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Biomedical subjects

M Melbye

Publications and source records attributed to M Melbye.

At least 19 recordsLinked to original sources
PubMed2003

Reproductive history and allergic rhinitis among 31145 Danish women.

BACKGROUND AND OBJECTIVE: A successful pregnancy is associated with a strong skewing of the immune system towards a Th2-type immune response. Because such a deviation is also the hallmark of allergic disease, it was investigated whether allergic rhinitis in women was associated with an increased likelihood of becoming pregnant and having a successful outcome of pregnancies. MATERIAL AND METHODS: Information on allergic rhinitis and reproductive history was obtained for 31145 pregnant women who participated in a national birth cohort study in Denmark during September 1997 to March 2000, and for whom complete information on siblings and place of residence and birth was available via the Civil Registration System. Data were analysed using logistic regression. RESULTS: Women who had previously been pregnant (OR = 0.91, 95% CI 0.85-0.98) or who had given birth previously (OR = 0.91, 95% CI 0.85-0.98) were less likely to report allergic rhinitis than others. The number of previous spontaneous abortions, gestational week of the first spontaneous abortion and fertility treatment were not associated with allergic rhinitis. Women who had waited less than a year to become pregnant more often had allergic rhinitis (OR = 1.18, 95% CI 1.06-1.32, P = 0.002) than women who had waited for more than a year. Early age at menarche was associated with an increased likelihood of allergic rhinitis (Ptrend = 0.003). CONCLUSIONS: Our findings did not support the hypothesis that an atopic genotype overall should be associated with an increased likelihood of successful outcome of pregnancies, but it might be associated with a decreased waiting time to pregnancy.

Abortion, Spontaneous↗
PubMed2002

Presence of clone-specific markers at birth in children with acute lymphoblastic leukaemia.

Recent studies have suggested that development of childhood acute lymphoblastic leukaemia may often be initiated in utero. To provide further evidence of an prenatal origin of childhood leukaemia, we conducted a molecular biological investigation of nine children with B-precursor acute lymphoblastic leukaemia carrying the chromosomal translocation t(12;21), the most common subtype of all childhood acute lymphoblastic leukaemia. Specifically, for each child we identified the non-constitutive chromosomal sequences made up by the t(12;21) fusion gene. From these, leukaemia clone-specific DNA primers were constructed and applied in nested polymerase chain reaction analyses of DNA extracted from the patients' Guthrie cards obtained at birth. Leukaemia clone-specific fusion gene regions were demonstrated in Guthrie card DNA of three patients, age 2 years 11 months, 3 years 4 months, and 5 years 8 months at leukaemia diagnosis. Our findings are consistent with previous observations, and thus provide further evidence that the development of t(12;21) B-precursor acute lymphoblastic leukaemia may be initiated in utero. Review of the current literature moreover indicates that age at leukaemia may be inversely correlated with the burden of cells with leukaemia clonal markers, i.e. leukaemia predisposed cells at birth, and that certain types of childhood acute lymphoblastic leukaemia develop as a multiple step process involving both pre- and postnatal genetic events.

Adolescent↗
PubMed2002

Atopic sensitization among children in an arctic environment.

BACKGROUND: Asthma has been reported to be rare among Inuits, but so far total and specific IgE levels have never been determined in arctic populations. OBJECTIVE: To determine the prevalence of atopy in children living in an arctic environment, and to examine whether atopy and total IgE levels were associated with parental place of birth, as a measure of ethnicity, and travel history. MATERIAL AND METHODS: All schoolchildren in Sisimiut, a community on the West coast of Greenland, were screened for atopy. Blood samples were analysed for total IgE and for specific IgE against inhalant and food allergens. Information on place of birth of children and their parents was obtained from national registries. Information on travel history was obtained from self-administered questionnaires. RESULTS: A total of 1031 schoolchildren aged 5 to 18 years had a blood sample drawn (85% of available children for the study). Of these, 151 (14.6%) children were sensitized to at least one inhalant allergen and 42 (4.1%) to at least one food allergen. Sensitization to grass was most common, whereas sensitization to mugwort, birch, animal-dander and house-dust mite was infrequent. Children whose parents were both born abroad had a higher risk of sensitization to inhalant allergens compared with children born of Greenlandic parents (OR = 8.6, 95% CI 2.8-27.1). Furthermore, children who had been abroad had a higher risk of sensitization towards pollen (OR = 1.6, 95% CI 1.0-2.5) and animal-dander (OR = 2.1, 95% CI 1.0-4.6) after adjustment for confounders. Both atopic and non-atopic children demonstrated high levels of total IgE (medians of 251 and 58 kU/L). CONCLUSIONS: Compared with European findings Greenlandic children have high levels of total IgE but a low prevalence of allergic sensitization towards inhalant allergens. This may be due to a low genetic susceptibility to atopy and less allergen exposure, as well as to living conditions in an arctic environment.

Adolescent↗
PubMed2002

Age at childhood infections and risk of atopy.

BACKGROUND: It has been proposed that early age at exposure to common childhood infections is associated with a decreased risk of allergy. Previous studies on the possible association between allergy and infection with measles, mumps, rubella, and varicella have not been conclusive as most did not include information on exact age at exposure. The objective of our study was to investigate whether early age at exposure to these infections was associated with a decreased risk of atopy using information on exact age at infection. METHODS: The study population consisted of 889 pregnant women who participated in a national birth cohort study in Denmark and for whom detailed information on history of measles, rubella, varicella, and mumps before school entry (age 7 years) was available from school health records from Copenhagen. Atopic status was assessed serologically by a specific response to 11 common inhalant allergens using serum samples obtained from the women during pregnancy. RESULTS: Measles in the first year of life was associated with a higher risk of atopy than no measles before age 7 years (OR 3.36, 95% CI 1.47 to 7.68). There was no association between atopy and mumps, rubella, or varicella in the first 7 years of life or with measles acquired after the first year of life. The risk of atopy increased significantly with increasing number of childhood infections in the first 2 years of life (p(trend)=0.01). CONCLUSIONS: These findings do not support the suggestion that childhood exposure to measles, rubella, varicella, or mumps protects against atopy, even if acquired very early in life.

Adolescent↗
PubMed2001

[The significance of reproductive history for prognosis of primary breast cancer].

The aetiological impact of a woman's reproductive history on breast cancer is well established, whereas the prognostic influence of the reproductive pattern is less well described. A literature search with focus on three Danish studies is described. Status as parous/nulliparous and number of births appear to have no prognostic influence. Women who have their first child at an early age have a lower survival than women who have postponed their first childbirth. This may eventually be explained by selection, i.e. that women with an early first full-term pregnancy represent a group with a more malignant disease. Women diagnosed in the first two years after childbirth have a significantly lower survival, probably because the cancer, being subclinical during pregnancy, is affected by the high oestrogen concentrations with aggressive growth as the outcome. Pregnancy after treatment of breast cancer does not appear to have a negative influence on the prognosis.

Breast Neoplasms↗
PubMed2001

[Sibships characteristics, influenza and risk of schizophrenia. A population-based cohort study].

INTRODUCTION: To address the hypothesis that infections, perhaps prenatal exposure to influenza virus, might increase the risk of schizophrenia we studied the possible association between schizophrenia risk and birth order, sibship size, interval between siblings, and influenza prevalence. MATERIAL AND METHODS: We established a population-based cohort of 1,746,366 persons born to Danish woman who themselves were born since 1935 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. Influenza notifications per month in Denmark were obtained from the National Board of Health and Statens Serum Institut. RESULTS: We found 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 and having a short interval to the nearest older or younger sibling was associated with an increased risk of schizophrenia. DISCUSSION: Our findings do not add support to the hypothesis that schizophrenia is associated with prenatal exposure to influenza virus or other common infections, but are compatible with the hypothesis that environmental exposure, perhaps to common infections in childhood, may be a risk factor.

Adolescent↗
PubMed2001

Risk of late-stage breast cancer after a childbirth.

A pregnancy may lead to hormone-induced growth of breast tumors. The authors investigated whether women in the first years after childbirth had a higher incidence of breast cancer and, in particular, a higher incidence of late-stage tumors (i.e., a large tumor, nodal involvement, or histologic grading II + III). The study was based on a population-based cohort of 1.5 million Danish women born between 1935 and 1978. Between 1978 and 1994, 10,790 incident cases of breast cancer were identified in a nationwide cancer registry. Overall, uniparous and biparous mothers experienced a transient increased risk that did not appear to be attributable to delayed cancer diagnosis. The risk of being diagnosed with a tumor whose diameter was larger than 5 cm was, on average, 53% higher during the first 10 years after birth compared with later. The risk of tumors of less than 2 cm was not significantly associated with time since the latest birth. In conclusion, after a childbirth, mothers experience a transient increased risk of breast cancer and, in particular, a relatively high risk of late-stage disease. This finding suggests that pregnancy-related factors transiently induce a high growth rate in cells that are already malignant and stimulate new tumor growth.

Adult↗
PubMed2001

Cancer risk in a cohort of polio patients.

Poliomyelitis has hypothetically been associated with an increased risk of central nervous system (CNS) tumors. The present study was performed to examine not only the risk of CNS tumors but also the overall risk of cancer among a cohort of 5,883 polio patients. Patients diagnosed with acute poliomyelitis in the Danish capital, Copenhagen, between 1919 and 1954 were identified and followed with respect to cancer. Information on vital status and cancer diagnoses was obtained through linkage with the Danish Civil Registration System and the Danish Cancer Registry, respectively. The ratio of observed number of cancers to the number expected from population-based incidence rates, i.e., the standardized incidence ratio (SIR), served as measure of the relative cancer risk. Overall, 717 cases of cancer were observed among 5,883 polio patients during 249,084 person-years of follow-up vs. an expected number of 645 (SIR = 1.11 [95% confidence interval 1.03 to 1.20])). The increased risk was restricted to female polio patients (SIR = 1.18 [1.07 to 1.30]), among whom the risk was particularly high for breast cancer (SIR = 1.35 [1.12 to 1.61]) and for skin cancer (SIR = 1.66 [1.32 to 2.07]). The risk of breast cancer was highest among women with a history of paralytic polio (SIR = 1.62 [1.24 to 2.10]). The observed number of CNS tumors did not exceed the expected (SIR = 1.09 [0.72 to 1.60]). Women diagnosed with poliomyelitis, in particular paralytic polio, may be at increased risk of breast cancer. There was no association between malignancies of the CNS and poliomyelitis.

Age Factors↗
PubMed2001

Risk factors and confounders in the geographical clustering of schizophrenia.

In response to previous reports of geographical clustering of individuals with psychosis, a study was carried out in Denmark utilizing the national case register. Two-thousand one-hundred and ninety-nine (2199) individuals with schizophrenia were divided by place of birth into 217 geographical areas and analyzed by age, gender, month of birth, genetic relatedness, and degree of urbanization of birthplace. Heterogeneity was ascertained using log-linear Poisson regression. The greatest amount of heterogeneity was associated with degree of urbanization of place of birth. Heterogeneity was also associated with age-gender interaction and calendar period. When adjusted for these factors, there was no remaining heterogeneity, suggesting that all geographical clustering in our study was explained by the above factors.

Cluster Analysis↗
PubMed2001

Acute respiratory tract infections and mannose-binding lectin insufficiency during early childhood.

CONTEXT: Hospital-based studies have found that increased susceptibility to certain infections is associated with low serum levels of mannose-binding lectin (MBL) due to MBL variant alleles. However, the contribution of MBL insufficiency to incidence of common childhood infections at a population level is unknown. OBJECTIVE: To investigate the effect of MBL insufficiency on risk for acute respiratory tract infection (ARI) in unselected children younger than 2 years. DESIGN AND SETTING: Population-based, prospective, cohort study conducted in Sisimiut, Greenland. PARTICIPANTS: Two hundred fifty-two children younger than 2 years who were followed up weekly between August 1996 and August 1998 for morbidity surveillance. MAIN OUTCOME MEASURE: Risk of ARI, based on medical history and clinical examination, compared by MBL genotype, determined from blood samples based on presence of structural and promoter alleles. RESULTS: A 2.08-fold (95% confidence interval [CI], 1.41-3.06) increased relative risk (RR) of ARI was found in MBL-insufficient children (n = 13) compared with MBL-sufficient children (n = 239; P<.001). The risk association was largely restricted to children aged 6 to 17 months (RR, 2.92; 95% CI, 1.78-4.79) while less effect (RR, 1.47; 95% CI, 0.45-4.82) and no effect (RR, 1.00; 95% CI, 0.42-2.37) was shown among children aged 0 to 5 months and 18 to 23 months, respectively. CONCLUSION: These data suggest that genetic factors such as MBL insufficiency play an important role in host defense, particularly during the vulnerable period of childhood from age 6 through 17 months, when the adaptive immune system is immature.

Acute Disease↗
PubMed2001

Second-trimester maternal serum alpha-fetoprotein and risk of adverse pregnancy outcome(1).

OBJECTIVE: To determine the risk of adverse pregnancy outcome by maternal serum alpha-fetoprotein (MSAFP) level. METHODS: We followed 77,149 pregnant women and their infants from MSAFP screening in the 15th to 20th week of gestation until 1 year after birth. Information on pregnancy outcome was obtained from national registries. The relative risks (RRs) and 95% confidence intervals (CIs) for adverse pregnancy outcome were estimated according to the level of MSAFP, with adjustment for confounders. RESULTS: A total of 638 pregnancies resulted in spontaneous abortion, 289 in stillbirth, and 437 in infant death. Compared with women with MSAFP levels at 0.75-1.24 multiples of the median (MoM), those with MSAFP levels greater than or equal to 2.5 MoM had an increased risk of spontaneous abortion (RR 12.5; 95% CI 9.7, 16.1), preterm birth (RR 4.8; 95% CI 4.1, 5.5), small for gestational age (RR 2.8; 95% CI 2.4, 3.2), low birth weight (RR 5.8; 95% CI 5.0, 6.6), and infant death (RR 1.9; 95% CI 1.2, 2.8). Women with MSAFP levels below 0.25 MoM had an increased risk of spontaneous abortion (RR 15.1; 95% CI 9.3, 24.8), preterm birth (RR 2.2; 95% CI 1.3, 3.8), and stillbirth (RR 4.0; 95% CI 1.0, 16.0); those with levels less than 0.5 MoM had an increased risk of infant death (RR 1.9; 95% CI 1.2, 3.0). The increased risk of infant death remained after the subtraction of recognized conditions associated with extreme MSAFP values. CONCLUSION: Pregnant women with extreme MSAFP values in the second trimester have an increased risk of fetal and infant deaths. Obstet Gynecol 2001;97:277-82.

Abortion, Spontaneous↗
PubMed2001

Intensive exposure as a risk factor for severe polio: a study of multiple family cases.

To examine the importance of intensity of exposure for the outcome of the poliomyelitis infection 429 polio cases were identified belonging to families with 2, 3 or 4 polio cases, all hospitalized in Copenhagen from 1919 to 1953. Furthermore, 87 pairs of polio cases living on the same stairway, but not in the same household, were identified. Severity among multiple cases in families analysed according to time of appearance showed a U-shaped curve. Initial cases had a higher risk of developing paralysis [relative risk (RR) = 1.5, 95% confidence interval (CI) 1.2-1.91 and of dying (RR = 2.5, 95% CI 0.9-6.9). Decreased severity was observed among subsequent cases appearing within 11 d after the initial case (RR = 1.0); however, severity increased again, with higher mortality for cases likely to have been infected by the initial case (cases appearing more than 11 d later) (RR = 5.7, 95% CI 1.8-17.8). The pattern described among multiple family cases was not found among cases from the same stairway. Since family cases appearing within 11 d were probably infected simultaneously, a short incubation period is associated with severe disease and a prolonged incubation period with milder infections. Furthermore, intensive exposure from being infected in the household increased severity. These observations therefore suggest that intensity of exposure and dose of infection are important factors in the severity of poliomyelitis.

Denmark↗
PubMed2001

Incidence and predictors of atopic dermatitis in an open birth cohort in Sisimiut, Greenland.

UNLABELLED: The frequency of atopic dermatitis (AD) is unknown among children in Greenland. To determine the incidence of AD and to identify risk factors for onset of AD within the first 2 y of life among Greenlandic children an open cohort of 143 children aged 0-2 y in Sisimiut, West Greenland, was followed for a median of 335 d. The children were visited on a weekly basis, where clinical examinations revealed any cases of AD. In total, 24 of the 143 children developed AD. The incidence rate of AD was 177 cases per 1000 child years at risk, corresponding to a cumulative risk of 16% per year. Maternal history of AD [hazard ratio (HR) 2.6, 95% confidence interval (CI) 1.03-6.57], high social class of the family (HR 6.18, CI 2.19-17.41) and living in a detached house compared with living in a terraced house or an apartment (HR 2.81, CI 1.16-6.28) were associated with increased risks of AD. In a multivariate model these risk factors all remained significant. CONCLUSION: The findings confirm that AD represents a health problem among Greenlandic infants and that the pattern of predictive risk factors associated with the development of AD is comparable to that found in northern European countries.

Child, Preschool↗
PubMed2001

Age at any birth is associated with breast cancer risk.

The period before the first birth is traditionally viewed as particularly critical for a woman's breast cancer risk. Nonetheless, the importance of early timing of a woman's first compared with subsequent births is not well understood. In the present study we examine this question using a population-based cohort of 1.5 million Danish women born between 1935 and 1978. Between 1968 and 1994, 13,049 incident cases of breast cancer were identified in the Danish Cancer Registry. According to our results, a woman's breast cancer risk is related to her age at any of her births. The risk increase per 5 year's increase in maternal age at first, second, third, and fourth birth was 9%, 7%, 5%, and 14%, respectively. For fifth and sixth births it was 5%. We observed a risk reduction after any birth occurring before 30 years of age (in uniparous women before 25 years of age). These effects were strongest more than 10 years after birth. Thus, our study shows that early timing of any additional birth induces an additional long-term reduction in maternal risk of breast cancer; that is, early reproductive years, rather than just the nulliparous years, constitute the critical period.

Adolescent↗