Alcohol, tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease.

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for >/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver.

Effects of smoking reduction during pregnancy on the birth weight of term infants.

This study was undertaken to determine 1) whether reducing tobacco exposure during pregnancy increases the birth weight of term infants and 2) the relative effects of early- and late-pregnancy exposure to tobacco on infant birth weight. Data were obtained from the Smoking Cessation in Pregnancy project, conducted in public clinics in three states (Colorado, Maryland, and Missouri) between 1987 and 1991. Self-reported cigarette use and urine cotinine concentration were collected from 1,583 pregnant smokers at study enrollment and in the third trimester. General linear models were used to generate mean adjusted birth weights for women who reduced their tobacco exposure by 50 percent or more and for those who did not change their exposure. Regression smoothing techniques were used to characterize the relation between birth weight and early exposure and birth weight and third-trimester exposure. Reducing cigarette use was associated with an increase in mean adjusted birth weight of only 32 g, which was not significant (p = 0.33). As third-trimester cigarette use increased, birth weight declined sharply but leveled off at more than eight cigarettes per day. Findings were similar when urine cotinine concentration was used. Women who smoke during pregnancy may need to reduce to low levels of exposure (less than eight cigarettes per day) to improve infant birth weight.

Rates of and factors associated with recurrence of preterm delivery.

CONTEXT: Information about risk of recurrent preterm delivery is useful to clinicians, researchers, and policy makers for counseling, generating etiologic leads, and measuring the related public health burden. OBJECTIVES: To identify the rate of recurrence of preterm delivery in second pregnancies, factors associated with recurrence, and the percentage of preterm deliveries in women with a history of preterm delivery. DESIGN AND SETTING: Population-based cohort study of data from birth and fetal death certificates from the state of Georgia between 1980 and 1995. SUBJECTS: A total of 122 722 white and 56174 black women with first and second singleton deliveries at 20 to 44 weeks' gestation. MAIN OUTCOME MEASURE: Length of gestation (categorized as 20-31, 32-36, or > or =37 weeks) at second delivery compared with length of gestation at first delivery, by age and race. RESULTS: Most women whose first delivery was preterm subsequently had term deliveries. Of 1023 white women whose first delivery occurred at 20 to 31 weeks, 8.2% (95% confidence interval [CI], 6.6%-10.1%) delivered their second birth at 20 to 31 weeks and 20.1% (95% CI, 17.7%-22.8%) at 32 to 36 weeks. Of 1084 comparable black women, 13.4% (95 % CI, 11.4%-15.6%) delivered at 20 to 31 weeks and 23.4% (95% CI, 20.9%-26.1%) delivered at 32 to 36 weeks. Among women whose first delivery occurred at 32 to 36 weeks, all corresponding rates were lower than those whose first birth was at 20 to 31 weeks; the rates of second birth at 20 to 31 weeks were substantially lower (for white women, 1.9% [95% CI, 1.7%-2.2%]; for black women, 3.8% [95% CI, 3.4%-4.2%]). Compared with women aged 20 to 49 years at their second delivery, women younger than 18 years had twice the risk of recurrence of delivery at 20 to 31 weeks. Of all second deliveries at 20 to 31 weeks, 29.4% for white women and 37.8% for black women were preceded by a preterm delivery. CONCLUSIONS: Our data suggest that recurrence of preterm delivery contributes a notable portion of all preterm deliveries, especially at the shortest gestations.

Patterns of prenatal care initiation in Georgia, 1980-1992.

OBJECTIVE: To determine whether characteristics in a woman's first pregnancy were associated with the trimester in which she initiated prenatal care in her second pregnancy. METHODS: Data for white and black women whose first and second pregnancies resulted in singleton live births between 1980 and 1992 were obtained from Georgia birth certificates (n = 177,041). Adjusted relative risks (RRs) for early prenatal care in the second pregnancy were computed by logistic regression models that included trimester of prenatal care initiation, infant outcomes, or maternal conditions in the woman's first pregnancy as the exposure and controlled for maternal age, education, child's year of birth, interval between first and second pregnancy, presence of father's name on the birth certificate, and the interaction between prenatal care and education. Models were stratified by race. RESULTS: Women of both races who initiated prenatal care in the first trimester of their first pregnancies were more likely than those with delayed care to initiate prenatal care in the first trimester of their second pregnancies (RR = 1.25 and 1.63 for white and black women educated beyond high school, respectively). Both white and black women who delivered a baby with very low birth weight (RR = 1.06 and 1.15, respectively) or who suffered an infant death (RR = 1.09 and 1.31, respectively) in their first pregnancies were more likely than those who did not experience these events to begin prenatal care in the first trimester of their second pregnancies. CONCLUSION: Women with some potentially preventable adverse infant outcomes tend to obtain earlier care in their next pregnancy. Unfortunately, women who delayed prenatal care in their first pregnancy frequently delay prenatal care in their next.

Constructing reproductive histories by linking vital records.

Certificates of 1,449,287 live births and fetal deaths filed in Georgia from 1980 through 1992 were linked to create chronologies that, excluding induced abortions and ectopic pregnancies, constituted the reproductive experience of individual women. The authors initially used a deterministic method (whereby linking rules were not based on probability theory) to link as many records as possible, knowing that some of the linkages would be incorrect. They subsequently used a probabilistic method (whereby evaluation of linkages was developed from probability theory) to evaluate each linkage, and they broke those that were judged to be incorrect. Of the 1.4 million records, 38% did not link to another record. From the remaining records, 369,686 chains of two or more events were constructed. The longest chain included 12 events. Of the chains, 69% included two events; 22% included three events. Longer chains tended to have lower scores for probable validity. The probability-based evaluation of chains affected 3.0% of the records that had been in chains at the end of the deterministic linkage. A greater percentage of records in longer chains were affected by the evaluation. Unfortunately, the small subset of records that were the most difficult to link tended to overrepresent groups with the greatest risk of adverse pregnancy outcomes. Researchers contemplating a similar linkage can anticipate that, for the majority of records, linkage can be accomplished with a relatively straightforward, deterministic approach.

Evaluation of reproductive histories constructed by linking vital records.

We used 1.4 million fetal death and birth certificates filed in Georgia between 1980 and 1992 to construct 369,686 chains of two or more reproductive events occurring to the same woman. We evaluated these chains using both information on the certificates and information independently collected in interviews with 1311 women. Overall, 86.6% of the chains had the expected number of events, based on the certificate's information about previous pregnancies. Seventy-nine per cent of the chains had the expected number of events based on the maternal interviews. Consistency between the observed number of events in the chain and the number expected, based either on data from the certificates or from the maternal interviews, was greatest for chains with two or three events. Mothers born in Georgia were more likely to have complete chains than mothers born elsewhere. Among the 551,391 non-linked certificates, 48.7% were the mother's first birth, 40.2% were second or higher-order births to women whose previous pregnancy occurred before 1980, and 11.1% were second or higher-order births to women whose previous pregnancy occurred after 1980. Fetal death and livebirth certificates can be linked to construct pregnancy histories with reasonably low levels of underlinkage and overlinkage.

Confidence intervals, hypothesis tests, and sample sizes for the prevented fraction in cross-sectional studies.

The prevented fraction (PF) is the proportion of disease occurrence in a population averted due to a protective risk factor or public health intervention. The PF is not equivalent to the population attributable risk (AR). The AR is appropriate for epidemiologic studies of disease etiology, and for estimating the potential impact of modifying risk factor prevalence. The PF more directly measures the impact of public health interventions, however, and thus is an important evaluation tool. We derived the variance of the estimated PF by using maximum likelihood theory for cross-sectional studies. We used simulations to compare the performance of confidence intervals based on various transformations of the estimated PF. The logit transformation was the best choice when PF > or = 0.3, whereas the untransformed estimate was best when PF < 0.3. We present formulae for hypothesis testing and sample size calculations, discuss the issues of interaction and confounding and give two estimators adjusted for confounding.

An organized approach to the control of hazards to health at work.

Shell U.K. has an approach which facilitates the implementation of its occupational hygiene programme in its many locations. The main elements of the system are Company Policy, Standards, Methods and Management. The Policy sets the scene and is rigorous in its aims. The new COSHH legislation has emphasized particular duties which have influenced the approach. The Company Occupational Health Guidelines [Guidelines on Health at Work for Shell in the U.K. Shell U.K. Ltd, London (1989)] set the standards for control of exposure, among other things, and the Company adopts appropriate methods to achieve them. Of particular note is the Company's COSHH Programme [Implementation of the Shell U.K. Policy on the Control of Substances Hazardous to Health. Shell U.K. Ltd, London (1989)] which applies to all hazards to health (including physical and biological agents) in the workplace. Its introduction has been given full corporate support and is in the process of implementation. Appropriate procedures have been introduced for assessments of risk and for work histories. Guidance has been given on competence, reflecting a philosphy based on a team approach using local resources to the full, supported by corporate resources as required. The awards of the British Examining and Registration Board in Occupational Hygiene (1987) are used as the professional standard. Because of difficulties in obtaining basic hazard data, an internal core hazard data system (CHADS) [Core Hazard Data System. Shell U.K Ltd, London (1989)] has been introduced. The whole programme is managed through Occupational Hygiene Focal Points (OHFP) which represent local activities but also participate in corporate strategy. Through them the multidisciplinary approach is promoted, working in conjunction with local and sector Medical Advisers. Work done by the central Occupational Hygiene Unit is recorded and the reports are used for time management and recovery of costs. In its entirety, the approach is being used successfully to implement a comprehensive occupational hygiene programme in a diversified and dispersed industrial organization.

Q fever endocarditis in Queensland.

Thirteen patients with proven Q fever endocarditis and three additional patients with probable endocarditis are reviewed. The most helpful diagnostic test is the demonstration of a high complement fixing antibody titre to Phase 1 antigen of Coxiella burneti. The macroscopic pathology of the aortic valve is described and includes aneurysmal pockets in the aortic wall and valve annulus which are demonstrable angiographically. Evidence is presented that the infection may be controlled by prolonged tetracycline therapy and that this is accompanied by a falling antibody titre to Phase 1 antigen. Valve replacement is undertaken only for symptomatic and hemodynamic indications. The combined tetracycline therapy and valve replacement have produced a fall in titres with eradication of infection and palliation of the cardiac disability in all patients followed for long periods.