Maternal opioid use during pregnancy and the risk of neonatal opioid withdrawal syndrome in the offspring.

INTRODUCTION: Neonatal opioid withdrawal syndrome (NOWS) is caused by sudden cessation from in utero exposure to opioids. The indications for opioid use during pregnancy are diverse including medication for opioid use disorder and analgesia. The opioid dose typically depends on the indication, with higher doses used for medication for opioid use disorder and lower doses used for analgesia. The aim of this study was to investigate the relationship between maternal opioid dose during pregnancy and the risk of NOWS. MATERIAL AND METHODS: We conducted a historical multicenter cohort study of neonates prenatally exposed to opioids in Eastern Denmark during a six-year period from 2013 to 2018. The data was extracted from reviewing the individual's medical record(s), which were identified through a search of the Danish National Patient Register. Four groups (quartiles) according to maternal opioid dose during the last four weeks prior to delivery were compared. Unadjusted and adjusted logistic regression analyses were conducted to examine the risk of NOWS while controlling for relevant covariates. RESULTS: A total of 130 in utero opioid exposed neonates were included. The majority of the pregnant patients (88%) were treated with opioids for analgesic purposes. Overall, 52% of neonates developed NOWS. The cumulative incidence of NOWS was 21%, 28%, 67% and 91% at maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery of 0.7-14 (group I), 14.3-38.6 (group II), 40-90 (group III) and 90.9-1440 (group IV), respectively. Compared to group I the adjusted odds (aOR) of NOWS increased significantly in group III (aOR 10.6 [2.9-39.1]) and group IV (aOR 37.8 [7.6-188.2]) but not in group II (aOR 1.5 [0.4-5.2]). No cases of NOWS were reported at maternal dose less than an average daily dose of five morphine milligram equivalent during the last four weeks prior to delivery. No significant changes in the incidence of NOWS were observed between 2013 and 2018. CONCLUSIONS: The odds of neonatal opioid withdrawal syndrome increased significantly as the maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery surpassed 40.

Exposure to Tramadol During Early Pregnancy and Risk of Spontaneous Abortion or Major Congenital Malformations.

OBJECTIVE: To investigate whether exposure to tramadol during early pregnancy is associated with an increased risk of spontaneous abortion or major congenital malformations. METHODS: The study is a nationwide cohort study including all registered pregnancies in Denmark between January 1, 1997, and December 31, 2016. The Danish National Prescription Register was used to identify maternal exposure to tramadol. Pregnancies with maternal exposure to tramadol were matched with pregnancies without maternal exposure to tramadol in a ratio of up to 1:4 using propensity scoring. The primary outcomes were spontaneous abortion and major congenital malformations. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) of spontaneous abortion, and log binominal models were used to estimate the relative risk ratios (RRs) of major congenital malformations. RESULTS: A total of 36,467 (tramadol exposure n=7,310) and 18,907 (tramadol exposure n=3,796) pregnancies were included in the analyses of spontaneous abortion and major congenital malformations, respectively. Spontaneous abortion occurred in 893 (12.2%) pregnancies with maternal exposure to tramadol and in 3,471 (11.9%) pregnancies without maternal exposure to tramadol (HR 1.06, 95% CI 0.99-1.14). A major congenital malformation occurred in the offspring of 151 (4.0%) pregnancies with maternal exposure to tramadol, compared with 579 (3.8%) in pregnancies without maternal exposure to tramadol (RR 1.04, 95% CI 0.87-1.24). CONCLUSION: Exposure to tramadol during early pregnancy does not appear to be associated with an increased risk of spontaneous abortion or major congenital malformations.

Processing of infant emotion in mothers with mood disorders and implications for infant development.

BACKGROUND: Atypical neurocognitive responses to emotional stimuli are core features of unipolar depression (UD) and bipolar disorder (BD). For mothers with these mood disorders, this may influence interactions with their infants and consequently infant development. The study aimed to investigate psychophysiological and cognitive responses to infant emotional stimuli, and their relation to mother-infant interaction and infant development, in mothers with BD or UD in full or partial remission. METHODS: Four months after birth, mothers' cognitive responses to emotional infant stimuli were assessed with computerized tasks, while their facial expressions, galvanic skin responses (GSR), gazes, and fixations were recorded. Infant development and mother-infant interactions were also assessed. RESULTS: We included 76 mothers: 27 with BD, 13 with UD, and 36 without known psychiatric disorders, and their infants. Mothers with BD and UD were in full or partial remission and showed blunted GSR and spent less time looking at infant stimuli (unadjusted p values < 0.03). Mothers with BD showed subtle positive neurocognitive biases (unadjusted p values<0.04) and mothers with UD showed negative biases (unadjusted p values < 0.02). Across all mothers, some measures of atypical infant emotion processing correlated with some measures of delays in infant development and suboptimal mother-infant interaction (unadjusted p values<0.04). CONCLUSIONS: Mothers with mood disorders in full or partial remission showed atypical cognitive and psychophysiological response to emotional infant stimuli, which could be associated with mother-infant interactions and infant development. The study is explorative, hypothesis generating, and should be replicated in a larger sample. Investigation of the long-term implications of reduced maternal sensitivity is warranted.

Short-term oestrogen as a strategy to prevent postpartum depression in high-risk women: protocol for the double-blind, randomised, placebo-controlled MAMA clinical trial.

INTRODUCTION: Postpartum depression affects 10%-15% of women and has a recurrence rate of 40% in subsequent pregnancies. Women who develop postpartum depression are suspected to be more sensitive to the rapid and large fluctuations in sex steroid hormones, particularly estradiol, during pregnancy and postpartum. This trial aims to evaluate the preventive effect of 3 weeks transdermal estradiol treatment immediately postpartum on depressive episodes in women at high risk for developing postpartum depression. METHODS AND ANALYSIS: The Maternal Mental Health Trial is a double-blind, randomised and placebo-controlled clinical trial. The trial involves three departments of obstetrics organised under Copenhagen University Hospital in Denmark. Women who are singleton pregnant with a history of perinatal depression are eligible to participate. Participants will be randomised to receive either transdermal estradiol patches (200 µg/day) or placebo patches for 3 weeks immediately postpartum. The primary outcome is clinical depression, according to the Diagnostic and Statistical Manual of Mental Disorders-V criteria of Major Depressive Disorder with onset at any time between 0 and 6 months postpartum. Secondary outcomes include, but are not limited to, symptoms of depression postpartum, exclusive breastfeeding, cortisol dynamics, maternal distress sensitivity and cognitive function. The primary statistical analysis will be performed based on the intention-to-treat principle. With the inclusion of 220 participants and a 20% expected dropout rate, we anticipate 80% power to detect a 50% reduction in postpartum depressive episodes while controlling the type 1 error at 5%. ETHICS AND DISSEMINATION: The study protocol is approved by the Regional Committees on Health Research Ethics in the Capital Region of Denmark, the Danish Medicines Agency and the Centre for Data Protection Compliance in the Capital Region of Denmark. We will present results at scientific meetings and in peer-reviewed journals and in other formats to engage policymakers and the public. TRIAL REGISTRATION NUMBER: NCT04685148.

Prediction of ABO hemolytic disease of the newborn using pre- and perinatal quantification of maternal anti-A/anti-B IgG titer.

BACKGROUND: Hemolysis in fetus/newborns is often caused by maternal antibodies. There are currently no established screening procedures for maternal ABO antibodies harmful to fetus/newborn. We investigated the clinical significance, and predictive value of maternal anti-A/B titer for hyperbilirubinemia in ABO-incompatible newborns. METHODS: We conducted a case-control study of blood group O mothers and their ABO-compatible (O) vs. -incompatible (A/B) newborns receiving phototherapy, and of ABO-incompatible newborns receiving phototherapy vs. no phototherapy. Newborn data and treatment modalities were recorded, and total serum bilirubin and hemoglobin were measured. Maternal anti-A/B immunoglobulin-γ (IgG) titers were measured prenatally and perinatally, and negative and positive predictive values (NPV, PPV) were calculated to assess the risk of developing hyperbilirubinemia requiring phototherapy. RESULTS: We found a significantly higher maternal IgG antibody titer in the case group (p < 0.001). Maternal anti-A/B titers at first trimester had modest predictive values: NPV = 0.82 and PPV = 0.65 for neonatal hyperbilirubinemia; titers at birth improved the predictive values: NPV = 0.93 and PPV = 0.73. Newborn hemoglobin was significantly lower in incompatibles compared to compatibles (p = 0.034). Furthermore, increased anti-A/B IgG production during pregnancy was associated with hyperbilirubinemia and hemolysis in incompatible newborns. CONCLUSIONS: There was a significant association between maternal anti-A/B IgG titer and hyperbilirubinemia requiring treatment. IMPACT: Maternal anti-A/B IgG titer in the first trimester and at birth is predictive of hemolytic disease of the ABO-incompatible newborn. Increased IgG anti-A/B production throughout pregnancy in mothers to ABO-incompatible newborns developing hyperbilirubinemia contrasts a constant or reduced production in mothers to newborns not developing hyperbilirubinemia. Screening tools available in most immunohematology laboratories can identify clinically important IgG anti-A/B. Use of maternal samples taken at birth yielded NPV = 0.93 and PPV = 0.73.

Prevalence and treatment of group B streptococcus colonization based on risk factors versus intrapartum culture screening.

OBJECTIVES: To estimate the prevalence of group B streptococcus at onset of labor and to compare the accuracy of intrapartum antibiotic prophylaxis based on a risk factor strategy versus an intrapartum screening. STUDY DESIGN: In this cross-sectional study, 700 women referred for intended vaginal delivery were tested for group B streptococcus at onset of labor by gold standard culture in vaginal and rectal swabs. The results were blinded, and intrapartum antibiotic prophylaxis was given to women with risk factors for group B streptococcus infection: previous neonatal group B streptococcus infection, group B streptococcus in urine and/or vagina in current pregnancy, gestational age <36 + 0 weeks, temperature ≥38.0 °C or rupture of membranes ≥18 h. RESULTS: Of 642 women, who delivered within three days of specimen collection, 170 (26.5%) received benzylpenicillin as intrapartum antibiotic prophylaxis based on risk factors. The prevalence of group B streptococcus at onset of labor was 17.8% (114/642), with 62 women positive for group B streptococcus in both the vagina and rectum, 12 in the vagina only and 40 in rectum only. Intrapartum antibiotic prophylaxis was administered correctly in 31.6% (36/114) of GBS positive women at time of delivery and 78.8% (134/170) of women who received antibiotics were actually GBS negative. The positive predictive value of intrapartum antibiotic prophylaxis based on risk factors was 21.2%. The sensitivity was 31.6% and the specificity was 74.6%. CONCLUSION: The accuracy of predicting maternal group B streptococcus infection from risk factors is low. Intrapartum group B streptococcus diagnostics is more precise and will not increase the overall use of intrapartum antibiotic prophylaxis.

Changing incidence of obstetric anal sphincter injuries-A result of formal prevention programs?

INTRODUCTION: Obstetric anal sphincter injuries (OASIS) are serious complications to vaginal delivery causing anal incontinence in 50% of the women in the long term. In Norway, the incidence of OASIS has been significantly reduced from 4%-5% to 1%-2% after implementation of prevention programs focusing on perineal protection. The aim of our study was to evaluate whether implementation of formal prevention programs was associated with a reduced incidence of OASIS over time. MATERIAL AND METHODS: We performed a historical cohort study, evaluating incidence, change of incidence and risk factors of OASIS during the years 2011-2015 at the four delivery departments in the Capital Region of Denmark. Two of the four departments implemented formal prevention programs in 2012-2013. We performed trend tests and uni- and multivariable analyses, adjusting for important risk factors and calculating interactions between risk factors. RESULTS: There were 75 173 vaginal deliveries during the study period; of those, 2670 (3.6%) were complicated by OASIS. The incidence of OASIS decreased during the study period from 4.3% (n = 636) in 2011 to 2.6% (n = 399) in 2015. There was a significant decrease in the incidence of OASIS at both the departments with formal prevention programs and those without. After adjustment for other important risk factors of OASIS, we found no significant difference in the risk reduction between departments with and without formal prevention programs. CONCLUSIONS: We found that the general focus on prevention of OASIS in Denmark was associated with a significant decrease in the incidence of OASIS, but implementation of formal prevention programs did not lead to a further reduction. It is possible that more rigorous interventions at the hospitals with formal prevention programs could have resulted in a significant difference in incidence of OASIS.

[Posterior reversible encephalopathy syndrome - an MRI diagnosis often missed in pregnancy].

Posterior reversible encephalopathy syndrome (PRES) is a complex clinical condition with a wide clinical spectrum. In this report two cases illustrate two different onsets. The first patient presented with general seizures, whereas the other presented with symptoms of pre-eclampsia, which developed into sudden blindness. Both patients had uneventful caesarean sections performed, with delivery of healthy children. Due to CT scans of the cerebrum, correct treatment and diagnosis were delayed in both cases, but subsequently, PRES was confirmed by MRI. Both patients were discharged in good health.

Successfully reducing newborn asphyxia in the labour unit in a large academic medical centre: a quality improvement project using statistical process control.

BACKGROUND: A safe delivery is part of a good start in life, and a continuous focus on preventing harm during delivery is crucial, even in settings with a good safety record. In January 2013, the labour unit at Copenhagen University Hospital, Hvidovre, undertook a quality improvement (QI) project to prevent asphyxia and reduced the percentage of newborns with asphyxia by 48%. METHODS: The change theory consisted of two primary elements: (1) the clinical content, including three clinical bundles of evidence-based care, a 'delivery bundle', an 'oxytocin bundle' and a 'vacuum extraction bundle'; (2) an implementation theory, including improving skills in interpretation of cardiotocography, use of QI methods and participation in a national learning network. The Model for Improvement and Deming's system of profound knowledge were used as a methodological framework. Data on compliance with the care bundles and the number of deliveries between newborns with asphyxia (Apgar <7 after 5 min or pH <7) were analysed using statistical process control. RESULTS: Compliance with all three clinical care bundles improved to 95% or more, and the percentages of newborns with pH <7 and Apgar <7 after 5 min were reduced by 48% and 31%, respectively. In general, the QI approach strengthened multidisciplinary teamwork, systematised workflow and structured communication around the deliveries. Changes included making a standard memo in the medical record, the use of a bedside whiteboard, bedside handovers, shared decisions with a peer when using an oxytocin infusion and the use of a checklist before vacuum extractions. CONCLUSION: This QI project illustrates how aspects of patient safety, such as the prevention of asphyxia, can be improved using QI methods to more reliably implement best practice, even in high-performing systems.

A nationwide study of serous "borderline" ovarian tumors in Denmark 1978-2002: centralized pathology review and overall survival compared with the general population.

OBJECTIVE: To describe the study population and estimate overall survival of women with a serous "borderline" ovarian tumor (SBT) in Denmark over 25 years relative to the general population. METHODS: The Danish Pathology Data Bank and the Danish Cancer Registry were used to identify 1487 women diagnosed with SBTs from 1978 to 2002. The histologic slides were collected from Danish pathology departments and reviewed by expert pathologists and classified as SBT/atypical proliferative serous tumor (APST) or noninvasive low-grade serous carcinoma (LGSC). Associated implants were classified as noninvasive or invasive. Medical records were collected from hospital departments and reviewed. Data were analyzed using Kaplan-Meier and relative survival was estimated with follow-up through September 2, 2013. RESULTS: A cohort of 1042 women with a confirmed SBT diagnosis was identified. Women with stage I had an overall survival similar to the overall survival expected from the general population (p=0.3), whereas women with advanced stage disease had a poorer one (p<0.0001). This was evident both in women with noninvasive (p<0.0001) and invasive implants (p<0.0001). Only among women with advanced stage, overall survival of women with SBT/APST (p<0.0001) and noninvasive LGSC (p<0.0001) was poorer than expected from the general population. CONCLUSIONS: To date this is the largest nationwide cohort of SBTs where all tumors have been verified by expert pathologists. Only in women with advanced stage SBT, overall survival is poorer than in the general population which applies both to women with noninvasive and invasive implants as well as to women with SBT/APST and noninvasive LGSC.

A binary histologic grading system for ovarian serous carcinoma is an independent prognostic factor: a population-based study of 4317 women diagnosed in Denmark 1978-2006.

OBJECTIVE: To evaluate the prognostic significance of histologic grade on survival of ovarian serous cancer in Denmark during nearly 30 years. METHODS: Using the nationwide Danish Pathology Data Bank, we evaluated 4317 women with ovarian serous carcinoma in 1978-2006. All pathology reports were scrutinized and tumors classified as either low-grade serous carcinomas (LGSC) or high-grade serous carcinomas (HGSC). Tumors in which the original pathology reports were described as well-differentiated were classified as LGSC, and those that were described as moderately or poorly differentiated were classified as HGSC. We obtained histologic slides from the pathology departments for women with a diagnosis of well-differentiated serous carcinoma during 1997-2006, which were then reviewed by expert gynecologic pathologists. Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression analysis with follow-up through June 2009. RESULTS: Women with HGSC had a significantly increased risk of dying (HR=1.9; 95% CI: 1.6-2.3) compared with women with LGSC while adjusting for age and stage. Expert review of 171 women originally classified as well-differentiated in 1997-2006 were interpreted as LGSC in 30% of cases, whereas 12% were interpreted as HGSC and 50% as serous borderline ovarian tumors (SBT). Compared with women with confirmed LGSC, women with SBT at review had a significantly lower risk of dying (HR=0.5; 95% CI: 0.22-0.99), and women with HGSC at review had a non-significantly increased risk of dying (HR=1.6; 95% CI: 0.7-3.4). CONCLUSIONS: A binary grading system is a significant predictor of survival for ovarian serous carcinoma.

Trends in incidence of borderline ovarian tumors in Denmark 1978-2006.

OBJECTIVE: To examine period-, age- and histology-specific trends in the incidence rate of borderline ovarian tumors in Denmark in 1978-2006. DESIGN: Register-based cohort study. SETTING: Denmark 1978-2006. POPULATION: 5079 women diagnosed with a borderline ovarian tumor in at least one of two nationwide registries (4312 epithelial tumors and 767 non-epithelial/unspecified tumors). METHODS: Estimation of overall incidence rates and period-, age- and histology-specific incidence rates. Age-adjustment was done using the World Standard POPULATION. To evaluate incidence trends over time, we estimated average annual percentage change and 95% confidence intervals (CI) using log-linear Poisson models. MAIN OUTCOME MEASURES: Age-standardized and age-specific incidence rates and average annual percentage change. RESULTS: The incidence of epithelial borderline ovarian tumors increased from 2.6 to 5.5 per 100,000 women-years between 1978 and 2006, with an average annual percentage change of 2.6% (95% CI: 2.2-3.0). The median age at diagnosis was 52 years. Women 40 years or older had a higher average annual percentage change than women younger than 40 years. Most tumors were mucinous (49.9%) and serous tumors (44.4%). Women with mucinous tumors were younger at diagnosis (50 years) compared with women with serous tumors (53 years). Women with serous tumors had a higher average annual percentage incidence change than women with mucinous tumors. CONCLUSIONS: The incidence rate of borderline ovarian tumors increased significantly in Denmark in 1978-2006. In line with results for ovarian cancer, Denmark had a higher incidence rate of borderline ovarian tumors compared with the other Nordic countries in 1978-2006.

[Primary ovarian cancer. A comparison of registrations in the Danish Cancer Registry and the Pathology Data Bank]. / Primaer ovariecancer. En sammenligning af registreringer i Cancerregisteret og Patologidatabanken.

INTRODUCTION: Ovarian cancer (OC) registrations in the Danish Cancer Registry (CR) and the Danish Pathology Data Bank (PDB) 1978-99 were compared in order to assess the possibility of identifying OC cases from another data source than the CR. MATERIAL AND METHODS: A total of 13,320 OC were identified in the CR/PDB and comparisons of the registrations were performed. RESULTS: The frequency of cases registered in both registries increased during 1978-99. Agreement in registration of histological subtypes in the two registries was found in 82% of the cases. Diagnosis among the rest was most often consistent; however, a more specific diagnosis was often found in one or the other registry. The frequency of women only registered with OC in the CR decreased from 81% to 35%, as the number of women with no diagnoses at all in the PDB declined from 1978 to 1997, whereafter it stabilised, primarily because all pathology departments now reported data to the PDB. In 1997-99, 29% of OC registered in the CR with a histologically verified OC diagnosis was still not registered with cancer in the ovaries in the PDB. Most of these, however, could be identified in the PDB with diagnoses consistent with metastases from OC. In total, 749 OC were not registered in the CR, though explanations for their missing registrations could be found in most cases. CONCLUSION: Data from the PDB may not be useful in complete identification of ovarian cancer cases for research purposes. However, it is a good supplement to data from the CR.

CA125 expression pattern, prognosis and correlation with serum CA125 in ovarian tumor patients. From The Danish "MALOVA" Ovarian Cancer Study.

OBJECTIVES: To determine the CA125 tissue expression levels in borderline and invasive epithelial ovarian tumor tissues. Secondly, to evaluate whether CA125 tissue expression levels correlate with clinico-pathological parameters and serum CA125 levels and finally to investigate the prognostic value of tissue CA125 expression levels in ovarian cancer (OC) patients. METHODS: We designed tissue arrays (TA) and analyzed the CA125 expression in tissues from 778 Danish women with an ovarian tumor. Furthermore, corresponding preoperative blood samples obtained before surgery were collected from 382 women with OC. RESULTS: Significantly more CA125 expression positive tumors (no expression vs. expression) were found in the serous subtype compared to the percentage of positive tumors in mucinous, endometroid and other subtypes for patients both with borderline ovarian tumors and with OC (p<0.00001, p<0.00001). Similarly, a positive significant correlation was found between elevated serum CA125 levels and elevated levels of CA125 tissue expression (N=382 stage I-IV OC, Spearman rho=0.31, p<0.0001) (N=206 stage III OC, Spearman rho=0.30, p<0.0001). We found a significantly shorter survival for stage III/IV OC patients with no CA125 tissue expression compared to stage III/IV OC patients with positive CA125 tissue expression (p=0.0003). CONCLUSION: Our finding that tissue CA125 expression was lacking in late stage primary OC tumor of Danish women with poor survival may be of value in selecting patients as eligible candidates for individually based treatments.

Smoking and overweight: negative prognostic factors in stage III epithelial ovarian cancer.

OBJECTIVE: Smoking and overweight are associated with poorer prognosis in several cancer types. The prognostic effect of smoking and body mass index (BMI) on ovarian cancer is unknown. METHODS: Ovarian cancer cases were from the Danish MALOVA (MALignant OVArian cancer) study. Information on smoking status and BMI was obtained from a personal interview conducted closely after primary surgery. Cox regression models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for ovarian cancer-specific death in relation to smoking variables and BMI. RESULTS: A total of 295 women with stage III epithelial ovarian cancer were identified and followed to death or for a median of 7.3 years (range, 5.4-9.5 years). Median survival time for normal-weight never smokers was 2.8 years (95% CI, 2.3-3.2) compared with 1.2 years (95% CI, 0.8-2.3) for overweight current smokers. Current smokers had a significantly increased risk of ovarian cancer death compared with never smokers in multivariate Cox analysis (HR, 1.65; 95% CI, 1.22-2.24). The negative effect of smoking diminished with increasing time since a former smoker had stopped smoking (HR, 0.89; 95% CI, 0.80-0.98 per 5 years since stop of smoking). Overweight women also had an increased risk of ovarian cancer death (HR, 1.83; 95% CI, 1.38-2.42) compared with normal-weight women. CONCLUSION: Smoking at the time of diagnosis and premorbid overweight were negative prognostic factors for ovarian cancer-specific survival. The negative effect of smoking decreased with increasing time since stop of smoking.

Trends in the incidence and mortality of ovarian cancer in Denmark 1978-2002. Comparison with other Nordic countries.

BACKGROUND: The Nordic countries are well-known high-incidence areas of ovarian cancer, but even within the Nordic countries, differences exist. METHODS: Focus in this descriptive epidemiological study is to assess developments in incidence and mortality of ovarian cancer in Denmark 1978-2002 and to make a comparison with the development in the other Nordic countries. The results are based on data from the nationwide Danish Cancer Registry as well as the other Nordic Cancer Registries. RESULTS: A total of 14,325 cases of ovarian cancer were registered from 1978 to 2002 in Denmark. In this period, the age-standardized incidence decreased slightly from 14.3 (1978-1982) to 13.3 per 100,000 woman-years (1998-2002). The histology-specific time trends showed a tendency towards more specified histological diagnoses. Iceland had the highest age-adjusted ovarian cancer incidence in the Nordic countries, whereas Denmark had the highest mortality rate. In the entire period, the Danish mortality rate declined from 10.8 (1978-1982) to 9.0 per 100,000 woman-years (1998-1999). Only 19% of ovarian cancers in Denmark from 1978 to 2002 were localized at the time of diagnosis, while 30% had distant metastases. Older women were more likely to have advanced disease at diagnosis. The Danish distribution of stage at diagnosis seems less favorable compared to results from other countries. CONCLUSIONS: The Danish incidence of ovarian cancer seemed to decrease slightly from 1978 to 2002. Even though the mortality rate of ovarian cancer also declined, Denmark had the highest mortality rate of ovarian cancer in the world. Part of it may be explained by a less-favorable distribution of stage at diagnosis.

Why do slim women consider themselves too heavy? A characterization of adult women considering their body weight as too heavy.

OBJECTIVE: The purpose of this study was to characterize women who, in spite of a low body mass index (BMI), considered themselves too heavy. METHOD: Of 11,905 women (27-38 years of age), we focused on 2,443 nonpregnant women with a low BMI (18.5-21.0 kg/m(2)), who considered their weight acceptable or too heavy. Participants completed a comprehensive questionnaire. By multiple logistic regression we examined associations between lifestyle and health variables and the risk of considering own body weight too heavy. RESULTS: Approximately 10 % considered their body weight too heavy. Risk factors included early severe life events, young age at start of risky lifestyle behaviors, weight fluctuation, self-reported lifetime history of eating disorders, perception of too heavy workload, and poor physical form and self-rated health. Body dissatisfaction decreased with increasing age. DISCUSSION: Our results indicate that body dissatisfaction is established in childhood and adolescence. It is unknown if this body dissatisfaction influences the life of the women, but it might influence the values they pass on to their children.