Physical health of singleton children born after frozen embryo transfer using slow freezing: a 3-year follow-up study.

STUDY QUESTION: Are there differences in the physical health of singleton children born after frozen embryo transfer (FET) compared with children born after fresh embryo transfer (fresh ET)? SUMMARY ANSWER: Register-based health indicators were similar among FET and fresh ET singletons during a 3-year follow-up. WHAT IS KNOWN ALREADY: Large cohort studies have shown that perinatal outcomes are similar or even better in FET than fresh ET children. The early childhood morbidity among FET and fresh ET children has been shown to be quite similar, but so far these studies have been small. The short-term health outcomes of assisted reproductive technology (ART) children have been shown to be slightly worse compared with spontaneously conceived children. STUDY DESIGN, SIZE, DURATION: This register-based study includes women who had undergone ART treatments leading to singleton live births (n = 4758 children) in 1995-2006. A 10% random sample of women with spontaneous pregnancies from the Finnish Medical Birth Register (FMBR) served as the reference group (n = 31 137 children). The children were identified through the FMBR by using the mother's personal identification (ID) number. Children's ID numbers were linked with two nationwide registries; the Finnish Hospital Discharge Register and the Cause-of-Death Register at Statistics Finland. Information on all visits was received until 2009 using ICD-10 codes. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study includes 1825 children born after FET, 2933 children born after fresh ET and 31 137 children born after spontaneous pregnancies. The risk estimates for diseases were adjusted for the child's year of birth and maternal age, parity, socio-economic status and prematurity. The study focused on the differences between FET and fresh ET children. MAIN RESULTS AND THE ROLE OF CHANCE: Most health indicators were similar among FET and fresh ET children during the 3-year follow-up. The most common discharge diagnoses, including gastroenteritis and colitis, otitis, upper and lower respiratory diseases, asthma and allergies were similar between the ART groups. A large proportion of FET children (70.1%) and fresh ET children (69.9%) had visited a hospital at least once (P = 0.877). The risk of hospital admission did not differ between the two groups after adjusting for premature births [adjusted odds ratio (aOR) 1.01; 0.88-1.17]. Comparing with children born after spontaneously conceived pregnancies, the risk of hospital admission was slightly increased in the ART group, even after adjusting for premature births (aOR 1.10; 1.02-1.19). LIMITATIONS, REASONS FOR CAUTION: Due to the study design, we were not able to control for some parental background factors, such as the cause and length of infertility. Furthermore, the health registries do not include data on the growth of the children. Our findings are generalizable only to the slow-freezing method. WIDER IMPLICATIONS OF THE FINDINGS: Our study provides further evidence of the safety of embryo cryopreservation. The early physical health of FET children is similar to that of children born after fresh ET. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the University Hospital of Oulu and Helsinki, Finland. The National Institute for Health and Welfare (THL) covered the data linkages and the work of Mika Gissler. There are no competing interests to be reported.

How do changes in body mass index in infancy and childhood associate with cardiometabolic profile in adulthood? Findings from the Northern Finland Birth Cohort 1966 Study.

BACKGROUND/OBJECTIVE: Postnatal growth patterns leading to obesity may have adverse influences on future cardiometabolic health. This study evaluated age and body mass index (BMI) at infant BMI peak (BMIP) and childhood BMI rebound (BMIR) in relation to adult cardiometabolic outcomes in the Northern Finland Birth Cohort 1966. METHODS: BMI at various ages was calculated from frequent height and weight measurements obtained from child health and welfare clinical records. Age and BMI at BMIP and BMIR were derived from random effect models fitted at >0-1.5 years (N=3 265) and >1.5-13 years (N=4 121). Cardiometabolic outcomes were obtained from a clinical examination at age 31 years. Multiple regression models were used to analyse associations between the derived growth parameters and cardiometabolic outcomes. RESULTS: Age and BMI at BMIP were positively associated with adult BMI and waist circumference (WC), independently of birth weight and infant height growth (P<0.05). Later BMIR was associated with a better cardiometabolic profile: adult BMI and insulin were 14% lower, WC and triglycerides were 10% lower and the odds of metabolic syndrome (MetS) were 74% lower per 2 s.d. (1.86 years) higher age at BMIR (P<0.0001). BMI at rebound had generally weaker associations with cardiometabolic outcomes, which attenuated after adjustment for age at BMIR. CONCLUSIONS: Age and BMI at infant BMIP were associated with adult adiposity but not with other cardiometabolic outcomes. Earlier timing of BMIR was a risk factor of an adverse cardiometabolic profile, independently of early growth or BMI at rebound. Identifying growth patterns harmful to cardiovascular health will give opportunities for early interventions.

Major congenital anomalies in children born after frozen embryo transfer: a cohort study 1995-2006.

STUDY QUESTION: Is there a different risk for major congenital anomalies (CAs) in children born after frozen-thawed embryo transfer (FET) compared with children born after fresh embryo transfer (ET)? SUMMARY ANSWER: Children born after FET have a similar risk of developing major CAs as children born after fresh ET. WHAT IS KNOWN ALREADY: The perinatal outcome in children born after FET is as good as that after fresh ET. Children born as a result of assisted reproductive technology (ART) have an increased risk for CAs when compared with spontaneously conceived children, but the knowledge on the risk for CAs in specific organ systems of children born after FET is limited. STUDY DESIGN, SIZE, DURATION: This register-based cohort study includes women who have undergone ART treatments with ET leading to singleton births (n = 4772) between the years 1995 and 2006. The women were identified from the registers of the infertility clinics, and the corresponding births were matched with data from the Finnish Medical Birth Register (FMBR). The 10% random sample of women with spontaneous pregnancies from the FMBR served as the reference group (n = 31,243). The study data were linked with the Register of Congenital Malformations using the mothers' and children's personal identification numbers to get information on CAs. Furthermore, the personal identification numbers of the ART women were linked with the Register of Induced Abortions to find their selective terminations of pregnancy for severe foetal anomalies. PARTICIPANTS, SETTING, METHODS: The study was focused on singleton births and included 1830 children born after FET, 2942 children born after fresh ET and 31 243 children born after spontaneous pregnancies. Only major CAs were analysed in keeping with European Concerted Action on Congenital Anomalies and Twins. The risk estimates for CAs were adjusted for the children's year of birth and maternal age, parity and socioeconomic status. The total prevalence of major CAs was counted, including both births and selective terminations of pregnancy for major fetal anomalies (n = 33). MAIN RESULTS AND THE ROLE OF CHANCE: Among singletons at least one major CA was reported in 77 cases (4.2%) in the FET group, 132 cases (4.5%) in the fresh ET group and 994 cases (3.2%) in the reference group. The risk for at least one major CA of the children born after FET was not increased compared with the children born after fresh ET [adjusted odd ratio (aOR) 0.95; 0.71-1.27]. Furthermore, no increased risks according to the organ system affected were found between these two ART groups. When comparing the children born after ART (FET and fresh ET) with the reference group children, the risk of having at least one major CA was moderately increased in the ART group (aOR 1.24; 1.05-1.47). LIMITATIONS, REASONS FOR CAUTION: Because of the study design we were neither able to examine the aetiology of infertility nor could we compare the data with a group of subfertile women to account for the effect of infertility per se on CAs. WIDER IMPLICATIONS OF THE FINDINGS: Perinatal outcomes of FET children, including the risks for CAs, are good and comparable with outcomes of other ART children indicating that slow freezing is a safe method to use during ART treatments. STUDY FUNDING/COMPETING INTEREST(S): University Hospital of Oulu and Helsinki, Finland. THL covered the data linkages and the work of Annukka Ritvanen and Mika Gissler. There are no competing interests to be reported.

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.

Black carbon and particle lung-deposited surface area in residential wood combustion emissions: Effects of an electrostatic precipitator and photochemical aging.

Residential wood combustion (RWC) remains a significant global source of particulate matter (PM) emissions with adverse impacts on regional air quality, climate, and human health. The lung-deposited surface area (LDSA) and equivalent black carbon (eBC) concentrations have emerged as important metrics to assess particulate pollution. In this study we estimated combustion phase-dependent emission factors of LDSA for alveolar, tracheobronchial, and head-airway regions of human lungs and explored the relationships between eBC and LDSA in fresh and photochemically aged RWC emissions. Photochemical aging was simulated in an oxidative flow reactor at OH• exposures equivalent to 1.4 or 3.4 days in the atmosphere. Further, the efficiency of a small-scale electrostatic precipitator (ESP) for reducing LDSA and eBC from the wood stove was determined. For fresh emission eBC correlated extremely well with LDSA, but the correlation decreased after aging. Soot-dominated flaming phase showed the highest eBC dependency of LDSA whereas for ignition and char burning phases non-BC particles contributed strongly the LDSA. Deposition to the alveolar region contributed around 60 % of the total lung-deposition. The ESP was found as an effective method to mitigate particulate mass, LDSA, as well as eBC emissions from wood stoves, as they were reduced on average by 72%, 71%, and 69%, respectively. The reduction efficiencies, however, consistently dropped over the span of an experiment, especially for eBC. Further, the ESP was found to increase the sub-30 nm ultrafine particle number emissions, with implications for LDSA. The results of this study can be used for assessing the contribution of RWC to LDSA concentrations in ambient air.

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.

Maternal weight gain during the first half of pregnancy and offspring obesity at 16 years: a prospective cohort study.

OBJECTIVE: To assess the association between maternal gestational weight gain (GWG) during the first 20 weeks of gestation and overweight/obesity and abdominal obesity of offspring at the age of 16 years. DESIGN: A prospective cohort study. SETTING: The two northernmost provinces of Finland. POPULATION: Mothers and their adolescent offspring born from singleton pregnancies (3265 boys; 3372 girls) in the Northern Finland Birth Cohort 1986. METHODS: Maternal weight at 20 weeks of gestation was measured in municipal maternity clinics. Maternal GWG was based on the difference between the measured weight and self-reported pre-pregnancy weight, and was classified into quartiles. Offspring weight, height and waist circumference were measured by study nurses during a clinical examination. Logistic regression analyses [with and without adjustment for maternal pre-pregnancy body mass index (BMI), glucose metabolism, education level, haemoglobin, smoking status, parity, and gender of offspring] were performed. MAIN OUTCOME MEASURE: Offspring overweight/obesity, based on BMI and abdominal obesity at 16 years. RESULTS: The highest quartile of maternal weight gain (>7.0 kg during the first 20 weeks of gestation) was independently associated with BMI-based overweight/obesity and abdominal obesity in the 16-year-old offspring (OR 1.46, 95% CI 1.16-1.83, and OR 1.37, 95% CI 1.10-1.72, respectively). Among all covariates, maternal pregravid obesity showed the highest odds for both overweight/obesity and abdominal obesity (OR 4.57, 95% CI 3.18-6.57, and OR 4.43, 95% CI 3.10-6.34, respectively). CONCLUSIONS: Maternal overnutrition during the first half of gestation predicts offspring overweight/obesity and abdominal obesity in adolescence, yet a high pregravid BMI appears to be a more important determinant of both outcomes.

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.

Farming environment and prevalence of atopy at age 31: prospective birth cohort study in Finland.

BACKGROUND: Cross-sectional studies have shown an association between the farming environment and a decreased risk of atopic sensitization, mainly related to contact with farm animals in the childhood. OBJECTIVE: Investigate the association of a farming environment, especially farm animal contact, during infancy, with atopic sensitization and allergic diseases at the age of 31. METHODS: In a prospective birth cohort study, 5509 subjects born in northern Finland in 1966 were followed up at the age of 31. Prenatal exposure to the farming environment was documented before or at birth. At age 31, information on health status and childhood exposure to pets was collected by a questionnaire and skin prick tests were performed. RESULTS: Being born to a family having farm animals decreased the risk of atopic sensitization [odds ratio (OR) 0.67; 95% confidence interval (CI) 0.56-0.80], atopic eczema ever (OR 0.77; 95% CI 0.66-0.91), doctor-diagnosed asthma ever (OR 0.74; 95% CI 0.55-1.00), allergic rhinitis at age 31 (OR 0.87; 95% CI 0.73-1.03) and allergic conjunctivitis (OR 0.86; 95% CI 0.72-1.02) at age 31. There was a suggestion that the reduced risk of allergic sensitization was particularly evident among the subjects whose mothers worked with farm animals during pregnancy, and that the reduced risk of the above diseases by farm animal exposure was largely explained by the reduced risk of atopy. Having cats and dogs in childhood revealed similar associations as farm animals with atopic sensitization. CONCLUSION AND CLINICAL RELEVANCE: Contact with farm animals in early childhood reduces the risk of atopic sensitization, doctor-diagnosed asthma and allergic diseases at age 31.

Perinatal outcome of children born after frozen and fresh embryo transfer: the Finnish cohort study 1995-2006.

BACKGROUND: The number of children born after frozen embryo transfer (FET) is steadily rising. However, studies on obstetric and perinatal outcomes are limited. Our primary aim was to compare the perinatal health of children born after FET and fresh embryo transfer, and to use data from children born after spontaneous conception as a reference. METHODS: In a register-based cohort study we evaluated the obstetric and perinatal outcomes of children born after FET (n = 2293), fresh embryo transfer (n = 4151) and those born after spontaneous pregnancy (reference group; n = 31 946). Data were collected from the registers of two infertility outpatient clinics, two university hospitals and the Finnish Medical Birth Register (1995-2006). RESULTS: After adjusting for confounding factors the FET group showed decreased risks of preterm birth [adjusted odd ratio (AOR) 0.83, 95% confidence interval (CI) 0.71-0.97], low birthweight (AOR 0.74; 0.62-0.88) and being small for gestational age (AOR 0.63; 0.49-0.83) compared with the fresh embryo transfer group. Mean birthweight was 134 g higher in the FET singletons versus the fresh embryo transfer singletons (P< 0.0001). When FET singletons were compared with the reference group, increased risks of preterm birth (AOR 1.45; 1.25-1.68) and low birthweight (AOR 1.22; 1.03-1.45) and a decreased risk of being small for gestational age (AOR 0.71; 0.54-0.92) were found. No excess of perinatal and infant mortality occurred between the groups. CONCLUSIONS: Embryo freezing does not adversely affect perinatal outcome in terms of prematurity, low birthweight and being small for gestational age versus the fresh embryo transfer and the outcome is similar or even better, particularly regarding fetal growth. Our study, which is one of the largest on FET pregnancies, provides further evidence on the safety of FET.

Common genetic variation near MC4R is associated with eating behaviour patterns in European populations.

Both rs17782313 (near MC4R) and rs1421085 (FTO) polymorphisms have been consistently associated with increased risk of obesity and with body mass index (BMI) variation. An effect of both polymorphisms on satiety has recently been suggested. We genotyped rs17782313 and rs1421085 in 5764 relatives from 1109 French pedigrees with familial obesity, 1274 Swiss class III obese adults as well as in 4877 French adults and 5612 Finnish teenagers from two randomly selected population cohorts. In all subjects, eating behaviour traits were documented through questionnaires. We first assessed the association of both single nucleotide polymorphisms with BMI and then studied eating behaviour. Under an additive model, the rs17782313-C MC4R allele showed a trend towards higher percentages of snacking in both French obese children (P=0.01) and Swiss obese adults (P=0.04) as well as in adolescents from the Finnish general population (P=0.04). In French adults with familial obesity, this allele tended to be also associated with a higher Stunkard hunger score (P=0.02) and in obese children with a higher prevalence of eating large amounts of food (P=0.04). However, no consistent association of the FTO rs1421085-C allele and available eating behaviour trait was found in our studied populations. The rs17782313-C allele nearby MC4R may modulate eating behaviour-related phenotypes in European obese and randomly selected populations, in both children and adults, supporting a regulatory role of this genetic variant on eating behaviour, as previously shown for MC4R non-synonymous loss-of-function mutations. The potential effect of the obesity-associated FTO gene on eating behaviour deserves additional investigation.

Treating miscarriages: a randomised study of cost-effectiveness in medical or surgical choice.

OBJECTIVE: The aim was to carry out a cost effectiveness analysis (CEA) of medical and surgical treatment of miscarriage using quantitative and qualitative indicators. DESIGN: A prospective study where the data of the clinical course of the treatment and the patients; experiences (pain and satisfaction) were collected from a previous randomised study. SETTING: Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu, Finland. POPULATION: Ninety-eight eligible women with a diagnosed miscarriage. METHODS: The incremental cost-effectiveness ratio (ICER) was calculated by using institutional prices (provider's aspect) of the medical care and the number of patients who experienced pain, dissatisfaction or unsuccessful treatment while treated for the miscarriage. MAIN OUTCOME MEASURES: Primary (uncomplicated treatment) and secondary (complications and other unplanned events) costs of the treatments. RESULTS: Primary costs of the surgical treatment were higher, but the more frequent unplanned events and complications in the medical group brought the costs to the same level. In the medical group, based on the ICER, 12 patients more experienced pain, 7 patients more were dissatisfied with the treatment and 5 patients more had unsuccessful treatment compared with surgically treated patients. In theory, these negative outcomes could have been avoided by investing euro1688 more in the surgical treatment. CONCLUSIONS: Medical treatment of miscarriage was not more cost-effective, when the adverse events were considered. As neither of these two methods was economically superior, the treatment choice should be made on an individual basis by respecting the patient's choice.

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.

High birth weight, asthma and atopy at the age of 16 yr.

The association between high birth weight and asthma has been suggested. The Northern Finland Birth Cohort 1986, a longitudinal cohort originally including 9479 participants, has been followed up since birth until the age of 16 yr. Using the data of this study, we analyzed the association of high birth weight with asthma and atopic sensitization at the age of 16 yr. The analysis included the 5995 subjects with complete skin prick test data and the 5500 subjects with data on doctor-diagnosed asthma (written questionnaire) at the age of 16 yr. Atopy was defined as at least one positive skin prick test reaction, which definition was also used to separate atopic and non-atopic asthma. There was a significant association between high birth weight (>4510 g) and asthma among the atopic subjects (OR 2.40, 95% CI 1.33-4.32). When looking at atopy, the highest risk was observed among the subjects with highest birth weight category (>4510 g) (OR 1.44, 95% CI 1.05-1.97) and the adjacent (4200-4500 g) birth weight category (OR 1.24, 95% CI 1.01-1.53), when compared with the reference category (2500-3340 g). Our results support the notion that high birth weight is associated with an increased risk of asthma and suggest that the association is mostly explained by an increased risk of atopy. The biological mechanisms behind the associations are unknown, but they could be related to obesity.

Does vitamin D supplementation in infancy reduce the risk of pre-eclampsia?

Vitamin D has been suggested to affect the balance between T helper (Th1) and (Th2) type cytokines by favouring Th2 domination. We investigated the association between infant vitamin D supplementation and later pre-eclampsia, a disorder suggested to be dominated by Th1 response. We used data on 2969 women born in the Northern Finland Birth Cohort 1966 of whom 68 (2.3%) had pre-eclampsia in their first pregnancy. Risk of pre-eclampsia was halved (OR 0.49, 95% confidence interval (CI) 0.26-0.92) in participants who had received vitamin D supplementation regularly during the first year of life and this association was not affected by adjustment for own birth order, birth weight, gestational age, social class in 1966 and hospitalizations or pregnancy-induced hypertension of their mothers. Together with earlier observations on a reduced risk of type 1 diabetes after vitamin D supplementation, these data suggest that vitamin D intake in infancy may affect long-term programming of the immune response pattern.

Does parity affect mortality among parous women?

OBJECTIVE: To find out whether there is an association between parity and mortality. DESIGN: Prospective cohort study. SETTING: Northern Finland, 1966-2001. PARTICIPANTS AND METHODS: 12,055 women in the two northernmost provinces of Finland were followed up from pregnancy in 1966-2001, the coverage percentage being 96%. The data on age, smoking, body mass index, socioeconomic position, age at menarche and age at first birth were collected during pregnancy, and data on deaths were obtained from the National Cause of Death Statistics, maintained by Statistics Finland. The Cox proportional hazard model was used to estimate relative mortality between parity groups. RESULTS: Total mortality was lowest among the women with 2-4 children (reference group). High parity was associated with an up to twofold risk of mortality from vascular complications, but after adjustment for all background factors, this significance disappeared. Mortality from haemorrhagic stroke was fourfold higher among the women with > or = 10 births compared with those of the reference group. No differences in cerebral infarction or total cancer mortality were seen between the groups. Primiparity was associated with increased mortality from accidental death (relative risk 2.6, 95% confidence interval 1.6 to 4.4). CONCLUSIONS: High parity was associated with an increased risk of mortality from vascular complications, especially haemorrhagic stroke, and primiparity with an increased risk of accidental death.

Schizophrenia as a long-term outcome of pregnancy, delivery, and perinatal complications: a 28-year follow-up of the 1966 north Finland general population birth cohort.

OBJECTIVE: The 1966 North Finland general population birth cohort was studied to determine whether abnormalities during pregnancy, delivery, and the neonatal period are associated with adult-onset schizophrenia. METHOD: The authors included all 11,017 subjects alive in Finland at age 16. For each individual, standardized assessments made during pregnancy, delivery, and infancy were linked to national psychiatric case registers covering the period up to age 28. Subjects with DSM-III-R schizophrenia were identified by using a two-stage screen that included perusal of individual case records. Associations (adjusted odds ratios) between schizophrenia and specific pregnancy, delivery, and neonatal characteristics were calculated. RESULTS: Within this cohort, 76 cases of DSM-III-R schizophrenia arose by age 28 years; 51 (67.1%) of these persons were men. Demographic characteristics and previous obstetric histories of the mothers were similar in the case and unaffected comparison groups, although the former were more likely to have been more depressed than usual during pregnancy. Low birth weight (< 2500 g) and the combination of low birth weight and short gestation (< 37 weeks) were more common among the schizophrenic subjects. Being small for gestational age (< 10th percentile) was not more common. Of 125 survivors of severe perinatal brain damage, six (4.8%) later developed schizophrenia. CONCLUSIONS: The spectrum of adverse outcomes after fetal and perinatal insults unfolded beyond childhood and included adult-onset schizophrenia. The findings have implications for understanding the mechanisms involved in the development of schizophrenia and, possibly, for its prevention.

Use of psychotropic drugs and pregnancy outcome.

This study reports the use of psychotropic drugs and pregnancy outcome in a prospective survey carried out in northern Finland in 1985-1986, consisting of 7933 pregnant women and their 8030 births. Of the mothers, 120 (1.5%) used psychotropic drugs during pregnancy and of them 26 (0.3% of the total) used these drugs before and during the pregnancy. According to the logistic regression analysis, the biological and social background variables associating significantly with the use of these drugs were maternal advanced age and multiparity (> 35 years and > 4 parous), overweight (body mass index > the 90th percentile), smoking, alcohol use, belonging to social class IV, and failure to ensure contraception. The users needed hospital observation significantly more often during pregnancy (regular users, 80.8%; occasional users, 38.3; nonusers, 27.4%) and the adjustment of the background variables did not change this result. Of the pregnancy complications bleeding was significantly more common among users than nonusers (23.3 vs. 13.2%) and this difference was not explained by difference in background variables. The mean birth weight of infants of the regular users was significantly lower (255 g) when background variables were standardized by linear regression analysis. No association of increased number of birth defects was found with usage of psychotropic drugs.

Maternal infections in pregnancy and the development of asthma among offspring.

BACKGROUND: Previous studies have suggested that asthma phenotype could probably be programmed before birth. The current study examined the impact of maternal vaginitis and febrile infections during pregnancy on the subsequent development of asthma among children. METHODS: The analyses were based on 8088 children from the northern Finland birth cohort, 1985-1986. RESULTS: The prevalence of asthma at age 7 was 3.5%. Children had a higher risk of asthma if their mothers experienced vaginitis and febrile infections during pregnancy, odds ratio (OR) = 1.41, (95% CI: 1.08-1.84) and 1.65 (95% CI: 1.25-2.18), respectively, after adjusting for other covariates. There was a clear time trend in risk of childhood asthma corresponding to the timing of maternal febrile infections in pregnancy. The adjusted OR for the first, second and third trimesters were 2.08 (95% CI: 1.13-3.82), 1.73 (95% CI: 1.09-2.75) and 1.44 (95% CI: 0.97-2.15), respectively. Maternal history of allergic diseases, birthweight <2500 g and male gender also seemed to be risk factors for childhood asthma. CONCLUSIONS: Our results suggest that further investigation of the relation of maternal infections during pregnancy to asthma among children seems warranted.

Midtrimester N-terminal proatrial natriuretic peptide, free beta hCG, and alpha-fetoprotein in predicting preeclampsia.

OBJECTIVE: To determine whether maternal midtrimester serum N-terminal peptide of proatrial natriuretic peptide, free beta subunit of human chorionic gonadotropin (hCGbeta), or alpha-fetoprotein (AFP) levels can predict preeclampsia. METHODS: A population-based cohort included 1037 nulliparous women, of whom 637 (61%) participated in a maternal serum Down syndrome screening program. Measurements of hCGbeta, AFP, and N-terminal peptide of proatrial natriuretic peptide were made from maternal serum collected at 15-19 weeks' gestation. Sensitivity, specificity, and predictive values were calculated for elevated AFP (at least 2.0 multiples of the median [MoM]) and hCGbeta (at least 2.0 MoM) values. RESULTS: No difference was found in the concentrations of the N-terminal peptide of proatrial natriuretic peptide among the 30 women in whom preeclampsia developed later (median 270 [range 142-604] pmol/L) compared with 536 women who remained normotensive (274 [51-2626] pmol/L). The sensitivity and specificity of elevated AFP in predicting preeclampsia were 3% and 98% and those of elevated hCGbeta were 20% and 84%, respectively. When a stepwise multiple logistic regression model was used, only mean arterial pressure was an independent risk factor in predicting preeclampsia. CONCLUSION: Determinations of the proposed new marker N-terminal peptide of proatrial natriuretic peptide, as well as serum hCGbeta or AFP, are not helpful in predicting preeclampsia.