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1.
Diabetes Care ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601636

RESUMO

OBJECTIVE: Maternal gestational diabetes mellitus (GDM) has been associated with adverse outcomes in the offspring. Growing evidence suggests that the epigenome may play a role, but most previous studies have been small and adjusted for few covariates. The current study meta-analyzed the association between maternal GDM and cord blood DNA methylation in the Pregnancy and Childhood Epigenetics (PACE) consortium. RESEARCH DESIGN AND METHODS: Seven pregnancy cohorts (3,677 mother-newborn pairs [317 with GDM]) contributed results from epigenome-wide association studies, using DNA methylation data acquired by the Infinium HumanMethylation450 BeadChip array. Associations between GDM and DNA methylation were examined using robust linear regression, with adjustment for potential confounders. Fixed-effects meta-analyses were performed using METAL. Differentially methylated regions (DMRs) were identified by taking the intersection of results obtained using two regional approaches: comb-p and DMRcate. RESULTS: Two DMRs were identified by both comb-p and DMRcate. Both regions were hypomethylated in newborns exposed to GDM in utero compared with control subjects. One DMR (chr 1: 248100345-248100614) was located in the OR2L13 promoter, and the other (chr 10: 135341870-135342620) was located in the gene body of CYP2E1. Individual CpG analyses did not reveal any differentially methylated loci based on a false discovery rate-adjusted P value threshold of 0.05. CONCLUSIONS: Maternal GDM was associated with lower cord blood methylation levels within two regions, including the promoter of OR2L13, a gene associated with autism spectrum disorder, and the gene body of CYP2E1, which is upregulated in type 1 and type 2 diabetes. Future studies are needed to understand whether these associations are causal and possible health consequences.

2.
Mech Ageing Dev ; 183: 111145, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31491428

RESUMO

Telomere length has been suggested a biomarker of aging and is associated with several chronic diseases. However, the association between telomere length and physical performance is not well known. Using both cross-sectional and longitudinal data, we studied 582 women and 453 men from the Helsinki Birth Cohort Study at two time-points; a baseline examination in 2001-2004 at a mean age of 61 years and a follow-up examination approximately 10 years later in 2011-2013. Telomere length was measured both at baseline and at follow-up using real-time quantitative polymerase chain reaction. Physical performance was evaluated only at follow-up using the Senior Fitness Test (SFT), which assesses strength, flexibility and endurance. In women, shorter telomere length at follow-up (p = 0.044) and greater telomere attrition during follow-up time (p = 0.022) were associated with poorer physical performance after adjusting for covariates (age at baseline, smoking status, body mass index at baseline, follow-up time and educational attainment). No similar associations were found for men. This indicates that, at least in women, telomere length could potentially be used as a biomarker for physical performance, however, more longitudinal studies are needed to confirm this association.

3.
PLoS One ; 14(8): e0221549, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31465425

RESUMO

AIMS: Gestational diabetes (GDM) is often accompanied by maternal overweight. Our aim was to evaluate the separate and concomitant effects of GDM and maternal overweight/obesity on perinatal outcomes. METHODS: We used the Finnish Medical Birth Register to identify all 24,577 women with a singleton pregnancy who delivered in 2009 in Finland and underwent an oral glucose tolerance test (OGTT). Women were divided into groups according to the result of OGTT (GDM/no GDM) and pre-pregnancy body mass index (BMI): normal weight (≤24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (≥30.0 kg/m2). Primary outcomes included macrosomia, caesarean delivery, and treatment at neonatal ward. Normal weight women without GDM constituted the reference group. RESULTS: Compared to reference group, overweight or obese women without GDM had an increased risk of macrosomia [odds ratio adjusted for age, parity, smoking and socio-economic status (aOR)1.18 (95% CI 1.09-1.28) and 1.50 (95% CI 1.19-1.88)], and caesarean delivery [aORs 1.17 (95% CI 1.07-1.28) and 1.52 (95% CI 1.37-1.69)], respectively. In normal weight GDM women the risk of macrosomia [aOR 1.17 (95% CI 0.85-1.62)] and caesarean delivery [aOR 1.10 (95% CI 0.96-1.27)] was not significantly increased as compared to normal weight women without GDM. GDM increased the risk of treatment at neonatal ward in all BMI categories and maternal obesity without GDM was also a risk factor for treatment at neonatal ward. Interaction p values between BMI and GDM on these outcomes were <0.001. CONCLUSIONS: Maternal overweight and obesity without GDM increased the risk of macrosomia and caesarean delivery when compared to the reference group. These risks were amplified when overweight/obesity was accompanied by GDM. Obesity without GDM was a risk factor for treatment at neonatal ward; GDM increased this risk in all BMI categories. Our results suggest that especially maternal obesity should be considered as a risk factor for adverse pregnancy outcomes and GDM further amplifies this risk.

4.
J Pediatr ; 214: 89-95.e3, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31399247

RESUMO

OBJECTIVE: To evaluate postexercise heart rate recovery (HRR) in adults born preterm. STUDY DESIGN: We studied the association between preterm birth and postexercise HRR in 545 adults (267 women) at 23.3 years of age (range 19.9-26.3 years). One hundred three participants were born early preterm (<34 completed weeks), 178 late preterm (34-36), and 264 were full term (control group). HRR was calculated as change in heart rate (HR) 30 seconds and 60 seconds after cessation of submaximal step test and maximum HR slope during the first minute after. RESULTS: Mean peak HR was 159.5 bpm in the early preterm (P = .16 with controls), 157.8 bpm in the late preterm (P = .56), and 157.0 bpm in the control group. Mean HRR 30 seconds after exercise was 3.2 bpm (95% CI 1.1-5.2) lower in the early preterm group and 2.1 bpm (0.3-3.8) lower in the late preterm group than the full term controls. Mean 60s HRR was 2.5 (-0.1 to 5.1) lower in the early preterm group and 2.8 bpm (0.6-4.9) lower in the late preterm group. Mean maximum slope after exercise was 0.10 beats/s (0.02-0.17) lower in the early preterm group and 0.06 beats/s (0.00-0.12) lower in the late preterm group. CONCLUSIONS: Our results suggest reduced HRR after exercise in adults born preterm, including those born late preterm. This suggests altered reactivation of the parasympathetic nervous system, which may contribute to cardiovascular risk among adults born preterm.

5.
Psychol Med ; : 1-13, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31439060

RESUMO

BACKGROUND: Maternal depression during pregnancy increases the risk for adverse developmental outcomes in children. However, the underpinning biological mechanisms remain unknown. We tested whether depression was associated with levels of and change in the inflammatory state during pregnancy, if early pregnancy overweight/obesity or diabetes/hypertensive pregnancy disorders accounted for/mediated these effects, and if depression added to the inflammation that typically accompanies these conditions. METHODS: We analyzed plasma high-sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls at three consecutive stages during pregnancy, derived history of depression diagnoses before pregnancy from Care Register for Healthcare (HILMO) (N = 375) and self-reports (N = 347) and depressive symptoms during pregnancy using the Center for Epidemiological Studies Depression Scale completed concurrently to blood samplings (N = 295). Data on early pregnancy body mass index (BMI) and diabetes/hypertensive pregnancy disorders came from medical records. RESULTS: Higher overall hsCRP levels, but not change, during pregnancy were predicted by history of depression diagnosis before pregnancy [HILMO: mean difference (MD) = 0.69 standard deviation (s.d.) units; 95% confidence interval (CI) 0.26-1.11, self-report: MD = 0.56 s.d.; 95% CI 0.17-0.94] and higher depressive symptoms during pregnancy (0.06 s.d. per s.d. increase; 95% CI 0.00-0.13). History of depression diagnosis before pregnancy also predicted higher overall glycoprotein acetyls (HILMO: MD = 0.52 s.d.; 95% CI 0.12-0.93). These associations were not explained by diabetes/hypertensive disorders, but were accounted for and mediated by early pregnancy BMI. Furthermore, in obese women, overall hsCRP levels increased as depressive symptoms during pregnancy increased (p = 0.006 for interaction). CONCLUSIONS: Depression is associated with a proinflammatory state during pregnancy. These associations are mediated by early pregnancy BMI, and depressive symptoms during pregnancy aggravate the inflammation related to obesity.

6.
Sci Rep ; 9(1): 9439, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31263163

RESUMO

Type 2 diabetes (T2D) affects the health of millions of people worldwide. The identification of genetic determinants associated with changes in glycemia over time might illuminate biological features that precede the development of T2D. Here we conducted a genome-wide association study of longitudinal fasting glucose changes in up to 13,807 non-diabetic individuals of European descent from nine cohorts. Fasting glucose change over time was defined as the slope of the line defined by multiple fasting glucose measurements obtained over up to 14 years of observation. We tested for associations of genetic variants with inverse-normal transformed fasting glucose change over time adjusting for age at baseline, sex, and principal components of genetic variation. We found no genome-wide significant association (P < 5 × 10-8) with fasting glucose change over time. Seven loci previously associated with T2D, fasting glucose or HbA1c were nominally (P < 0.05) associated with fasting glucose change over time. Limited power influences unambiguous interpretation, but these data suggest that genetic effects on fasting glucose change over time are likely to be small. A public version of the data provides a genomic resource to combine with future studies to evaluate shared genetic links with T2D and other metabolic risk traits.

7.
Scand J Med Sci Sports ; 29(11): 1797-1804, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31206811

RESUMO

The aim of the study was to examine the association between change in leisure-time physical activity (LTPA) and change in health-related quality of life (HRQoL) and symptoms of depression during a 10-year follow-up. This prospective study included 1036 men and women (mean age at baseline = 61.2 years) from the Helsinki Birth Cohort Study. Leisure-time physical activity was measured with a questionnaire, HRQoL with SF36 and depression symptoms with Beck's depression inventory (BDI). The association between the change in LTPA and change in HRQoL and BDI were investigated with sex-stratified general linear models adjusted for age, smoking, educational attainment, comorbidity score, and baseline value of outcomes. One standard deviation (SD) increase in LTPA was associated with increase in physical summary component of HRQoL in women (B = 0.7 unit, 95% CI = 0.1-1.3, P = 0.032) and in men (B = 0.8 unit, 95% CI = 0.2-1.5, P = 0.014). In women, the 1SD increase in LTPA was also associated with an increase in mental summary component score (B = 1.0, 95% CI = 0.3-1.7, P = 0.005) and a reduction in depressive symptoms (B = -0.7, 95% CI = -1.1 to -0.2, P = 0.003). In conclusion, increase in the volume of LTPA over a 10-year period in late adulthood was associated with improved HRQoL in both men and women, and also diminished depressive symptoms in women. The findings support the promotion of physical activity in later years to enhance HRQoL and mental well-being.

8.
Nat Commun ; 10(1): 2548, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31186427

RESUMO

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.


Assuntos
Metilação de DNA/genética , DNA/sangue , Interação Gene-Ambiente , Estudos de Coortes , Epigênese Genética , Feminino , Sangue Fetal , Genótipo , Humanos , Recém-Nascido , Masculino , Gravidez , Fatores de Risco
9.
Lancet Respir Med ; 7(8): 677-686, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31078498

RESUMO

BACKGROUND: Maximal expiratory airflow peaks early in the third decade of life, then gradually declines with age. The pattern of airflow through adulthood for individuals born very preterm (at <32 weeks' gestation) or with very low birthweight (<1501 g) is unknown. We aimed to compare maximal expiratory airflow in these individuals during late adolescence and early adulthood with that of control individuals born with normal birthweight (>2499 g) or at term. METHODS: We did a meta-analysis of individual participant data from cohort studies, mostly from the pre-surfactant era. Studies were identified through the Adults born Preterm International Collaboration and by searching PubMed and Embase (search date May 25, 2016). Studies were eligible if they reported on expiratory flow rates beyond 16 years of age in individuals born very preterm or with very low birthweight, as well as controls born at term or with normal birthweight. Studies with highly selected cohorts (eg, only participants with bronchopulmonary dysplasia) or in which few participants were born very preterm or with very low birthweight were excluded. De-identified individual participant data from each cohort were provided by the holders of the original data to a central site, where all the data were pooled into one data file. Any data inconsistencies were resolved by discussion with the individual sites concerned. Individual participant data on expiratory flow variables (FEV1, forced vital capacity [FVC], FEV1/FVC ratio, and forced expiratory flow at 25-75% of FVC [FEF25-75%]) were converted to Z scores and analysed with use of generalised linear mixed models in a one-step approach. FINDINGS: Of the 381 studies identified, 11 studies, comprising a total of 935 participants born very preterm or with very low birthweight and 722 controls, were eligible and included in the analysis. Mean age at testing was 21 years (SD 3·4; range 16-33). Mean Z scores were close to zero (as expected) in the control group, but were reduced in the very preterm or very low birthweight group for FEV1 (-0·06 [SD 1·03] vs -0·81 [1·33], mean difference -0·78 [95% CI -0·96 to -0·61], p<0·0001), FVC (-0·15 [0·98] vs -0·38 [1·18], -0·25 [-0·40 to -0·10], p=0·0012), FEV1/FVC ratio (0·14 [1·10] vs -0·64 [1·35], -0·74 [-0·85 to -0·64], p<0·0001), and FEF25-75% (-0·04 [1·10] vs -0·95 [1·47], -0·88 [-1·12 to -0·65], p<0·0001). Similar patterns were observed when we compared the proportions of individuals with values below the fifth percentile. INTERPRETATION: Individuals born very preterm or with very low birthweight are at risk of not reaching their full airway growth potential in adolescence and early adulthood, suggesting an increased risk of chronic obstructive pulmonary disease in later adulthood. FUNDING: National Health and Medical Research Council (Australia), University of Bergen, Western Norway Regional Authority, National Institute for Health Research (UK), Stichting Astmabestrijding, St Olav's Hospital's Research Fund, Academy of Finland, European Commission, National Institute of Child Health and Human Development (USA), Victorian Government's Operational Infrastructure Support Program.

10.
Eur J Obstet Gynecol Reprod Biol ; 238: 44-48, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31082743

RESUMO

OBJECTIVE: To test whether maternal hemoglobin during pregnancy associates with offspring perinatal outcomes in a developed country. Changes in maternal hemoglobin concentration during pregnancy are partly physiological phenomena reflecting alterations of maternal blood volume. Especially hemoglobin measures outside the physiological range may influence maternal health and fetal growth with long-lasting consequences. STUDY DESIGN: We studied an unselected sample drawn from two regional birth cohorts born 20 years apart: The Northern Finland Birth Cohorts 1966 and 1986. These are two mother-and-child population-based birth cohorts together comprising 21,710 mothers and their children. After exclusions, the sample size of the current study was 20,554. Concentrations of maternal hemoglobin at first and last antenatal visits were categorized as low (lowest 10%), medium (reference) or high (highest 10%). Multinomial logistic regression analyses for categories of maternal hemoglobin and perinatal outcomes such as preterm delivery and full-term small and large for gestational age were conducted with adjustments for maternal cofactors. RESULTS: Low maternal hemoglobin at early pregnancy associated with decreased risk of full-term small for gestational age (adjusted OR 0.73, 95% CI [0.58, 0.93], p = 0.010). At late pregnancy, low maternal hemoglobin associated with increased risk of preterm delivery (adjusted OR 1.60, 95% CI [1.26, 2.02], p < 0.0005) whereas high maternal hemoglobin associated with increased risk of full-term small for gestational age (adjusted OR 1.29, 95% CI [1.07, 1.56], p = 0.009). Maternal hemoglobin did not show constant association with risk of large for gestational age. CONCLUSION: The results from this study support evidence that both low and high maternal hemoglobin associate with adverse perinatal outcomes. Low maternal hemoglobin associated with preterm delivery and high with full-term small for gestational age. Association was mainly present when maternal hemoglobin was measured during the third trimester. These results indicate that it is important to monitor both extremes of maternal hemoglobin throughout the pregnancy.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31095700

RESUMO

Circulating amino acids are potential markers of body composition. Previous studies are mainly limited to middle age and focus on either fat or lean mass, thereby ignoring overall body composition. We investigated the associations of fat and lean body mass with circulating amino acids in older men and women. We studied 594 women and 476 men from the Helsinki Birth Cohort Study (age 62-74 years). Bioelectrical impedance analysis was used to indicate two main body compartments by fat (fat mass/height2) and lean mass indices (lean mass/height2), dichotomized based on sex-specific medians. Eight serum amino acids were quantified using nuclear magnetic resonance spectroscopy. General linear models were adjusted for age, smoking and fasting glucose. Higher lean mass index was associated with higher concentrations of branched-chain amino acids in both sexes (p≤0.001). In men, lean mass index was also positively associated with tyrosine (p=0.006) and inversely with glycine (p<0.001). Higher fat mass index was associated with higher concentrations of all branched-chain amino acids, aromatic amino acids (phenylalanine and tyrosine), and alanine in both sexes (p≤0.008). Associations between body composition and amino acids are largely similar in older men and women. The associations are largely similar to those previously observed in younger adults.

12.
Sci Rep ; 9(1): 4395, 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30867476

RESUMO

Early life stress (ELS) may increase the risk of anxiety throughout the life course. Whether this effect extends to late adulthood is poorly known. In our study comprising 1872 participants from the Helsinki Birth Cohort Study born in 1934-1944, we investigated the association of various forms of ELS and their accumulation with self-reported anxiety symptoms at the age of 65-77 years. Data on childhood socioeconomic status and separation from parents were based on national registers for all participants. Information on self-reported emotional and physical trauma, parental divorce, and death of a family member in childhood was obtained from 1277 participants. We found that experiencing emotional trauma, physical trauma, and low socioeconomic status in childhood were associated with increased anxiety symptoms in late adulthood [B = 0.44 (95% CI = 0.31-0.58); B = 0.33 (95% CI = 0.20-0.46); B = 0.10 (95% CI = 0.01-0.19), respectively]. These associations remained significant even after controlling for other forms of ELS. Accumulation of early life stress also increased the levels of late-adulthood anxiety symptoms and the risk of anxiety regarded as clinically significant. Screening for potentially stressful childhood experiences in elderly populations may help identifying individuals with increased anxiety symptoms and planning preventive and therapeutic interventions for those exposed to ELS.

13.
Psychoneuroendocrinology ; 104: 89-99, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30826632

RESUMO

Background Maternal early pregnancy overweight (body mass index [BMI] 25.0-29.9 kg/m2) and obesity (BMI ≥ 30 kg/m2) are associated with mental and physical health adversities in the offspring. Prenatal programming of the hypothalamic-pituitary-adrenal (HPA) axis has been put forward as one of the mechanisms that may play pathophysiological role. However, evidence linking maternal overweight and obesity with offspring HPA-axis activity is scarce. We studied if maternal early pregnancy BMI is associated with diurnal salivary cortisol, a marker of HPA-axis activity, in young adult offspring. Methods At a mean age of 25.3 (standard deviation [SD) = 0.6) years, 653 Arvo Ylppö Longitudinal Study participants collected saliva samples for cortisol analyses, at awakening, 15 and 30 min thereafter, 10:30AM, 12:00PM, 5:30PM and at bedtime. Maternal BMI was calculated from weight and height verified by a measurement in the first antenatal clinic visit before 12 weeks of gestation derived from healthcare records. Results Per each one kg/m2 higher maternal early pregnancy BMI offspring diurnal average salivary cortisol was -1.4% (95% CI:-2.6, -0.2, pFDR = 0.033) lower, at awakening it was -2.4% (95% CI:-4.0, -0.7, pFDR = 0.025) lower and the morning average salivary cortisol was -2.0% (95% CI:-3.4, -0.5, pFDR=0.017) lower. These associations were independent of the offspring's own young adulthood BMI, and other important covariates. Conclusion Our findings show that young adult offspring born to mothers with higher early pregnancy BMI show lower average levels of diurnal cortisol, especially in the morning. Whether these findings reflect prenatal programming of the offspring HPA-axis activity warrants further investigation.

14.
Sleep Med ; 56: 201-210, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30819657

RESUMO

OBJECTIVE: Maternal depressive symptoms during pregnancy have been associated with poor offspring sleep. Yet, it remains unknown whether depressive symptoms throughout pregnancy are more harmful to the child than depressive symptoms only during certain time periods in pregnancy, whether associations are specific to pregnancy stage, whether maternal symptomatology after pregnancy mediates or adds to the prenatal effects, and whether any effects are specific to some child sleep characteristics. METHODS: A total of 2321 mothers from the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) study completed the Center for Epidemiological Studies Depression Scale biweekly between gestational weeks + days 12 + 0/13 + 6 and 38 + 0/39 + 6. At child's mean age of 3.5 (standard deviation = 0.7) years, mothers completed the Beck Depression Inventory-II and answered questions on child sleep quantity and quality using the Brief Infant Sleep Questionnaire (BISQ) and sleep disorders using the Sleep Disturbance Scale for Children. RESULTS: Maternal depressive symptoms showed high stability throughout pregnancy. Children of mothers with clinically significant symptomatology throughout pregnancy had shorter mother-rated sleep duration, longer sleep latency, higher odds for waking up two or more times during the night and for total and several specific sleep disorders. These associations were robust to covariates. However, maternal depressive symptoms at the child follow-up fully mediated the associations with sleep duration and awakenings, partially mediated those with sleep latency and disorders, and added to the effects on sleep disorders. CONCLUSION: Maternal depressive symptoms throughout pregnancy are associated with mother-rated child sleep quantity, quality, and disorders. Maternal depressive symptoms at child follow-up mediate and add to the prenatal adverse effects on child sleep characteristics.

15.
J Clin Endocrinol Metab ; 104(7): 2785-2795, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30835282

RESUMO

CONTEXT: Maternal gestational diabetes mellitus (GDM) and prepregnancy overweight/obesity [body mass index (BMI) ≥25 kg/m2] might adversely affect offspring cardiometabolic health. OBJECTIVE: To assess the associations between maternal GDM and prepregnancy overweight/obesity with adult offspring cardiometabolic risk factors. DESIGN: Longitudinal cohort study (ESTER Maternal Pregnancy Disorders Study and the Arvo Ylppö Longitudinal Study). SETTING: Province of Uusimaa and Northern Finland. PARTICIPANTS: At a mean age of 24.1 ± 1.3 years, we classified offspring as offspring of mothers with GDM regardless of the prepregnancy BMI (OGDM; n = 193); normoglycemic mothers with prepregnancy overweight/obesity (ONO; n = 157); and normoglycemic mothers with prepregnancy BMI <25 kg/m2 (controls; n = 556). MAIN OUTCOME MEASURES: We assessed the cardiometabolic biomarkers from blood and measured the blood pressure at rest and heart rate. RESULTS: Compared with the controls, the OGDM and ONO groups had greater fasting glucose (1.6%; 95% CI, 0.1% to 3.1%; and 2.3%; 95% CI, 0.5% to 4.3%, respectively) and insulin (12.7%; 95% CI, 4.4% to 21.9%; and 8.7%; 95% CI, 0.2% to 17.8%). These differences attenuated to nonsignificance when adjusted for confounders and/or current offspring characteristics, including BMI or body fat percentage. The OGDM group had lower SHBG (men, -12.4%; 95% CI, -20.2% to -3.9%; women, -33.2%; 95% CI, -46.3% to -16.8%), high-density lipoprotein (-6.6%; 95% CI, -10.9% to -2.2%), and apolipoprotein A1 (-4.5%; 95% CI, -7.5% to -1.4%). These differences survived the adjustments. The heart rate and other biomarkers were similar among the groups. CONCLUSIONS: Adult offspring of mothers with GDM have increased markers of insulin resistance and a more atherogenic lipid profile. These were only partly explained by confounders or current offspring adiposity. Maternal prepregnancy overweight/obesity was associated with impaired offspring glucose regulation, which was explained by confounders and/or current adiposity.

16.
J Pediatr ; 208: 96-103.e4, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30732997

RESUMO

OBJECTIVE: To evaluate cardiac autonomic function in adults born preterm. STUDY DESIGN: We studied the association between prematurity and cardiac autonomic function using heart rate variability measurements in 600 adults (mean age of 23.3 years) from a geographically based cohort in Northern Finland. There were 117 young adults born early preterm (<34 weeks), 207 born late preterm (34-36 weeks), and 276 born at term (≥37 weeks, controls). Autonomic function was analyzed by calculating time and frequency domain heart rate variability measurements using linear regression. RESULTS: Compared with controls, the mean difference in root mean square of successive differences (indicating cardiac vagal activity) was -12.0% (95% CI -22.2%, -0.5%, adjusted for sex, age, source cohort, and season P = .04) for the early preterm group and -7.8% (-16.8%, 2.0%, P = .12) for the late preterm group. Mean differences with controls in low frequency power (indicating cardiac vagal activity, including some sympathetic- and baroreflex-mediated effects) were -13.6% (-26.7%, 1.8%, P = .08) for the early preterm group and -16.4% (-27.0%, -4.3%, P = .01) for the late preterm group. Mean differences in high frequency power (quantifying cardiac vagal modulation in respiratory frequency) were -19.2% (-36.6%, 2.9%, P = .09) for the early preterm group and -13.8% (-29.4%, 5.3%, P = .15) for the late preterm group. Differences were attenuated when controlled for body mass index and physical activity. CONCLUSIONS: Our results suggest altered autonomic regulatory control in adults born preterm, including those born late preterm. Altered autonomic regulatory control may contribute to increased cardiovascular risk in adults born preterm.

17.
J Psychosom Res ; 118: 63-68, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30782356

RESUMO

INTRODUCTION: Traumatic experiences, such as separation from parents in childhood causing early life stress (ELS) may increase the risk of adverse long-term health outcomes and biological age-related changes. This may have an impact on work career. Our aim was to examine long term consequences of ELS due to temporary separation from parents during World War II (WWII) in relation to work career. MATERIAL AND METHODS: The Helsinki Birth Cohort Study comprises 13,345 individuals born in Helsinki, Finland, between the years 1934-1944. From the original cohort, 1781 individuals were identified as being separated temporarily from their parents due to World War II. Information on date and type of pension was provided by the Finnish Centre for Pensions and the Social Insurance Institution of Finland. The cohort members either transitioned into old age pension at the statutory retirement age or retired earlier and transitioned into disability, unemployment, part-time pension or died before retirement. RESULTS: Those who were separated were more likely to have transitioned into disability pension (RRR: 1.26: 95% CI: 1.06-1.48), especially due to diseases of the musculoskeletal system (OR: 1.57; 95% CI: 1.20-2.07), or into unemployment pension (RRR: 1.25; 95% CI: 1.02-1.53) compared with those not separated from their parents. Longer duration of separation was associated with early exit from the workforce compared with non-separation. CONCLUSIONS: Exposure to ELS may have an impact upon lifetime work career. Early interventions preventing exposure to ELS or mitigating its negative effects may prolong future work careers along with healthier aging across the life-span.

18.
Psychol Med ; : 1-11, 2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30688183

RESUMO

BACKGROUND: Synthetic glucocorticoids, to enhance fetal maturation, are a standard treatment when preterm birth before 34 gestational weeks is imminent. While morbidity- and mortality-related benefits may outweigh potential neurodevelopmental harms in children born preterm (<37 gestational weeks), this may not hold true when pregnancy continues to term (⩾37 gestational weeks). We studied the association of antenatal betamethasone exposure on child mental health in preterm and term children. METHODS: We included 4708 women and their children, born 2006-2010, from the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction Study with information on both antenatal betamethasone treatment and child mental and behavioral disorders from the Finnish Hospital Discharge Register from the child's birth to 31 December 2016. Additional follow-up data on mother-reported psychiatric problems and developmental milestones were available for 2640 children at 3.5 (s.d. = 0.07) years-of-age. RESULTS: Of the children, 187 were born preterm (61 betamethasone-exposed) and 4521 at term (56 betamethasone-exposed). The prevalence of any mental and behavioral, psychological development, emotional and behavioral, and comorbid disorders was higher in the betamethasone-exposed, compared to non-exposed children [odds ratio 2.76 (95% confidence interval 1.76-4.32), 3.61 (2.19-5.95), 3.29 (1.86-5.82), and 6.04 (3.25-11.27), respectively]. Levels of psychiatric problems and prevalence of failure to meet the age-appropriate development in personal-social skills were also higher in mother-reports of betamethasone-exposed children. These associations did not vary significantly between preterm and term children. CONCLUSIONS: Antenatal betamethasone exposure may be associated with mental health problems in children born preterm and in those who end up being born at term.

19.
J Allergy Clin Immunol ; 143(6): 2062-2074, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30579849

RESUMO

BACKGROUND: Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis. OBJECTIVE: We sought to identify differential DNA methylation in newborns and children related to childhood asthma. METHODS: Within the Pregnancy And Childhood Epigenetics consortium, we performed epigenome-wide meta-analyses of school-age asthma in relation to CpG methylation (Illumina450K) in blood measured either in newborns, in prospective analyses, or cross-sectionally in school-aged children. We also identified differentially methylated regions. RESULTS: In newborns (8 cohorts, 668 cases), 9 CpGs (and 35 regions) were differentially methylated (epigenome-wide significance, false discovery rate < 0.05) in relation to asthma development. In a cross-sectional meta-analysis of asthma and methylation in children (9 cohorts, 631 cases), we identified 179 CpGs (false discovery rate < 0.05) and 36 differentially methylated regions. In replication studies of methylation in other tissues, most of the 179 CpGs discovered in blood replicated, despite smaller sample sizes, in studies of nasal respiratory epithelium or eosinophils. Pathway analyses highlighted enrichment for asthma-relevant immune processes and overlap in pathways enriched both in newborns and children. Gene expression correlated with methylation at most loci. Functional annotation supports a regulatory effect on gene expression at many asthma-associated CpGs. Several implicated genes are targets for approved or experimental drugs, including IL5RA and KCNH2. CONCLUSION: Novel loci differentially methylated in newborns represent potential biomarkers of risk of asthma by school age. Cross-sectional associations in children can reflect both risk for and effects of disease. Asthma-related differential methylation in blood in children was substantially replicated in eosinophils and respiratory epithelium.

20.
Neurobiol Aging ; 73: 230.e5-230.e8, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30293724

RESUMO

We tested if the ε4 major isoform of the APOE gene and rs405509 and rs440446 promoter and intron-1 polymorphisms predicted risk of any dementia or Alzheimer's disease with diagnoses derived from the Hospital Discharge and Causes of Death Registers in 1453 participants of the Helsinki Birth Cohort Study. We used Cox proportional hazard models adjusted for sex, year of birth, maximum lifetime occupational status and education, and diagnoses of stroke, coronary heart disease, mood disorders, and depressive symptoms. APOE ε4 predicted higher risk of any dementia (hazard ratios >3.68; 95% confidence interval [CI] 1.76, 7.70) across all statistical models, and when adjusted for rs405509 and rs440446. The number of minor alleles in rs405509 or rs440446 was not associated with dementia risk (hazard ratios<1.43; 95% CI 0.87, 2.36). As rs405509 or rs440446 has been associated with nonpathological cognitive aging in this and other cohorts independent of the APOE major isoforms, these findings lend credence that APOE locus may be linked with dementia risk and nonpathological cognitive aging via separate mechanisms.

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