Objective To compare the effects of continuous use of oral (OC), transdermal, and vaginal combined contraceptives on the pituitary-ovarian axis and inhibition of follicular development. Design ...Spin-off study of a prospective, randomized trial. Setting University clinic. Patient(s) Forty-two of 54 healthy women completed the study. Intervention(s) Treatment with combined OCs (ethinyl E2 EE and desogestrel), transdermal patches (EE and norelgestromin), or vaginal rings (EE and etonogestrel) for 9 weeks continuously. Blood sampling was performed before and at 5 and 9 weeks of treatment. Main Outcome Measure(s) Changes in serum hormone levels induced by combined contraceptives. Result(s) Serum antimüllerian hormone (AMH), FSH, inhibin B, LH, and E2 levels had decreased significantly in all study groups after 9 weeks of treatment. Significant declines were already detected after 5 weeks' use of combined contraceptives with regard to all hormone levels apart from those of serum AMH, where the decrease between baseline and 5 weeks was only moderate. Between groups, serum levels of AMH, inhibin B, LH, and E2 were comparable at baseline and after 5 and 9 weeks of treatment. Conclusion(s) The decrease of serum AMH levels during the use of all combined contraceptives indicates that folliculogenesis is arrested independently of administration route. Clinical Trial Registration Number NCT01087879.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective To compare the metabolic profiles of normo- and hyperandrogenic women with polycystic ovary syndrome (PCOS) with those of control women at different ages during reproductive life. Design ...Case-control study. Setting Not applicable. Patient(s) In all, 1,550 women with normoandrogenic (n = 686) or hyperandrogenic (n = 842) PCOS and 447 control women were divided into three age groups: <30, 30–39, and >39 years). Interventions(s) None. Main Outcome Measure(s) Body mass index (BMI), waist circumference, blood pressure, glucose, insulin, cholesterol, lipoproteins, triglycerides and high-sensitivity C-reactive protein. Result(s) Both normo- and hyperandrogenic women with PCOS were more obese, especially abdominally. They had increased serum levels of insulin (fasting and in oral glucose tolerance tests), triglycerides, low-density lipoprotein, and total cholesterol, higher blood pressure, and lower high-density lipoprotein levels independently from BMI compared with the control population as early as from young adulthood until menopause. The prevalence of metabolic syndrome was two- to fivefold higher in women with PCOS compared with control women, depending on age and phenotype, and the highest prevalence was observed in hyperandrogenic women with PCOS at late reproductive age. Conclusion(s) When evaluating metabolic risks in women with PCOS, androgenic status, especially abdominal obesity and age, should be taken into account, which would allow tailored management of the syndrome from early adulthood on.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Adolescents and adults born as small preterm infants show more pronounced risk factors of cardiovascular disease. Whether similar risks apply across all degrees of preterm birth is poorly known.
We ...studied the association between preterm birth and cardiovascular risk factors in 6642 16-year-old adolescents of the population-based Northern Finland Birth Cohort 1986. Of these, 79 (1.2%) were born at <34 gestational weeks (early preterm), 238 (3.6%) at 34 to 36 weeks (late preterm), and 6325 at term (controls).
Girls born early preterm had 6.7 mm Hg (95% confidence interval: 3.1-10.2) higher systolic blood pressure (BP) and 3.5 mm Hg (1.1-5.8) higher diastolic BP, but no difference in serum lipid levels compared with control girls. Boys showed no differences in BP, but boys born early preterm had 6.7% (0.2%-13.7%) higher total cholesterol, 11.7% (2.1%-22.3%) higher low-density lipoprotein cholesterol, and 12.3% (3.1%-22.4%) higher apolipoprotein B concentrations. The differences were similar (BP) or stronger (lipids) when adjusted for maternal smoking, birth weight SD score, parental education, pubertal stage, BMI, and lifestyle. There were similar associations with length of gestation as a continuous variable. Accordingly, mean differences between late preterm and controls were in the same direction but weaker, although most were not statistically significant.
Preterm birth was associated with elevated BP in adolescent girls and an atherogenic lipid profile in boys. Because these associations were strongest among those born early preterm, our findings are consistent with a dose-response relationship between shorter length of gestation and cardiovascular risk factors.
Genome-wide association studies (GWAS) of longitudinal birth cohorts enable joint investigation of environmental and genetic influences on complex traits. We report GWAS results for nine quantitative ...metabolic traits (triglycerides, high-density lipoprotein, low-density lipoprotein, glucose, insulin, C-reactive protein, body mass index, and systolic and diastolic blood pressure) in the Northern Finland Birth Cohort 1966 (NFBC1966), drawn from the most genetically isolated Finnish regions. We replicate most previously reported associations for these traits and identify nine new associations, several of which highlight genes with metabolic functions: high-density lipoprotein with NR1H3 (LXRA), low-density lipoprotein with AR and FADS1-FADS2, glucose with MTNR1B, and insulin with PANK1. Two of these new associations emerged after adjustment of results for body mass index. Gene-environment interaction analyses suggested additional associations, which will require validation in larger samples. The currently identified loci, together with quantified environmental exposures, explain little of the trait variation in NFBC1966. The association observed between low-density lipoprotein and an infrequent variant in AR suggests the potential of such a cohort for identifying associations with both common, low-impact and rarer, high-impact quantitative trait loci.
Full text
Available for:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Context: Knowledge is scarce concerning the significance of thyroid dysfunction/antibodies during pregnancy in regard to pregnancy complications/later maternal morbidity.
Objective: The aim of this ...study was to evaluate the association between maternal thyroid dysfunction/antibodies during pregnancy and pregnancy complications or later maternal hypertension, diabetes, and thyroid disease.
Design and Setting: We studied a prospective population-based cohort, Northern Finland Birth Cohort 1986 (NFBC 1986), with follow-up of 20 yr. Medication and hospital discharge records were used to assess maternal morbidity to hypertension, diabetes, and thyroid diseases.
Participants: The study consisted of mothers of NFBC 1986 with early pregnancy serum samples for thyroid function and antibody analyses (n = 5805). Mothers were grouped and compared according to these test results.
Main Outcome Measures: We focused on preeclampsia and gestational diabetes during index pregnancy, later maternal hypertension, diabetes, and thyroid disease morbidity and total mortality.
Results: Thyroid dysfunction and antibodies were not associated with pregnancy complications. Overt hypothyroidism was associated with subsequent maternal thyroid disease hazard ratio (HR) (95% confidence interval), 17.7 (7.8–40.6) and diabetes 6.0 (2.2–16.4). Subclinical hypothyroidism 3.3 (1.6–6.9), TPO-Ab-positivity 4.2 (2.3–7.4), and TG-Ab-positivity 3.3 (1.9–6.0) were also associated with later thyroid disease. No association was found between thyroid dysfunction/antibodies and hypertension or overall mortality.
Conclusions: Thyroid dysfunction and antibodies during pregnancy seem to predict later thyroid disease. Overt hypothyroidism poses risk of diabetes.
Thyroid dysfunction and antibodies during pregnancy seem to predict later maternal morbidity to thyroid diseases.
Low grade inflammation is associated with many noncommunicable diseases. The association between skin diseases in general and systemic inflammation has not previously been studied at the population ...level. A whole-body investigation on 1,930 adults belonging to Northern Finland Birth Cohort 1966 was performed and high sensitive C-reactive protein (CRP) level was measured as a marker of low grade inflammation in order to determine the association between low grade inflammation and skin diseases in an unselected adult population. After adjustment for confounding factors the following skin disorders were associated with low grade inflammation in multinomial logistic regression analysis: atopic eczema (OR 2.2, 95% CI 1.2-3.9), onychomycosis (OR 2.0, 1.2-3.2) and rosacea (OR 1.7, 1.1-2.5). After additionally adjusting for body mass index and systemic diseases, the risks for atopic eczema (OR 2.4, 1.3-4.6) and onychomycosis (OR 1.9, 1.1-3.1) remained statistically significant. In conclusion, low grade inflammation is present in several skin diseases.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Prevention of obesity should start as early as possible after birth. We aimed to build clinically useful equations estimating the risk of later obesity in newborns, as a first step towards focused ...early prevention against the global obesity epidemic.
We analyzed the lifetime Northern Finland Birth Cohort 1986 (NFBC1986) (N = 4,032) to draw predictive equations for childhood and adolescent obesity from traditional risk factors (parental BMI, birth weight, maternal gestational weight gain, behaviour and social indicators), and a genetic score built from 39 BMI/obesity-associated polymorphisms. We performed validation analyses in a retrospective cohort of 1,503 Italian children and in a prospective cohort of 1,032 U.S. children.
In the NFBC1986, the cumulative accuracy of traditional risk factors predicting childhood obesity, adolescent obesity, and childhood obesity persistent into adolescence was good: AUROC = 0·780·74-0.82, 0·750·71-0·79 and 0·850·80-0·90 respectively (all p<0·001). Adding the genetic score produced discrimination improvements ≤1%. The NFBC1986 equation for childhood obesity remained acceptably accurate when applied to the Italian and the U.S. cohort (AUROC = 0·700·63-0·77 and 0·730·67-0·80 respectively) and the two additional equations for childhood obesity newly drawn from the Italian and the U.S. datasets showed good accuracy in respective cohorts (AUROC = 0·740·69-0·79 and 0·790·73-0·84) (all p<0·001). The three equations for childhood obesity were converted into simple Excel risk calculators for potential clinical use.
This study provides the first example of handy tools for predicting childhood obesity in newborns by means of easily recorded information, while it shows that currently known genetic variants have very little usefulness for such prediction.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims Low-grade inflammation might mediate associations between size at birth, early life growth, excessive weight gain, and subsequent risk of cardiovascular disease in adult life. Our aim was to ...investigate relationships between fetal growth, weight over the life course, and low-grade inflammation measured by serum high sensitivity C-reactive protein (CRP) levels at 31 years. Methods and results General population-based northern Finland 1966 Birth Cohort study of 5840 participants attending a clinical examination at 31 years, including measurement of CRP. Weight and height were assessed at birth, 12 months, and 14 and 31 years of age. CRP levels at 31 years were 16% 95% confidence interval (CI) 8, 23 higher per 1 kg lower birth weight, 21% (95% CI 2, 37) higher per 10 cm lower birth length, and 24% (95% CI 10, 36) higher per 1 kg/m3 lower ponderal index, after adjustment for potential confounders. Participants with highest tertile body mass index (BMI) at 31 years and lowest tertile birth weight had the highest average CRP levels. Per unit increase in BMI from 14 to 31 years was associated with 16% (95% CI 14, 17) higher CRP levels; the association was larger for those in the top BMI tertile at age 14 years. Conclusion Systemic low-grade inflammation may lie on the causal pathway that relates impaired fetal growth and weight gain from childhood to adulthood to adverse adult cardiovascular health. Lifestyle changes from early life might be an important step in reducing cardiovascular risk in adults.
Diabetes is undiagnosed disease and easy screening tools for it are warranted. Because foot complications are usual in diabetes, we aimed to test hypothesis that skin abnormalities are found already ...from patients who are not aware of having diabetes, by studying the possible association between unhealthy toe web skin and abnormal glucose metabolism. 1,849 cases without previously diagnosed diabetes participated to the 46-year follow-up study of the Northern Finland Birth Cohort. A skin investigation was performed for all, and abnormal skin findings in toe web spaces were taken as explanatory variables. Abnormal glucose tolerance was the main outcome and it was tested with an oral glucose tolerance test (OGTT), glycosylated haemoglobin fraction (HbA
) Values are numbers (percentages) of sub and fasting blood glucose. The participants who had any abnormal skin findings in toe webs were associated with 2.5-fold (OR 2.5, 95% CI 1.3-4.9) and 6-fold (OR 6.2, 1.4-27.6) increased risk of having previously undiagnosed diabetes detected by a 2-hour OGTT and HbA
, respectively. The predictive power of toe web findings was comparable with FINDRISC score. Abnormal skin findings in the toe webs show increased risk of occult diabetes, and may, thus serve as an additional sign of undiagnosed diabetes.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
