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1.
Clin Exp Allergy ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33705581

RESUMO

BACKGROUND: Several maternal conditions can affect fetal growth, and asthma during pregnancy is known to be associated with lower birth weight and shorter gestational age. OBJECTIVE: In a new Swedish cohort study on maternal asthma exposure and stress during pregnancy (MAESTRO), we have assessed if there is evidence of early fetal growth restriction in asthmatic women or if a growth restriction might come later during pregnancy. METHODS: We recruited women from eight antenatal clinics in Stockholm, Sweden. Questionnaires on background factors, asthma status and stress were assessed during pregnancy. The participants were asked to consent to collection of medical records including ultrasound measures during pregnancy, and linkage to national health registers. In women with and without asthma, we studied reduced or increased growth by comparing the second-trimester ultrasound with first-trimester estimation. We defined reduced growth as estimated days below the 10th percentile and increased growth as days above the 90th percentile. At birth, the weight and length of the newborn and the gestational age was compared between women with and without asthma. RESULTS: We enrolled 1693 participants in early pregnancy and collected data on deliveries and ultrasound scans in 1580 pregnancies, of which 18% of the mothers had asthma. No statistically significant reduced or increased growth between different measurement points were found when women with and without asthma were compared; adjusted odds ratios for reduced growth between first and second trimester 1.11 95% CI (0.63-1.95) and increased growth 1.09 95% CI (0.68-1.77). CONCLUSION AND CLINICAL RELEVANCE: In conclusion, we could not find evidence supporting an influence of maternal asthma on early fetal growth in the present cohort: Although the relatively small sample size, which may enhance the risk of a type II error, it is concluded that a potential difference is likely to be very small.

2.
Chest ; 2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33727032

RESUMO

BACKGROUND: Studies have reported an increased risk for asthma following lower respiratory tract infections, but few studies have specifically assessed this risk in children diagnosed with pneumonia in infancy. Further, it is not fully understood whether this association is indicative of a causal relationship or if certain children have a predisposition for both diseases. RESEARCH QUESTION: Are children diagnosed with pneumonia in infancy at increased risk for asthma and what is the role of familial confounding and pneumococcal conjugate vaccine immunization on the association? STUDY DESIGN AND METHODS: We performed a nationwide register-based cohort study of >900.000 Swedish children to assess the association between pneumonia in infancy and prevalent asthma at 4 years. A secondary aim was to assess if the association has changed after the introduction of nationwide pneumococcal conjugate vaccine (PCV) immunization as this has led to a shift in pneumonia etiology. We controlled for important confounders including shared environmental and familial confounding by using sibling analyses. RESULTS: There was a strong association between pneumonia diagnosis in infancy and prevalent asthma at 4 years (adjusted OR 3.38; 95% CI: 3.26-3.51) as well as in the full sibling analyses (adjusted OR 2.81; 95% CI: 2.58-3.06). The risk for asthma following pneumonia diagnosis in infancy was slightly higher for those born in the PCV period as compared to the pre-PCV period (adjusted ORs 3.80; 95% CI: 3.41-4.24 versus 3.28; 95% CI: 3.15-3.42) when also the proportion of viral pneumonia etiology was higher (14.5% versus 10.7% respectively) and the overall asthma prevalence was lower (5.3% versus 6.6%). INTERPRETATION: Children diagnosed with pneumonia in infancy have a highly increased risk for prevalent asthma at 4 years, which might have implications for future asthma preventive measures and needs to be considered when assessing the morbidity that can be attributed to pneumonia.

3.
PLoS One ; 16(3): e0247724, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33730071

RESUMO

BACKGROUND: Individuals with ADHD are at increased risk for poor occupational outcomes. Educational attainment and psychiatric comorbidity may be important contributing factors for these outcomes, but the role of these factors is not well characterized. This study aimed to investigate the associations between ADHD and occupational outcomes, and to examine the influence of educational attainment, comorbid developmental disorders and intellectual disability on these associations. METHODS: We linked the Swedish population graduating from compulsory school 1998-2008 (N = 1.2 millions) to population-wide register-based data on clinical psychiatric diagnoses and medications, objective annual measures of educational, and occupational outcomes. Individuals were followed for between 6 to 16 years after graduation. RESULTS: Individuals with ADHD had annually on average 17 percent lower income, ratio = 0.83 (95% CI 0.83-0.84), 12.19 (11.89-12.49) more days of unemployment, and a higher likelihood of receiving disability pension, odds-ratio = 19.0 (18.4-19.6), compared to controls. Comorbid diagnoses of intellectual disability and developmental disorder explained most of the association between ADHD and disability pension, while lifetime educational attainment partially explained associations between ADHD and all occupational outcomes. Analyses of occupational trajectories found that income was lower and unemployment elevated relative to controls with the same educational attainment. Higher educational attainment correlated with higher income similarly among individuals with ADHD and controls after accounting for individual background factors. CONCLUSIONS: The occupational burden associated with ADHD is substantial. Comorbid developmental disorders, intellectual disability and educational difficulties (e.g., failing grades) from childhood to adulthood are important factors to consider when designing interventions to improve occupational outcomes in individuals with ADHD.

4.
J Crohns Colitis ; 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33640971

RESUMO

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is linked to psychiatric morbidity, but few studies have assessed general population comparators. We aimed to investigate the risk of psychiatric morbidity and suicide in adult-onset IBD patients. METHODS: Nationwide population-based cohort study in Sweden (1973-2013). We studied the risk of psychiatric disorders and suicide in 69,865 adult-onset IBD patients (ulcerative colitis, UC: n=43,557; Crohn's disease, CD: n=21,245; and IBD-unclassified: n=5063) compared to 3,472,913 general population references and 66,292 siblings. RESULTS: During a median follow-up of 11 years, we found 7,465 (10.7%) first psychiatric disorders in IBD (incidence rate, IR/1000 person-years 8.4) and 306,911 (9.9%) in the general population (IR 6.6), resulting in 1.8 extra psychiatric morbidity per 100 patients followed-up for 10 years and a hazard ratio (HR) of 1.3 (95% confidence interval, 95%CI=1.2-1.3). The highest risk of overall psychiatric morbidity was seen in the first year after IBD diagnosis (HR=1.4, 95%CI=1.2-1.6) and in patients with extraintestinal manifestations (HR=1.6, 95%CI=1.5-1.7). Psychiatric morbidity was more common in all IBD subtypes (HRs 1.3 to 1.5). An increased risk of suicide attempts was observed among all IBD types (HRs=1.2 to 1.4), whereas completed suicide was explicitly associated with CD (HR=1.5) and elderly-onset (diagnosed at the age of >60 years) IBD (HR=1.7). CONCLUSION: Adult-onset IBD was associated with an increased risk of psychiatric disorders and suicide attempts. Psychological follow-up should be provided to patients with IBD, especially those with extraintestinal manifestations and elderly-onset IBD. This follow-up should transpire within the first year after IBD diagnosis.

6.
Elife ; 102021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33507148

RESUMO

Twins suffering a co-twin loss at birth have reported feelings of loneliness and grief while it remains unexplored if they suffer increased risk of psychiatric disorders. We contrasted rate of first-onset psychiatric disorders among all Swedish-born twins whose co-twin died within 60 days after birth between 1973 and 2011 (n = 787) to that of 3935 matched unexposed twins, 3935 matched singletons (both matched to the exposed twins by birth year, sex, and birth characteristics), and 880 full siblings of the exposed twins. During a median of 19-year follow-up, exposed twins were at increased risk of first-onset psychiatric disorders (hazard ratio = 1.56, 95%CI 1.30-1.87) compared with unexposed twins. We observed the strongest association for emotional disorders and for psychiatric disorders diagnosed before the age of 25. Comparisons with matched singletons and the twin's full siblings rendered similar results, corroborating an association of loss of a co-twin at birth with subsequent risk of psychiatric disorders.

7.
Andrology ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33470034

RESUMO

BACKGROUND: It is not known if impaired fertility in men with hypospadias is caused by decreased semen quality or other factors. Semen quality in men born with hypospadias may be impaired due to effects of androgens or testicular dysgenesis but has been very little studied. OBJECTIVES: To study semen quality in men with hypospadias using dizygotic twinning rates as an epidemiological indicator. We further aimed to study men treated for cryptorchidism, given a hypothesized mutual etiology for decreased semen quality. MATERIALS AND METHODS: We conducted a population-based study using national Swedish registers. A total of 4,363,165 births between 1964 and 2013 were included. The association between hypospadias and cryptorchidism, and fathering dizygotic multiple births was estimated using logistic regression and presented as odds ratios. The main analyses excluded births conceived using assisted reproductive technology (ART). RESULTS: We identified a total of 5317 births with fathers with hypospadias, including 26 dizygotic births conceived unassisted. No significant association was found between hypospadias and dizygotic twinning (OR 1.10, 0.75-1.61). We estimated a significantly increased odds for dizygotic multiple births in men treated for cryptorchidism (OR 1.35, 1.01-1.81) which was decreased after exclusion of ART, but the estimate was not significant (OR 0.75, 0.48-1.18). DISCUSSION: Using dizygotic twinning rates as an indicator of semen quality, we did not find any difference between fathers with hypospadias and controls. Due to sample size, we could not analyze phenotypes separately and can therefore not exclude impaired semen quality in severe hypospadias. We could not demonstrate any association between dizygotic twinning and cryptorchidism. Men treated for cryptorchidism were more likely than controls to use ART to conceive. CONCLUSION: Men with hypospadias who conceived without ART were not shown to have impaired semen quality using dizygotic twinning as an epidemiological indicator.

8.
Paediatr Perinat Epidemiol ; 35(2): 184-193, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33350491

RESUMO

BACKGROUND: Pregnant women with painful conditions often have mental health problems, including depression and anxiety. Co-morbid conditions may cause pregnant women to use multiple medications, although safety of such practice is poorly understood. OBJECTIVES: We investigated the influence of combined prescriptions of opioid analgesics and selective serotonin reuptake inhibitors (SSRIs) during pregnancy on two adverse birth outcomes. METHODS: We analysed Swedish population-based births (n = 688 914) between 2007 and 2013. Using national registers, we obtained data on filled medication prescriptions, birth outcomes, and a wide range of parental characteristics. We estimated preterm birth and small-for-gestational-age risk following independent or combined prescriptions of the two medications compared with no filled prescriptions for either medication. We adjusted for confounders using inverse probability of treatment weights. RESULTS: After adjusting for confounders, preterm birth risk was higher among women with opioid analgesic prescriptions only (5.9%; risk ratio [RR] 1.27, 95% confidence interval [CI] 1.22, 1.33), SSRIs only (6.2%; RR 1.34, 95% CI 1.27, 1.42), and both medications (7.8%; RR 1.70, 95% CI 1.47, 1.96) compared with unexposed women (4.6%). The interaction between the medications on preterm birth was small (risk difference [RD] 0.4%, 95% CI -0.8%, 1.6%); relative excess risk due to interaction [RERI] 0.09, 95% CI -0.17, 0.34; RR 1.00, 95% CI 0.85, 1.17). For small for gestational age, risk was approximately 2% across all groups, and there was no interaction between the medications (RD 0.3%, 95% CI -0.4%, 1.1%); RERI 0.15, 95% CI -0.16, 0.47; RR 1.15, 95% CI 0.87, 1.52). CONCLUSIONS: Compared with unexposed pregnancies, those with either medication alone had a small increased risk for preterm birth but no increased risk for small for gestational age. The magnitude of associations with combined exposure to both medications were not greater than the sum of the associations with each medication considered individually.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33349970

RESUMO

BACKGROUND: Exhaled nitric oxide and blood eosinophils are clinical asthma T-helper type 2 markers in use. Immunoglobulin E (IgE) is often involved in the inflammation associated with atopic asthma. The effect of both blood eosinophils and allergen-specific IgE on exhaled nitric oxide levels is not completely understood. Twin-design studies can improve understanding of the underlying contribution of genetically and/or environmentally driven inflammation markers in asthma. Our aim was to disentangle the covariance between asthma and exhaled nitric oxide into genetic and environmental contributions that can account for inflammation markers in a paediatric population. METHODS: This population-based, cross-sectional twin study enrolled 612 monozygotic (MZ) and same-sex dizygotic (DZ) schoolchildren. Multivariate structural equation modelling was utilized to separate the covariance between asthma and exhaled nitric oxide into genetic and/or environmental effects, taking allergen-specific IgE level and blood eosinophil count into account while controlling for confounding factors. RESULTS: The cross-twin/cross-trait correlations had a higher magnitude in the MZ twins than in the DZ twins, indicating that genes affect the association. The likelihood ratio test for model fitting resulted in the AE model (ie additive genetic effects, A, and non-shared environmental effects, E) as the most parsimonious. A majority, 73%, of the phenotypic correlation between asthma and exhaled nitric oxide, r = .19 (0.05-0.33), was attributable to genetic effects which mainly was due to the allergen-specific IgE level. CONCLUSIONS: This study indicates that the association between asthma and exhaled nitric oxide in children is to a large extent explained by genetics via allergen-specific IgE level and not blood eosinophils. This might partly explain the clinical heterogeneity in this group. A next step could be to include allergen-specific IgE level in multivariate omic studies.

10.
Hum Reprod ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33227132

RESUMO

STUDY QUESTION: Is there a relation between ART and DNA methylation (DNAm) patterns in cord blood, including any differences between IVF and ICSI? SUMMARY ANSWER: DNAm at 19 CpGs was associated with conception via ART, with no difference found between IVF and ICSI. WHAT IS KNOWN ALREADY: Prior studies on either IVF or ICSI show conflicting outcomes, as both widespread effects on DNAm and highly localized associations have been reported. No study on both IVF and ICSI and genome-wide neonatal DNAm has been performed. STUDY DESIGN, SIZE, DURATION: This was a cross-sectional study comprising 87 infants conceived with IVF or ICSI and 70 conceived following medically unassisted conception. The requirement for inclusion in the study was an understanding of the Swedish language and exclusion was the use of donor gametes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were from the UppstART study, which was recruited from fertility and reproductive health clinics, and the Born into Life cohort, which is recruited from the larger LifeGene study. We measured DNAm from DNA extracted from cord blood collected at birth using a micro-array (450k array). Group differences in DNAm at individual CpG dinucleotides (CpGs) were determined using robust linear models and post-hoc Tukey's tests. MAIN RESULTS AND THE ROLE OF CHANCE: We found no association of ART conception with global methylation levels, imprinted loci and meta-stable epialleles. In contrast, we identify 19 CpGs at which DNAm was associated with being conceived via ART (effect estimates: 0.5-4.9%, PFDR < 0.05), but no difference was found between IVF and ICSI. The associated CpGs map to genes related to brain function/development or genes connected to the plethora of conditions linked to subfertility, but functional annotation did not point to any likely functional consequences. LIMITATIONS, REASONS FOR CAUTION: We measured DNAm in cord blood and not at later ages or in other tissues. Given the number of tests performed, our study power is limited and the findings need to be replicated in an independent study. WIDER IMPLICATIONS OF THE FINDINGS: We find that ART is associated with DNAm differences in cord blood when compared to non-ART samples, but these differences are limited in number and effect size and have unknown functional consequences in adult blood. We did not find indications of differences between IVF and ICSI. STUDY FUNDING/COMPETING INTEREST(S): E.W.T. was supported by a VENI grant from the Netherlands Organization for Scientific Research (91617128) and JPI-H2020 Joint Programming Initiative a Healthy Diet for a Healthy Life (JPI HDHL) under proposal number 655 (PREcisE Project) through ZonMw (529051023). Financial support was provided from the European Union's Seventh Framework Program IDEAL (259679), the Swedish Research Council (K2011-69X-21871-01-6, 2011-3060, 2015-02434 and 2018-02640) and the Strategic Research Program in Epidemiology Young Scholar Awards, Karolinska Institute (to A.N.I.) and through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework grant no 340-2013-5867, grants provided by the Stockholm County Council (ALF-projects), the Strategic Research Program in Epidemiology at Karolinska Institutet and the Swedish Heart-Lung Foundation and Danderyd University Hospital (Stockholm, Sweden). The funders had no role in study design, data collection, analysis, decision to publish or preparation of the manuscript. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

12.
Int J Epidemiol ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33179025

RESUMO

BACKGROUND: Development of the gut-brain axis in early life may be disturbed by antibiotic use. It has been hypothesized that this disturbance may contribute to development of neurodevelopmental disorders, including autism spectrum disorder and attention-deficit hyperactivity disorder. We aimed to assess the association between antibiotic use in early life and the risk of developing attention-deficit hyperactivity disorder or autism spectrum disorder, while controlling for shared genetic and environmental factors in a discordant twin design. METHODS: We conducted a cohort study in twins (7-12 years; 25 781 twins) from the Netherlands Twin Register (NTR) and a replication study in the Childhood and Adolescent Twin Study in Sweden (CATSS; 7946 9-year-old twins). Antibiotic use was recorded before age 2 years. Attention-deficit hyperactivity disorder and autism spectrum disorder were parent-reported in the Netherlands Twin Register and register-based in the Childhood and Adolescent Twin Study in Sweden. RESULTS: Early-life antibiotic use was associated with increased risk of attention-deficit hyperactivity disorder development [pooled odds ratio (OR) 1.10, 95% confidence interval (CI) 1.02-1.17] and autism spectrum disorder (pooled OR 1.15, 95% CI 1.06-1.25) in a case-control design. When restricting to monozygotic twin pairs discordant for the outcome, associations disappeared for both disorders in both cohorts (attention-deficit hyperactivity disorder OR 0.90, 95% CI 0.48-1.69 and OR 0.80, 95% CI 0.37-1.76, and autism spectrum disorder OR 0.66, 95% CI 0.38-1.16 and OR 0.29, 95% CI 0.02-4.50, respectively). CONCLUSIONS: Our findings suggest that the association between early-life antibiotic use and risk of attention-deficit hyperactivity and autism spectrum disorder may be confounded by shared familial environment and genetics.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33135723

RESUMO

CONTEXT: Reduced fertility has been reported for women with congenital adrenal hyperplasia (CAH), especially for those with the salt-losing form. However, data are sparse on reproductive and perinatal outcomes in these women. OBJECTIVE: To investigate reproductive and perinatal outcomes in women with CAH. DESIGN AND SETTING: Population-based and nationwide study using the National CAH Register, the Total Population Register and the Medical Birth Register of Sweden. PARTICIPANTS: 272 women with CAH due to 21-hydroxylase deficiency and 27 200 controls matched by sex, age and place of birth. The median age was 31 years. MAIN OUTCOME MEASURES: The proportion of CAH women that have given birth, reproductive and perinatal outcomes. RESULTS: Of the 272 women with CAH, 69 gave birth to at least one child (25.4%), which was a lower frequency than for the controls (45.8%) (p<0.001). Furthermore, women with CAH had fewer children than controls and were slightly older at birth of their first child. More women with CAH were diagnosed with gestational diabetes than controls, 4.9% vs 1.4% (p<0.05), and more women with CAH were delivered through caesarean section, 51.4% vs 12.3% (p<0.05). There was no difference in Apgar score or frequency of small-for-gestational age between children born to mothers with CAH and controls. CONCLUSIONS: This is, to our knowledge, the largest cohort designed to investigate reproductive and perinatal outcomes in women with CAH. We found the birth rate to be lower in women with CAH, gestational diabetes and caesarean section were more common, but perinatal outcomes were comparable to controls.

14.
Sci Rep ; 10(1): 17819, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33082373

RESUMO

The maternal immune system is going through considerable changes during pregnancy. However, little is known about the determinants of the inflammatory proteome and its relation to pregnancy stages. Our aim was to investigate the plasma inflammatory proteome before, during and after pregnancy. In addition we wanted to test whether maternal and child outcomes were associated with the proteome. A cohort of 94 healthy women, enrolled in a longitudinal study with assessments at up to five time points around pregnancy, ninety-two inflammatory proteins were analysed in plasma with a multiplex Proximity Extension Assay. First, principal components analysis were applied and thereafter regression modelling while correcting for multiple testing. We found profound shifts in the overall inflammatory proteome associated with pregnancy stage after multiple testing (p < .001). Moreover, maternal body mass index (BMI) was associated with inflammatory proteome primarily driven by VEGFA, CCL3 and CSF-1 (p < .05). The levels of most inflammatory proteins changed substantially during pregnancy and some of these were related to biological processes such as regulation of immune response. Maternal BMI was significantly associated with higher levels of three inflammation proteins calling for more research in the interplay between pregnancy, inflammation and BMI.

15.
ERJ Open Res ; 6(4)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33083440

RESUMO

Background: Maternal stress during pregnancy may negatively affect the health of mother and child. We therefore aimed to identify the proportion of women reporting high maternal stress in mid and late pregnancy and explore whether symptoms of maternal allergic disease are associated with perceived maternal stress in late pregnancy. Method: The population-based Preventing Atopic Dermatitis and Allergy in Children (PreventADALL) study enrolled 2697 pregnant women at their 18-week routine ultrasound examination in Norway and Sweden. Information about sociodemographic factors, symptoms and doctor-diagnosed asthma, allergic rhinitis, atopic dermatitis, food allergy, and anaphylaxis and stress using the 14-item perceived stress scale (PSS) was collected at 18 weeks (mid) and 34 weeks (late) pregnancy. High stress was defined as a PSS score ≥29. Scores were analysed using multivariate logistic and linear regression. Results: Among the 2164 women with complete PSS data, 17% reported asthma, 20% atopic dermatitis, 23% allergic rhinitis, 12% food allergy and 2% anaphylaxis. The proportion of women reporting high stress decreased from 15% at mid to 13% at late pregnancy (p<0.01). The adjusted odds ratio for high stress in late pregnancy was 2.25 (95% CI 1.41-3.58) for self-reported symptoms of asthma, 1.46 (95% CI 1.02-2.10) for allergic rhinitis and 2.25 (95% CI 1.32-3.82) for food allergy. A multivariate linear regression model confirmed that symptoms of asthma (ß coefficient 2.11; 0.71-3.51), atopic dermatitis (ß coefficient 1.76; 0.62-2.89) and food allergy (ß coefficient 2.24; 0.63-3.84) were independently associated with increased PSS score. Conclusion: Allergic disease symptoms in pregnancy were associated with increased stress, highlighting the importance of optimal disease control in pregnancy.

16.
Thorax ; 75(12): 1040-1046, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32963117

RESUMO

BACKGROUND: Studies suggest an increased all-cause mortality among adults with asthma. We aimed to study the relationship between asthma in children and young adults and all-cause mortality, and investigate differences in mortality rate by also having a life-limiting condition (LLC) or by parental socioeconomic status (SES). METHODS: Included in this register-based study are 2 775 430 individuals born in Sweden between January 1986 and December 2012. We identified asthma cases using the National Patient Register (NPR) and the Prescribed Drug Register. Those with LLC were identified using the NPR. Parental SES at birth (income and education) was retrieved from Statistics Sweden. We estimated the association between asthma and all-cause mortality using a Cox proportional hazards regression model. Effect modification by LLC or parental SES was studied using interaction terms in the adjusted model. RESULTS: The adjusted hazard rate (adjHR) for all-cause mortality in asthma cases versus non-asthma cases was 1.46 (95% CI 1.33 to 1.62). The highest increased rate appeared to be for those aged 5-15 years. In persons with asthma and without LLC, the adjHR remained increased at 1.33 (95% CI 1.18 to 1.50), but differed (p=0.002) from those with asthma and LLC, with an adjHR of 1.87 (95% CI 1.57 to 2.22). Parental SES did not alter the association (income, p=0.55; education, p=0.83). CONCLUSION: This study shows that asthma is associated with an increased mortality in children and young adults regardless of LLC or parental SES. Further research is warranted to investigate the possible mechanisms for this association.

17.
Epigenet Insights ; 13: 2516865720930701, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32964196

RESUMO

Background: How epigenetic modifications of DNA are associated with gestational age at birth is not fully understood. We investigated potential effects of differential paternal DNA methylation (DNAm) on offspring gestational age at birth by conducting an epigenome-wide search for cytosine-phosphate-guanine (CpG) sites. Methods: Study participants in this study consist of male cohort members or partners of the F1-generation of the Isle of Wight Birth Cohort (IoWBC). DNAm levels in peripheral blood from F1-fathers (n = 92) collected around pregnancy of their spouses were analyzed using the Illumina 450K array. A 5-step statistical analysis was performed. First, a training-testing screening approach was applied to select CpG sites that are potentially associated with gestational age at birth. Second, functional enrichment analysis was employed to identify biological processes. Third, by centralizing on biologically informative genes, Cox proportional hazards models were used to assess the hazard ratios of individual paternal CpGs on gestational age adjusting for confounders. Fourth, to assess the validity of our results, we compared our CpG-gestational age correlations within a Born into Life Study in Sweden (n = 15). Finally, we investigated the correlation between the detected CpGs and differential gene expression in F2 cord blood in the IoWBC. Results: Analysis of DNAm of fathers collected around their partner's pregnancy identified 216 CpG sites significantly associated with gestational age at birth. Functional enrichment pathways analyses of the annotated genes revealed 2 biological pathways significantly related to cell-cell membrane adhesion molecules. Differential methylation of 9 cell membrane adhesion pathway-related CpGs were significantly associated with gestational age at birth after adjustment for confounders. The replication sample showed correlation coefficients of 2 pathway-related CpGs with gestational age at birth within 95% confidence intervals of correlation coefficients in IoWBC. Finally, CpG sites of protocadherin (PCDH) gene clusters were associated with gene expression of PCDH in F2 cord blood. Conclusions: Our findings suggest that differential paternal DNAm may affect gestational age at birth through cell-cell membrane adhesion molecules. The results are novel but require future replication in a larger cohort.

18.
Reprod Sci ; 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32754889

RESUMO

This study aims to evaluate the association of maternal DNA methylation (DNAm) during pregnancy and offspring birthweight. One hundred twenty-two newborn-mother dyads from the Isle of Wight (IOW) cohort were studied to identify differentially methylated cytosine-phosphate-guanine sites (CpGs) in maternal blood associated with offspring birthweight. Peripheral blood samples were drawn from mothers at 22-38 weeks of pregnancy for epigenome-wide DNAm assessment using the Illumina Infinium HumanMethylation450K array. Candidate CpGs were identified using a course of 100 repetitions of a training and testing process with robust regressions. CpGs were considered informative if they showed statistical significance in at least 80% of training and testing samples. Linear mixed models adjusting for covariates were applied to further assess the selected CpGs. The Swedish Born Into Life cohort was used to replicate our findings (n = 33). Eight candidate CpGs corresponding to the genes LMF1, KIF9, KLHL18, DAB1, VAX2, CD207, SCT, SCYL2, DEPDC4, NECAP1, and SFRS3 in mothers were identified as statistically significantly associated with their children's birthweight in the IOW cohort and confirmed by linear mixed models after adjusting for covariates. Of these, in the replication cohort, three CpGs (cg01816814, cg23153661, and cg17722033 with p values = 0.06, 0.175, and 0.166, respectively) associated with four genes (LMF1, VAX2, CD207, and NECAP1) were marginally significant. Biological pathway analyses of three of the genes revealed cellular processes such as endocytosis (possibly sustaining an adequate maternal-fetal interface) and metabolic processes such as regulation of lipoprotein lipase activity (involved in providing substrates for the developing fetus). Our results contribute to an epigenetic understanding of maternal involvement in offspring birthweight. Measuring DNAm levels of maternal CpGs may in the future serve as a diagnostic tool recognizing mothers at risk for pregnancies ending with altered birthweights.

19.
Sci Rep ; 10(1): 13371, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32770128

RESUMO

The use of proton pump inhibitors (PPIs) has been proposed as a potential risk factor for neurodegenerative diseases, but little is known regarding its role in amyotrophic lateral sclerosis (ALS). We therefore aimed to assess the association of PPI use with the subsequent risk of ALS, and performed a register-based nationwide nested case-control study, including 2,484 ALS cases diagnosed during July 2006-December 2013 in Sweden and 10 population controls per case that were individually matched to the case by sex, age, and area of residence. Dispenses and cumulative defined daily doses (cDDDs) of PPIs were extracted from the Swedish Prescribed Drug Register. The association of PPI use with the risk of ALS was assessed using conditional logistic regression, after applying different lag windows to avoid reverse causation. ALS patients were more likely to be dispensed with PPIs before diagnosis than controls. However, previous PPI use was not associated with an increased risk of ALS (OR = 1.08, 95% CI 0.97-1.19), and there was no dose-response relationship between cDDDs of PPIs and ALS risk (p = 0.0874), after excluding dispenses during the year before ALS diagnosis. The results were similar after excluding dispenses during the 2 or 3 years before ALS diagnosis.

20.
Acta Paediatr ; 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32649776

RESUMO

AIM: Neonatal jaundice is associated with higher risk of attention deficit hyperactivity disorder (ADHD), but it is unclear if the association is influenced by genetic and other familial factors. In this large population-based study, we investigated the association between neonatal jaundice and ADHD while adjusting for familial factors. METHODS: We linked several Swedish registers to identify all singleton births without congenital malformations between 1992 and 2000 (n = 814 420, including 384 290 full siblings) and followed them up until 2009. We calculated hazard ratios (HRs) for the association between neonatal jaundice and ADHD, adjusting for pregnancy, delivery and neonatal characteristics including prematurity, and parental age and education. We repeated the analyses among siblings to adjust for shared familial factors. RESULTS: At a population level, children treated for neonatal jaundice had an increased risk of ADHD (adjusted HR (aHR): 1.13, 95% CI: 1.05-1.22). In the sibling comparisons, there was no clear association between neonatal jaundice and ADHD (aHR: 1.03, 95% CI: 0.82-1.29). CONCLUSION: We found no evidence of an independent association between neonatal jaundice and ADHD within siblings in this large population-based study, suggesting that the association is probably influenced by shared familial factors, such as parental genetic and/or lifestyle effects.

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