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1.
J Intern Med ; 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31587396

RESUMO

BACKGROUND: There is limited evidence linking type 2 diabetes (T2D) to influenza-related complications. OBJECTIVES: To test a set of research questions relating to pandemic influenza vaccination, hospitalization and mortality in people with and without T2D. METHODS: In this population-based cohort study, we linked individual-level data from several national registers for all Norwegian residents aged 30 years or older as of January 2009. People with or without T2D at baseline (n=2,992,228) were followed until December 2013. We used Cox regression to estimate adjusted hazard ratios (aHRs). RESULTS: Pandemic influenza hospitalization was more common in individuals with T2D (aHR=2.46, 95%CI 2.04-2.98). The mortality hazard ratio associated with hospitalization for pandemic influenza was lower in people with T2D (aHR=1.82, 95%CI 1.21-2.74) than in those without T2D (aHR=3.89, 95%CI 3.27-4.62). The same pattern was observed when restricting to 90 days mortality (aHR=3.89, 95%CI 1.25-12.06 among those with T2D and aHR=10.79, 95%CI 7.23-16.10 among those without T2D). The rate of hospitalization for pandemic influenza was 78% lower in those vaccinated compared to non-vaccinated among people with T2D (aHR=0.22, 95% CI 0.11-0.39), while the corresponding estimate for those without T2D was 59% lower (aHR=0.41, 95%CI 0.33-0.52). Mortality was 25% lower in those vaccinated compared to non-vaccinated among people with T2D (aHR=0.75, 95% CI 0.73-0.77), while the corresponding estimate for those without T2D was 9% (aHR=0.91, 95%CI 0.90-0.92). CONCLUSIONS: There may have been a lower threshold for pandemic influenza hospitalization for people with T2D, rather than more severe influenza infection. Our combined results support the importance of influenza vaccination among people with T2D, especially during pandemics.

2.
Epigenomics ; 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31536415

RESUMO

Aim: Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for in utero exposure in newborns is unknown. Materials & methods: We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and personal smoking (16 cohorts, 15907 participants, 2433 current smokers). Results & conclusion: Comparing meta-analyses, we identified numerous signatures specific to newborns along with many shared between newborns and adults. Unique smoking-associated genes in newborns were enriched in xenobiotic metabolism pathways. Our findings may provide insights into specific health impacts of prenatal exposure on offspring.

3.
Sci Rep ; 9(1): 9519, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266998

RESUMO

Maternal fever during pregnancy is associated with several adverse child outcomes. We investigated associations between maternal fever and ADHD among offspring, as well as the sub-dimensions of ADHD - inattention and hyperactivity/impulsivity. Data came from the Norwegian Mother and Child Cohort Study, including more than 114,000 children. Information about children's ADHD diagnoses was obtained from the Norwegian Patient Register. Mothers reported on inattention and hyperactivity/impulsivity symptoms in questionnaires at 8 years. Logistic regression analysis showed that children exposed to maternal fever in the first trimester received an ADHD diagnosis more often than unexposed children (Odds Ratio (OR) = 1.31, 95% confidence interval (CI) = 1.06-1.61). For children exposed twice or more in the first trimester, the OR was 2.64 (CI = 1.36-5.14). Linear regression analysis showed elevated inattention symptoms among children exposed to fever in the first (Cohen's d = 0.09, CI = 0.03-0.15) and second (Cohen's d = 0.05, CI = 0.01-0.09) trimester. Results were similar whether the mother had taken acetaminophen for their fever or not. Hyperactivity/impulsivity symptoms were not related to maternal fever. The results indicate that maternal fever in early pregnancy may be a risk factor for ADHD, and particularly for inattention problems. This risk is neither mitigated nor inflated by use of acetaminophen.

4.
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
5.
Hypertension ; 74(2): 375-383, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31230546

RESUMO

Hypertensive disorders of pregnancy (HDP) are associated with low birth weight, shorter gestational age, and increased risk of maternal and offspring cardiovascular diseases later in life. The mechanisms involved are poorly understood, but epigenetic regulation of gene expression may play a part. We performed meta-analyses in the Pregnancy and Childhood Epigenetics Consortium to test the association between either maternal HDP (10 cohorts; n=5242 [cases=476]) or preeclampsia (3 cohorts; n=2219 [cases=135]) and epigenome-wide DNA methylation in cord blood using the Illumina HumanMethylation450 BeadChip. In models adjusted for confounders, and with Bonferroni correction, HDP and preeclampsia were associated with DNA methylation at 43 and 26 CpG sites, respectively. HDP was associated with higher methylation at 27 (63%) of the 43 sites, and across all 43 sites, the mean absolute difference in methylation was between 0.6% and 2.6%. Epigenome-wide associations of HDP with offspring DNA methylation were modestly consistent with the equivalent epigenome-wide associations of preeclampsia with offspring DNA methylation (R2=0.26). In longitudinal analyses conducted in 1 study (n=108 HDP cases; 550 controls), there were similar changes in DNA methylation in offspring of those with and without HDP up to adolescence. Pathway analysis suggested that genes located at/near HDP-associated sites may be involved in developmental, embryogenesis, or neurological pathways. HDP is associated with offspring DNA methylation with potential relevance to development.

6.
Int J Cancer ; 2019 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-31054169

RESUMO

Parental occupational exposures to pesticides, animals and organic dust have been associated with an increased risk of childhood cancer based mostly on case-control studies. We prospectively evaluated parental occupational exposures and risk of childhood leukemia and central nervous system (CNS) tumors in the International Childhood Cancer Cohort Consortium. We pooled data on 329,658 participants from birth cohorts in five countries (Australia, Denmark, Israel, Norway and United Kingdom). Parental occupational exposures during pregnancy were estimated by linking International Standard Classification of Occupations-1988 job codes to the ALOHA+ job exposure matrix. Risk of childhood (<15 years) acute lymphoblastic leukemia (ALL; n = 129), acute myeloid leukemia (AML; n = 31) and CNS tumors (n = 158) was estimated using Cox proportional hazards models to generate hazard ratios (HR) and 95% confidence intervals (CI). Paternal exposures to pesticides and animals were associated with increased risk of childhood AML (herbicides HR = 3.22, 95% CI = 0.97-10.68; insecticides HR = 2.86, 95% CI = 0.99-8.23; animals HR = 3.89, 95% CI = 1.18-12.90), but not ALL or CNS tumors. Paternal exposure to organic dust was positively associated with AML (HR = 2.38 95% CI = 1.12-5.07), inversely associated with ALL (HR = 0.55, 95% CI = 0.31-0.99) and not associated with CNS tumors. Low exposure prevalence precluded evaluation of maternal pesticide and animal exposures; we observed no significant associations with organic dust exposure. This first prospective analysis of pooled birth cohorts and parental occupational exposures provides evidence for paternal agricultural exposures as childhood AML risk factors. The different risks for childhood ALL associated with maternal and paternal organic dust exposures should be investigated further.

7.
Lancet ; 393(10180): 1527-1535, 2019 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-30827781

RESUMO

BACKGROUND: WHO recommends that women wait at least 2 years after a livebirth and at least 6 months after a miscarriage or induced abortion before conceiving again, to reduce the risk of adverse birth outcomes in the subsequent pregnancy. No recommendation exists for the optimal interval after a stillbirth. We investigated the association between interpregnancy interval after stillbirth and birth outcomes in the subsequent pregnancy. METHODS: In this international cohort study, we used data from birth records from Finland (1987-2016), Norway (1980-2015), and Western Australia (1980-2015). Consecutive singleton pregnancies in women whose most recent pregnancy had ended in stillbirth of at least 22 weeks' gestation were included in the analysis. Interpregnancy interval was defined as the time between the end of pregnancy (delivery date) and the start of the next pregnancy (delivery date of next pregnancy minus gestational age at birth). We calculated odds ratios (ORs) for stillbirth, preterm birth, and small-for-gestational-age birth by interpregnancy interval by country, adjusted for maternal age, parity, decade of delivery, and gestational length of the previous pregnancy. A fixed-effects meta-analysis was used to estimate pooled ORs. FINDINGS: We identified 14 452 births in women who had a stillbirth in the previous pregnancy; median interpregnancy interval after stillbirth was 9 months (IQR 4-19). 9109 (63%) women conceived within 12 months of the stillbirth. Of the 14 452 births, 228 (2%) were stillbirths, 2532 (18%) were preterm births, and 1284 (9%) were small-for-gestational-age births. Compared with an interpregnancy interval of 24-59 months, intervals shorter than 12 months were not associated with increased odds of subsequent stillbirth (pooled adjusted OR 1·09 [95% CI 0·63-1·91] for <6 months; 0·90 [0·47-1·71] for 6-11 months), preterm birth (0·91 [0·75-1·11] for <6 months; 0·91 [0·74-1·11] for 6-11 months), or small-for-gestational-age birth (0·66 [0·51-0·85] for <6 months; 0·64 [0·48-0·84] for 6-11 months). Further, we noted no difference in the association between interpregnancy interval and birth outcomes by gestational length of the previous stillbirth. INTERPRETATION: Conception within 12 months of a stillbirth was common and was not associated with increased risk of adverse outcomes in the subsequent pregnancy. These findings could be used when counselling women who are planning future pregnancies after a stillbirth and for informing future recommendations for pregnancy spacing in a high-income setting. FUNDING: National Health and Medical Research Council (Australia), and Research Council of Norway.


Assuntos
Intervalo entre Nascimentos , Internacionalidade , Complicações na Gravidez/epidemiologia , Natimorto , Austrália , Estudos de Coortes , Feminino , Finlândia , Humanos , Noruega , Gravidez
8.
BMJ ; 364: l869, 2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30894356

RESUMO

OBJECTIVES: To estimate the burden of miscarriage in the Norwegian population and to evaluate the associations with maternal age and pregnancy history. DESIGN: Prospective register based study. SETTING: Medical Birth Register of Norway, the Norwegian Patient Register, and the induced abortion register. PARTICIPANTS: All Norwegian women that were pregnant between 2009-13. MAIN OUTCOME MEASURE: Risk of miscarriage according to the woman's age and pregnancy history estimated by logistic regression. RESULTS: There were 421 201 pregnancies during the study period. The risk of miscarriage was lowest in women aged 25-29 (10%), and rose rapidly after age 30, reaching 53% in women aged 45 and over. There was a strong recurrence risk of miscarriage, with age adjusted odds ratios of 1.54 (95% confidence interval 1.48 to 1.60) after one miscarriage, 2.21 (2.03 to 2.41) after two, and 3.97 (3.29 to 4.78) after three consecutive miscarriages. The risk of miscarriage was modestly increased if the previous birth ended in a preterm delivery (adjusted odds ratio 1.22, 95% confidence interval 1.12 to 1.29), stillbirth (1.30, 1.11 to 1.53), caesarean section (1.16, 1.12 to 1.21), or if the woman had gestational diabetes in the previous pregnancy (1.19, 1.05 to 1.36). The risk of miscarriage was slightly higher in women who themselves had been small for gestational age (1.08, 1.04 to 1.13). CONCLUSIONS: The risk of miscarriage varies greatly with maternal age, shows a strong pattern of recurrence, and is also increased after some adverse pregnancy outcomes. Miscarriage and other pregnancy complications might share underlying causes, which could be biological conditions or unmeasured common risk factors.


Assuntos
Aborto Espontâneo/epidemiologia , Idade Materna , Aborto Habitual/epidemiologia , Aborto Espontâneo/etiologia , Adulto , Fatores Etários , Feminino , Humanos , Pessoa de Meia-Idade , Noruega/epidemiologia , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Recidiva , Sistema de Registros , História Reprodutiva , Medição de Risco/métodos , Fatores de Risco , Natimorto/epidemiologia , Adulto Jovem
9.
Influenza Other Respir Viruses ; 13(3): 240-247, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30637942

RESUMO

BACKGROUND: The burden of influenza in Norway remains uncertain, and data on seasonal variations and differences by age groups are needed. OBJECTIVE: To describe number of patients diagnosed with influenza in Norway each season and the number treated in primary or specialist health care by age. Further, to compare the burden of seasonal influenza with the 2009-2010 pandemic outbreak. METHODS: We used Norwegian national health registries and identified all patients diagnosed with influenza from 2008 to 2017. We calculated seasonal rates, compared hospitalized patients with patients in primary care and compared seasonal influenza with the 2009-2010 pandemic outbreak. RESULTS: Each season, on average 1.7% of the population were diagnosed with influenza in primary care, the average rate of hospitalization was 48 per 100 000 population while the average number of hospitalized patients each season was nearly 2500. The number of hospitalized influenza patients ranged from 579 in 2008-2009 to 4973 in 2016-2017. Rates in primary care were highest among young adults while hospitalization rates were highest in patients 80 years and older and in children below 5 years. The majority of in-hospital deaths were in patients 70 years and older. Fewer patients were hospitalized during the 2009-2010 pandemic than in seasonal outbreaks, but during the pandemic, more people in the younger age groups were hospitalized and fatal cases were younger. CONCLUSION: Influenza causes a substantial burden in primary care and hospitals. In non-pandemic seasons, people above 80 years have the highest risk of influenza hospitalization and death.

10.
Int J Cancer ; 144(1): 26-33, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30098208

RESUMO

The "delayed infection hypothesis" states that a paucity of infections in early childhood may lead to higher risks of childhood leukemia (CL), especially acute lymphoblastic leukemia (ALL). Using prospectively collected data from six population-based birth cohorts we studied the association between birth order (a proxy for pathogen exposure) and CL. We explored whether other birth or parental characteristics modify this association. With 2.2 × 106 person-years of follow-up, 185 CL and 136 ALL cases were ascertained. In Cox proportional hazards models, increasing birth order (continuous) was inversely associated with CL and ALL; hazard ratios (HR) = 0.88, 95% confidence interval (CI): (0.77-0.99) and 0.85: (0.73-0.99), respectively. Being later-born was associated with similarly reduced hazards of CL and ALL compared to being first-born; HRs = 0.78: 95% CI: 0.58-1.05 and 0.73: 0.52-1.03, respectively. Successive birth orders were associated with decreased CL and ALL risks (P for trend 0.047 and 0.055, respectively). Multivariable adjustment somewhat attenuated the associations. We found statistically significant and borderline interactions between birth weight (p = 0.024) and paternal age (p = 0.067), respectively, in associations between being later-born and CL, with the lowest risk observed for children born at <3 kg with fathers aged 35+ (HR = 0.18, 95% CI: 0.06-0.50). Our study strengthens the theory that increasing birth order confers protection against CL and ALL risks, but suggests that this association may be modified among subsets of children with different characteristics, notably advanced paternal age and lower birth weight. It is unclear whether these findings can be explained solely by infectious exposures.


Assuntos
Ordem de Nascimento , Peso ao Nascer , Idade Paterna , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Humanos , Análise Multivariada , Modelos de Riscos Proporcionais , Sistema de Registros/estatística & dados numéricos
11.
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.

12.
Paediatr Perinat Epidemiol ; 32(6): 568-583, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30466188

RESUMO

BACKGROUND: Childhood cancer is a rare but leading cause of morbidity and mortality. Established risk factors, accounting for <10% of incidence, have been identified primarily from case-control studies. However, recall, selection and other potential biases impact interpretations particularly, for modest associations. A consortium of pregnancy and birth cohorts (I4C) was established to utilise prospective, pre-diagnostic exposure assessments and biological samples. METHODS: Eligibility criteria, follow-up methods and identification of paediatric cancer cases are described for cohorts currently participating or planning future participation. Also described are exposure assessments, harmonisation methods, biological samples potentially available for I4C research, the role of the I4C data and biospecimen coordinating centres and statistical approaches used in the pooled analyses. RESULTS: Currently, six cohorts recruited over six decades (1950s-2000s) contribute data on 388 120 mother-child pairs. Nine new cohorts from seven countries are anticipated to contribute data on 627 500 additional projected mother-child pairs within 5 years. Harmonised data currently includes over 20 "core" variables, with notable variability in mother/child characteristics within and across cohorts, reflecting in part, secular changes in pregnancy and birth characteristics over the decades. CONCLUSIONS: The I4C is the first cohort consortium to have published findings on paediatric cancer using harmonised variables across six pregnancy/birth cohorts. Projected increases in sample size, expanding sources of exposure data (eg, linkages to environmental and administrative databases), incorporation of biological measures to clarify exposures and underlying molecular mechanisms and forthcoming joint efforts to complement case-control studies offer the potential for breakthroughs in paediatric cancer aetiologic research.

13.
BMC Infect Dis ; 18(1): 525, 2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-30348103

RESUMO

BACKGROUND: The effects of maternal influenza infection on the fetus remain unclear. We studied mild influenza and influenza antibodies in relation to birth weight and risks of pre-eclampsia, preterm birth (PTB), and small for gestational age (SGA) birth among the unvaccinated participants in the Norwegian Influenza Pregnancy Cohort. METHODS: Pregnant women attending a routine ultrasound were recruited from four hospitals in Norway shortly after the 2009 A(H1N1) pandemic. The present study was restricted to unvaccinated participants who were pregnant during the pandemic. Information on the participants was obtained through questionnaires and linkage with national registries. Maternal blood samples were collected at delivery. Women with laboratory-confirmed A(H1N1)pdm09 influenza, a clinical diagnosis of influenza, or self-reported influenza during the pandemic were classified as having had influenza. A(H1N1)pdm09-specific antibodies in serum were detected with the hemagglutination-inhibition assay. Detection of antibodies was considered an indicator of infection during the pandemic in the unvaccinated participants. Odds ratios were estimated with logistic regression. Quantile regression was used to estimate differences in the distribution of birth weight. RESULTS: Among the 1258 women included in this study, there were 37 cases of pre-eclampsia, 41 births were PTB, and 103 births were SGA. 226 women (18.0%) had influenza during the pandemic. The majority of cases did not receive medical care, and only a small proportion (1.3%) of the cases were hospitalized. Thus, the cases consisted primarily of women with mild illness. No significant associations between influenza and risk of pre-eclampsia, PTB, or SGA birth were observed. Detection of A(H1N1)pdm09-specific antibodies was associated with a lower 10th percentile of birth weight, ß = - 159 g (95% CI - 309, - 9). CONCLUSIONS: Mild influenza illness during pregnancy was not associated with increased risk of pre-eclampsia, PTB or SGA birth. However, influenza infection during pregnancy may reduce the birth weight of the smallest children.

14.
Diabetologia ; 61(11): 2310-2318, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29995214

RESUMO

AIMS/HYPOTHESIS: This study aimed to examine recent time trends in the incidence and prevalence of type 2 diabetes in Norway. METHODS: In this Norwegian nationwide cohort study, we linked data from national registries with prospectively collected data on diabetes medication and diabetes diagnoses for all residents in Norway aged 30 to 89 years (>3.2 million people). We analysed trends in incidence and prevalence of type 2 diabetes from 2009 to 2014 by type of treatment, sex, age, education level and place of birth. RESULTS: During 15,463,691 person-years of follow-up from 2009 to 2014, we identified 75,496 individuals with new-onset type 2 diabetes. Of these, 36,334 (48%) were treated with blood-glucose-lowering drugs within 6 months of diagnosis. A low education level and being born in Asia, Africa or South America were significant risk factors for incident type 2 diabetes. While the prevalence of type 2 diabetes increased from 4.9% to 6.1% during the study period, the incidence decreased significantly from 609 cases per 100,000 person-years in 2009 to 398 cases per 100,000 in 2014, an annual reduction of 10.1% (95% CI -10.5, -9.6). A declining incidence was seen for both pharmacologically and non-pharmacologically treated type 2 diabetes, and in all subgroups defined by sex, age group, education level and place of birth. CONCLUSIONS/INTERPRETATIONS: This nationwide study shows that, despite a decreasing incidence of type 2 diabetes in Norway, the prevalence continues to rise, probably due to diagnosis at a younger age and increased longevity.

15.
Diabetologia ; 2018 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-29934759

RESUMO

AIMS/HYPOTHESIS: Case reports have linked influenza infections to the development of type 1 diabetes. We investigated whether pandemic and seasonal influenza infections were associated with subsequent increased risk of type 1 diabetes. METHODS: In this population-based registry study, we linked individual-level data from national health registries for the entire Norwegian population under the age of 30 years for the years 2006-2014 (2.5 million individuals). Data were obtained from the National Registry (population data), the Norwegian Patient Registry (data on inpatient and outpatient specialist care), the Primary Care Database, the Norwegian Prescription Database and the Norwegian Surveillance System for Communicable Diseases. Pandemic influenza was defined as either a clinical influenza diagnosis during the main pandemic period or a laboratory-confirmed test. Seasonal influenza was defined by a clinical diagnosis of influenza between 2006 and 2014. We used Cox regression to estimate HRs for new-onset type 1 diabetes after an influenza infection, adjusted for year of birth, sex, place of birth and education. RESULTS: The adjusted HR for type 1 diabetes after pandemic influenza infection was 1.19 (95% CI 0.97, 1.46). In the subgroup with laboratory-confirmed influenza A (H1N1), influenza was associated with a twofold higher risk of subsequent type 1 diabetes before age 30 years (adjusted HR: 2.26, 95% CI 1.51, 3.38). CONCLUSIONS/INTERPRETATION: Overall, we could not demonstrate a clear association between clinically reported pandemic influenza infection and incident type 1 diabetes. However, we found a twofold excess of incident diabetes in the subgroup with laboratory-confirmed pandemic influenza A (H1N1).

16.
Early Hum Dev ; 122: 1-7, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29803166

RESUMO

BACKGROUND: Studies investigating gestational influenza and child neurodevelopment are still scarce, particularly concerning timing of infection in pregnancy. This is the first study to investigate associations between gestational influenza and infant psychomotor development and temperament at 6 months. METHODS: Data from The Norwegian Influenza Pregnancy Cohort, established during the 2009 swine flu pandemic, were utilized. Information on influenza infection, vaccination, maternal health and child health and development is available from questionnaires, national registry data and maternal blood samples drawn at delivery. Maternal influenza A H1N1 pdm09 infection was serologically confirmed. 609 children with complete data were identified. Children of exposed and non-exposed mothers were compared using generalized linear models. RESULTS: Children exposed to influenza during gestational weeks (gw) 0-8 had adjusted general development scores indicating slightly delayed development compared to non-exposed children (0.28 standard deviations (SD) 95% confidence interval (CI): -0. 01; 0.58; p = 0.06). The temperamental scores of children exposed during gw 0-8 were slightly higher (0.31 SD; 95% CI: -0. 03; 0.64; p = 0.07) than non-exposed children indicating a more difficult temperament. In comparison, the developmental scores for children exposed in gw 9-40 were -0.31 SD (95% CI: -0. 65; 0.04; p = 0.09) better than non-exposed children, while the temperamental scores were 0.17 (95% CI: -0. 23; 0.56; p = 0.36) for the same period. CONCLUSION: Modest associations were found between maternal influenza A (H1N1) pdm infection during gestational weeks 0-8 and psychomotor development at 6 months.

17.
Am J Clin Nutr ; 107(5): 789-798, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29722838

RESUMO

Background: Western diets may provide excess vitamin A, which is potentially toxic and could adversely affect respiratory health and counteract benefits from vitamin D. Objective: The aim of this study was to examine child asthma at age 7 y in relation to maternal intake of vitamins A and D during pregnancy, infant supplementation with these vitamins, and their potential interaction. Design: We studied 61,676 school-age children (born during 2002-2007) from the Norwegian Mother and Child Cohort with data on maternal total (food and supplement) nutrient intake in pregnancy (food-frequency questionnaire validated against biomarkers) and infant supplement use at age 6 mo (n = 54,142 children). Linkage with the Norwegian Prescription Database enabled near-complete follow-up (end of second quarter in 2015) for dispensed medications to classify asthma. We used log-binomial regression to calculate adjusted RRs (aRRs) for asthma with 95% CIs. Results: Asthma increased according to maternal intake of total vitamin A [retinol activity equivalents (RAEs)] in the highest (≥2031 RAEs/d) compared with the lowest (≤779 RAEs/d) quintile (aRR: 1.21; 95% CI: 1.05, 1.40) and decreased for total vitamin D in the highest (≥13.6 µg/d) compared with the lowest (≤3.5 µg/d) quintile (aRR: 0.81; 95% CI: 0.67, 0.97) during pregnancy. No association was observed for maternal intake in the highest quintiles of both nutrients (aRR: 0.99; 95% CI: 0.83, 1.18) and infant supplementation with vitamin D or cod liver oil. Conclusions: Excess vitamin A (≥2.5 times the recommended intake) during pregnancy was associated with increased risk, whereas vitamin D intake close to recommendations was associated with a reduced risk of asthma in school-age children. No association for high intakes of both nutrients suggests antagonistic effects of vitamins A and D. This trial was registered at http://www.clinicaltrials.gov as NCT03197233.

18.
Pediatrics ; 141(3)2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29449342

RESUMO

OBJECTIVES: To determine if pandemic influenza vaccination was associated with an increased risk of epilepsy in children. METHODS: Information from Norwegian registries from 2006 through 2014 on all children <18 years living in Norway on October 1, 2009 was used in Cox regression models to estimate hazard ratios for incident epilepsy after vaccination. A self-controlled case series analysis was used to estimate incidence rate ratios in defined risk periods after pandemic vaccination. RESULTS: In Norway, the main period of the influenza A subtype H1N1 pandemic was from October 2009 to December 2009. On October 1, 2009, 1 154 113 children <18 years of age were registered as residents in Norway. Of these, 572 875 (50.7%) were vaccinated against pandemic influenza. From October 2009 through 2014 there were 3628 new cases of epilepsy (incidence rate 6.09 per 10 000 person-years). The risk of epilepsy was not increased after vaccination: hazard ratio: 1.07; 95% confidence interval: 0.94-1.23. Results from the self-controlled case series analysis supported the finding of no association between vaccination and subsequent epilepsy. CONCLUSIONS: Pandemic influenza vaccination was not associated with increased risk of epilepsy. Concerns about pandemic vaccination causing epilepsy in children seem to be unwarranted.

20.
Am J Epidemiol ; 187(6): 1199-1209, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29244063

RESUMO

Prenatal maternal psychosocial stress might influence the development of childhood asthma. Evaluating paternal psychosocial stress and conducting a sibling comparison could provide further insight into the role of unmeasured confounding. We examined the associations of parental psychosocial stress during and after pregnancy with asthma at age 7 years in the Norwegian Mother and Child Cohort Study (n = 63,626; children born in 2000-2007). Measures of psychosocial stress included lifetime major depressive symptoms, current anxiety/depression symptoms, use of antidepressants, anxiolytics, and/or hypnotics, life satisfaction, relationship satisfaction, work stress, and social support. Childhood asthma was associated with maternal lifetime major depressive symptoms (adjusted relative risk (aRR) = 1.19, 95% confidence interval (CI): 1.09, 1.30), in addition to symptoms of anxiety/depression during pregnancy (aRR = 1.17, 95% CI: 1.06, 1.29) and 6 months after delivery (aRR = 1.17, 95% CI: 1.07, 1.28). Maternal negative life events during pregnancy (aRR = 1.10, 95% CI: 1.06, 1.13) and 6 months after delivery (aRR = 1.14, 95% CI: 1.11, 1.18) were also associated with asthma. These associations were not replicated when evaluated within sibling groups. There were no associations with paternal psychosocial stress. In conclusion, maternal anxiety/depression and negative life events were associated with offspring asthma, but this might be explained by unmeasured maternal background characteristics that remain stable across deliveries.

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