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 ~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 128 381 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 10th 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. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the research funds of the Helsinki and Uusimaa hospital system, by a personal grant from Viipurin Tuberkuloosisäätiö to R.L. and by a personal grant from The Finnish Cultural Foundation to N.H. The authors have no conflicts of interest to declare.

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.

Irregular menstruation and hyperandrogenaemia in adolescence are associated with polycystic ovary syndrome and infertility in later life: Northern Finland Birth Cohort 1986 study.

STUDY QUESTION: Do teenage girls with a history of menstrual irregularity and/or elevated androgen levels in adolescence exhibit an increased risk of polycystic ovary syndrome (PCOS) and/or infertility later on in adulthood? SUMMARY ANSWER: Our results suggest that menstrual irregularity and/or elevated androgen levels at 16 years are still associated with symptoms of PCOS at 26 years as well as infertility problems at 26 years but not with decreased pregnancy or delivery rates at 26 years. WHAT IS KNOWN ALREADY: Hyperandrogenaemia is associated with menstrual irregularity, hirsutism, acne and potentially higher risk for PCOS, but there are few follow-up studies investigating whether adolescent hyperandrogenaemia and/or menstrual irregularity are an early sign of PCOS. STUDY DESIGN, SIZE, DURATION: A prospective population-based cohort study was conducted using two postal questionnaires targeting girls in the Northern Finland Birth Cohort 1986 (NFBC1986, n = 4567). The NFBC1986 comprises all expected births from the year 1986 in the two northernmost provinces of Finland. Collection of the database was performed at the age of 16 and 26. The 16-year and 26-year questionnaires included one question about the regularity and length of the menstrual cycle. The 26-year questionnaire also included questions about symptoms of PCOS, reproduction and infertility problems. PARTICIPANTS, SETTING, METHODS: The response rates for the questionnaires were 80% (n = 3669) at 16 years and 50% (n = 2270) at 26 years. At 15-16 years, of 2448 girls, 709 (29%) girls reported menstrual irregularity (symptomatic girls) and 1739 (71%) had regular periods (non-symptomatic girls). After combining data from the two questionnaires a total of 2033 girls were included in the analyses. The χ(2) and Student's t-test was used to compare reproductive outcome and prevalence of clinical hyperandrogenaemia, PCOS and infertility at 26 years between the study groups. Univariate and multivariate logistic regression models were employed to estimate the association of menstrual irregularity at 16 years with clinical hyperandrogenaemia, PCOS and infertility at 26 years. MAIN RESULTS AND THE ROLE OF CHANCE: At follow-up, the proportion of symptomatic girls who had conceived at least once (68.0 versus 67.9%) and had delivered at least one child (25.7 versus 28.1%) was similar to the non-symptomatic women and the groups had similar miscarriage rates (11.6 versus 12.1%). Logistic regression analyses indicated that menstrual irregularity at 16 years was associated with an increased risk of menstrual irregularity [adjusted odds ratio (OR) 1.37, 95% confidence interval (CI) 1.00-1.88, P = 0.050], PCOS (adjusted OR 2.91, 95% CI 1.74-4.84, P < 0.001) and infertility problems (adjusted OR 2.07, 95% CI 1.16-3.76, P = 0.013) at 26 years. At 26 years, women with PCOS (P = 0.013), hirsutism (P = 0.001) and acne (P < 0.001) exhibited significantly higher values of free androgen index (FAI) at 16 years than control women. There was a significant linear trend in the higher FAI quartiles at 16 years towards higher prevalence of PCOS (P = 0.005), hirsutism (P < 0.001) and acne (P < 0.001) at 26 years. Only 10.5% of the girls with menstrual irregularity at 16 years had PCOS at 26 years. LIMITATIONS, REASONS FOR CAUTION: The diagnosis of menstrual irregularity was based on a self-reported questionnaire, thus introducing a risk of information bias in reporting the symptoms. Moreover, ovarian ultrasonography was not available to aid the diagnosis of PCOS and there was no clinical evaluation of hyperandrogenism. The relatively low rate of participation to the questionnaire at 26 years may also have biased the results. WIDER IMPLICATIONS OF THE FINDINGS: Our findings confirm that menstrual irregularity and/or elevated androgen levels are already present in adolescence in women with PCOS and infertility in later life, which strengthens the importance of early identification of menstrual irregularity. STUDY FUNDING/COMPETING INTERESTS: This work was supported by grants from the Finnish Medical Society Duodecim, the North Ostrobothnia Regional Fund, the Academy of Finland, the Sigrid Juselius Foundation, University Hospital Oulu and University of Oulu, the European Commission and the Medical Research Council, UK, Welcome Trust (089549/Z/09/Z). None of the authors have any conflict of interest.

Anti-Müllerian 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 CAUTION: 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. STUDY FUNDINGS AND COMPETING INTERESTS: The study was funded by a grant from Wellcome Trust (089549/Z/09/Z) to H.L., S.F. and M.-R.J. Study funding was also received from Oulu University Hospital Research Funds, Sigrid Juselius Foundation and the Academy of Finland. None of the authors have any competing interest to declare.

The impact of self-reported oligo-amenorrhea and hirsutism on fertility and lifetime reproductive success: results from the Northern Finland Birth Cohort 1966.

STUDY QUESTION: To what extent do self-reported oligo-amenorrhea and hirsutism affect reproductive performance (childlessness, age at first delivery, family size and miscarriage rates)? SUMMARY ANSWER: At the age of 44, among women with both self-reported oligo-amenorrhea and hirsutism the prevalence of childlessness was not significantly different from non-symptomatic women but they had a smaller family size than non-symptomatic women. WHAT IS KNOWN ALREADY: Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by oligo-amenorrhea or amenorrhea, hyperandrogenism and hirsutism and it is the most frequent cause of anovulatory infertility, but there are few studies on the reproductive capacity of women with PCOS. In our previous population-based cohort study the women with self-reported oligo-amenorrhea and hirsutism were found to have more infertility problems and smaller family size than non-symptomatic women at the age of 31. STUDY DESIGN, SIZE, DURATION: A prospective population-based cohort study. The population of the study is derived from the prospective Northern Finland Birth Cohort 1966 (NFBC1966), comprising all expected births from the year 1966 in the two northernmost provinces of Finland (n = 12 058). Of them, 5889 were females. Enrollment in this database begun at the 24th gestational week and so far data have been collected from the subjects at the ages of 1, 14 and 31 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: A postal questionnaire including questions about oligo-amenorrhea and hirsutism was sent to all women at the age of 31 (n = 5608, response rate 81%, n = 4535) and a clinical examination was performed (attendance rate 76.5%). Those who reported both hirsutism and oligo-amenorrhea were defined as women with both symptoms (n = 153). Data on pregnancies/deliveries were obtained from the Finnish Medical Birth Register (FMBR) in 2010 when the women were 44 years old. MAIN RESULTS AND THE ROLE OF CHANCE: Women with both symptoms had delivered at least one child as often as non-symptomatic women [75.2 versus 79.0%, adjusted odds ratio (OR) 0.86, 95% confidence intervals (CI) 0.57-1.30], were of similar age [mean (SD)] at first delivery [27.7 (4.81) versus 27.3 (4.71)] and had similar incidence of miscarriages. However, non-symptomatic women had more often ≥2 deliveries (61.6 versus 52.9%, adjusted OR 0.70, 95% CI 0.49-1.00, P = 0.048) and had larger family size [mean (SD)] [2.4 (1.4) versus 1.9 (0.8), P < 0.001]. Women with both symptoms had been treated more often for infertility than non-symptomatic women (6.1 versus 2.4%, adjusted OR 2.74, 95% CI 1.14-6.60, P = 0.024). LIMITATIONS, REASONS FOR CAUTION: The diagnosis of oligo-amenorrhea and hirsutism was based on a questionnaire, suggesting a risk of information bias in reporting the symptoms. However, we have previously shown that self-reported oligo-amenorrhea and hirsutism can distinguish most women with the typical profile of PCOS. Only the women who had delivered at least once were recorded in the FMBR, thus excluding from the study those who had experienced miscarriages and/or infertility treatments but did not have a live birth. This feature could potentially decrease the differences in incidence of miscarriages and/or infertility treatment between symptomatic and non-symptomatic subjects. WIDER IMPLICATIONS OF THE FINDINGS: This is one of the few studies, in which the impact of self-reported oligo-amenorrhea and hirsutism on lifetime reproductive success can be measured. Our results suggest that even at more advanced age, women with both symptoms do not quite match the parity of healthy non-symptomatic women, and that infertility treatment does not always restore normal reproductive capacity in these women. Obese women with both symptoms had the worst prognostic as regards reproduction, which emphasizes the importance of life intervention and preventive politics against obesity in this group of women. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the Finnish Medical Society Duodecim, the North Ostrobothnia Regional Fund, the Academy of Finland, University Hospital Oulu, Biocenter, University of Oulu, Finland, the European Commission and the Medical Research Council, UK, the National Institute for Health Research (NIHR). None of the authors has any conflict of interest to declare.

Medical versus surgical termination of pregnancy in primigravid women--is the next delivery differently at risk? A population-based register study.

OBJECTIVE: To compare the effect of medical versus surgical termination of pregnancy (TOP), performed in primigravid women, on subsequent delivery. DESIGN: Population-based register study. SETTING: Finland 2000-2009. POPULATION: All primigravid women (n = 8294) who underwent TOP during first trimester of pregnancy by medical (n = 3441) or surgical (n = 4853) method, and whose subsequent pregnancy resulted in singleton delivery. METHODS: The women were identified in the Finnish Register of Induced Abortions, and the data were linked to the Medical Birth and the Hospital Discharge Registries. MAIN OUTCOME MEASURES: Risk of preterm birth, low birthweight, small-for-gestational-age (SGA) infant and placental complications (placenta praevia, placental abruption, retained placenta, placenta accreta). RESULTS: No statistically significant differences in the incidences of preterm birth (4.0% in the medical group versus 4.9% in the surgical group), low birthweight (3.4% versus 4.0%), SGA infants (2.6% versus 2.9%) or placental complications (2.6% versus 2.8%) emerged between the two groups. After adjusting for various background factors, medical TOP was not associated with significantly altered risks of preterm birth (odds ratio [OR] 0.87, 95% confidence interval [95% CI] 0.68-1.13), low birthweight (OR 0.90, 95% CI 0.68-1.19), SGA infant (OR 0.87, 95% CI 0.64-1.20) or placental complications (OR 0.98, 95% CI 0.72-1.34) versus surgical TOP. In a sub-analysis excluding women who underwent surgical evacuation following the index TOP, medical TOP was associated with a reduced risk of preterm birth (P < 0.01), but the difference became insignificant after adjusting for gestational age at the time of TOP, inter-pregnancy interval, maternal age, cohabitation status, socio-economic status, residence and smoking during pregnancy. CONCLUSIONS: A history of one medical versus surgical TOP, performed in primigravid women, is associated with similar obstetric risks in the subsequent delivery.

Menstrual disorders in adolescence: a marker for hyperandrogenaemia and increased metabolic risks in later life? Finnish general population-based birth cohort study.

STUDY QUESTION: Are self-reported menstrual disorders associated with hyperandrogenaemia and metabolic disturbances as early as in adolescence? SUMMARY ANSWER: Menstrual disorders at the age 16 are a good marker of hyperandrogenaemia, and an adverse lipid profile was associated with higher androgen levels. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Hyperandrogenism per se has been suggested to be a significant metabolic risk factor in women and a cause of physical and psychological morbidity in adolescent girls. A weak positive correlation has been described between hyperandrogenaemia and obesity in adolescent girls, but the clinical consequences are still poorly understood. Hyperandrogenism and insulin resistance are also key features of polycystic ovary syndrome (PCOS), and women with PCOS are consequently at an increased risk of developing type 2 diabetes mellitus and/or metabolic syndrome, and may have increased cardiovascular morbidity. Our findings confirm that the association between menstrual disorders, hyperandrogenism, obesity and metabolic risks is already evident in adolescence. STUDY DESIGN: This population-based, cross-sectional study used postal questionnaires to targeting 15-16-year-old girls in the Northern Finland Birth Cohort 1986 (n= 4567). PARTICIPANTS AND SETTING: There were 3669 girls who answered the postal questionnaire and out of 3373 girls who also underwent clinical examinations and blood tests, 2448 were included in the analyses. The questionnaire included one question about the regularity and length of the menstrual cycle: 'Is your menstrual cycle (the interval from the beginning of one menstrual period to the beginning of the next period) often (more than twice a year) longer than 35 days?' The girls who answered 'yes' to this question were considered to be suffering from menstrual disorders and were classified as 'symptomatic'. The girls who answered 'no' were defined as 'non-symptomatic'. MAIN RESULTS AND THE ROLE OF CHANCE: There were 709 (29%) girls who reported menstrual disorders (symptomatic girls) and 1739 who had regular periods (non-symptomatic girls). In the whole population and in both study groups, there were significant correlations between body mass index (BMI) (and waist-to-hip ratio), hyperandrogenaemia and metabolic parameters. Symptomatic girls exhibited significantly higher serum concentrations of testosterone (P= 0.010), lower levels of sex hormone-binding globulin (P =0.042) and higher free androgen indices [FAIs; geometric mean 3.38 (interquartile range (IQR): 2.27, 5.18) versus 3.08 (IQR: 2.15, 4.74), P= 0.002]. The two groups had comparable BMI and insulin sensitivity, and serum levels of glucose, insulin and lipids. There was a significant linear trend towards higher FAI values in the higher BMI quartiles in both symptomatic and non-symptomatic girls. In the whole population, there was a statistically significant linear decrease in high-density lipoprotein concentrations (P < 0.001) and higher triglyceride concentrations (P =0.004) in the upper FAI quartile. IMPLICATIONS: Information regarding menstrual disorders in adolescence is a good marker of hyperandrogenaemia and may be an early risk factor for the development of PCOS in adulthood. The association between obesity, hyperandrogenism and metabolic risks is already evident in adolescence, which strengthens the importance of noting menstrual disorders at an early stage. BIAS, LIMITATIONS, GENERALIZABILITY: The cross-sectional nature of the study does not allow us to draw conclusions concerning the metabolic risks of this population in later life. The diagnosis of menstrual disorders was based on a questionnaire, suggesting a risk of information bias in reporting the symptoms. This study was not designed to diagnose PCOS, as ultrasonography was not available and there was no clinical evaluation of hyperandrogenism (i.e. hirsutism). However, we were able to take into account potential confounding factors in the analyses. STUDY FUNDING/COMPETING INTERESTS: This work was supported by grants from the Finnish Medical Society Duodecim, the North Ostrobothnia Regional Fund, the Academy of Finland (project grants 104781, 120315, 129269, 1114194, SALVE), University Hospital Oulu, Biocenter, University of Oulu, Finland (75617), the European Commission (EURO-BLCS, Framework 5 award QLG1-CT-2000-01643) and the Medical Research Council, UK (PrevMetSyn/SALVE). None of the authors have any conflict of interest to declare.

The association of body mass index, waist and hip circumference, and waist-hip ratio with Chlamydia pneumoniae IgG antibodies and high-sensitive C-reactive protein at 31 years of age in Northern Finland Birth Cohort 1966.

BACKGROUND: Viruses and bacteria like Chlamydia pneumoniae and Helicobacter pylori have been suggested to have a role in pathogenesis of overweight and obesity. OBJECTIVE: We studied whether C. pneumoniae-specific IgG antibodies are associated with elevated body mass index (BMI), waist and hip circumference, and/or waist-hip ratio (WHR), and whether the risk is more pronounced in the simultaneous presence of an ongoing inflammation as measured by elevated high-sensitive C-reactive protein (hsCRP) levels. SUBJECTS AND METHODS: Our study population was derived from the Northern Finland Birth Cohort 1966 (NFBC1966), a general population sample of 12,058 live-born children. This cross-sectional study consisted of 5044 persons at 31 years of age. Serum C. pneumoniae IgG titers were measured by microimmunofluorescence test, and hsCRP levels by immunoenzymometric assay. RESULTS: C. pneumoniae IgG positivity (titer ≥ 32), both alone and jointly with elevated hsCRP (≥ 1.64 mg l(-1), an upper quartile), was found to significantly associate with elevated BMI in the whole study population and with elevated hip and waist circumference in women, yet no association with WHR was seen. The analyses were adjusted for sex (when appropriate), smoking, socioeconomic position, glucose, insulin, high- and low-density lipoprotein cholesterols, triglycerides, leukocytes and pulse pressure. CONCLUSION: These findings suggest that especially in women, persistent C. pneumoniae infection may be associated with overweight/obesity, independently of more traditional risk factors.

Chlamydia pneumoniae infection is associated with elevated body mass index in young men.

Chlamydia pneumoniae infection is said to be associated with obesity. We studied the association between C. pneumoniae infection and inflammation and increased BMI in 891 Finnish military recruits. IgG seropositivity in arrival and departure serum samples during 6-12 months of military service was considered as persistence of antibodies and a possible indication of chronic infection. Persistently high C-reactive protein (CRP) level (elevated on arrival and departure) (OR 2.2, 95% CI 1.3-3.9), and persistent C. pneumoniae antibodies (OR 2.1, 95% CI 1.5-2.8) were significant risk factors for overweight (BMI 25 kg/m2). In addition, those who had persistent antibodies and persistently elevated CRP levels, or those who had either of them, had a significantly higher BMI (kg/m2) compared to those who had neither of them (25.8 vs. 24.6 vs. 23.5, respectively; P<0.001). These results provide new information about the association between possible chronic C. pneumoniae infection and obesity in young men.

Fecundability and spontaneous abortions in women with self-reported oligo-amenorrhea and/or hirsutism: Northern Finland Birth Cohort 1966 Study.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) suffer from anovulatory infertility and hospital-based studies suggest that they have an increased risk of spontaneous abortion. Our aim was to investigate the proportion of women, with self-reported oligo-amenorrhea and/or hirsutism in a general population, who had suffered from infertility, the percentage of them managing to conceive and their rate of spontaneous abortion. METHODS: At age 31, a postal questionnaire including questions about hirsutism and oligo-amenorrhea was sent to all women from the population-based Northern Finland Birth Cohort 1966 (total n = 5889). Of these, 4535 (79.5%) answered the questionnaire, 1103 reported hirsutism and/or oligo/amenorrhea (symptomatic women) and 3420 were non-symptomatic. The fecundability ratio (FR) was defined as the probability of conception of a clinically detectable pregnancy within 12 months. RESULTS: The overall pregnancy (77.7% versus 75.6%) and spontaneous abortion (19.3% versus 18.6%) rates did not differ between the two groups and the risk of spontaneous abortion was not associated with body mass index (BMI), waist-to-hip ratio (WHR) or waist circumference. Symptomatic women had suffered more often from infertility than non-symptomatic women (19.4% versus 11.1%, P < 0.01). Oligo-amenorrhea and/or hirsutism (FR = 0.74, P < 0.001) and obesity (FR = 0.68, P = 0.002) were both independently associated with decreased fecundability, but symptomatic women had become pregnant and had one or two successful deliveries as often as non-symptomatic women. CONCLUSIONS: Women with self-reported oligo-amenorrhea and/or hirsutism had lower fecundability and suffered more often from infertility, but had at least one delivery as often as non-symptomatic women, and did not exhibit an increased risk of spontaneous abortion.

Prevalence of metabolic syndrome at age 16 using the International Diabetes Federation paediatric definition.

OBJECTIVE: We estimated the prevalence of metabolic syndrome (MS) in adolescents, using the new International Diabetes Federation (IDF) paediatric definition and compared this with prevalence estimated using the IDF adult definition and five other previously published definitions. DESIGN: Cross-sectional survey in the prospective general population-based Northern Finland Birth Cohort 1986 (NFBC 1986) at age 16 years. SETTING: Birth cohort in Finland. PARTICIPANTS: 5665 adolescents (2862 males and 2803 females) clinically examined in 2001-2002. MAIN OUTCOME MEASURES: The prevalence of MS using different definitions. RESULTS: The overall prevalence of MS using the IDF paediatric definition was 2.4% (95% CI 2.0 to 2.8%) at the age of 16 years. Using the IDF adult definition the overall prevalence was lower, 1.7% (CI 1.3 to 2.0%, European cut-offs for waist circumference) and 1.0% (CI 0.7 to 1.3%, North American cut-offs). CONCLUSION: In 16-year-old adolescents, the paediatric IDF definition rendered a higher prevalence estimate than the adult definition.

Prediction of placental abruption by testing for C-reactive protein and chlamydial antibody levels in early pregnancy.

OBJECTIVE: Placental abruption may be a manifestation of acute and chronic inflammatory process. We wanted to assess the association of first-trimester serum C-reactive protein (CRP), Chlamydia pneumoniae antibodies, Chlamydia trachomatis antibodies or chlamydial heat-shock protein 60 (CHSP60) antibodies to placental abruption. DESIGN: Retrospective case-control study. SETTING: University Hospital. POPULATION: A total of 181 women with subsequent placental abruption and 261 control women with normal pregnancy. METHODS: Serum samples collected at first trimester (mean 10.4 gestational weeks) were analysed for CRP levels, C. pneumoniae-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies and C. trachomatis-specific IgG, IgA and CHSP60 antibodies. MAIN OUTCOME MEASURE: Placental abruption. RESULTS: The levels of CRP showed no difference between the cases and the controls (median 2.35 mg/l [interquartile range {IQR} 1.09-5.93] versus 2.28 mg/l [IQR 0.92-5.01], not significant). C. pneumoniae-specific IgG and IgA as well as C. trachomatis-specific IgG, IgA and CHSP60 antibody frequencies were similar between the groups. There was no association between CRP levels and chlamydial antibodies. CONCLUSION: These markers of inflammation in early pregnancy failed to predict subsequent placental abruption.

Acute Chlamydia pneumoniae infections in asthmatic and non-asthmatic military conscripts during a non-epidemic period.

Chlamydia pneumoniae respiratory tract infections were studied in 512 male military conscripts (123 asthmatic and 389 non-asthmatic) taking part in 180-day service between July 2004 and July 2005 in Kajaani, Finland. Respiratory tract infections requiring a medical consultation were analysed prospectively. At baseline, at end of service, and during each episode of respiratory infection, blood samples were obtained for measurement of C. pneumoniae antibodies. Data concerning the clinical features of each infection episode were collected. Serological evidence of acute C. pneumoniae infection was found in 34 of the 512 conscripts with antibody data available, including 9.8% of the asthmatic subjects and 5.7% of the non-asthmatic subjects (p 0.111). A serological diagnosis could be made for 25 clinical episodes in 24 conscripts. The spectrum of respiratory tract infections included 13 episodes of mild upper respiratory tract infection and seven episodes of sinusitis, with five episodes involving asthma exacerbation. Two of three pneumonias were primary infections. Primary infections were diagnosed in five subjects, and re-infection/reactivation in 19 subjects, with the latter comprising 12 non-asthmatic subjects and seven asthmatic subjects (p 0.180). Prolonged infections were present in six asthmatic subjects and one non-asthmatic subject (p 0.001). A wide variety of respiratory tract infections, ranging from common cold to pneumonia, were associated with serologically confirmed C. pneumoniae infections. Infections were often mild, with common cold and sinusitis being the most common manifestations. Acute, rapidly resolved C. pneumoniae infections were equally common among asthmatic subjects and non-asthmatic subjects, whereas prolonged infections were more common among subjects with asthma.

Pathogenic bacteria and viruses in induced sputum or pharyngeal secretions of adults with stable asthma.

BACKGROUND: Respiratory infections are well known triggers of asthma exacerbations, but their role in stable adult asthma remains unclear. METHODS: 103 asthmatics and 30 control subjects were enrolled in the study. Sputum was induced by inhalation of 3% NaCl solution. Oropharyngeal swab specimens were obtained from the posterior wall of the oropharynx. Respiratory specimens were analysed by RT-PCR for rhinovirus, enterovirus and respiratory syncytial virus and by PCR for adenovirus, Chlamydia pneumoniae, Mycoplasma pneumoniae and Bordetella pertussis. RESULTS: Sputum samples from two of the 30 healthy controls (6.7%), five of 53 patients with mild asthma (9.4%), and eight of 50 with moderate asthma (16.0%) were positive for rhinovirus. Rhinovirus positive asthmatic subjects had more asthma symptoms and lower forced expiratory volume in 1 second (FEV(1)) (79% predicted) than rhinovirus negative cases (93.5% predicted; p = 0.020). Chlamydia pneumoniae PCR was positive in 11 healthy controls (36.6%), 11 mild asthmatics (20.8%), and 11 moderate asthmatics (22%), and PCR positive asthmatics had lower FEV(1)/FVC than negative cases (78.2% v 80.8%, p = 0.023). Bordetella pertussis PCR was positive in 30 cases: five healthy controls (16.7%), 15 mild asthmatics (28.3%), and 10 moderate asthmatics (20%). Bordetella pertussis positive individuals had lower FEV(1)/FVC (77.1% v 80.7%, p = 0.012) and more asthma symptoms than B pertussis negative cases. CONCLUSIONS: Rhinovirus, C pneumoniae, and B pertussis are found in the sputum or pharyngeal swab specimens of asthmatic subjects without concurrent symptoms of infection or asthma exacerbation, as well as in some healthy controls. Positivity is associated with lower lung function and more frequent asthma symptoms.

Chlamydia trachomatis and chlamydial heat shock protein 60-specific antibody and cell-mediated responses predict tubal factor infertility.

BACKGROUND: To evaluate the role of Chlamydia trachomatis-induced humoral and cell-mediated immune (CMI) responses in predicting tubal factor infertility (TFI). METHODS: Blood samples were taken from 88 women with TFI and 163 control women. C. trachomatis and chlamydial heat shock protein 60 (CHSP60)-specific immunoglobulin G (IgG) antibodies were analysed using enzyme-linked immunosorbent assay (ELISA) kits. Proliferative reactivity of peripheral blood mononuclear cells was studied in vitro against Chlamydia elementary body (EB) and recombinant CHSP60 antigens. RESULTS: C. trachomatis-specific IgG antibodies were found more frequently (43.2 versus 13.5%), and the antibody levels were higher in the TFI cases than in the controls (P < 0.001). C. trachomatis EB-induced lymphocyte responses were positive in 81.8% of the TFI cases and 58.9% of the controls (P < 0.001). Similarly, CHSP60-induced lymphocyte responses were found in 45.5% of the TFI cases and 30.7% of the controls (P < 0.001). CHSP60 antibody test was the best single test predicting TFI. Compared to cases with all four markers negative, the estimated risk for TFI was 4.1 (95% CI 1.4-11.9) among those with one positive marker and 19.9 (95% CI 6.9-57.4) among those with three to four positive markers. CONCLUSION: Our results show that TFI prediction model can be improved by combining tests for humoral and CMI response to chlamydial antigens.

Antibodies to Chlamydia trachomatis heat shock proteins Hsp60 and Hsp10 and subfertility in general population at age 31.

PROBLEM: To assess the association between antibodies to Chlamydia trachomatis heat shock proteins 60 and 10 (Hsp60 and Hsp10) and subfertility in a general population sample. METHOD OF STUDY: A nested case (n = 146)-control (n = 278) study in a population-based birth cohort. Serum immunoglobulin (Ig)G and IgA antibodies against C. trachomatis Hsp60 and Hsp10, explanatory factors, were measured by enzyme immunoassay, using recombinant proteins as antigens. The main outcome variable was subfertility (time to pregnancy > or =12 months). RESULTS: The prevalence and medians of serum IgA antibodies to Hsp60 and Hsp10 were significantly higher in the female partners of subfertile couple than in their fertile controls. On the contrary, among male partners of subfertile couple, especially among smokers serum antibody levels to Hsp antigens were lower than in the controls. CONCLUSION: The results indicate a serological association of antibodies to chlamydial Hsp antigens with female subfertility in a population-based sample.

Association between Chlamydia trachomatis antibodies and subfertility in the Northern Finland Birth Cohort 1966 (NFBC 1966), at the age of 31 years.

The objective of this study was to assess the serological association between previous Chlamydia trachomatis infection and subfertility in a general population sample. A nested case (n = 493)-control (n = 986) study in a population-based birth cohort consisting of 12,058 live births from the year 1966 was conducted. The analysis was restricted to those 6007 cohort members who replied to a postal inquiry and participated in a health examination including blood samples at the age of 31 years. The presence of C. trachomatis-specific serum IgG antibodies was screened by a synthetic peptide-based enzyme-linked immunosorbent assay. All the positive sera were further tested by the microimmunofluorescence method using immunotype pools and individual immunotypes of C. trachomatis as antigens. An association was found between the detection of immunotype-specific C. trachomatis antibodies and subfertility both in men and women. The results of the present study confirm the serological association between past C. trachomatis infections and subfertility in male or female partners of the couple in the population-based sample.

The effects of pre-emptive epidural sufentanil on human immune function.

BACKGROUND: Surgical stress and general anaesthesia suppress immune functions, including natural killer cell (NK) activity. This suppression could be attributed, at least in part, to the effect of opiates. METHODS: Twenty patients undergoing abdominal hysterectomy received epidural sufentanil (50 microg) either before (pre-emptive) or at the end (control group) of surgery. Post-operative pain relief was provided using sufentanil from a patient-controlled epidural analgesia (PCEA) system. Systemic immunity was assessed by determining leucocyte counts, NK cell counts and activity, lymphocyte response to mitogen stimulation, and secretion of pro-inflammatory cytokines. RESULTS: In the pre-emptive group there was a significant decrease in NK activity on the first and third post-operative day (P < 0.05) compared with baseline values and on the third postoperative day (P < 0.05) compared with the control group. The number of total leucocytes and neutrophiles increased in both groups post-operatively, but no differences were found in the levels of mononuclear lymphocyte populations or in their mitogen responses. Interleukin-6 (IL-6) concentration increased in both groups after the operation. In addition, at the end of the surgery the IL-6 level was greater in the control group than in the pre-emptive group. Interleukin-1 (IL-1) levels had decreased significantly at the end of surgery and 4 h later compared with baseline levels in the pre-emptive, but not in the control group. CONCLUSIONS: Pre-emptive epidural sufentanil during combined propofol and isoflurane anaesthesia had minor effects on the immune response after hysterectomy. The lower production of pro-inflammatory cytokines (IL-1, IL-6) in the pre-emptive group compared with the control group is beneficial, but its clinical importance remains to be determined.

Chlamydia pneumoniae infection and inflammation in adults with asthma.

BACKGROUND: Chlamydia pneumoniae infection and immune response to the C. pneumoniae heat shock protein 60 (CpHsp60) have been suggested to be associated with asthma. OBJECTIVES: To study whether a slightly elevated C-reactive protein (CRP) level as a marker of low-grade systemic inflammation has a role in this association, we collected serum and sputum samples from 103 asthma patients with disease severity ranging from mild to moderate and from 30 healthy volunteers. METHODS: IgA and IgG antibodies to C. pneumoniae elementary bodies (CpEB) and CpHsp60 were measured by enzyme immunoassay. Serum CRP levels were measured with a rapid two-site ultra-sensitive assay based on time-resolved immunofluorometry. RESULTS: The asthma patients, especially those with moderate asthma, had higher serum IgA antibody levels to CpHsp60 than the healthy controls (test for trend, p = 0.05), whereas antibody levels to CpEB antigen did not differ between the study groups. CRP levels were higher in both asthma groups compared to the control group and moreover, the patients with moderate asthma had higher CRP levels than those with mild asthma (test for trend, p < 0.01). The subjects with a slightly elevated CRP level, defined as > or =1.8 mg/l, had higher CpEB IgA (p = 0.001), CpEB IgG (p = 0.008) and CpHsp60 IgA (p = 0.023) antibody levels in serum compared to the subjects with lower CRP levels. CONCLUSIONS: Slightly elevated CRP levels as a marker of low-grade systemic inflammation may be associated with C. pneumoniae infection in asthma patients.

Effect of acute Chlamydia pneumoniae infection on lipoprotein metabolism in NIH/S mice.

Chlamydia pneumoniae is a well-known cause of respiratory infections, globally. Chronic C. pneumoniae infection has been associated with atherosclerosis. The aim of the present study was to investigate the effects of acute C. pneumoniae infection on serum lipid levels and some regulatory proteins/enzymes in NIH/S mice. Female mice (n=30) were intranasally infected with 5.3*10(5) inclusion forming units (IFU) of C. pneumoniae and control mice (n = 30) were inoculated with buffer. Six uninoculated mice at day 0 and then six mice from each group 3, 6, 9, 14 and 20 days post-inoculation were killed and serum samples were collected for analysis. Successful infection was confirmed by IgG response to C. pneumoniae and positive Chlamydia cultivation from the lungs. Serum triglycerides and total cholesterol, as well as the activities of hepatic lipase (HL), lecithin-cholesterol acyltransferase (LCAT) and phospholipid transfer protein (PLTP) and the concentration of lipopolysaccharide-binding protein (LBP) were analyzed. In C. pneumoniae infected mice, a minor change in triglyceride (corrected p-value 0.020) levels was observed 9 days post-infection (p.i.). LCAT activity declined remarkably, and the lowest activities were measured on day 9 p.i. (67% from the baseline value). HL and PLTP activities did not differ from those in the control group during the whole experimental period. There was a 2.5-fold increase in the serum LBP concentration owing to the C. pneumoniae infection 9 days p.i. The data indicate that acute C. pneumoniae infection, although clinically almost asymptomatic, causes small, transient changes in serum total lipids and some key proteins involved in lipoprotein metabolism in mice.