Maternal reproductive history and premenopausal risk of hypertension and cardiovascular disease: a Danish cohort study.

OBJECTIVES: The metabolic changes of pregnancy resemble a cardiovascular risk profile and may persist postpartum, with body mass index (BMI) as a potential modifier. We examined the association between the number of live-birth pregnancies and maternal premenopausal risks of hypertension and cardiovascular disease (CVD), accounting for pre-pregnancy BMI as well as abortions and stillbirths. DESIGN: A prospective cohort study. SETTING: Mothers from the Danish National Birth Cohort (1996 to 2002). For each of these women, registry data on all pregnancies from 1973 to 2011 were obtained, as were self-reported pre-pregnancy weight and height. PARTICIPANTS: A total of 44 552 first-time mothers in the Danish National Birth Cohort. OUTCOME MEASURES: Risks of hypertension and CVD during and between live-birth pregnancies separately and combined as live-birth cycles. RESULTS: After adjustment for abortions, stillbirths, pre-pregnancy BMI and other covariates, a higher risk of hypertension was observed in the first (HR 1.53, 95% CI: 1.37 to 1.72) and fourth and subsequent live-birth cycles (HR 1.72, 95% CI: 1.15 to 2.58), compared with the second. However, as number of live-birth pregnancies increased, risk of hypertension decreased during live-birth pregnancies and increased between live-birth pregnancies (tests for trend, p<0.01). For CVD, we found an overall J-shaped but non-significant association with number of live-birth pregnancies. No interaction with pre-pregnancy BMI (<25 versus ≥25 kg/m2) was observed. CONCLUSIONS: Premenopausal women had the highest risk of hypertension and CVD during their first live-birth pregnancy and after their fourth live-birth pregnancy. All risks were independent of BMI before the first live-birth pregnancy and of number of abortions and stillbirths.

Breastfeeding and later maternal risk of hypertension and cardiovascular disease - The role of overall and abdominal obesity.

In this study, we examined how any, full, and partial breastfeeding durations were associated with maternal risk of hypertension and cardiovascular disease (CVD), and how prepregnancy body mass index (BMI) and waist circumference 7 years postpartum influenced these associations. A total of 63,260 women with live-born singleton infants in the Danish National Birth Cohort (1996-2002) were included. Interviews during pregnancy and 6 and 18 months postpartum provided information on prepregnancy weight, height, and the duration of full and partial breastfeeding. Waist circumference was self-reported 7 years postpartum. Cox regression models were used to estimate hazard ratios of incident hypertension and CVD, registered in the National Patient Register from either 18 months or 7 years postpartum through 15 years postpartum. Any breastfeeding ≥4 months was associated with 20-30% lower risks of hypertension and CVD compared to <4 months in both normal/underweight and overweight/obese women. At follow-up starting 7 years postpartum, similar risk reductions were observed after accounting for waist circumference adjusted for BMI. Partial breastfeeding >2 months compared to ≤2 months, following up to 6 months of full breastfeeding, was associated with 10-25% lower risk of hypertension and CVD. Compared with short breastfeeding duration, additional partial breastfeeding was as important as additional full breastfeeding in reducing risk of hypertension and CVD. Altogether, longer duration of breastfeeding was associated with lower maternal risk of hypertension and CVD irrespective of prepregnancy BMI and abdominal adiposity 7 years after delivery. Both full and partial breastfeeding contributed to an improved cardiovascular health in mothers.

Menstrual cycle characteristics in fertile women from Greenland, Poland and Ukraine exposed to perfluorinated chemicals: a cross-sectional study.

STUDY QUESTION: Does perfluorooctane sulfonate (PFOS) and perfluorooctanate (PFOA) exposure disrupt the menstrual cyclicity? SUMMARY ANSWER: The female reproductive system may be sensitive to PFOA exposure, with longer menstrual cycle length at higher exposure. WHAT IS KNOWN ALREADY: PFOS and PFOA are persistent man-made chemicals. Experimental animal studies suggest they are reproductive toxicants but epidemiological findings are inconsistent. STUDY DESIGN, SIZE, DURATION: A cross-sectional study including 1623 pregnant women from the INUENDO cohort enrolled during antenatal care visits between June 2002 and May 2004 in Greenland, Poland and Ukraine. PARTICIPANTS/MATERIALS, SETTING, METHODS: Information on menstrual cycle characteristics was obtained by questionnaires together with a blood sample from each pregnant woman. Serum concentrations of PFOS and PFOA were measured by liquid chromatography tandem mass spectrometry. Multiple imputations were performed to account for missing data. The association between PFOS/PFOA and menstrual cycle length (short cycle: ≤24 days, long cycle: ≥32 days) and irregularities (≥7 days in difference between cycles) was analyzed using logistic regression with tertiles of exposure. Estimates are given as adjusted odds ratios (ORs) with 95% confidence intervals (CIs). MAIN RESULTS AND THE ROLE OF CHANCE: Higher exposure levels of PFOA were associated with longer menstrual cycles in pooled estimates of all three countries. Compared with women in the lowest exposure tertile, the adjusted OR of long cycles was 1.8 (95% CI: 1.0; 3.3) among women in the highest tertile of PFOA exposure. No significant associations were observed between PFOS exposure and menstrual cycle characteristics. However, we observed a tendency toward more irregular cycles with higher exposure to PFOS [OR 1.7 (95% CI: 0.8; 3.5)]. The overall response rate was 45.3% with considerable variation between countries (91.3% in Greenland, 69.1% in Poland and 26.3% in Ukraine). LIMITATIONS, REASONS FOR CAUTION: Possible limitations in our study include varying participation rates across countries; a selected study group overrepresenting the most fertile part of the population; retrospective information on menstrual cycle characteristics; the determination of cut-points for all three outcome variables; and lacking information on some determinants of menstrual cycle characteristics, such as stress, physical activity, chronic diseases and gynecological disorders, thus confounding cannot be excluded. WIDER IMPLICATIONS OF THE FINDINGS: The generalizability of the study results is restricted to fertile women who manage to conceive and women who do not use oral contraceptives when getting pregnant or within 2 months before getting pregnant. To our knowledge only one previous epidemiological study has addressed the possible association between perfluorinated chemical exposure and menstrual disturbances. Though pointing toward different disturbances in cyclicity, both studies suggest that exposure to PFOA may affect the female reproductive function. This study contributes to the limited knowledge on effects of exposure to PFOA and PFOS on female reproductive function and suggests that the female reproductive system may be affected by environmental exposure to PFOA. STUDY FUNDING/COMPETING INTEREST(S): Supported by a scholarship from Aarhus University Research Foundation. The collection of questionnaire data and blood samples was part of the INUENDO project supported by The European Commission (Contract no. QLK4-CT-2001-00 202), www.inuendo.dk. The Ukrainian part of the study was possible by a grant from INTAS (project 012 2205). Determination of PFOA and PFOS in serum was part of the CLEAR study (www.inuendo.dk/clear) supported by the European Commission's 7th Framework Program (FP7-ENV-2008-1-226217). No conflict of interest declared.

Cost and health consequences of treatment of primary biliary cirrhosis with ursodeoxycholic acid.

BACKGROUND: Long-term use of ursodeoxycholic acid (UDCA) is the recommended therapy in primary biliary cirrhosis (PBC). The lifetime effectiveness and cost-effectiveness of UDCA in PBC have, however, not been assessed. AIM: To estimate the health outcomes and lifetime costs of a Norwegian cohort of PBC patients on UDCA. METHODS: Norwegian PBC patients (n = 182) (90% females; mean age 56.3 ± 8.9 years; Mayo risk score 4.38) who were included in a 5-year open-label study of UDCA therapy were subsequently followed up for up to 11.5 years. The lifetime survival was estimated using a Weibull survival model. The survival benefit from UDCA was based on a randomised clinical trial from Canada, comparing the effect of non-UDCA and UDCA. Survival and costs of standard care vs. standard care plus UDCA were simulated in a Markov model with death and liver transplantation as major events, invoking transition of a patient's state in the model. RESULTS: The gain in life expectancy for a PBC patient on UDCA compared with standard care was 2.24 years (1.19 years discounted). The lifetime treatment costs were EUR 151,403 and EUR 157,741 (EUR 102,912 and EUR 115,031 discounted) for patients with and without UDCA respectively. A probabilistic sensitivity analysis indicated an 82% probability that UDCA entails both greater life expectancy and lower costs than standard care. CONCLUSIONS: The results of this study indicate that UDCA therapy is a dominant strategy as it confers reduced morbidity and mortality, as well as cost savings, compared with standard therapy.

Maternal cigarette smoking during pregnancy and pubertal development in sons. A follow-up study of a birth cohort.

Epidemiological studies have raised concern about the reproductive consequences of prenatal cigarette smoking exposure, possibly affecting semen quality and onset of pubertal development of the offspring. The aim of this study was to further investigate pubertal development in young men exposed to cigarette smoking in foetal life. In a Danish pregnancy cohort, information on maternal smoking during pregnancy was available from questionnaires administered in 1984-1987, and information on pubertal development, assessed by age at first nocturnal emission, acne, voice break and regular shaving, was obtained from a follow-up questionnaire administered in 2005 to the young men (age: 18-21). We found no significant association between prenatal cigarette smoking exposure and earlier onset of puberty, but we did observe a tendency towards earlier age of first nocturnal emission, acne and voice break, indicating an accelerated age of pubertal development. Men exposed to ≥15 cigarettes/day had 3.1 months (95% CI: -6.4; 0.2) earlier age at acne and 2.2 months (95% CI: -7.3; 3.0) earlier age at first nocturnal emission, 1.2 months (95% CI: -4.6; 2.2) earlier age at voice break, however, 1.3 months (95% CI: -1.6; 4.3) later age at regular shaving, compared with unexposed men. Prenatal cigarette smoking exposure may induce an earlier age at onset of puberty in young men, but larger studies with prospectively collected data on pubertal development are needed to explore this hypothesis further.

Short-term impact of HbA1c on morbidity and all-cause mortality in people with type 2 diabetes: a Danish population-based observational study.

AIMS/HYPOTHESIS: In a population-based setting, we investigated whether diabetes-related morbidity and all-cause mortality within 2 years of HbA(1c) measurement were associated with that HbA(1c) level in individuals with type 2 diabetes. The main objective was to compare outcomes in those with HbA(1c) ≥ and <7% (53 mmol/mol). METHODS: Individuals with type 2 diabetes from Aarhus County, Denmark, were identified from public data files in a 3 year period (2001-2003). Stratifying the 17,760 individuals by HbA(1c), we estimated HRs for diabetes-related morbidities and all-cause mortality using Cox regression. Results were also stratified by treatment modality. RESULTS: In total, 1,805 individuals experienced at least one diabetes-related morbidity and 1,859 individuals died. In general, the HRs in adjusted analyses of diabetes-related morbidity and mortality were increased for HbA(1c) ≥ 7% (53 mmol/mol): morbidity, HR 1.48 (95% CI 1.34, 1.63); and mortality, HR 1.26 (95% CI 1.15, 1.39). On grouping individuals according to HbA(1c) <5% (31 mmol/mol), 5.0-5.9% (31-41 mmol/mol), 6.0-6.9% (42-52 mmol/mol), 7.0-7.9% (53-63 mmol/mol), 8.0-8.9% (64-74 mmol/mol) and ≥ 9% (75 mmol/mol), the HRs for mortality formed a U shape, with HbA(1c) 6.0-6.9% (42-52 mmol/mol) at the lowest point. For diabetes-related morbidity, a dose-response pattern appeared (lowest for HbA(1c) < 5% [31 mmol/mol]). Patterns of HR differed with treatment modality. CONCLUSIONS/INTERPRETATION: An HbA(1c) level ≥ 7% (53 mmol/mol) was associated with increased morbidity and mortality. Both high and very low levels of HbA(1c) were associated with increased mortality. A dose-response pattern appeared for morbidity. The impact of HbA(1c) level on morbidity and mortality depended on treatment modality.

The effect of different alcohol drinking patterns in early to mid pregnancy on the child's intelligence, attention, and executive function.

OBJECTIVE: To conduct a combined analysis of the estimated effects of maternal average weekly alcohol consumption, and any binge drinking, in early to mid pregnancy on general intelligence, attention, and executive function in 5-year-old children. DESIGN: Follow-up study. SETTING: Neuropsychological testing in four Danish cities 2003-2008. POPULATION: A cohort of 1628 women and their children sampled from the Danish National Birth Cohort. METHODS: Participants were sampled based on maternal alcohol consumption during early pregnancy. At age 5 years, the children were tested for general intelligence, attention, and executive function. The three outcomes were analysed together in a multivariate model to obtain joint estimates and P values for the association of alcohol across outcomes. The effects of low to moderate alcohol consumption and binge drinking in early pregnancy were adjusted for a wide range of potential confounding factors. MAIN OUTCOME MEASURES: Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R), the Test of Everyday Attention for Children at Five (TEACh-5), and the Behavior Rating Inventory of Executive Functions (BRIEF) scores. RESULTS: Multivariate analyses showed no statistically significant effects arising from average weekly alcohol consumption or any binge drinking, either individually or in combination. These results replicate findings from separate analyses of each outcome variable. CONCLUSIONS: The present study contributes comprehensive methodological and statistical approaches that should be incorporated in future studies of low to moderate alcohol consumption and binge drinking during pregnancy. Furthermore, as no safe level of drinking during pregnancy has been established, the most conservative advice for women is not to drink alcohol during pregnancy. However, the present study suggests that small volumes consumed occasionally may not present serious concern.

The effects of low to moderate prenatal alcohol exposure in early pregnancy on IQ in 5-year-old children.

OBJECTIVE: To examine the effects of low to moderate maternal alcohol consumption during early pregnancy on children's intelligence (IQ) at age 5 years. DESIGN: Prospective follow-up study. SETTING: Neuropsychological testing in four Danish cities 2003-2008. POPULATION: A cohort of 1628 women and their children sampled from the Danish National Birth Cohort. METHODS: Participants were sampled based on maternal alcohol consumption during pregnancy. At 5 years of age, children were tested with the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R). Parental education, maternal IQ, maternal smoking in pregnancy, the child's age at testing, gender, and tester were considered core confounding factors, whereas the full model also controlled for maternal binge drinking, age, BMI, parity, home environment, postnatal smoking in the home, health status, and indicators for hearing and vision impairments. MAIN OUTCOME MEASURES: The WPPSI-R. RESULTS: No differences in test performance were observed between children whose mothers reported consuming between one and four or between five and eight drinks per week at some point during pregnancy, compared with children of mothers who abstained. For women who reported consuming nine or more drinks per week no differences were observed for mean differences; however, the risks of low full-scale IQ (OR 4.6; 95% CI 1.2-18.2) and low verbal IQ (OR 5.9; 95% CI 1.4-24.9) scores, but not low performance IQ score, were increased. CONCLUSIONS: Maternal consumption of low to moderate quantities of alcohol during pregnancy was not associated with the mean IQ score of preschool children. Despite these findings, acceptable levels of alcohol use during pregnancy have not yet been established, and conservative advice for women continues to be to avoid alcohol use during pregnancy.

The effect of alcohol binge drinking in early pregnancy on general intelligence in children.

OBJECTIVE: To examine the effects of binge alcohol consumption during early pregnancy, including the number of binge episodes and the timing of binge drinking, on general intelligence in 5-year-old children. DESIGN: Follow-up study. SETTING: Neuropsychological testing in four Danish cities 2003-2008. POPULATION: A cohort of 1617 women and their children sampled from the Danish National Birth Cohort. METHODS: Participants were sampled on the basis of maternal alcohol consumption during pregnancy. At 5 years of age the children were tested with six subtests from the Wechsler Preschool and Primary Scale of Intelligence - Revised (WPPSI-R). Parental education, maternal IQ, prenatal maternal smoking, the child's age at testing, the gender of the child, and tester were considered core confounding factors, whereas the full model also controlled for prenatal maternal average alcohol intake, maternal age, maternal pre-pregnancy body mass index (BMI), parity, home environment, postnatal parental smoking, health status, and indicators for hearing and vision impairment. MAIN OUTCOME MEASURE: WPPSI-R. RESULTS: There were no systematic or significant differences in general intelligence between children of mothers reporting binge drinking and children of mothers with no binge episodes, except that binge drinking in gestational weeks 1-2 significantly reduced the risk of low, full-scale IQ (OR 0.54; 95% CI 0.31-0.96) when adjusted for core confounding factors. The results were otherwise not statistically significantly related to the number of binge episodes (with a maximum of 12) and timing of binge drinking. CONCLUSIONS: We found no systematic association between binge drinking during early pregnancy and child intelligence. However, binge drinking reduced the risk of low, full-scale IQ in gestational weeks 1-2. This finding may be explained by residual confounding.

The effects of low to moderate alcohol consumption and binge drinking in early pregnancy on executive function in 5-year-old children.

OBJECTIVE: To examine the effects of low to moderate maternal alcohol consumption and binge drinking in early pregnancy on children's executive functions at the age of 5 years. DESIGN: Follow-up study. SETTING: Neuropsychological testing in four Danish cities 2003-2008. Population A cohort of 1628 women and their children sampled from the Danish National Birth Cohort. METHODS: Participants were sampled based on maternal alcohol drinking patterns during early pregnancy. When the children were 5 years old, the parent and teacher forms of the Behaviour Rating Inventory of Executive Function (BRIEF) were completed by the mothers and a preschool teacher. Parental education, maternal IQ, prenatal maternal smoking, the child's age at testing, and the child's gender were considered core confounding factors. The full model also included maternal binge drinking or low to moderate alcohol consumption, maternal age, parity, maternal marital status, family home environment, postnatal parental smoking, pre-pregnancy maternal body mass index (BMI), and the health status of the child. MAIN OUTCOME MEASURES: The BRIEF parent and teacher forms. RESULTS: Adjusted for all potential confounding factors, no statistically significant associations between maternal low to moderate average weekly consumption and BRIEF index scores were observed.In adjusted analyses, binge drinking in gestational week 9 or later was significantly associated with elevated Behavioural Regulation Index parent Scores (2.04, 95% CI 0.33­3.76), and with the risk of high scores on the Metacognitive Index assessed by the teacher (OR 2.06, 95% CI 1.01­4.23) [corrected]. CONCLUSIONS: This study did not observe significant effects of low to moderate alcohol consumption during pregnancy on executive functioning at the age of 5 years. Furthermore, only weak and no consistent associations between maternal binge drinking and executive functions were observed.

A primary healthcare-based intervention to improve a Danish cervical cancer screening programme: a cluster randomised controlled trial.

BACKGROUND: The proportion of non-attenders in cervical cancer screening is high, and should be minimised. A targeted invitation to women not participating for the last 5 years in cervical screening was evaluated to determine whether it would decrease the number of these women. Increasing general practitioners' attention to the screening programme for cervical cancer was also evaluated to determine whether it would increase participation. METHODS: A cluster randomised controlled trial conducted in the county of Aarhus, Denmark. All women registered with a GP were randomised. Regardless of group allocation, all women received a normal invitation. In the intervention arm, GPs were visited to facilitate quality enhancements of the screening programme, combined with a special targeted invitation to women aged 23-59 registered with the GP but not attending screening for the last 5 years. The main outcome was the proportion of non-attenders and the secondary outcome was coverage rate. RESULTS: 117 129 women registered with 190 GPs were included in the study. 1737 non-attenders had a Papanicolaou smear during follow-up. The decline in non-attenders was 0.87% (95% CI 0.57% to 1.16%) after 9 months in favour of the intervention. A difference of 0.94% (95% CI 0.21% to 1.67%) in the change of coverage rate was observed at 6 months, which increased to 1.97% (95% CI 0.03% to 3.91%) at 9 months in favour of the intervention. CONCLUSION: It is possible to decrease the proportion of non-attenders and increase the coverage rate in a screening programme for cervical cancer using a special targeted invitation to non-attenders combined with a visit to GPs. To further improve participation, other barriers must be identified and addressed.

Defining cancer patients as being in the terminal phase: who receives a formal diagnosis, and what are the effects?

PURPOSE: Physicians either do not define cancer patients as being terminal, or their prognostic estimates tend to be optimistic. This might affect patients' appropriate and timely referral to specialist palliative care services or can lead to unintended acute hospitalization. PATIENTS AND METHODS: We used the Danish Cancer Register and four administrative registers to perform a retrospective cohort study in 3,445 patients who died as a result of cancer. We used the Danish "terminal declaration" issued by a physician as a proxy for a formal terminal diagnosis (prognosis of death within 6 months). The terminal declaration gives right to economic benefits and increased care for the dying. We investigated patient-related factors of receiving an explicit terminal diagnosis by logistic regression and then analyzed the effects of such a diagnosis on admission rate per week and place of death. RESULTS: Thirty-four percent of patients received a formal terminal diagnosis. Age of > or = 70 years (odds ratio [OR], 0.44; 95% CI, 0.34 to 0.56; P < .001), women (OR, 0.81; 95% CI, 0.69 to 0.96; P = .02), hematologic cancer (OR, 0.20; 95% CI, 0.09 to 0.41; P < .001), and a less than 1-month survival time (OR, 0.10; 95% CI, 0.07 to 0.15; P < .001) were associated with a lesser likelihood of receiving a formal terminal diagnosis. Explicit terminal diagnosis was associated with lower admission rate and an adjusted OR of hospital death of 0.25 (95% CI, 0.21 to 0.29). CONCLUSION: Women and the elderly were less likely to receive a formal terminal diagnosis. The formal terminal diagnosis reduced hospital admissions and increased the possibilities of dying at home.

Do genetic factors contribute to the association between birth weight and blood pressure?

OBJECTIVES: To evaluate whether genetic factors contribute to the association between low birth weight and increased blood pressure among adolescents. DESIGN: Historical cohort study of twin pairs. It was evaluated whether (1) a negative association between birth weight and systolic blood pressure was found in the overall twin sample and (2) whether the intrapair difference in birth weight correlated with the intrapair difference in systolic blood pressure-thereby controlling for the effect of genetic factors (all in monozygotic and on average half in dizygotic pairs). SETTING: The Minnesota Twin Family Study. PARTICIPANTS: 1311 pairs of adolescent twins. MAIN RESULTS: A negative association between birth weight and systolic blood pressure was retrieved in the overall sample. The regression coefficient after controlling for current weight was -1.88 mm Hg/kg (SE 0.61), which corresponds to results from previous studies of singleton adolescents. The regression coefficient fell to -0.64 mm Hg/kg (SE 0.86) when the intrapair analyses were used. The largest reduction was observed among monozygotic twins: from -2.44 mm Hg/kg (SE 0.75) in the overall monozygotic twin sample to -1.06 mm Hg/kg (SE 1.14) in the analyses of the within monozygotic pair differences. CONCLUSION: The association between low birth weight and increased blood pressure later in life is well established. "The fetal programming hypothesis" suggests that the association is caused by intrauterine malnutrition while a new hypothesis "the fetal insulin hypothesis" proposes that genetically determined insulin resistance also contributes significantly to the association. A recent twin study of middle aged twins showed no evidence for an influence of genetic factors while this larger study provides support for the fetal insulin hypothesis: the association between birth weight and blood pressure attenuated among adolescents when genetic factors were controlled. Together this suggests an important contribution of genetic factors to the association between fetal growth and systolic blood pressure in adolescence.

Maximal oxygen uptake, muscle strength and walking speed in 85-year-old women: effects of increased physical activity.

This study explores the effect of regular training on blood pressure, maximal oxygen uptake, maximal isometric muscle strength, and walking speed in the very old. A total of 55 community-dwelling women, 85-year-old, were enrolled in a training group (N = 22) or a control group (N = 33). These groups were reduced to 19 and 26 subjects, respectively, after the training period. Training was performed once a week over eight months, and consisted of various exercises with particular attention to movements important for everyday activities. Training reduced diastolic blood pressure (p < 0.05), and showed a similar trend for systolic blood pressure. Measurements of maximal oxygen uptake before the start of the training (15 mL min-1 kg-1) revealed a level close to the presumed limit for independent living (13 mL min-1 kg-1). Training improved VO2 max by 18% (p < 0.05), whereas the control group experienced a trend towards a reduction. Maximal isometric muscle strength of both the right and left leg showed a tendency to increase with training, but no significant changes were evident in the trunk flexor and extensor muscles. The training group showed a significant increase of 17% in maximal walking speed after the training period. However, one year later, without training, this improvement was reduced to 8% (p < 0.05). No major changes were observed in the control group for any of these parameters. This study demonstrates a maximal oxygen capacity in very old community-dwelling women close to a threshold level indicating dependency. Furthermore, 8 months of regular training appears to lower blood pressure, and to increase maximal oxygen uptake and maximal walking speed. This suggests that physical reactivation of the very old may reduce the risk for acquiring age-related diseases associated with an elevated blood pressure, and may improve parameters crucial for independence.

How well do patient and general practitioner agree about the content of consultations?

OBJECTIVE: To analyse agreement between patients' and general practitioners' perception of content of consultations. DESIGN: Cross-sectional study based on paired questionnaires answered by patients and general practitioners (GPs). SETTING: General practices in the County of Funen, Denmark. SUBJECTS: All 291 GPs in the County were invited to join the investigation, and 137 accepted. All patients who consulted the participating GPs in a 3 day period were included in the investigation. The GPs registered 6021 patients, of whom 3578 (59%) returned the completed questionnaire. MAIN OUTCOME MEASURES: GPs and patients were asked about the urgency of the consultation, number of problems presented, duration of consultation, and quality of communication. The GPs' and patients' answers were matched, and variables of agreement were made. Patients were furthermore asked about their satisfaction with the consultation. RESULTS AND CONCLUSION: Agreement for the four matched answers varied from 69% to 83%. Disagreement was observed more often in consultations where the patient's self-evaluated health was poor, the patient was female, had a chronic disease, expected a prescription or felt that the GP had little knowledge of his/her life circumstances. Agreement concerning urgency, number of problems and quality of communication was associated with a higher degree of patient satisfaction.

Oral clefts, transforming growth factor alpha gene variants, and maternal smoking: a population-based case-control study in Denmark, 1991-1994.

Studies in the United States have indicated that maternal first trimester smoking and infant transforming growth factor alpha (TGFA) locus mutations are associated with non-syndromic cleft lip and/or palate (CLP) and that a synergistic effect of these two risk factors occurs. Based on a Danish case-control study of CLP, the authors studied the effects of smoking and TGFA alleles in an ethnically homogeneous setting. Interview information was obtained for mothers of 302 CLP cases (96% of eligible) and for 567 mothers of nonmalformed children (94% of eligible). Multivariate logistic regression analyses revealed that smoking was associated with a moderately increased risk of cleft lip +/- cleft palate (CL(P)) (odds ratio = 1.40, 95% confidence interval 0.99-2.00). No association between smoking and isolated cleft palate (CP) was observed. TGFA genotype was not associated with either CL(P) or CP, and no synergistic effect with smoking was observed. The "rare" TGFA allele occurred in 25% of both cases and controls compared with an average of 14% in other white control groups. Furthermore, the frequency of CLP in Scandinavia is among the highest in the world. Hence, it is possible that the previously reported association between TGFA and CLP to some degree can be attributable to confounding by ethnicity.