Interval between pregnancies and risk of spontaneous abortion.
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Abortion, Spontaneous↗
Biomedical subjects
J Wohlfahrt
Publications and source records attributed to J Wohlfahrt.
Is maternal age an independent risk factor for fetal loss?
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Journal Article↗
Reproductive history and stage of breast cancer.
A woman's reproductive history influences her risk of breast cancer. The authors hypothesized that reproductive history also influences stage of disease at the time of diagnosis. The authors analyzed a population-based cohort of 1.5 million Danish women born between 1935 and 1978 for whom individual information on births was available. Between 1978 and 1994, 10,790 incident cases of breast cancer in women under 60 years of age were identified. Nulliparous women compared with parous women and women with a late age at first birth compared with an early age were at significantly increased risk of being diagnosed with a large tumor and with cancer that had spread to regional lymph nodes. However, such an association was not seen for women diagnosed with a small tumor and women with cancer that had not spread to regional lymph nodes. Reproductive history did not appear to influence the time interval from first symptoms to first physician visit ("patient delay") or the time interval from first physician visit to surgery ("doctor delay"). The authors conclude that reproductive history is associated both with incidence of breast cancer and with stage of the disease at diagnosis, indicating possible influences on tumor progression and growth rate. Intensified awareness is warranted to achieve earlier diagnosis among nulliparous women and women with a late age at first childbirth, with the hope of improving their prognosis.
Adult↗
Sex ratios, family size, and birth order.
In many countries, the male:female ratio at birth has varied significantly over the past century, but the reasons for these changes have been unclear. The authors observed a close parallel between decreasing family size and declining male:female sex ratio in Denmark from 1960 to 1994. To explain this finding, they examined the sex ratio and birth order of 1,403,021 children born to 700,030 couples. Overall, 51.2% of the first births were male. However, families with boys were significantly more likely than expected to have another boy (biologic heterogeneity). By the fourth birth to families with three prior boys, 52.4% were male. The increase varied directly with the number of prior boys (p for trend = 0.0007). Furthermore, couples with boys were more likely to continue to have children. In summary, the authors found that the declining male:female ratio in Denmark and probably other European populations is mainly attributable to three effects: declining family size, biologic heterogeneity, and child sex preference. Why families with boys are more likely to have additional boys is unknown.
Birth Certificates↗
Multivariate competing risks.
Competing risks models can be used to compare the effect of risk factors for different causes of death or subtypes of a disease. However, sometimes more than one outcome classification is available and if two such classifications are correlated, one may speculate whether differences in the effect of a risk factor according to one classification simply may be an effect of differences according to the other correlated classification. We introduce in this paper the new concept of multivariate competing risks to test formally such a hypothesis.
Breast Neoplasms↗
Tobacco smoking as a risk factor in anal carcinoma: an antiestrogenic mechanism?
BACKGROUND: Human papillomavirus-associated anogenital carcinogenesis depends on poorly defined cofactors. Smoking was recently suggested to increase the risk of anal cancer more in premenopausal women than in postmenopausal women. Thus, we used our population-based anal cancer case-control study in Denmark and Sweden to test this hypothesis. METHODS: Our study included 417 patients (324 women and 93 men) who were diagnosed with anal cancer (84% invasive cancer) from 1991 through 1994; it also included five patients diagnosed in 1995. Two control groups were used: 1) 554 population control subjects (349 women and 205 men) and 2) 534 patients with rectal adenocarcinoma (343 women and 191 men). Odds ratios (ORs), calculated from logistic regression analyses, were used as measures of relative risk. All P values are two-sided. RESULTS: Compared with the risk for lifelong nonsmokers, the risk of anal cancer was high among premenopausal women who currently smoked tobacco (multivariate OR = 5.6; 95% confidence interval [CI] = 2.4-12.7) and increased linearly by 6.7% per pack-year smoked (one pack-year is equivalent to one pack of cigarettes smoked per day for 1 year) (P for trend <.001). Smoking was not statistically significantly associated with anal cancer risk in postmenopausal women or men. Women whose menstrual periods started late were at high risk (multivariate OR = 3.6; 95% CI = 1.8-7.3, for > or = 17 years of age versus < or = 12 years of age; P for trend <.001), and body mass index (weight in kg/[height in m]2) was inversely associated with risk among women (P<.001). CONCLUSIONS: Because the risk of anal cancer associated with smoking was restricted to premenopausal women and because higher risk was associated with late menarche and lean body composition, female sex hormones may be a factor in anal cancer development in women. Since the anal mucosa is an estrogen-sensitive area, we hypothesize an antiestrogenic mechanism of action for smoking in anal carcinogenesis.
Adult↗
Reproductive risk factors for breast cancer by receptor status, histology, laterality and location.
It is well established that a woman's reproductive history influences her risk of breast cancer. We examined whether the effect of reproductive history was similar for different sub-types of breast cancer. The study was based on a population-based cohort of 1.5 million Danish women born between 1935 and 1978, with individual information on births. Between 1978 and 1994, 10,790 incident cases of breast cancer were identified in a nationwide cancer registry, including detailed information on receptor status, histology, laterality and location of the tumour. Overall, the incidence of breast cancer was 13% lower in parous compared with nulliparous women. This reduction was significantly stronger for mucinous than for ductal carcinomas and for tumours located centrally than for those non-central in the breast. Overall, the incidence in parous women increased by 10% by each 5-year postponement of their first birth. For the incidence of lobular carcinomas this increase was significantly stronger, and for mucinous carcinomas it tended to be stronger than for ductal carcinomas. For the incidence of centrally located tumours the increase was stronger than for non-centrally located tumours. On average, there was a 10% decrease in breast-cancer risk by each additional birth. This decrease was seen in most sub-types, but not for lobular carcinomas of for centrally located tumours. According to our findings, lobular and mucinous carcinomas and centrally located tumours may have risk-factor profiles that differ from other types of breast cancer.
Adolescent↗
Effects of family history and place and season of birth on the risk of schizophrenia.
BACKGROUND: Although a family history of schizophrenia is the best-established risk factor for schizophrenia, environmental factors such as the place and season of birth may also be important. METHODS: Using data from the Civil Registration System in Denmark, we established a population-based cohort of 1.75 million persons whose mothers were Danish women born between 1935 and 1978. We linked this cohort to the Danish Psychiatric Central Register and identified 2669 cases of schizophrenia among cohort members and additional cases among their parents. RESULTS: The respective relative risks of schizophrenia for persons with a mother, father, or sibling who had schizophrenia were 9.31 (95 percent confidence interval, 7.24 to 11.96), 7.20 (95 percent confidence interval, 5.10 to 10.16), and 6.99 (95 percent confidence interval, 5.38 to 9.09), as compared with persons with no affected parents or siblings. The risk of schizophrenia was associated with the degree of urbanization of the place of birth (relative risk for the capital vs. rural areas, 2.40; 95 percent confidence interval, 2.13 to 2.70). The risk was also significantly associated with the season of birth; it was highest for births in February and March and lowest for births in August and September. The population attributable risk was 5.5 percent for a history of schizophrenia in a parent or sibling, 34.6 percent for urban place of birth, and 10.5 percent for the season of birth. CONCLUSIONS: Although a history of schizophrenia in a parent or sibling is associated with the highest relative risk of having the disease, the place and season of birth account for many more cases on a population basis.
Adolescent↗
Exposure to prenatal and childhood infections and the risk of schizophrenia: suggestions from a study of sibship characteristics and influenza prevalence.
BACKGROUND: It has been proposed that infections, perhaps prenatal exposure to the influenza virus, might increase the risk of schizophrenia. To address this hypothesis, we studied the possible influence on schizophrenia risk of sibship characteristics and ecological influenza prevalence data. Birth order and influenza prevalence were used as proxy measures for exposure to prenatal infection, and sibship size and interval to siblings were used as proxy measures for exposure to common childhood infections. METHODS: We established a population-based cohort of 1746366 persons whose mothers were Danish-born women born since 1935 by using data from the Civil Registration System. Schizophrenia in cohort members (n = 2669) and their parents was identified by linkage with the Danish Psychiatric Case Register. Birth order, sibship size, and interval to siblings were calculated for each cohort member based on person-identifiable information on all siblings. The number of notifications of influenza per month in Denmark was obtained from the National Board of Health and Statens Serum Institut. RESULTS: There was no association between birth order and schizophrenia risk or between schizophrenia risk and influenza prevalence during any month of prenatal life. Coming from a large sibship was associated with an increased schizophrenia risk. The relative risks were 1.26 (95% confidence interval [CI], 1.11-1.44) and 1.46 (95% CI, 1.22-1.75) for sibships of 4 and 5 or more, respectively, vs. a sibship of 2. Short interval (<2 years) to the nearest older sibling and nearest younger sibling was associated with a risk of 1.22 (95% CI, 1.05-1.38) and 1.15 (95% CI, 1.03-1.28), respectively, compared with longer intervals. CONCLUSIONS: Our findings do not support the hypothesis that schizophrenia is associated with prenatal exposure to common infections or influenza. However, they are compatible with the hypothesis that environmental exposure, perhaps to common infections in childhood, may be a risk factor, although other explanations are also possible.
Adult↗
Preterm delivery and risk of breast cancer.
To explore the risk of breast cancer in relation to the length of a pregnancy we tested whether a preterm delivery carries a higher risk of breast cancer than does a full-term delivery. Based on information from the Civil Registration System, and the National Birth Registry in Denmark, we established a population-based cohort of 474 156 women born since April 1935, with vital status and detailed parity information, including the gestational age of liveborn children and stillbirths. Information on spontaneous and induced abortions was obtained from the National Hospital Discharge Registry and the National Registry of Induced Abortions. Incident cases of breast cancer in the cohort (n = 1363) were identified through linkage with the Danish Cancer Registry. The period at risk started in 1978 and continued until a breast cancer diagnosis, death, emigration, or 31 December, 1992, whichever occurred first. After adjusting for attained age, parity, age at first birth and calendar period, we observed the following relative risks of breast cancer for different lengths of the pregnancy: < 29 gestational weeks = 2.11 (95% confidence interval 1.00-4.45); 29-31 weeks = 2.08 (1.20-3.60); 32-33 weeks = 1.12 (0.62-2.04); 34-35 weeks = 1.08 (0.71-1.66); 36-37 weeks = 1.04 (0.83-1.32); 38-39 weeks = 1.02 (0.89-1.17); 40 weeks = 1 (reference). Parous women who had a preterm delivery below 32 weeks gestation had a 1.72-fold (1.14-2.59) increased risk of breast cancer compared with other parous women. In conclusion, a preterm delivery of 32+ weeks gestation did not significantly increase a woman's risk of contracting breast cancer. Only for the very small group of women with preterm deliveries of less than 32 weeks gestation did we observe an increased risk.
Adult↗
Maternal risk of breast cancer and birth characteristics of offspring by time since birth.
We examined the association between birth characteristics of offspring and the subsequent maternal risk of breast cancer in a population-based cohort of 998,499 women, 13 to 48 years of age at entry. There were 9,495 incident cases of breast cancer during 12.8 million person-years of follow-up among these women. Compared with mothers of singleton infants, mothers having a multiple birth had an increased risk of breast cancer in the first 5 years after a birth (relative risk (RR) = 1.8; 95% confidence interval (CI) = 1.1-2.8). The risk for mothers having a heavy-weighted child (>3.75 kg), as compared with a child of light weight (< or =3 kg), was also slightly increased (RR = 1.2; 95% CI = 0.9-1.5). This latter effect was primarily due to an increased incidence of tumors larger than 2 cm at diagnosis (RR = 1.4; 95% CI = 0.9-1.9). Our findings are compatible with the hypothesis that the hormonal level during pregnancy influences the risk of breast cancer in the early years after delivery.
Adolescent↗
Adjustment for age at first birth in etiologic studies of breast cancer involving exposures that may effect age at first birth.
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Abortion, Induced↗
[Sexually transmitted infection as a cause of anal cancer].
Interviews were carried out with 423 women and 93 men with invasive or in situ anal cancer in Denmark and Sweden in a search for clues to the aetiology of this neoplasm. Patients with rectal adenocarcinoma (n = 534) and persons drawn from the background population (n = 554) served as controls. Multivariate logistic regression analyses confirmed previous observations of a strong association between either male homosexual experience or a history of anogenital warts and the risk for anal cancer. Moreover, hitherto unknown, but strong and consistent associations were observed between measures of high heterosexual activity and the risk for anal cancer among both sexes. Polymerase chain reaction analysis revealed human papilloma-virus DNA in the majority (88%) of anal cancer specimens but in none of 20 examined rectal adenocarcinomas. It is concluded that most anal cancers appear to be caused by sexually transmitted types of human papillomaviruses and, consequently, that anal cancer is a potentially preventable neoplasm.
Adenocarcinoma↗
[Multiple pregnancies in Denmark 1980-1994].
The objective was to study trends in national rates of multiple pregnancies that were not explained by changes in maternal age and parity. Information on childbirths to Danish-born women were obtained from national registers. The national incidence of multiple pregnancies increased 1.7-fold during 1980-1994, the increase primarily in 1989-1994 and almost exclusively in primiparous women > or = 30 years, for whom the adjusted population-based twinning rate increased 2.7-fold and the triplet rate 9.1-fold. The proportion of multiple births among infant deaths in primiparous women > or = 30 years increased from 11.5% to 26.9%. In conclusion, the marked increase in the rate of multiple pregnancies, which in particular was observed during the 1990s and in primiparous women > or = 30 years, could not be explained by changes in maternal age or parity. Fertility-enhancing treatments are believed to have caused this increase.
Adult↗
[Induced abortion and risk of breast cancer].
It has been hypothesized that an interrupted pregnancy might increase the risk of breast cancer, because proliferation of breast cells will take place without the protective effect of subsequent differentiation. In a cohort of 1.5 million women (28.5 million person-years) we identified 370,715 induced abortions in 280,965 women (2.7 million person-years) and 10,246 women with breast cancer. After adjustment for other risk factors, induced abortion was not associated with the risk of breast cancer (relative risk: 1.00; 95 percent confidence interval 0.94 to 1.06). However, the relative risk of breast cancer increased with increasing gestational age of the most recently induced abortion: < 7 weeks: 0.81; 7 to 8 weeks; 1.01; 9 to 10 weeks: 1 (reference); 11 to 12 weeks: 1.12; 13 to 14 weeks: 1.13; 15 to 18 weeks: 1.23; > 18 weeks: 1.89; P(trend) = 0.016. On a population basis, induced abortion was not associated with an increased risk of breast cancer. An increase was only seen for the special group of late second trimester abortions, but this finding was based on small numbers.
Abortion, Induced↗
Parity, age at first childbirth and the prognosis of primary breast cancer.
Reproductive factors are known to be aetiologically important in breast cancer, but less is known regarding their effect on breast cancer prognosis. We have investigated the prognostic effect of age at first birth and total parity using data from the Danish Breast Cancer Cooperative Group that, since 1977, has collected population-based information on tumour characteristics, treatment regimes and follow-up status on Danish women with breast cancer. Details of pregnancy history were added from the Danish Civil Registration System and the National Birth Registry. Included in the study were 10,703 women with primary breast cancer. After adjusting for age and stage of disease (tumour size, axillary nodal status and histological grading), the number of full-term pregnancies was found without prognostic value. However, women with primary childbirth between 20 and 29 years experienced a significantly reduced risk of death compared with women with primary childbirth below the age of 20 years [20-24 years: relative risk (RR) = 0.88, 95% confidence interval (CI) 0.78-0.99; 25-29 years: RR = 0.80, 95% CI 0.70-0.91]. Further adjustment for oestrogen receptor status did not influence these results. The effect was not modified by age at diagnosis, tumour size or nodal status. In conclusion, low age at first childbirth, but not parity, was associated with a poor prognosis of breast cancer. We speculate whether women who develop breast cancer despite an early first full-term pregnancy might represent a selected group with a more malignant disease.
Adult↗
Benign anal lesions, inflammatory bowel disease and risk for high-risk human papillomavirus-positive and -negative anal carcinoma.
A central role in anal carcinogenesis of high-risk types of human papillomaviruses (hrHPV) was recently established, but the possible role of benign anal lesions has not been addressed in hrHPV-positive and -negative anal cancers. As part of a population-based case-control study in Denmark and Sweden, we interviewed 417 case patients (93 men and 324 women) diagnosed during the period 1991-94 with invasive or in situ anal cancer, 534 patients with adenocarcinoma of the rectum and 554 population controls. Anal cancer specimens (n = 388) were tested for HPV by the polymerase chain reaction. Excluding the 5 years immediately before diagnosis, men, but not women, with anal cancer reported a history of haemorrhoids [multivariate odds ratio (OR) 1.8; 95% confidence interval (CI) 1.04-3.2] and unspecific anal irritation (OR 4.5; CI 2.3-8.7) significantly more often than controls. Women with anal cancer did not report a history of benign anal lesions other than anal abscess to any greater extent than controls, but they had used anal suppositories more often (OR 1.5; CI 1.1-2.0). Patients with hrHPV in anal cancer tissue (84%) and those without (16%) reported similar histories of most benign anal lesions, but anal fissure or fistula was more common among hrHPV-positive cases. Ulcerative colitis and Crohn's disease, reported by <1% of study participants, were not associated with anal cancer risk. The higher proportion of hrHPV-positive anal cancers among case patients with anal fissure or fistula suggests that such mucosal lesions may provide direct viral access to basal epithelial layers. Since risk associations with benign anal lesions in men may be confounded by unreported sexual behaviour, and since risk associations in women were generally negative, it seems unlikely that benign anal lesions act as promoters in hrHPV-associated anal carcinogenesis. Moreover, benign anal lesions appear not to be linked to an alternative, hrHPV-unassociated causal pathway to anal cancer. Ulcerative colitis and Crohn's disease were not supported as causal factors for anal cancer.
Abscess↗
Sexually transmitted infection as a cause of anal cancer.
BACKGROUND: The incidence of anal cancer has increased in recent decades, particularly among women. To identify underlying risk factors, we conducted a population-based case-control study in Denmark and Sweden. METHODS: We conducted telephone interviews with 324 women and 93 men in whom invasive or in situ anal cancer was diagnosed between 1991 and 1994, 534 controls with adenocarcinoma of the rectum, and 554 population controls. The interviews covered a wide spectrum of possible risk factors for anal cancer. Odds ratios were calculated by logistic regression. Specimens of anal-cancer tissue and samples of rectal adenocarcinomas were tested for human papillomavirus (HPV) DNA with the polymerase chain reaction. RESULTS: Multivariate analysis revealed consistent and statistically significant associations between measures of sexual promiscuity and the risk of anal cancer in both men and women. There was a significant trend toward an association between higher numbers of partners of the opposite sex in women (P<0.001) and men (P<0.05) and strong associations with a variety of venereal diseases. In women, receptive anal intercourse, particularly before the age of 30 years, and venereal infections in the partner were also associated with an increased risk (odds ratios, 3.4 and 2.4, respectively). Fifteen percent of the men with anal cancer reported having had homosexual contact, as compared with none of the controls (P<0.001). High-risk types of HPV, notably HPV-16, were detected in 84 percent of the anal-cancer specimens examined, whereas all rectal-adenocarcinoma specimens tested were negative for HPV. CONCLUSIONS: Our study provides strong evidence that a sexually transmitted infection causes anal cancer. The presence of high-risk types of HPV, notably HPV-16 (which is known to cause cancer of the cervix), in the majority of anal-cancer tissue specimens suggests that most anal cancers are potentially preventable.
Adult↗