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Background: The pre- and peri-natal drug exposures reported by women participating in a case-control study of children in Colorado were examined for association with infant craniosynostosis.Methods: Mothers of case and control children underwent a standardized telephone interview and obstetric and newborn medical record review. The interview included questions on the use of prescription and non-prescription drugs, nutritional supplements, recreational and drugs of abuse. The mother's obstetric record was abstracted for information about pharmacologic agents taken before and during the antepartum period.Results: There were no statistically significant risk ratios associating craniosynostosis with prenatal exposure to hydantoin, valproic acid, or cocaine. Mothers of four case children and one control child reported specific exposure to retinoic acid. There were no statistically significant increases in the odds ratio (OR) for any suture type among children exposed to hypoxigenic agents, sympathomimetic or parasympatholytic agents, or metal-containing agents. The OR was 1.87 (lower bound of the two-sided 95% test-based confidence interval (CI): 1.08) among children with sagittal/lambdoid suture synostosis who were exposed to nitrosatable drugs chlorpheniramine, chlordiazepoxide, and nitrofurantoin compared to controls.Conclusions: Certain nitrosatable drugs may be associated with increased risk of infant sagittal/lambdoid craniosynostosis. A possible mechanism related to ischaemia/reperfusion injury is suggested. [ABSTRACT FROM AUTHOR]

Background: Clubfoot is a relatively common and potentially disabling birth defect. The etiology of clubfoot (talipes equinovarus [TEV]) is not known. Joint laxity, or hypermobility, is a suspected risk factor for congenital hip dislocation and clubfoot., Methods: We conducted a case-control study of TEV in five western Washington counties. A total of 239 cases of TEV were identified from hospital and outpatient sources from 1986 to 1994. Controls (n = 356) were identified by random-digit dialing (RDD). Parents were interviewed over the telephone, and medical records were abstracted. In-person measurements of four joint laxity indices in parents and the index child were obtained., Results: Moderately elevated adjusted odds ratios (ORs) were found for extension > 90 degrees of the entire little finger, and extension of all four fingers to a position parallel to the forearm (OR = 1.6; 95% CI = 0.9-2.9; and OR = 1.7; CI = 1.1-2.5; respectively). No elevation in the OR was found for the wrist and elbow laxity measures. No consistent pattern of association between joint laxity measures in parents and an elevated OR of clubfoot among their children was found., Conclusions: The results of this study suggest a role for joint laxity in the etiology of TEV.

Background: Talipes equinovarus (TEV), also called congenital idiopathic clubfoot, true clubfoot and common clubfoot, is one of the most common major birth defects. Its correction is often difficult and expensive. Its etiology is poorly understood and few analytic epidemiological studies have been devoted to exploring specific risk factors for TEV., Methods: Our population-based study consists of 239 documented cases of idiopathic TEV obtained from hospital and outpatient sources and 365 controls identified via random digit dialing from five Western Washington counties. Structured maternal interviews were conducted by trained interviewers and multiple logistic regression used to evaluate associations between maternal smoking and birth of a child with TEV., Results: Our study shows strong associations between maternal smoking and idiopathic TEV. Case mothers were more likely to have smoked during pregnancy (OR = 2.2; 95% CI = 1.5, 3.3). Increased TEV risk was seen with increased smoking and estimates ranged from 1.5 for the lightest smokers to 3.9 for the heaviest smokers. Gender specific differences in risk were also noted with risk estimates of 1.8 (95% CI = 1.2, 3.0) for boys whose mothers smoked during pregnancy and 2.8 (95% CI = 1.4, 5.4) for girls. Trends for increased risk with higher numbers of cigarettes were noted for both genders. For isolated TEV, the overall odds ratio (OR) for smoking was 2.4 (95% CI = 1.6, 3.6) with a range from 1.4-4.6. No confounders were noted., Conclusions: As postulated, maternal smoking during pregnancy appears to increase the risk of having a child with idiopathic clubfoot and the number of cigarettes smoked influence that risk. Further delineation of dose-response is warranted as are continued efforts to decrease maternal smoking during pregnancy., (Copyright 2002 Wiley-Liss, Inc.)

Purpose: To estimate the effect of several types of maternal physical activity in pregnancy on size for gestational age and length of gestation., Methods: Telephone interviews, birth certificates, and medical records provided data on physical activity and other factors for a random sample of 291 Colorado residents. Backward polychotomous logistic regression modeling yielded estimates of the odds ratios for size for gestational age (appropriate versus small or large) and length of gestation (term versus pre-term or post-term) in relation to second and third trimester maternal physical activity., Results: Performance of any moderate or vigorous physical activity for two hours per week or more in any month was associated with a decreased risk of large infant size for gestational age (LGA; odds ratio = 0.3, 95% confidence interval = 0.2, 0.7), but had no significant effect on risk of small infant size for gestational age (SGA; odds ratio (OR) = 0.8, 95% confidence interval (CI) = 0.3, 2.3). Length of gestation was not affected by prenatal physical activity., Conclusions: These results suggest that prenatal physical activity may decrease risk of LGA, as might be expected given its salutary effects on glucose tolerance.

Background: In the late 1980s, evidence of an epidemic of craniosynostosis in Colorado included reports of clusters from selected high-altitude communities and an investigation showing the high and rapidly rising rates of surgically corrected synostosis. Some evidence suggested that local diagnostic practice could account for the epidemic., Objective: To determine the contributions of any excess rates of disease occurrence, surgery-based ascertainment, and diagnosis to the reported epidemic., Design: Population-based birth prevalence study with diagnostic evaluation., Setting: The Colorado Department of Health, April 15, 1986, to July 14, 1989., Patients or Other Participants: Children in the Craniosynostosis Registry or state birth record files., Main Outcome Measures: Birth prevalence was estimated from registry and birth record data; case classification by suture type and malformation patterns were determined by review of radiographs and medical records., Results: The period birth prevalence of radiographically confirmed nonsyndromic synostosis was 14.1 per 10,000 live births. Of a total of 605 children, 307 (51%) had definite radiographic evidence of synostosis, for which the intrarater reliability was good (except for the coronal suture on plain films) and the interrater reliability was fair or good (except for the metopic suture on plain films). Between the first and third years, case reports fell from 347 to 103., Conclusions: Diagnostic criteria strongly influenced the rate of synostosis. The rate of radiographically confirmed synostosis was within the range of published estimates. Low diagnostic thresholds, which changed over time, created the semblance of a severe statewide epidemic and may have obscured excess rates of disease at high altitude.

In a population-based case-control study, we examined relations between maternal and paternal occupations and the risk of infant craniosynostosis. Cases were 212 children born to Colorado residents and diagnosed during 1986-1989 with radiographically confirmed synostosis of unknown etiology. Controls were 291 children randomly selected from state birth records and frequency matched to cases on month and year of birth. Trained staff conducted telephone interviews of mothers of case and control children. Information was obtained about each job held by either parent during the pregnancy, and any job that the father held during the 3 months before the last menstrual period before conception. Jobs were coded using 1980 Census occupation and industry codes. We found no strong associations for maternal occupations. Of paternal occupations, two groups were associated with moderately increased odds ratios after adjustment for maternal smoking and altitude: agriculture and forestry (odds ratio = 2.3; 95% confidence interval = 1.0-5.2), and mechanics and repairmen (odds ratio = 2.7; 95% confidence interval = 1.2-6.1). For both, the odds ratios were higher for males.

Background: During the 1980s, the Colorado Department of Health received reports from several high-altitude communities of clusters of the malformation craniosynostosis. In a population-based, case-control study, we examined the association between overall and trimester-specific maternal antenatal altitude exposure and the occurrence of infant craniosynostosis., Methods: We identified case children through a statewide registry and randomly sampled control children from birth records. By telephone interview, each mother provided data on the locations of all antenatal residences and places of employment as well as other factors. Staff mapped all locations and abstracted the corresponding altitudes., Results: The odds ratio (OR) of any synostosis for a time-weighted mean antenatal altitude of > or = 2000 metres (high altitude) versus < 2000 metres (low altitude) was 1.4 (lower bound of the one-sided 95% test-based confidence interval (CI): 0.9). The OR was elevated in smokers but not in non-smokers. As compared to non-smokers, the OR of any synostosis for high-altitude smokers was 4.6 (lower bound of the 95% one-sided exact CI: 1.7). Particularly elevated were the corresponding OR of coronal (18.1, 4.4) and metopic synostosis (16.3, 2.8), and OR for high-altitude exposure during the second trimester (any synostosis: 6.4, 1.99; coronal: 28.6, 6.1; metopic: 26.7, 4.1)., Conclusions: Antenatal maternal high-altitude exposure and smoking are associated with increased risk of infant craniosynostosis, perhaps through generation of intermittent hypoxaemia.

We analyzed data from a population-based case control study to determine whether maternal prenatal smoking or alcohol drinking might increase the risk of craniosynostosis. Between 1986 and 1989, the Colorado Craniosynostosis Registry ascertained 233 children whose diagnoses were confirmed by an independent radiologist. Of the 212 (91%) cases who participated 86 had lambdoid, 69 had sagittal, 25 had coronal, 18 had metopic, and 14 had multiple suture synostosis. Random sampling of birth certificate records yielded 367 eligible controls, of whom 291 (79%) participated. Study staff interviewed case and control mothers between 1989 and 1991 for prenatal smoking and alcohol drinking. We used Mantel-Haenszel and polychotomous logistic regression techniques to estimate the relative odds of craniosynostosis for smoking and drinking in all cases and in relevant case subgroups. Smoking was associated with a relative odds of craniosynostosis of 1.7 (95% confidence interval, 1.2-2.6). For smoking of more than one pack per day, the relative odds were 3.5 (1.5-8.4) for all types of synostosis combined, and 5.6 (2.1-15.3) for coronal synostosis. No strong or significant association was noted for drinking. Maternal prenatal smoking may increase the risk of craniosynostosis in this population.

Objective: To ascertain whether childbearing would decrease oral glucose-stimulated insulin and C-peptide levels and increase the risk of NIDDM and impaired glucose tolerance in a population of Hispanic and non-Hispanic white women residing in the San Luis Valley of Colorado. Several investigators have related childbearing to subsequent abnormal glucose tolerance., Research Design and Methods: In a population-based case-control epidemiological study, diabetic patients 20-74 yr of age (n = 196) and randomly sampled control women subjects (n = 735) underwent a glucose tolerance test, a physical examination, and an in-person standardized interview. The relations between the live-birth number and fasting and oral glucose stimulated glucose, insulin and C-peptide concentrations, and NIDDM and impaired glucose tolerance were estimated using linear or logistic regression to adjust for extraneous variables., Results: In women selected as control subjects, the live-birth number was related to a significant decrease in the sum of 1- and 2-h C-peptide concentrations (coefficient = -0.077, P < 0.001) and the logarithm of the sum of 1- and 2-h insulin concentrations (coefficient = -0.014, P = 0.02). After adjustment for subscapular skin-fold thickness, the relative odds of NIDDM for the live-birth number, which was small and of borderline significance, diminished (odds ratio = 1.04 for one birth, P = 0.18). Findings were similar for impaired glucose tolerance., Conclusions: Childbearing was related to lower C-peptide and insulin levels in Hispanic and non-Hispanic women of the San Luis Valley. It had little apparent effect on later risk of NIDDM or impaired glucose tolerance.

When lacking information on confounding variables, epidemiologists have used surrogates which are antecedents of both the exposures and confounders of interest. The usefulness of this strategy is explored in a series of scenarios for a prospective epidemiologic study wherein risk ratios relating antecedent to confounder, antecedent to exposure, and confounder to exposure were varied. Antecedent-adjusted, confounder-adjusted, and crude risk ratios were calculated and compared. The antecedent-adjusted risk ratio was useful, that is, was closer to the confounder-adjusted risk ratio than was the crude risk ratio, in 1,067 (49%) of 2,187 scenarios. The antecedent-adjusted risk ratio, the crude risk ratio, and the risk ratio relating confounder to exposure together predicted the usefulness of the antecedent (or any variable) as a confounder proxy. The antecedent was useful in 97% of scenarios wherein: 1) the antecedent-adjusted risk ratio was less than the crude risk ratio, and the risk ratio relating confounder to exposure was greater than 1.0, or 2) the antecedent-adjusted risk ratio was greater than the crude risk ratio, and the risk ratio relating confounder to exposure was less than 1.0. In the remaining scenarios, it was useful only 5% of the time.

The authors developed a method that utilizes logistic regression analysis to 1) calculate the disease probability with confidence intervals at which any specified proportion of physicians reaches a clinical decision, 2) statistically test whether factors other than disease probability affect this clinical decision, and 3) statistically test whether physician decision making in relation to disease probability varies by other factors. They apply the method to analyze the relationship between disease probability and the proportion of physicians who diagnosed coronary artery disease (CAD) in 127 consecutive subjects who completed the treadmill exercise tolerance test (ETT) at two hospitals. Twenty-five percent of the physicians decided that CAD was possible or definite at a post-ETT disease probability of 0.24 (95% CL= 0.07-0.35); 50% at 0.54 (95% CL = 0.43-0.70); and 75% at 0.82 (95% CL = 0.67-1.0). Multivariate logistic regression analysis revealed three factors significantly and independently related to the diagnosis of CAD: post-ETT disease probability, positive ETT result, and cigarette smoking. The proportion of physicians who reached a diagnosis of CAD did not differ by hospital setting (VA versus university), level of training (attending versus housestaff/fellow), or diagnosing service (cardiology versus other internal medicine). It is concluded that factors other than disease probability may affect physician diagnostic decisions.

The association between maternal low birthweight (LBW) and infant low birthweight has been explored in previous studies in mainly middle and upper income, Caucasian populations. This study investigated whether the association found in these populations is true in a racially mixed, low socio-economic group. A case-control methodology was used and estimates of association were derived by means of logistic regression analyses. Data were gathered for 167 LBW infant-mother dyads and 338 adequate weight infant-mother controls matched on race and parity. The odds of a LBW infant having a LBW mother were 80% more likely than for adequate weight infants (OR = 1.80, 95% CI 1.14-2.84). This association was stronger for Hispanic women and their infants than for Black or non-Hispanic White women and their infants. Women who were both preterm and LBW had the higher estimate of risk for infant LBW than women who were LBW due to intrauterine growth retardation (IUGR). As found in previous research, the estimate of association between maternal LBW and infant LBW was greater for those infants who were LBW due to IUGR than those who were LBW due to being premature. The question of whether maternal LBW is also associated with increased risk of neonatal mortality and morbidity is as yet left unanswered.

To identify risk indicators for talipes equinovarus, we compared 175 case children with talipes equinovarus of unknown etiology identified through the Washington State Birth Defect Registry with 1,470 control children sampled from resident live births. Infant gender, maternal smoking, death of a preterm sibling, and marital status were independently related to talipes equinovarus in an analysis based on information from birth certificate records. The findings differed by infant gender. The prevalence odds ratio for maternal smoking was 2.6 (95% confidence interval: 1.6-4.0) in males and 1.4 (95% confidence interval:0.6-3.2) in females.

The goal of this study was to estimate the effects of childbearing on subsequent glucose tolerance and non-insulin-dependent diabetes mellitus (NIDDM) prevalence. A sample of subjects from 64 different locations in the United States were recruited for inclusion in the Second National Health and Nutrition Examination Survey. A complex survey design was used to select a probability sample of subjects from each location. A total of 4577 women were recruited, of whom 3057 underwent clinical and laboratory evaluation for the presence of diabetes mellitus. Women were classified as to their glucose tolerance based on the results of an oral glucose tolerance test or previous physician diagnosis of diabetes mellitus combined with current use of hypoglycemic medication. Childbearing was defined as number of live births experienced by each woman at the time of the interview. Fasting plasma glucose increased linearly with increasing number of live births (coefficient 0.009, 95% confidence interval [CI] 0.006-0.012), as did the 2-h value (coefficient 0.015, 95% CI 0.009-0.021). Adjustment for age, body mass index (BMI), education, and income substantially reduced the magnitude of the association between childbearing and either plasma glucose measurement. When the prevalence of NIDDM in relation to childbearing was examined with logistic regression analysis, a significant linear increase in diabetes prevalence was seen with increasing number of live births (relative prevalence of NIDDM, 1 birth vs. 0 = 1.73, 95% CI 1.39-2.15), but adjustment for age, BMI, education, and income greatly reduced the magnitude of this association (relative prevalence of NIDDM, 1 birth vs. 0 = 1.07, 95% CI 0.98-1.17).(ABSTRACT TRUNCATED AT 250 WORDS)

We discuss in this paper the extent to which disease risk factors may assist in the diagnostic process. We caution that disease risk factors need not be very sensitive or specific. Risk factor specificity and sensitivity may be further reduced if, in the former case, the risk factor is related to other illnesses having the same clinical presentation as the disease of interest, or if, in the latter case, the risk factor disappears with the onset of illness. We illustrate these points in a discussion of the utility of smoking as a diagnostic test for malignancy in two clinical situations, the patient with asymptomatic microscopic hematuria and the patient with a solitary pulmonary nodule. Risk factors hold great promise as aids to medical diagnosis, as this information is readily available to clinicians at little or no cost. Clinicians, however, should exercise caution when using risk factors of unproven diagnostic utility in medical diagnosis, as their presence may have little or no effect on disease probability.

This case-control study investigated the potential association between ambient levels of carbon monoxide in a pregnant woman's neighborhood of residence and her chance of delivering a low birth weight infant. Low birth weight infants and normal birth weight infants were contrasted with respect to ambient levels of CO during the 3 months prior to delivery in the neighborhoods where their mothers lived at birth. After adjustment for the confounding effects of maternal race and education, there was no association between higher CO exposure and higher odds of low birth weight. These data do not support a strong association between maternal exposure to neighborhood CO during pregnancy and odds of delivering a low birth weight infant. Further investigation of the effects of CO exposure on birth weight, with direct measurement of total CO exposure, is needed.

This population-based case-control study was designed to investigate risk indicators for the occurrence of the birth defect craniosynostosis in Colorado. A total of 173 children who underwent craniectomy for craniosynostosis and 759 children without craniosynostosis were included in the study. Multivariable logistic regression analysis of birth certificate data showed that male sex (odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.1-2.2), maternal five-year age "increase" (OR = 1.3, 95% CI = 1.1-1.5), plural birth (OR = 3.0, 95% CI = 1.2-7.1) and black maternal race (OR = 0.0, 95 per cent CI = 0.0-0.6) were independently associated with craniosynostosis. There was a weak positive association between craniosynostosis and the altitude of the town closest to the maternal residence, but no association was found with maternal education, marital status, number of previous births, or previous pregnancy termination. The association of craniosynostosis with plural birth is consistent with the hypothesis of fetal head constraint.

A population based case-control study of the association between dissimilar race of parents and risk of pre-eclampsia was undertaken. Data on singleton births in Washington State in 1981 were available for analysis from birth certificates. All mothers recorded as having pre-eclampsia and a sample of mothers who did not have pre-eclampsia were eligible for comparison with regard to racial dissimilarity between parents. Women with previously diagnosed cardiovascular disease and diabetes were excluded. After the confounding effects of maternal parity and race had been controlled for, racial dissimilarity of parents was associated with a 1.9-fold increased risk of pre-eclampsia (95% confidence interval = 1.3-2.8; number of cases = 973, of controls = 1480). This finding supports the theory that genetic dissimilarity of father and mother has a role in pre-eclampsia and is consistent with an immunogenetic aetiology.

The authors performed a population-based case-control study of the association between weather and occurrence of eclampsia in Washington State. Women who were recorded as having eclampsia on Washington birth certificates from 1980 to 1983 were compared to a random sample of all women who gave birth during those years. For each woman studied, National Oceanic and Atmospheric Administration weather data were used to determine the temperature, relative humidity, precipitation, and wind speed on the date of birth at the station nearest the hospital of birth. Categorical analysis revealed that eclampsia was not associated with low temperature, high relative humidity, precipitation, or high wind speed. These results were unchanged after adjustment for race, parity, maternal age, and late initiation of prenatal care. These results do not support an association between eclampsia and weather on the date of delivery in this population.

This case-control study was designed to investigate the relation between reproductive history and occurrence of hip and forearm fractures in postmenopausal women. Three hundred and fifty-five King County, Washington women who sustained a fracture between 1976 and 1980 and 562 control women were interviewed regarding their reproductive history and other factors. After controlling for the confounding effects of age, obesity, and use of noncontraceptive estrogens, the authors found that women who gave birth four or more times had a risk of fracture similar to women who had not given birth (odds ratio = 1.2, 95% confidence interval = 0.7-2.2), and women who breastfed for more than two years had a risk of fracture similar to women who had never breastfed (odds ratio = 0.8, 95% confidence interval = 0.4-1.5).