Trends in the incidence, rate and treatment of miscarriage-nationwide register-study in Finland, 1998-2016

STUDY QUESTION: What changes have occurred in the incidence of miscarriage, its treatment options, and the profile of the women having miscarriages in Finland between 1998 and 2016? SUMMARY ANSWER: The annual incidence of registry-identified miscarriage has declined significantly between 1998 and 2016, and non-surgical management has become the dominant treatment. WHAT IS KNOWN ALREADY: Miscarriage occurs in 8-15% of clinically recognized pregnancies and in similar to 30% of all pregnancies. Increasing maternal age is associated with an increasing risk of miscarriage. The treatment of miscarriage has evolved significantly in recent years: previously, surgical evacuation of the uterus was the standard of care, but nowadays medical and expectant management are increasingly used. STUDY DESIGN, SIZE, DURATION: We conducted a nationwide retrospective cohort study of 128381 women that had experienced a miscarriage that was managed in public healthcare between 1998 and 2016 in Finland. PARTICIPANTS/MATERIALS, SETTING, METHODS: We used the National Hospital Discharge Registry for the data. Women aged 15-49 years that had experienced their first miscarriage during the follow-up period and had miscarriage-related diagnoses during their admission to public hospital were included in the study. Miscarriages were defined by the 10(th) Revision of the International Statistical Classification of Diseases and related Medical Problems (ICD-10) diagnostic codes O02*, O03* and O08*. Women with ectopic, molar and continuing pregnancies and induced abortions were excluded. Treatment was divided into surgical and non-surgical treatment using the surgical procedure codes. MAIN RESULTS AND THE ROLE OF CHANCE: The annual incidence of registry-identified miscarriage has declined from 6.8/1000 15-49-year-old women in 1998 to 5.0/1000 in 2016 (P <0.001). Also, the incidence rate of registry-identified miscarriage (i.e. the proportion of miscarriages of registry-identified pregnancies [i.e. deliveries, induced abortions, and miscarriages]) has declined from 112/1000 15-49-year-old pregnant women in 1998 to 83/1000 in 2016 (P <0.001). The largest decrease in this proportion occurred among women over 40 years of age, among whom 26.5% of registry-identified pregnancies in 1998 ended in miscarriage compared to that of 16.4% in 2016. The proportion of missed abortion has increased (30.3 to 38.8%, P <0.001) whereas that of blighted ovum has decreased (25.4 to 12.8%, P <0.001). The proportion of registry-identified miscarriages seen among nulliparous women has increased from 43.7 to 49.6% (P <0.001). Mean age at the time of miscarriage remained at 31 years throughout the study. Altogether, 29% of all miscarriages were treated surgically and 71% underwent medical or expectant management. The proportion of surgical management has decreased from 38.0 to 1.6% for spontaneous abortion, from 60.7 to 9.4% for blighted ovum and 70.9 to 11.2% for missed abortion between 1998 and 2016. LIMITATIONS, REASONS FOR CAUTION: This study includes only women with registry-identified pregnancies, i.e. women who were treated in public hospitals. However, the number of women treated elsewhere is presumed to be small. Neither can this study estimate the number of women having spontaneous miscarriage with no hospital contact. WIDER IMPLICATIONS OF THE FINDINGS: Both the annual incidence and incidence rate of miscarriage of all registry-identified pregnancies has decreased, and non-surgical management has become the standard of care. These findings are of value when planning allocation of healthcare resources and at individual level considering fertility and miscarriage questions. We speculate that improving ultrasound diagnostics explains the increasing proportion of missed abortion relative to other types of miscarriage. More investigation is needed to examine potential risk factors, complications and morbidity associated with miscarriages.Peer reviewe

Changes in objectively measured smoking in pregnancy by time and legislative changes in Finland: a retrospective cohort study

Objectives: To study the changes in prevalence, characteristics and outcomes of pregnant smokers over time and legislative changes.Design and setting: Retrospective nationwide cohort.Participants: Our study consisted of 9627 randomly selected pregnancies from the Finnish Maternity Cohort (1987-2011), with demographic characteristics and pregnancy and perinatal data obtained from the Medical Birth Registry and early pregnancy serum samples analysed for cotinine levels. Women were categorised based on their self-reported smoking status and measured cotinine levels (with >= 4.73 ng/mL deemed high). Data were stratified to three time periods based on legislative changes in the Tobacco Act.Primary and secondary outcome measures: Prevalence of pregnant smokers and demographics, and perinatal and pregnancy outcomes of pregnant smokers over time.Results: Overall, 71.6% of women were non-smokers, 16.2% were active cigarette smokers, 7.7% undisclosed smoking but had high cotinine levels and 4.5% were inactive cigarette smokers. The prevalence of active cigarette smokers decreased from mid-1990s onwards among women aged >= 30 years, probably due to the ban of cigarette smoking in most workplaces. We observed no changes in the prevalence of inactive smokers or women who undisclosed smoking by time or legislative changes. Women who undisclosed smoking had similar characteristics and perinatal outcomes as inactive and active smokers. Compared with non-smokers, women who undisclosed smoking were more likely to be young, unmarried, have a socioeconomic status lower than white-collar worker and have a preterm birth.Conclusions: Women who undisclosed smoking were very similar to pregnant cigarette smokers. We observed a reduction in the prevalence of active pregnant cigarette smokers after the ban of indoor smoking in workplaces and restaurants, mostly among women aged >= 30 years

Normal Gestational Weight Gain Protects From Large-for-Gestational-Age Birth Among Women With Obesity and Gestational Diabetes

Background: Pre-pregnancy obesity, excess gestational weight gain (GWG), and gestational diabetes (GDM) increase fetal growth. Our aim was to assess whether normal GWG is associated with lower risk for a large-for-gestational-age (LGA; over the 90th percentile of birth weight for sex and gestational age) infant and lower birth weight standard deviation (SD) score in the presence of GDM and maternal obesity. Methods: This multicenter case-control study is part of the Finnish Gestational Diabetes (FinnGeDi) Study and includes singleton pregnancies of 1,055 women with GDM and 1,032 non-diabetic controls. Women were divided into 12 subgroups according to their GDM status, pre-pregnancy body mass index (BMI; kg/m(2)), and GWG. Non-diabetic women with normal BMI and normal GWG (according to Institute of Medicine recommendations) served as a reference group. Results: The prevalence of LGA birth was 12.2% among women with GDM and 6.2% among non-diabetic women (p < 0.001). Among all women, normal GWG was associated with lower odds of LGA [odds ratio (OR) 0.57, 95% CI: 0.41-0.78]. Among women with both obesity and GDM, the odds for giving birth to a LGA infant was 2.25-fold (95% CI: 1.04-4.85) among those with normal GWG and 7.63-fold (95% CI: 4.25-13.7) among those with excess GWG compared with the reference group. Compared with excess GWG, normal GWG was associated with 0.71 SD (95% CI: 0.47-0.97) lower birth weight SD score among women with GDM and obesity. Newborns of normal weight women with GDM and normal GWG had 0.28 SD (95% CI: 0.05-0.51) lower birth weight SD scores compared with their counterparts with excess GWG. In addition, in the group of normal weight non-diabetic women, normal GWG was associated with 0.46 SD (95% CI: 0.30-0.61) lower birth weight SD scores compared with excess GWG. Conclusion: GDM, obesity, and excess GWG are associated with higher risk for LGA infants. Interventions aiming at normal GWG have the potential to lower LGA rate and birth weight SD scores even when GDM and obesity are present.Peer reviewe

Salivary IgA to MAA-LDL and Oral Pathogens Are Linked to Coronary Disease

A large body of literature has established the link between periodontal disease and cardiovascular disease. Oxidized low-density lipoproteins (OxLDLs) have a crucial role in atherosclerosis progression through initiation of immunological response. Monoclonal IgM antibodies to malondialdehyde-modified low-density lipoprotein (MDA-LDL) and to malondialdehyde acetaldehyde-modified low-density lipoprotein (MAA-LDL) have been shown to cross-react with the key virulence factors of periodontal pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. We have previously shown that salivary IgA antibodies to MAA-LDL cross-react with P. gingivalis in healthy humans. In this study, we aim to assess whether oral mucosal immune response represented by salivary IgA to MAA-LDL and oral pathogens is associated with coronary artery disease (CAD). Also, the molecular mimicry through antibody cross-reaction between salivary IgA to MAA-LDL and oral pathogens was evaluated. The study subjects consisted of 451 patients who underwent a coronary angiography with no CAD (n = 133), stable CAD (n = 169), and acute coronary syndrome (ACS, n = 149). Elevated salivary IgA antibody levels to MAA-LDL, Rgp44 (gingipain A hemagglutinin domain of P. gingivalis), and Aa-HSP60 (heat shock protein 60 of A. actinomycetemcomitans) were discovered in stable-CAD and ACS patients when compared to no-CAD patients. In a multinomial regression model adjusted for known cardiovascular risk factors, stable CAD and ACS were associated with IgA to MAA-LDL (P = 0.016, P = 0.043), Rgp44 (P = 0.012, P = 0.004), Aa-HSP60 (P = 0.032, P = 0.030), Tannerella forsythia (P = 0.002, P = 0.004), Porphyromonas endodontalis (P = 0.016, P = 0.020), Prevotella intermedia (P = 0.038, P = 0.005), and with total IgA antibody concentration (P = 0.002, P = 0.016). Salivary IgA to MAA-LDL showed cross-reactivity with the oral pathogens tested in the study patients. The study highlights an association between salivary IgA to MAA-LDL and atherosclerosis. However, whether salivary IgA to MAA-LDL and the related oral humoral responses play a causal role in the development in the CAD should be elucidated in the future.Peer reviewe

Salivary IgA to MAA-LDL and Oral Pathogens Are Linked to Coronary Disease

A large body of literature has established the link between periodontal disease and cardiovascular disease. Oxidized low-density lipoproteins (OxLDLs) have a crucial role in atherosclerosis progression through initiation of immunological response. Monoclonal IgM antibodies to malondialdehyde-modified low-density lipoprotein (MDA-LDL) and to malondialdehyde acetaldehyde-modified low-density lipoprotein (MAA-LDL) have been shown to cross-react with the key virulence factors of periodontal pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. We have previously shown that salivary IgA antibodies to MAA-LDL cross-react with P. gingivalis in healthy humans. In this study, we aim to assess whether oral mucosal immune response represented by salivary IgA to MAA-LDL and oral pathogens is associated with coronary artery disease (CAD). Also, the molecular mimicry through antibody cross-reaction between salivary IgA to MAA-LDL and oral pathogens was evaluated. The study subjects consisted of 451 patients who underwent a coronary angiography with no CAD (n = 133), stable CAD (n = 169), and acute coronary syndrome (ACS, n = 149). Elevated salivary IgA antibody levels to MAA-LDL, Rgp44 (gingipain A hemagglutinin domain of P. gingivalis), and Aa-HSP60 (heat shock protein 60 of A. actinomycetemcomitans) were discovered in stable-CAD and ACS patients when compared to no-CAD patients. In a multinomial regression model adjusted for known cardiovascular risk factors, stable CAD and ACS were associated with IgA to MAA-LDL (P = 0.016, P = 0.043), Rgp44 (P = 0.012, P = 0.004), Aa-HSP60 (P = 0.032, P = 0.030), Tannerella forsythia (P = 0.002, P = 0.004), Porphyromonas endodontalis (P = 0.016, P = 0.020), Prevotella intermedia (P = 0.038, P = 0.005), and with total IgA antibody concentration (P = 0.002, P = 0.016). Salivary IgA to MAA-LDL showed cross-reactivity with the oral pathogens tested in the study patients. The study highlights an association between salivary IgA to MAA-LDL and atherosclerosis. However, whether salivary IgA to MAA-LDL and the related oral humoral responses play a causal role in the development in the CAD should be elucidated in the future.Peer reviewe

Anti-Mullerian hormone: correlation with testosterone and oligo- or amenorrhoea in female adolescence in a population-based cohort study

Study questions: Can serum anti-Müllerian hormone (AMH) levels measured in female adolescents predict polycystic ovary syndrome (PCOS)-associated features in adolescence and early adulthood? Summary answer: AMH levels associated well with PCOS-associated features (such as testosterone levels and oligoamenorrhoea) in adolescence, but was not an ideal marker to predict PCOS-associated features in early adulthood. What is known already: Several studies have reported that there is a strong correlation between antral follicle count and serum AMH levels and that women with PCOS/PCO have significantly higher serum AMH levels than women with normal ovaries. Other studies have reported an association between AMH serum levels and hyperandrogenism in adolescence, but none has prospectively assessed AMH as a risk predictor for developing features of PCOS during adulthood. Study design, size, duration: A subset of 400 girls was selected from the prospective population-based Northern Finland Birth Cohort 1986 (n = 4567 at age 16 and n = 4503 at age 26). The population has been followed from 1986 to the present. Participants/material, setting, methods: At age 16, 400 girls (100 from each testosterone quartile: 50 with oligo- or amenorrhoea and 50 with a normal menstrual cycle) were selected at random from the cohort for AMH measurement. Metabolic parameters were also assessed at age 16 in all participants. Postal questionnaires enquired about oligo- or amenorrhoea, hirsutism, contraceptive use and reproductive health at ages 16 and 26. Main results and role of chance: There was a significant correlation between AMH and testosterone at age 16 (r = 0.36, P < 0.001). AMH levels at age 16 were significantly higher among girls with oligo- or amenorrhoea compared with girls with normal menstrual cycles (35.9 pmol/l [95% CI: 33.2;38.6] versus 27.7 pmol/l [95% CI: 25.0;30.4], P < 0.001). AMH at age 16 was higher in girls who developed hirsutism at age 26 compared with the non-hirsute group (31.4 pmol/l [95% CI 27.1;36.5] versus 25.8 pmol/l [95% CI 23.3;28.6], P = 0.036). AMH at age 16 was also higher in women with PCOS at age 26 compared with the non-PCOS subjects (38.1 pmol/l [95% CI 29.1;48.4] versus 30.2 pmol/l [95% CI 27.9;32.4], P = 0.044). The sensitivity and specificity of the AMH (cut-off 22.5 pmol/l) for predicting PCOS at age 26 was 85.7 and 37.5%, respectively. The addition of testosterone did not significantly improve the accuracy of the test. There was no significant correlation between AMH levels and metabolic indices at age 16. Implications, reasons for cauntion: AMH is related to oligo- or amenorrhoea in adolescence, but it is not a good marker for metabolic factors. The relatively low rate of participation in the questionnaire at age 26 may also have affected the results. AMH was measured in a subset of the whole cohort. AMH measurement is lacking international standardization and therefore the concentrations and cut-off points are method dependent. Wider implications for the findings: Using a high enough cut-off value of AMH to predict which adolescents are likely to develop PCOS in adulthood could help to manage the condition from an early age due to a good sensitivity. However, because of its low specificity, it is not an ideal diagnostic marker, and its routine use in clinical practice cannot, at present, be recommended

Accuracy of 1-Hour Plasma Glucose During the Oral Glucose Tolerance Test in Diagnosis of Type 2 Diabetes in Adults : A Meta-analysis

OBJECTIVE One-hour plasma glucose (1-h PG) during the oral glucose tolerance test (OGTT) is an accurate predictor of type 2 diabetes. We performed a meta-analysis to determine the optimum cutoff of 1-h PG for detection of type 2 diabetes using 2-h PG as the gold standard. RESEARCH DESIGN AND METHODS We included 15 studies with 35,551 participants from multiple ethnic groups (53.8% Caucasian) and 2,705 newly detected cases of diabetes based on 2-h PG during OGTT. We excluded cases identified only by elevated fasting plasma glucose and/or HbA(1c). We determined the optimal 1-h PG threshold and its accuracy at this cutoff for detection of diabetes (2-h PG >= 11.1 mmol/L) using a mixed linear effects regression model with different weights to sensitivity/specificity (2/3, 1/2, and 1/3). RESULTS Three cutoffs of 1-h PG, at 10.6 mmol/L, 11.6 mmol/L, and 12.5 mmol/L, had sensitivities of 0.95, 0.92, and 0.87 and specificities of 0.86, 0.91, and 0.94 at weights 2/3, 1/2, and 1/3, respectively. The cutoff of 11.6 mmol/L (95% CI 10.6, 12.6) had a sensitivity of 0.92 (0.87, 0.95), specificity of 0.91 (0.88, 0.93), area under the curve 0.939 (95% confidence region for sensitivity at a given specificity: 0.904, 0.946), and a positive predictive value of 45%. CONCLUSIONS The 1-h PG of >= 11.6 mmol/L during OGTT has a good sensitivity and specificity for detecting type 2 diabetes. Prescreening with a diabetes-specific risk calculator to identify high-risk individuals is suggested to decrease the proportion of false-positive cases. Studies including other ethnic groups and assessing complication risk are warranted.Peer reviewe

Temporal Trends in Vertebral Size and Shape from Medieval to Modern-Day

Human lumbar vertebrae support the weight of the upper body. Loads lifted and carried by the upper extremities cause significant loading stress to the vertebral bodies. It is well established that trauma-induced vertebral fractures are common especially among elderly people. The aim of this study was to investigate the morphological factors that could have affected the prevalence of trauma-related vertebral fractures from medieval times to the present day. To determine if morphological differences existed in the size and shape of the vertebral body between medieval times and the present day, the vertebral body size and shape was measured from the 4th lumbar vertebra using magnetic resonance imaging (MRI) and standard osteometric calipers. The modern samples consisted of modern Finns and the medieval samples were from archaeological collections in Sweden and Britain. The results show that the shape and size of the 4th lumbar vertebra has changed significantly from medieval times in a way that markedly affects the biomechanical characteristics of the lumbar vertebral column. These changes may have influenced the incidence of trauma- induced spinal fractures in modern populations