational age was controlled for, SIDS infants were found to have reductions in both weight and length; this suggests that responsible mechanisms begin early in pregnancy.

Biometry↗

Assessment of in utero hypoxia and risk of sudden infant death syndrome.

Few data are available on the role of hypoxia in sudden infant death syndrome (SIDS). The purpose of this study was to assess whether 10 antenatal factors consistent with in utero hypoxia were associated with an increased risk of SIDS. Cases and two sets of controls were chosen from the Upstate New York Live Birth Cohort for 1974 (n = 132,948). One hundred and forty-eight SIDS cases were identified, along with 114 dead controls made up of all other sudden deaths. Randomly selected live controls were frequency-matched to cases on mother's age, race, residence, parity, and infant's birthdate (n = 355). Data were collected from vital certificates (97% response), hospital delivery records (89%), and autopsy reports (100%). Odds ratios and 95% confidence intervals were calculated using Mantel-Haenszel techniques and logistic regression. Abnormal uterine bleeding was the only statistically significant (P less than 0.05) risk factor observed when dead controls were used (OR = 5.4). When live controls were used, statistically significant increases in risk were found for: placenta praevia (OR = 21.8), abruptio placentae (OR = 3.7), multiple birth (OR = 29.6), pregnancy interval less than or equal to 12 months (OR = 3.8), sexually transmitted disease (OR = 6.4), and eclampsia (OR = 17.7). These results lend support to a possible hypoxic aetiology of SIDS; however, differences by control group suggest that some factors are not specific to SIDS alone but may be risk factors for infant mortality in general.

Abruptio Placentae↗

A case-control study of congenital malformations and occupational exposure to low-level ionizing radiation.

In a case-control study, the authors investigated the association of parental occupational exposure to low-level external whole-body penetrating ionizing radiation and risk of congenital malformations in their offspring. Cases and controls were ascertained from births in two counties in southeastern Washington State, where the Hanford Site has been a major employer. A unique feature of this study was the linking of quantitative individual measurement of external whole-body penetrating ionizing radiation exposure of employees at the Hanford Site, using personal dosimeters, and the disease outcome, congenital malformations. The study population included 672 malformation cases and 977 matched controls from births occurring from 1957 through 1980. Twelve specific malformation types were analyzed for evidence of association with employment of the parents at Hanford and with occupational exposure to ionizing radiation. Two defects, congenital dislocation of the hip and tracheoesophageal fistula, showed statistically significant associations with employment of the parents at Hanford, but not with parental radiation exposure. Neural tube defects showed a significant association with parental preconception exposure, on the basis of a small number of cases. Eleven other defects, including Down syndrome, for which an association with radiation was considered most likely, showed no evidence of such an association. When all malformations were analyzed as a group, there was no evidence of an association with employment of the parents at Hanford, but the relation of parental exposure to radiation before conception was in the positive direction (one-tailed p value between 0.05 and 0.10). Given the number of statistical tests conducted, some or all of the observed positive correlations are likely to represent false positive findings. In view of strong contradictory evidence, based on no demonstrated effects in genetic studies of atomic bomb survivors in Hiroshima and Nagasaki, it is unlikely that these correlations result from a cause and effect association with parental radiation exposure.

Abnormalities, Radiation-Induced↗

The prevalence at birth of congenital malformations in communities near the Hanford site.

The authors examined the prevalence of congenital malformations among births in Benton and Franklin counties, in southeastern Washington State, from 1968 through 1980. The Hanford Site is in this area and serves as a major employer. In addition, various agriculturally and chemically related activities are in the area. Hospital and vital records were used to identify 454 malformation cases among 23,319 births; this yielded a malformation rate of 19.6 per 1,000 births, a rate similar to those reported in other studies. The rates of specific malformations ascertained during the first year of life were compared with combined rates from the states of Washington, Oregon, and Idaho from the Birth Defects Monitoring Program. Among defects that would be expected to be comparably ascertained, a statistically significant elevated rate of neural tube defects was observed (1.72 per 1,000 births vs. 0.99 per 1,000). Rates of cleft lip were significantly lower in Benton and Franklin counties than in the Birth Defects Monitoring Program (0.59 per 1,000 vs. 1.17 per 1,000). For congenital heart defects, pyloric stenosis, and Down syndrome, which are often not diagnosed in the newborn period, Birth Defects Monitoring Program data did not offer appropriate comparisons. The rates of these defects did not appear to be elevated in relation to rates found in other relevant populations. When rates of neural tube defects were compared with those in populations other than the Birth Defects Monitoring Program, the Benton and Franklin county rates were still considered to be elevated. The increased bicounty rate cannot be explained by employment of the parents at Hanford or by the impact of plant emissions on the local population.

Congenital Abnormalities↗

Acute nonlymphocytic leukemia and residential exposure to power frequency magnetic fields.

Recent research has suggested that nonionizing radiation in the form of power-frequency magnetic fields may play some role in carcinogenesis in general and in acute nonlymphocytic leukemia in particular. Much of the epidemiologic evidence is preliminary in nature and the methods of previous studies have been criticized. In order to further evaluate this hypothesis, a population-based case-control study of adult acute nonlymphocytic leukemia and residential exposure to power-frequency magnetic fields was carried out in western Washington state. Analyses were based on 114 cases who were newly diagnosed from 1981 to 1984 and identified from a population-based cancer registry, and 133 controls who were chosen from the study area by random digit dialing. Magnetic field exposure was estimated from external electrical wiring configurations within 140 ft (42.7 m) of each subject's residence. In addition, magnetic fields were measured inside the subject's residence at the time of interview. Neither the directly measured magnetic fields nor the surrogate values based on the wiring configurations were associated with acute nonlymphocytic leukemia.

Acute Disease↗

Teratogen update: valproic acid.

Valproic acid use during pregnancy results in an absolute risk for spina bifida of 1-2%. This increased risk is comparable to the recurrence risk for neural tube defects and warrants informed counselling and access to prenatal diagnosis. There is no substantial evidence that valproic acid use increases the risk for other specific major malformations above the increased risk due to maternal epilepsy. Valproic acid may cause a characteristic pattern of minor facial malformations. Further definition and confirmation are required, and the magnitude of the risk needs to be determined. There are inadequate data to assess the magnitude, if any, of the risks for postnatal growth abnormalities and developmental disabilities associated with the use of valproic acid during pregnancy. Birth-defect monitoring programs and international collaboration among the staffs of monitoring programs played a major role in determining that valproic acid is a human teratogen.

Abnormalities, Drug-Induced↗

Overall design considerations in male and female occupational reproductive studies.

Epidemiologic studies are extremely useful for examining the possible relationships between occupational exposures and reproductive outcomes in occupational populations. In this paper, we examine some of the major epidemiologic design considerations in male and female occupational reproductive studies. An important consideration in all epidemiologic studies is to choose appropriate outcome variables. One of the unique characteristics of reproductive studies is the wide range of potential outcome variables: from problems of infertility, through fetal development, and into childhood diseases and diseases of young adulthood. Usually, it is infeasible to look at all possible outcomes. By omitting certain outcomes, however, important associations between exposure and outcome may remain undetected. Epidemiology relies on observations of populations. Factors in data availability, collection, and analysis, and in study design often limit the inferences that may be drawn. The "exposed" or "at risk" groups are not likely to be randomly selected and the investigator has little control over the exposures of the study population. Unlike experimental investigations, epidemiologic observations are made on individuals exposed to a variety of hazards during their lives. The size of the population available for study is critical. Bias from potential confounding factors can be minimized through the use of appropriate matching and/or statistical techniques. Many of the topics discussed here will be expanded in subsequent chapters. Although this paper is designed to assist in planning occupational epidemiologic studies, we strongly recommend that, when attempting to conduct such studies, professional guidance from epidemiologists and biostatisticians be obtained.

Abnormalities, Drug-Induced↗

Epidemiologic approaches to the study of diseases of complex etiology.

In this preparation I have discussed some of the concepts and methods of epidemiologic studies of diseases of complex etiology. I have pointed out some of the relationships between epidemiology and genetics and examined briefly the relatively new field of genetic epidemiology. Epidemiology is a comparative science and is based on asking questions about the who, where, and when of disease occurrence in an attempt to understand "why." As a comparative science, it is necessary to have measures that can be meaningfully compared between places and times. In epidemiology, the measures we use are rates, and we have examined some of the commonly used types and kinds of rates and the information that is necessary for their generation. To a large degree, epidemiology is concerned with determining if there is an association between a characteristic or exposure and a disease. Epidemiologic reasoning involves an iterative process of hypothesis generation and testing. I described some of the study designs that are used in attempting to identify etiologic factors in diseases of complex etiology. I noted that we usually begin with descriptive studies and then move on to analytic studies where associations between exposure and disease are examined. In discussing study designs, I pointed out that studies can be based on examination of associations at either the group or individual level. I discussed the basic aspects of four epidemiologic study designs: ecologic studies, cross-sectional studies, case-control studies, and cohort studies. Illustrative examples of the study designs were presented from the literature. In addition, some of the basic statistical approaches were noted that are used to determine if the association between exposure and outcome is greater than that expected to occur by chance alone. Some of the strengths and weaknesses of various study designs were commented on briefly.

Cross-Sectional Studies↗

A population-based case-control study of anencephalus and spina bifida in a low-risk area.

For the period 1973 to 1977, a total of 536 cases of anencephalus and spina bifida were ascertained in Los Angeles County, California, a low-risk area, and compared with a 2 per cent random sample of all live births in the county. Women with Spanish surnames had an elevated risk for anencephalus and to a lesser extent for spina bifida; Blacks were at lowest risk, especially for spina bifida. The occurrence of a previous fetal death was a strong risk factor for anencephalus but there was no association between socio-economic status and either of the defects. Advanced maternal age was a stronger risk factor for spina bifida than for anencephalus but, as in other studies in low-risk areas, no increased risk was observed among teenage mothers. Paternal age did not show any independent association after controlling for mother's age. Finally, the association of high birth-order with the birth defects was weakened greatly after simultaneous adjustment for age and ethnicity.

Analysis of Variance↗

An epidemiologic study of neural tube defects in Los Angeles County I. Prevalence at birth based on multiple sources of case ascertainment.

Epidemiologic studies of the neural tube defects (NTDs), anencephalus and spina bifida, have for the most part been based on single sources of case ascertainment in past studies. The present investigation attempts total ascertainment of NTD cases in the newborn population of Los Angeles County residents for the period 1966-1972. Design of the study, sources of data, and estimates of prevalence rates based on single and multiple sources of case ascertainment are here discussed. Anencephalus cases totaled 448, spina bifida 442, and encephalocele 72, giving prevalence rates of 0.52, 0.51, and 0.08 per 1000 total births, respectively, for these neural tube defects--rates considered to be low. The Los Angeles County prevalence rates are compared with those of other recent North American studies and support is provided for earlier suggestions of low rates on the West Coast.

Anencephaly↗

An epidemiologic study of neural tube defects in Los Angeles County II. Etiologic factors in an area with low prevalence at birth.

Epidemiologic characteristics of neural tube defect (NTD) births occurring in Los Angeles County, California, residents during the period 1966-1972 are presented. The prevalence at birth was 0.52/1000 births for anencephalus, 0.51/1000 for spina bifida, and 0.08/1000 for encephalocele, rates considered to be low for a predominantly white population. We hypothesized that environmental (nongenetic) factors are of less etiologic importance in a low-prevalence population than in areas or time periods with high prevalence. We tested that hypothesis by examining epidemiologic characteristics of NTDs in Los Angeles County and comparing them with high-prevalence populations. The data did not support a major etiologic role for environmental factors: (1) no significant differences between rates by month of birth or conception; (2) no significant association with maternal age or parity for anencephalus; for spina bifida a significant maternal age effect (P less than 0.01) and for encephalocele a parity effect (P less than 0.02); and (3) no significant relationship with father's occupational class for either anencephalus or encephalocele but a marginally significant (P less than 0.05) inverse association for spina bifida when a statistic based on ordinal relationships was used. Findings supporting the importance of genetic factors in etiology included: (1) a high percentage of males; (2) a higher twin concordance rate than in high-prevalence populations; and (3) an anencephalus rate among blacks comparable with rates for blacks in other United States populations. Our findings in conjunction with those from other areas and times of low prevalence suggest environmental factors play a relatively insignificant role in the etiology of NTDs in such populations.

Anencephaly↗

The association of twinning and neural tube defects: studies in Los Angeles, California, and Norway.

Accurate, unbiased malformation rates in twins must be obtained unselectively from population-based studies that include livebirths and stillbirths after a thorough ascertainment of cases. This type of study was conducted in Los Angeles County, California, where 28 twins with a neural tube defect (NTD) were identified. The prevalence in twins (1.6/1,000) was significantly higher than in singletons (1.1/1,000). The study then was expanded to include population-based data from the Medical Birth Registry of Norway which has a comparable overall NTD prevalence (1.0/1,000) and twinning rate (2%). The combined material shows a higher prevalence of anencephaly and encephalocele but not of spina bifida in twins compared to singletons. The male/female ratios in total twin and singleton cases were comparable (0.8), but varied by specific defect. Like-sex twin females appeared at highest risk for NTD as well as for fetal death. This study supports theories which associate NTDs with monozygotic twins, either through developmental disruptions that cause susceptibility to environmental agents or through a common etiology. Furthermore, it suggests that twins and singletons differ in their response to etiologic factors for the development of NTDs and that the development of each type of NTD may be related to different factors.

California↗

Neural tube defects among twin births.

To obtain accurate, unbiased rates of neural tube defects (NTDs) in twins, we conducted a population-based study that included live births and fetal deaths in Los Angeles County, California, ascertaining cases by multiple methods. Twenty-eight twin cases yielded a prevalence-at-birth of 1.6/1,000 twin births, which is significantly higher than the singleton prevalence of 1.1/1,000 births. In twins compared with singletons, the prevalences of both encephalocele and anencephaly are increased, whereas spina bifida is decreased. The twin case male/female sex ratio (.55) is lower than the singleton case sex ratio (.77). Concordance is relatively low at 3.7%, but appears to be higher than recently reported recurrence risks in other low prevalence areas. Stillbirths were most common among female cases and like-sex twins. Our study tends to support proposed etiologic theories associating NTDs with females or monozygotic twins, or both. There is increasing evidence that the etiology of NTDs may differ in high and low prevalence areas. We suggest also that twins and singletons may differ in their response to etiologic factors. The variations among anencephaly, spina bifida, and encephalocele in their association with twinning suggest that there may be different factors that influence the development of each specific NTD. The noted differences among the malformations also indicate that some of the variation among results of other studies of NTDs and twinning may be due to case ascertainment. Including spina bifida cases would decrease the proportion of twins in a study population, while including anencephalics would increase the proportion. Importantly, ascertaining fetal deaths would increase the proportion of anencephalics and case females, so studies of NTDs that do not include fetal deaths will show fewer twins than expected. On the basis of our findings and those of Layde et al., excluding encephaloceles will also decrease the number of twins among NTD cases. When investigating etiologic hypotheses for NTDs, these potential biases must be recognized.

Adult↗