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Background There have been concerns about COVID-19 vaccination safety among frail older individuals. We investigated the relationship between COVID-19 mRNA vaccination and mortality among individuals aged ≥ 70 years and whether mortality varies across four groups of health services used. Methods In this nationwide cohort study, we included 688,152 individuals aged ≥ 70 years at the start of the Norwegian vaccination campaign (December 27, 2020). We collected individual-level data from the Norwegian Emergency Preparedness Register for COVID-19. Vaccinated and unvaccinated individuals were matched (1:1 ratio) on the date of vaccination based on sociodemographic and clinical characteristics. The main outcome was all-cause mortality during 21 days after first dose of COVID-19 mRNA vaccination. Kaplan-Meier survival functions were estimated for the vaccinated and unvaccinated groups. We used Cox proportional-hazards regression to estimate hazard ratios (HRs) of death between vaccinated and unvaccinated individuals, with associated 95% confidence intervals (CIs), overall and by use of health services (none, home-based, short- and long-term nursing homes) and age group. Results Between December 27, 2020, and March 31, 2021, 420,771 older individuals (61.1%) were vaccinated against COVID-19. The Kaplan-Meier estimates based on the matched study sample showed a small absolute risk difference in all-cause mortality between vaccinated and unvaccinated individuals, with a lower mortality in the vaccinated group (overall HR 0.28 [95% CI: 0.24–0.31]). Similar results were obtained in analyses stratified by use of health services and age group. Conclusion We found no evidence of increased short-term mortality among vaccinated individuals in the older population after matching on sociodemographic and clinical characteristics affecting vaccination and mortality. publishedVersion

Background: Whether the SARS-CoV-2 mRNA vaccines may cause a transient increased stroke risk is uncertain. Methods: In a registry-based cohort of all adult residents at December 27, 2020, in Norway, we linked individual-level data on COVID-19 vaccination, positive SARS-CoV-2 test, hospital admissions, cause of death, health care worker status, and nursing home resident status extracted from the Emergency Preparedness Register for COVID-19 in Norway. The cohort was followed for incident intracerebral bleeding, ischemic stroke, and subarachnoid hemorrhage within the first 28 days after the first/second or third dose of mRNA vaccination until January 24, 2022. Stroke risk after vaccination relative to time not exposed to vaccination was assessed by Cox proportional hazard ratio, adjusted for age, sex, risk groups, health care personnel, and nursing home resident. Results: The cohort included 4 139 888 people, 49.8% women, and 6.7% were ≥80 years of age. During the first 28 days after an mRNA vaccine, 2104 people experienced a stroke (82% ischemic stroke, 13% intracerebral hemorrhage, and 5% subarachnoid hemorrhage). Adjusted hazard ratios (95% CI) after the first/second and after the third mRNA vaccine doses were 0.92 (0.85–1.00) and 0.89 (0.73–1.08) for ischemic stroke, 0.81 (0.67–0.98) and 1.05 (0.64–1.71) for intracerebral hemorrhage, and 0.64 (0.46–0.87) and 1.12 (0.57–2.19) for subarachnoid hemorrhage, respectively. Conclusions: We did not find increased risk of stroke during the first 28 days after an mRNA SARS-CoV-2 vaccine.

The present study compared the effects of eccentric cycling (ECC) and conventional concentric cycling (CONC) training on muscle function, body composition, functional performance, and quality of life (QOL) of patients with moderate chronic obstructive pulmonary disease (COPD). Twenty patients (age: 69.6 ± 10.1 years, forced expiratory volume in 1-s: 73.2 ± 11.4% of predicted) were randomly allocated to ECC (n = 10) or CONC (n = 10) group. They performed 12 weeks of ECC or CONC training at similar perceived exertion. The workload, heart rate (HR), blood oxygen saturation (SpO2), and dyspnea were monitored during cycling. Outcomes measures included maximal voluntary isometric contraction (MVC) strength of the knee extensors, rate of force development (RFD), lower limb fat-free (LLFFM) and fat (LLFM) mass, 6-min walking test (6MWT), timed up-and-go test (TUG), stairs ascending (SAWT) and descending walking time (SDWT), and QOL assessed by the Saint George's respiratory questionnaire. ECC produced on average threefold greater (P

BackgroundSocioeconomic status in the risk of developing type 1 diabetes seems inconsistent. We investigated whether risk of childhood-onset type 1 diabetes differed by parental education or occupation in a nationwide cohort.MethodsThis cohort study included all children born in Norway from 1974 to 2013. In individually linked data from nationwide population registries following children born in Norway up to 15 years of age, we identified 4647 with newly diagnosed type 1 diabetes during 15,381,923 person-years of follow-up.ResultsChildren of mothers with a master’s degree had lower risk of type 1 diabetes than children of mothers with completed upper secondary education only: adjusted incidence rate ratio, aIRR=0.81 95% confidence interval: 0.69 - 0.95). There was no difference between upper secondary and lower secondary maternal education (aIRR=0.98, 95% confidence interval 0.89-1.08). Paternal education was not significantly associated with type 1 diabetes. While maternal elementary occupation was associated with a lower risk of type 1 diabetes, specific maternal- or paternal occupations were not.ConclusionsOur results suggested inverse U-shaped associations between maternal socioeconomic status and risk of type 1 diabetes. Non-linear associations be part of the reason why previous literature has been inconsistent.

Background and aim Genetic markers are established as predictive of type 1 diabetes, but unknown early life environment is believed to be involved. Umbilical cord blood may reflect perinatal metabolism and exposures. We studied whether selected polar metabolites in cord blood contribute to prediction of type 1 diabetes. Methods Using a targeted UHPLC-QQQ-MS platform, we quantified 27 low-molecular-weight metabolites (including amino acids, small organic acids, and bile acids) in 166 children, who later developed type 1 diabetes, and 177 random control children in the Norwegian Mother, Father, and Child cohort. We analyzed the data using logistic regression (estimating odds ratios per SD [adjusted odds ratio (aOR)]), area under the receiver operating characteristic curve (AUC), and k-means clustering. Metabolites were compared to a genetic risk score based on 51 established non-HLA single-nucleotide polymorphisms, and a 4-category HLA risk group. Results The strongest associations for metabolites were aminoadipic acid (aOR = 1.23; 95% CI, 0.97-1.55), indoxyl sulfate (aOR = 1.15; 95% CI, 0.87-1.51), and tryptophan (aOR = 0.84; 95% CI, 0.65-1.10), with other aORs close to 1.0, and none significantly associated with type 1 diabetes. K-means clustering identified 6 clusters, none of which were associated with type 1 diabetes. Cross-validated AUC showed no predictive value of metabolites (AUC 0.49), whereas the non-HLA genetic risk score AUC was 0.56 and the HLA risk group AUC was 0.78. Conclusions In this large study, we found no support of a predictive role of cord blood concentrations of selected bile acids and other small polar metabolites in the development of type 1 diabetes.

OBJECTIVE To study whether serum galectin-3 and other biomarkers of inflammation predict coronary heart disease (CHD) in subjects with long-standing childhood-onset type 1 diabetes. RESEARCH DESIGN AND METHODS A population-based nationwide cohort of 299 subjects with type 1 diabetes diagnosed in Norway at RESULTS Of 295 subjects, 40 (13.6%) had a documented CHD event during a mean follow-up of 14.4 years (range 0.5–16). IL-6 (aHR 1.32 [95% CI 1.07–1.63]), galectin-3 (aHR 1.44 [95% CI 1.09–1.80]), and TIMP-1 (aHR 1.37 [95% CI 1.04–1.81]) were significant predictors of CHD after adjustment for conventional risk factors. CONCLUSIONS Galectin-3 was significantly associated with future CHD in subjects with type 1 diabetes, and if the results are replicated in larger studies, it may aid in prediction together with conventional risk factors for CHD.

Maternal diet can influence the developing immune system of the offspring. We hypothesized that maternal fibre and gluten intake during pregnancy were associated with the risk of celiac disease in the child. In the Norwegian Mother, Father and Child Cohort Study (MoBa, n = 85,898) higher maternal fibre intake (median 29.5 g/day) was associated with a lower risk of celiac disease in the offspring (adjusted relative risk 0.90, 95% CI 0.83 to 0.98 per 10 g/d increase). Gluten intake during pregnancy (median 13.0 g/d) was associated with a higher risk of childhood CD (adjusted relative risk = 1.21, 95% CI 1.02 to 1.43 per 10 g/d increase). These results were largely unaffected by adjustment for the child’s gluten intake at 18 months. In an independent study of 149 mother/child dyads, maternal fibre intake did not predict concentrations of total or sub-types of short-chain fatty acids in repeated infant stool samples, or fecal microbiome diversity in the mother or child. Our results suggest that high fibre and low gluten intake during pregnancy could be protective factors for celiac disease, although the mechanism is unknown.

Disturbances in skeletal muscle lipid oxidation might induce ectopic fat deposition and lipotoxicity. Nevertheless, the cellular mechanisms that regulate skeletal muscle lipid oxidation have not been fully determined. We aimed to determine whether there was an association between relative whole body lipid oxidation and mitochondrial size or mitochondria-sarcoplasmic reticulum interactions in the skeletal muscle. Twelve healthy men were included [mean (standard deviation), 24.7 (1.5) yr old, 24.4 (2.6) kg/m2]. The respiratory quotient (RQ) was used to estimate relative lipid oxidation at rest and during exercise (50% maximal oxygen consumption, 600 kcal expended). A skeletal muscle biopsy was obtained from the vastus lateralis at rest. Transmission electron microscopy was used to determine mitochondrial size and mitochondria-sarcoplasmic reticulum interactions (≤50 nm of distance between organelles). Protein levels of fusion/fission regulators were measured in skeletal muscle by Western blot. Resting RQ and exercise RQ associated inversely with intermyofibrillar mitochondrial size ( r = −0.66 and r = −0.60, respectively, P < 0.05). Resting RQ also associated inversely with the percentage of intermyofibrillar mitochondria-sarcoplasmic reticulum interactions ( r = −0.62, P = 0.03). Finally, intermyofibrillar mitochondrial size associated inversely with lipid droplet density ( r = −0.66, P = 0.01) but directly with mitochondria fusion-to-fission ratio ( r = 0.61, P = 0.03). Our results show that whole body lipid oxidation is associated with skeletal muscle intermyofibrillar mitochondrial size, fusion phenotype, and mitochondria-sarcoplasmic-reticulum interactions in nondiabetic humans.

Maternal antibiotic use during pregnancy has been linked to asthma risk in children, but the role of underlying infections remains unclear. We investigated the association of maternal antibiotic use and infections during pregnancy with offspring risk of asthma. We used two population-based cohorts: the Norwegian Mother, Father and Child Cohort Study (MoBa) (n = 53 417) and a register-based cohort (n = 417 548). Asthma was defined based on dispensed asthma medications at 7 and 13 years from the Norwegian Prescription Database. Self-reported information on antibiotic use and infections during pregnancy was available in MoBa, while registrations of dispensed prescriptions were used to classify use of antibiotics in the register-based cohort. Maternal antibiotic use during pregnancy was associated with asthma at 7 in both cohorts (adjusted risk ratio (aRR) 1.23, 95% CI 1.11–1.37 in MoBa and 1.21, 1.16–1.25 in the register cohort) and asthma at 13 in the register cohort (1.13, 1.03–1.23) after adjusting for maternal characteristics. In MoBa, the estimate was attenuated after adjusting for infections during pregnancy. Maternal lower and upper respiratory tract infections (aRR 1.30, 95% CI 1.07–1.57 and 1.19, 1.09–1.30, respectively) and urinary tract infections (1.26, 1.11–1.42) showed associations with asthma at 7. Register cohort also showed an increased risk of asthma in relation to maternal antibiotics before and after pregnancy. Our findings suggest that both maternal antibiotics and infections during pregnancy have a role in the risk of offspring asthma. However, results from the register cohort suggest that the effect of antibiotics may reflect the shared underlying susceptibility.

Purpose To investigate incidence of end-stage renal disease (ESRD), and the association of education and coronary heart disease (CHD) with ESRD, in subjects throughout Norway followed from the diagnosis of childhood-onset type 1 diabetes. Methods All new onset cases of type 1 diabetes 1973–2016 were followed for CHD and ESRD in nation-wide registries through 2017. Ten matched controls per case were selected from the National Population Register. Cox regression was used to estimate hazard ratios, and probabilities were estimated by the cumulative incidence function accounting for competing risk. Results Among 9311 patients with type 1 diabetes, 130 developed ESRD with a probability of ESRD after 40 years of 5.5%. The rate was 35-fold higher than in controls (aHR = 35.5, 95% CI 23.1 – 54.6). Higher education was associated with lower risk of ESRD compared to low education (aHR = 0.14, 95% CI 0.07 – 0.27). Diagnosed CHD was associated with 14-fold increased rate of ESRD (aHR = 14.3, 95% CI 9.2 – 22.2). Conclusions The hazard rate of ESRD was 35-fold higher in cases compared to controls. CHD was associated with a 14-fold increased rate of subsequent ESRD, while higher education was associated with substantially lower rate of ESRD. publishedVersion

The present study compared the effects of eccentric cycling (ECC) and conventional concentric cycling (CONC) training on muscle function, body composition, functional performance, and quality of life (QOL) of patients with moderate chronic obstructive pulmonary disease (COPD).Twenty patients (age: 69.6 ± 10.1 years, forced expiratory volume in 1-s: 73.2 ± 11.4% of predicted) were randomly allocated to ECC (n = 10) or CONC (n = 10) group. They performed 12 weeks of ECC or CONC training at similar perceived exertion. The workload, heart rate (HR), blood oxygen saturation (SpOECC produced on average threefold greater (P 0.001) workload (211.8 ± 106.0 kJ) than CONC (78.1 ± 62.6 kJ) over 34 training sessions. ECC showed 1.5 ± 2.1% greater SpOThese results suggest that ECC training with less cardio-pulmonary demands was more effective in increasing functional performance and muscle mass for COPD patients than CONC training.

ObjectiveTo determine risk factors for SARS-CoV-2 infection and hospitalisation among children and adolescents.DesignNationwide, population-based cohort study. Setting: Norway from 1 March 2020 to 31 April 2021. Participants: All Norwegian residents Main outcome measuresPopulation-based health care and population registries were used to study risk factors for SARS-CoV-2 infection, including socioeconomic factors, country of origin, and pre-existing chronic comorbidities. All residents were followed until age 18, emigration, death, or end of follow-up. Hazard ratios (HR) estimated by Cox regression models were adjusted for testing frequency. Further, risk factors for admission to the hospital among the infected were investigated.ResultsOf 1 182 796 residents, 22608 (1.9%) tested positive by polymerase chain reaction or lateral flow tests, of whom 107 (0.5%) were admitted to a hospital. Low family income (aHR 1.40, 95% confidence interval 1.36 to 1.46), crowded housing (1.35, 1.30 to 1.39), household size, age, and area of living were independent risk factors for infection. A non-Nordic country of origin was the strongest risk factor (aHR 2.37, 95% CI 2.30 to 2.49), whereas chronic comorbidity was not associated with the risk of infection. Chronic comorbidity was associated with hospitalisation (aHR 4.15, 2.63 to 6.56), in addition to age, whereas socioeconomic status and country of origin did not predict hospitalisation among those infected.ConclusionsSocioeconomic factors, country of origin, and area of living were associated with the risk of SARS-CoV-2 infection. However, these factors did not predict hospitalisation among those infected. Chronic comorbidity was associated with the risk of admission but not with the overall risk of acquiring SARS-CoV-2.What is already known on this topicHospital admissions rates for covid-19 among children and adolescents are low compared to adults. Admission rates to hospitals and intensive care units for covid-19 have been higher in minority groups and in children and adolescents with chronic comorbidity.Whether underlying differences in susceptibility for severe disease or the incidence of infections are driving these associations have not been investigated.What this study addsLow family income, crowded housing and household size, and country of origin outside the Nordic countries were associated with increased risk of infection with SARS-CoV-2.None of these factors, but chronic comorbidities, were associated with the risk of hospital admission among those infected.

Microbiomes are vast communities of microorganisms and viruses that populate all natural ecosystems. Viruses have been considered to be the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared with that of other environments. Here, we investigate the origin, evolution and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboration, we obtained DNA sequences of crAssphage from more than one-third of the world's countries and showed that the phylogeography of crAssphage is locally clustered within countries, cities and individuals. We also found fully colinear crAssphage-like genomes in both Old-World and New-World primates, suggesting that the association of crAssphage with primates may be millions of years old. Finally, by exploiting a large cohort of more than 1,000 individuals, we tested whether crAssphage is associated with bacterial taxonomic groups of the gut microbiome, diverse human health parameters and a wide range of dietary factors. We identified strong correlations with different clades of bacteria that are related to Bacteroidetes and weak associations with several diet categories, but no significant association with health or disease. We conclude that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome. ispartof: NATURE MICROBIOLOGY vol:4 issue:10 pages:1727-1736 ispartof: location:England status: published

OBJECTIVE: To determine the association between the amount of gluten intake in childhood and later celiac disease (CD), for which data are currently scarce. METHODS: The prospective DAISY cohort includes 1875 at-risk children with annual estimates of gluten intake (grams/day) from age one year. From 1993 through January 2017, 161 children were, via repeated tissue transglutaminase (tTGA) screening, identified with CD autoimmunity (CDA, persistent tTGA positivity); of these, 85 children fulfilled CD criteria of biopsy-verified histopathology or persistently high tTGA levels. Cox regression, modeling gluten intake between ages one and two years (i.e., in one-year-olds), and joint modeling of cumulative gluten intake throughout childhood, were used to estimate hazard ratios adjusted for confounders (aHR). RESULTS: Children in the highest third of gluten intake between the ages of one and two years had a 2-fold greater hazard of CDA (aHR 2.17; 95%CI, 1.22–3.88; P-value=0.01) and CD (aHR 1.96; 95%CI, 0.90–4.24; P-value=0.09) than those in the lowest third. The risk of developing CDA increased by 5% per daily gram increase in gluten intake (aHR 1.05; 95%CI, 1.00–1.09; P-value=0.04) in one-year-olds. The association between gluten intake in one-year-olds and later CDA or CD did not differ by the child’s HLA genotype. The incidence of CD increased with increased cumulative gluten intake throughout childhood (e.g., aHR 1.15 per standard deviation increase in cumulative gluten intake at age six; 95%CI, 1.00–1.32; P-value=0.04). CONCLUSIONS: Gluten intake in one-year-olds is associated with the future onset of CDA and CD in children at risk for the disease.

OBJECTIVE Circumstantial evidence links 25-hydroxy vitamin D [25(OH)D], vitamin D–binding protein (DBP), vitamin D–associated genes, and type 1 diabetes (T1D), but no studies have jointly analyzed these. We aimed to investigate whether DBP levels during pregnancy or at birth were associated with offspring T1D and whether vitamin D pathway genetic variants modified associations between DBP, 25(OH)D, and T1D. RESEARCH DESIGN AND METHODS From a cohort of >100,000 mother/child pairs, we analyzed 189 pairs where the child later developed T1D and 576 random control pairs. We measured 25(OH)D using liquid chromatography–tandem mass spectrometry, and DBP using polyclonal radioimmunoassay, in cord blood and maternal plasma samples collected at delivery and midpregnancy. We genotyped mother and child for variants in or near genes involved in vitamin D metabolism (GC, DHCR7, CYP2R1, CYP24A1, CYP27B1, and VDR). Logistic regression was used to estimate odds ratios (ORs) adjusted for potential confounders. RESULTS Higher maternal DBP levels at delivery, but not in other samples, were associated with lower offspring T1D risk (OR 0.86 [95% CI 0.74–0.98] per μmol/L increase). Higher cord blood 25(OH)D levels were associated with lower T1D risk (OR = 0.87 [95% CI 0.77–0.98] per 10 nmol/L increase) in children carrying the VDR rs11568820 G/G genotype (Pinteraction = 0.01 between 25(OH)D level and rs11568820). We did not detect other gene-environment interactions. CONCLUSIONS Higher maternal DBP level at delivery may decrease offspring T1D risk. Increased 25(OH)D levels at birth may decrease T1D risk, depending on VDR genotype. These findings should be replicated in other studies. Future studies of vitamin D and T1D should include VDR genotype and DBP levels.

ImportanceCeliac disease is an increasingly common immune-mediated disorder. The potential role of infections in celiac disease development is not well characterized.ObjectiveTo test whether two frequent enteric viruses, parechovirus and anellovirus, were associated with subsequent celiac disease. Our a priori hypothesis was that children who later developed celiac disease would have a higher frequency of parechovirus infections before transglutaminase 2 antibody development. Anellovirus testing was exploratory, as a potential marker of immune status.DesignMatched case-control design nested within a longitudinal birth cohort (the MIDIA study) of children at genetic risk for celiac disease.SettingChildren carrying the HLA genotype DR4-DQ8/DR3-DQ2, recruited at birth from the general population throughout Norway during 2001–2007.ParticipantsOf 220 genetically at-risk children tested for celiac disease, 25 fulfilled the case criteria. Each case was matched for follow-up time, birthdate, and county of residence with two randomly selected children free from celiac disease (controls) from the cohort.ExposuresParechoviruses, the primary exposure, are infectious agents capable of replication at high virus loads. Anellovirus, previously proposed to reflect immune status, represent a ubiquitous viral exposure at low loads. Viruses were detected and quantified in monthly stool samples (collected from 3 through 35 months of age) using real-time PCR methods.Main outcome and measuresCeliac disease diagnosis according to ESPGHAN 2012 criteria. We retrospectively tested blood samples taken at age 3, 6, 9, and 12 months, and then annually to determine when transglutaminase 2 antibodies developed.ResultsParechovirus was detected in 222 of 2005 stool samples (11.1%), and was more frequent in samples from cases before developing transglutaminase 2 antibodies (adjusted odds ratio [aOR] 1.67, 95% CI 1.14–2.45, P=0.01). The odds ratio was higher when both parechovirus and enterovirus were positive in the same sample (aOR 4.73, 95% CI 1.26–17.67, P=0.02). Anellovirus was detected in 1540 of 1829 samples (84.2%). Anellovirus status did not differ significantly between case and control subjects.Conclusions and RelevanceParechovirus infections in early life were associated with development of celiac disease in genetically at-risk children, suggesting a novel preventive target if confirmed in future studies.Key pointsQuestionAre parechovirus infections associated with development of celiac disease in childhood?FindingsIn this case-control study, nested in a cohort of children genetically at risk for celiac disease, a higher frequency of parechovirus gut infections (tested in monthly stool samples) were associated with later celiac disease. Coinfection with both parechovirus and enterovirus was associated with a markedly increased risk for later celiac disease.MeaningThe association observed between parechovirus and future celiac disease, suggests that these common enteric infections could play a role in celiac disease development.

Objective To assess rates of cardiovascular and haemostatic events in the first 28 days after vaccination with the Oxford-AstraZeneca vaccine ChAdOx1-S in Denmark and Norway and to compare them with rates observed in the general populations. Design Population based cohort study. Setting Nationwide healthcare registers in Denmark and Norway. Participants All people aged 18-65 years who received a first vaccination with ChAdOx1-S from 9 February 2021 to 11 March 2021. The general populations of Denmark (2016-18) and Norway (2018-19) served as comparator cohorts. Main outcome measures Observed 28 day rates of hospital contacts for incident arterial events, venous thromboembolism, thrombocytopenia/coagulation disorders, and bleeding among vaccinated people compared with expected rates, based on national age and sex specific background rates from the general populations of the two countries. Results The vaccinated cohorts comprised 148 792 people in Denmark (median age 45 years, 80% women) and 132 472 in Norway (median age 44 years, 78% women), who received their first dose of ChAdOx1-S. Among 281 264 people who received ChAdOx1-S, the standardised morbidity ratio for arterial events was 0.97 (95% confidence interval 0.77 to 1.20). 59 venous thromboembolic events were observed in the vaccinated cohort compared with 30 expected based on the incidence rates in the general population, corresponding to a standardised morbidity ratio of 1.97 (1.50 to 2.54) and 11 (5.6 to 17.0) excess events per 100 000 vaccinations. A higher than expected rate of cerebral venous thrombosis was observed: standardised morbidity ratio 20.25 (8.14 to 41.73); an excess of 2.5 (0.9 to 5.2) events per 100 000 vaccinations. The standardised morbidity ratio for any thrombocytopenia/coagulation disorders was 1.52 (0.97 to 2.25) and for any bleeding was 1.23 (0.97 to 1.55). 15 deaths were observed in the vaccine cohort compared with 44 expected. Conclusions Among recipients of ChAdOx1-S, increased rates of venous thromboembolic events, including cerebral venous thrombosis, were observed. For the remaining safety outcomes, results were largely reassuring, with slightly higher rates of thrombocytopenia/coagulation disorders and bleeding, which could be influenced by increased surveillance of vaccine recipients. The absolute risks of venous thromboembolic events were, however, small, and the findings should be interpreted in the light of the proven beneficial effects of the vaccine, the context of the given country, and the limitations to the generalisability of the study findings.

Background and aimGenetic markers are established as predictive of type 1 diabetes, but unknown early life environment is believed to be involved. Umbilical cord blood may reflect perinatal metabolism and exposures. We studied whether selected polar metabolites in cord blood contribute to prediction of type 1 diabetes.MethodsUsing a targeted UHPLC-QQQ-MS platform, we quantified 27 low molecular weight metabolites (including amino acids, small organic acids and bile acids) in 166 children, who later developed type 1 diabetes, and 177 random control children in the Norwegian Mother, Father and Child (MoBa) cohort. We analysed the data using logistic regression (estimating odds ratios per standard deviation [aOR]), area under the receiver operating characteristic curve (AUC) and k-means clustering. Metabolites were compared to a genetic risk score based on 51 established non-HLA SNPs, and a four-category HLA risk group.ResultsThe strongest associations for metabolites were aminoadipic acid (aOR=1.23,95%CI:0.97–1.55), indoxyl sulfate (aOR=1.15,95%CI:0.87–1.51), and tryptophan (aOR=0.84,95%CI:0.65–1.10), with other aORs close to 1.0, and none significantly associated with type 1 diabetes. K-means clustering identified six clusters, none of which were associated with type 1 diabetes. Cross-validated AUC showed no predictive value of metabolites (AUC 0.49), while the non-HLA genetic risk score AUC was 0.56 and the HLA risk group AUC was 0.78.ConclusionsIn this large study, we found no support of a predictive role of cord blood concentrations of selected bile acids and other small polar metabolites in the development of type 1 diabetes.TweetPredicting childhood type 1 diabetes with cord blood biomarkers: genetic risk score works but metabolites do not@OsloDiabetes #T1D

Introduction: Previous studies have suggested that maternal antibiotic use during pregnancy increases the risk of offspring asthma, but the potential role of confounding by indication (infections) is unclear. Objectives: To investigate the association of maternal use of antibiotics and experience of infections during pregnancy on the risk of offspring asthma at 7 years of age. Methods: We used information from the Norwegian Mother, Father and Child Cohort Study (MoBa) conducted by The Norwegian Institute of Public health. Definition of asthma was based on information on dispensed asthma medication at 7 years from the Norwegian Prescription Database. Results: Maternal antibiotic use during pregnancy was associated with child asthma at 7 years (adjusted risk ratio (aRR) per course 1.14; 95% confidence interval (CI) 1.06-1.23). We adjusted for maternal and child characteristics, such as maternal asthma, smoking, education and preterm birth as well as urinary tract infections (UTIs) and respiratory tract infections (RTIs) during pregnancy and child early antibiotic use and infections, which suggests that mother antibiotic use was independently associated with child risk of asthma. Maternal experience of UTIs (aRR 1.23; 95% CI 1.03-1.46) and RTIs (aRR 1.23; 95% CI 1.09-1.39) alone during pregnancy and together with antibiotic use for that indication (aRR 1.27; 1.08-1.49 and aRR 1.41; 1.20-1.67, respectively), compared to no such infections or antibiotic use for any reason, tended also to be associated with child asthma. Conclusion: The results suggest that both maternal antibiotic use and infections during pregnancy, in addition to childhood exposures, have an independent role in the risk of offspring asthma.

Objectives: During pregnancy, small quantities of maternal cells are naturally transmitted to the fetus. This transmission, termed maternal microchimerism (MMc), has been implicated in autoimmune diseases but its potential role is unclear. We aimed to investigate if MMc at birth predicted childhood celiac disease (CD) risk, a common immune-mediated enteropathy often presenting in childhood. Methods: We designed a case-control study, nested in the Norwegian Mother, Father and Child Cohort. Participants were HLA class II typed to determine noninherited, nonshared maternal alleles (NIMA). Droplet digital (dd) PCR assays specific for common HLA class II NIMAs (HLA-DQB1∗03:01, ∗04:02 and ∗06:02/03) were used to estimate the quantity of maternal DNA, as a marker of maternal cells, in cord blood DNA from 124 children who later developed clinically diagnosed CD (median age at end of study 7.4 years, range 3.6–12.9) and 124 random controls. We tested whether presence of MMc was associated with CD using logistic regression, and compared ranks between cases and controls. Results: MMc, for example, maternal HLA antigens not inherited by the child, was found in 42% of cases and 43% of controls, and not associated with CD (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.58–1.60). The ranks of MMc quantities in cases and controls were also similar (Mann-Whitney U-test, P = 0.71). The subgroup with HLA-DQB1:03∗01 as their NIMA had a potential association with MMc, where levels greater than median was associated with CD (OR 3.78, 95% CI 1.28–11.18). Conclusion: MMc measured in cord blood was not associated with later risk of CD.

Coeliac disease is an immune-mediated intestinal disease characterised by lifelong intolerance to dietary gluten in genetically predisposed individuals. Microbial factors including infections or bacterial microbiota have long been suspected to be involved in the aetiology, but the scientific literature on the topic is scattered and heterogeneous.To review human observational studies on microbes and coeliac disease METHODS: We identified 135 publications judged relevant. Most studies were cross-sectional, and prone to reverse causation and other biases. Only a few were prospective. Cohort studies and longitudinal studies that have sampled biological specimens before disease onset are emphasised in the review.Infections during early childhood were associated with an increased risk of subsequent coeliac disease in nine studies , whereas maternal infections during pregnancy did not show a clear association. For the most frequently studied microbial factors, some evidence for an association was found, including Helicobacter pylori (four out of 16 studies), adenovirus (two out of nine studies) and enterovirus (two out of six studies). Rotavirus infections have been associated with disease development, and rotavirus vaccination may reduce the risk. Among the many studies of gut microbiota, most were cross-sectional and, therefore, potentially influenced by reverse causation. Only two smaller prospective case-control studies with sampling before disease onset were identified; they reported inconsistent findings regarding the faecal microbiome.Several microbes are potentially linked to coeliac disease. As microbial factors are amenable to interventions, larger prospective studies are still warranted.

Background The relationship between maternal gluten intake in pregnancy, offspring intake in childhood, and offspring risk of type 1 diabetes has not been examined jointly in any studies. Our aim was to study the relationship between maternal and child intake of gluten and risk of type 1 diabetes in children. Methods and findings We included 86,306 children in an observational nationwide cohort study, the Norwegian Mother and Child Cohort Study (MoBa), with recruitment from 1999 to 2008 and with follow-up time to April 15, 2018. We used registration of type 1 diabetes in the Norwegian childhood diabetes registry as the outcome. We used Cox proportional hazard regression to estimate hazard ratios (HRs) for the mother’s intake of gluten up to week 22 of pregnancy and offspring gluten intake when the child was 18 months old. The average time followed was 12.3 years (0.70–16.0). A total of 346 children (0.4%) children were diagnosed with type 1 diabetes, resulting in an incidence rate of 32.6/100,000 person-years. Mean gluten intake per day was 13.6 g for mothers and 8.8 g for children. There was no association between the mother’s intake of gluten in pregnancy and offspring type 1 diabetes, with an adjusted HR (aHR) of 1.02 (95% confidence interval [CI] 0.73–1.43, p = 0.91) for each 10-g-per-day increment. There was an association between offspring intake of gluten and a higher risk of type 1 diabetes, with an aHR of 1.46 (95% CI 1.06–2.01, p = 0.02) for each 10-g-per-day increment. Among the limitations are the likely imprecision in estimation of gluten intake and that we only had information regarding gluten intake at 2 time points in early life. Conclusions Our results show that, while the mother’s intake of gluten in pregnancy was not associated with type 1 diabetes, a higher intake of gluten by the child at an early age may give a higher risk of type 1 diabetes., Nicolai A Lund-Blix et al report the relationship between maternal gluten intake during pregnancy, gluten intake in children and the development of Type I diabetes in the children., Author summary Why was this study done? Results from another large Nordic cohort showed that the mother’s intake of gluten in pregnancy was associated with offspring risk of type 1 diabetes, but the study did not have information on the child’s diet. To our knowledge, the relationship between maternal gluten intake in pregnancy, offspring intake in childhood, and risk of type 1 diabetes has not been examined jointly in any studies. What did the researchers do and find? We studied the relationship between maternal and offspring intake of gluten and risk of type 1 diabetes in children from a Norwegian observational nationwide cohort study with recruitment during the period from 1999 to 2008 including more than 80,000 children. There was an association between the child’s intake of gluten and a higher risk of type 1 diabetes in the child, but not between maternal intake and risk. What do these findings mean? Our results show that, while the mother’s intake of gluten in pregnancy is not associated with type 1 diabetes, a higher gluten intake by the child at an early age may give a higher risk. These findings may motivate further research in the field, ideally a randomised controlled trial (RCT).

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 more 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-day mortality (aHR = 3.89, 95% CI 1.25-12.06 amongst those with T2D and aHR = 10.79, 95% CI 7.23-16.10 amongst those without T2D). The rate of hospitalization for pandemic influenza was 78% lower in those vaccinated compared to nonvaccinated amongst people with T2D (aHR = 0.22, 95% CI 0.11-0.39), whilst 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 nonvaccinated amongst people with T2D (aHR = 0.75, 95% CI 0.73-0.77), whilst 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 amongst people with T2D, especially during pandemics.

Objectives: Influenza has been linked to autoimmune conditions, but its relationship to subsequent celiac disease (CD) is unknown. Our primary aim was to determine the risk of CD after influenza. A secondary analysis examined the risk of CD following pandemic influenza vaccination. Methods: This nationwide register-based cohort study included 2,637,746 Norwegians (born between 1967–2013) followed during 2006–2014 with information on influenza diagnosed in primary or non-primary care, pandemic vaccination (Pandemrix), and subsequent CD. Cox regression yielded hazard ratios adjusted (HR) for socio-demographic characteristics and earlier healthcare use. Results: During 13,011,323 person-years of follow-up 7321 individuals were diagnosed with CD (56/100,000 person-years). There were 351,666 individuals diagnosed with influenza, including 82,980 during the 2009–2010 pandemic, and 969,968 individuals were vaccinated. Compared with participants without influenza, who had a CD incidence of 55/100,000 person-years, those diagnosed with seasonal and pandemic influenza had a rate of 68 and 78, per 100,000 person-years, respectively. The HR for CD was 1.29 (95%CI, 1.21–1.38) after seasonal influenza and 1.29 (95%CI, 1.15–1.44) after pandemic influenza; HRs remained significantly increased one year after exposure, when restricted to laboratory-confirmed influenza, and after multivariate adjustments. The reverse association, i.e., risk of influenza after CD, was not significant (HR 1.05; 95%CI, 0.98–1.12). The HR for CD after pandemic vaccination was 1.08 (95%CI, 1.03–1.14). Conclusion: A positive association with influenza diagnosis is consistent with the hypothesis that infections may play a role in CD development. We could neither confirm a causal association with pandemic vaccination, nor refute entirely a small excess risk.

Background Infections in early life have been linked to type 1 diabetes (T1D) risk, but no previous study has comprehensively analysed exposure to antibiotics, acetaminophen and infections during pregnancy and early childhood in relation to offspring risk of T1D. Methods Participants in the Norwegian Mother and Child Cohort Study (n = 114 215 children, of whom 403 children were diagnosed with T1D) reported infections and medication use through repeated questionnaires from pregnancy until the children were 18 months old. Adjusted hazard ratios (aHR) for offspring T1D were estimated through Cox regression adjusted for child's sex, maternal age and parity, maternal T1D, smoking in pregnancy, education level, pre-pregnancy body mass index (BMI) and birthweight. Antibiotic use was also analysed in a population-based register cohort of 541 036 children of whom 836 developed T1D. Results Hospitalization for gastroenteritis during the first 18 months of life was associated with increased risk (aHR 2.27, 95% CI 1.21 - 4.29, P = 0.01) of T1D. Childhood infections not requiring hospitalization, or any kind of maternal infection during pregnancy, did not predict offspring risk of T1D. Antibiotic or acetaminophen use in pregnancy, or child`s use in early childhood, was not associated with risk of T1D. Conclusions Our study, which is population-based and the largest of its kind, did not find support for general early life infections, infection frequency or use of antibiotics or acetaminophen to play a major role in childhood T1D. Hospital admission for gastroenteritis was associated with T1D risk, but must be interpreted cautiously due to scarcity of cases.

Objective Several genetic polymorphisms determine vitamin D status. We aimed to estimate the strength of association of established 25-hydroyxvitamin D (25OHD)-associated variants in the mother and in the fetus, with 25OHD concentration in newborn umbilical cord plasma. Methods We randomly selected 578 mother and child dyads from the prospective Norwegian Mother and Child Cohort study. 25OHD was assayed in maternal samples taken shortly after delivery and in cord samples. We genotyped the mother and child for single nucleotide polymorphisms in or near GC, DHCR7, CYP2R1, and CYP24A1, previously confirmed to be associated with 25OHD, and computed genetic risk score (GRS). The genetic associations were replicated in an independent sample of 594 subjects. Results Although both fetal and maternal GRS were associated with cord 25OHD, only fetal GRS remained significantly associated with cord 25OHD in a regression model with maternal and fetal GRS simultaneously (1.6 nmol/L per fetal 25OHD-increasing allele; 95% confidence interval, 0.6 to 2.5, P = 0.0001). Two fetal single nucleotide polymorphisms in the GC gene (rs2282679 and rs222040) were the strongest genetic predictors of cord 25OHD [4.0 (2.1 to 5.9) and 3.0 (1.3 to 4.8) nmol/L per fetal allele, P < 0.001], followed by rs12785878 in DHCR7 [2.0 (0.1 to 3.8) nmol/L, P = 0.037]. The independent replication sample gave similar results. With fetal genotype included in a regression model with environmental factors, R2 for cord 25OHD was 0.28. Conclusions We show that fetal 25OHD-modifying genotype was a stronger predictor of cord 25OHD than corresponding maternal genotype. This raises interesting questions about fetal acquisition and placental transfer of 25OHD.

(Abstracted from BMJ 2018;361:k2167)Observational studies have found that women with lower levels of 25-hydroxyvitamin D are at greater risk of preeclampsia. Although some small trials of vitamin D supplementation in pregnancy have suggested a potential benefit of supplementation, a recent meta-anal

Objectives Celiac disease (CD) may occur in genetically predisposed individuals exposed to gluten, but it is unclear whether the amount of gluten influences the risk of disease. We aimed at determining whether the amount of gluten intake at age 18 months predicted later risk of CD. Methods In an observational nationwide cohort study, the Norwegian Mother and Child Cohort Study (MoBa), we included 67,608 children born during 2000-2009 and followed up for a mean of 11.5 years (range 7.5-15.5) after exclusions for missing data. Information regarding CD diagnosis was obtained from the Norwegian Patient Register 2008-2016 and from parental questionnaires at child age 7 and 8 years. We estimated gluten intake at age 18 months from a prospectively collected parental questionnaire. Results CD was diagnosed in 738 children (1.1%, 62% girls). The mean estimated amount of gluten in the diet at 18 months was 8.8 g/d (SD 3.6). The adjusted relative risk of CD was 1.10 (95% confidence interval 1.03-1.18) per SD increase in daily gluten amount at age 18 months. Children in the upper quartile of gluten intake compared with the lower quartile had an increased risk of CD (adjusted relative risk 1.29, 95% confidence interval 1.06-1.58). The association with gluten amount was independent of the age at introduction of gluten. Gluten introduction ≥6 months was also an independent risk factor for CD. Discussion In this nationwide study, increased gluten intake at 18 months was associated with a modestly increased risk of CD later in childhood.

OBJECTIVETo examine the association between maternal and child gluten intake and risk of type 1 diabetes in children.DESIGNPregnancy cohortSETTINGPopulation-based, nation-wide study in NorwayPARTICIPANTS86,306 children in The Norwegian Mother and Child Cohort Study born from 1999 through 2009, followed to April 15, 2018.MAIN OUTCOME MEASURESClinical type 1 diabetes, ascertained in a nation-wide childhood diabetes registry. Hazard ratios were estimated using Cox regression for the exposures maternal gluten intake up to week 22 of pregnancy and child’s gluten intake when the child was 18 months old.RESULTSDuring a mean follow-up of 12.3 years (range 0.7-16.0), 346 children (0.4%) developed type 1 diabetes (incidence rate 32.6 per 100,000 person-years). The average gluten intake was 13.6 grams/day for mothers during pregnancy, and 8.8 grams/day for the child at 18 months of age. Maternal gluten intake in mid-pregnancy was not associated with the development of type 1 diabetes in the child (adjusted hazard ratio 1.02 (95% confidence interval 0.73 to 1.43) per 10 grams/day increase in gluten intake). However, the child’s gluten intake at 18 months of age was associated with an increased risk of later developing type 1 diabetes (adjusted hazard ratio 1.46 (95% confidence interval 1.06 to 2.01) per 10 grams/day increase in gluten intake).CONCLUSIONSThis study suggests that the child’s gluten intake at 18 months of age, and not the maternal intake during pregnancy, could increase the risk of type 1 diabetes in the child.WHAT IS ALREADY KNOWN ON THIS TOPICA national prospective cohort study from Denmark found that a high maternal gluten intake during pregnancy could increase the risk of type 1 diabetes in the offspring (adjusted hazard ratio 1.31 (95% confidence interval 1.001 to 1.72) per 10 grams/day increase in gluten intake). No studies have investigated the relation between the amount of gluten intake by both the mother during pregnancy and the child in early life and risk of developing type 1 diabetes in childhood.WHAT THIS STUDY ADDSIn this prospective population-based pregnancy cohort with 86,306 children of whom 346 developed type 1 diabetes we found that the child’s gluten intake at 18 months of age was associated with the risk of type 1 diabetes (adjusted hazard ratio 1.46 (95% confidence interval 1.06 to 2.01) per 10 grams/day increase in gluten intake). This study suggests that the child’s gluten intake at 18 months of age, and not the maternal intake during pregnancy, could increase the child’s risk of type 1 diabetes.

Ecological observations suggest an inverse relationship between smoking in pregnancy and celiac disease (CD) in offspring. While individual-level analyses have been inconsistent, they have mostly lacked statistical power or refined assessments of exposure. To examine the association between pregnancy-related smoking and CD in the offspring, as well as its consistency across data sets, we analyzed: (1) The Norwegian Mother and Child Cohort (MoBa) of 94,019 children, followed from birth (2000–2009) through 2016, with 1035 developing CD; (2) a subsample from MoBa (381 with CD and 529 controls) with biomarkers; and (3) a register-based cohort of 536,861 Norwegian children, followed from birth (2004–2012) through 2014, with 1919 developing CD. Smoking behaviors were obtained from pregnancy questionnaires and antenatal visits, or, in the MoBa-subsample, defined by measurement of cord blood cotinine. CD and potential confounders were identified through nationwide registers and comprehensive parental questionnaires. Sustained smoking during pregnancy, both self-reported and cotinine-determined, was inversely associated with CD in MoBa (multivariable-adjusted [a] OR = 0.61 [95%CI, 0.46–0.82] and aOR = 0.55 [95%CI, 0.31–0.98], respectively); an inverse association was also found with the intensity of smoking. These findings differed from those of our register-based cohort, which revealed no association with sustained smoking during pregnancy (aOR = 0.97 [95%CI, 0.80–1.18]). In MoBa, neither maternal smoking before or after pregnancy, nor maternal or paternal smoking in only early pregnancy predicted CD. In a carefully followed pregnancy cohort, a more-detailed smoking assessment than oft-used register-based data, revealed that sustained smoking during pregnancy, rather than any smoking exposure, predicts decreased likelihood of childhood-diagnosed CD. Electronic supplementary material The online version of this article (10.1007/s10654-019-00522-5) contains supplementary material, which is available to authorized users.

OBJECTIVE To study the association of gluten intake with development of islet autoimmunity and progression to type 1 diabetes. RESEARCH DESIGN AND METHODS The Diabetes Autoimmunity Study in the Young (DAISY) follows children with an increased risk of type 1 diabetes. Blood samples were collected at 9, 15, and 24 months of age, and annually thereafter. Islet autoimmunity was defined by the appearance of at least one autoantibody against insulin, IA2, GAD, or ZnT8 (zinc transporter 8) in at least two consecutive blood samples. Using food frequency questionnaires, we estimated the gluten intake (in grams per day) annually from 1 year of age. Cox regression modeling early gluten intake, and joint modeling of the cumulative gluten intake during follow-up, were used to estimate hazard ratios adjusted for confounders (aHR). RESULTS By August 2017, 1,916 subjects were included (median age at end of follow-up 13.5 years), islet autoimmunity had developed in 178 participants, and 56 of these progressed to type 1 diabetes. We found no association between islet autoimmunity and gluten intake at 1–2 years of age or during follow-up (aHR per 4 g/day increase in gluten intake 1.00, 95% CI 0.85–1.17 and 1.01, 0.99–1.02, respectively). We found similar null results for progression from islet autoimmunity to type 1 diabetes. Introduction of gluten at CONCLUSIONS Our findings indicate no strong rationale to reduce the amount of gluten in high-risk children to prevent development of type 1 diabetes.

ObjectiveTo determine whether infection with human enterovirus or adenovirus, both common intestinal viruses, predicts development of coeliac disease.DesignCase-control study nested within Norwegian birth cohort recruited between 2001 and 2007 and followed to September 2016.SettingNorwegian population.ParticipantsChildren carrying the HLA genotype DR4-DQ8/DR3-DQ2 conferring increased risk of coeliac disease.ExposuresEnterovirus and adenovirus detected using real time polymerase chain reaction in monthly stool samples from age 3 to 36 months.Main outcome measureCoeliac disease diagnosed according to standard criteria. Coeliac disease antibodies were tested in blood samples taken at age 3, 6, 9, and 12 months and then annually. Adjusted odds ratios from mixed effects logistic regression model were used to assess the relation between viral infections before development of coeliac disease antibodies and coeliac disease.ResultsAmong 220 children, and after a mean of 9.9 (SD 1.6) years, 25 children were diagnosed as having coeliac disease after screening and were matched to two controls each. Enterovirus was found in 370 (17%) of 2135 samples and was significantly more frequent in samples collected before development of coeliac disease antibodies in cases than in controls (adjusted odds ratio 1.49, 95% confidence interval 1.07 to 2.06; P=0.02). The association was restricted to infections after introduction of gluten. High quantity samples (>100 000 copies/μL) (adjusted odds ratio 2.11, 1.24 to 3.60; P=0.01) and long lasting infections (>2 months) (2.16, 1.16 to 4.04; P=0.02) gave higher risk estimates. Both the commonly detected enterovirus species Enterovirus A and Enterovirus B were significantly associated with coeliac disease. The association was not found for infections during or after development of coeliac disease antibodies. Adenovirus was not associated with coeliac disease.ConclusionsIn this longitudinal study, a higher frequency of enterovirus, but not adenovirus, during early childhood was associated with later coeliac disease. The finding adds new information on the role of viral infections in the aetiology of coeliac disease.

Background: Maternal microchimerism (MMc), the transmission of small quantities of maternal cells to the fetus, is relatively common and persistent. MMc has been detected with increased frequency in the circulation and pancreas of type 1 diabetes (T1D) patients. We investigated for the first time whether MMc levels at birth predict future T1D risk. We also tested whether cord blood MMc predicted MMc in samples taken at T1D diagnosis. Methods: Participants in the Norwegian Mother and Child Cohort study were human leukocyte antigen (HLA) class II typed to determine non‐inherited, non‐shared maternal alleles (NIMA). Droplet digital (dd) polymerase chain reaction (PCR) assays specific for common HLA class II NIMA (HLADQB1*03:01, *04:02, and *06:02/03) were developed and validated. MMc was estimated as maternal DNA quantity in the fetal circulation, by NIMA specific ddPCR, measured in cord blood DNA from 71 children who later developed T1D and 126 controls within the cohort. Results: We found detectable quantities of MMc in 34/71 future T1D cases (48%) and 53/126 controls (42%) (adjusted odds ratio [aOR] 1.27, 95% confidence interval (CI) 0.68‐2.36), and no significant difference in ranks of MMc quantities between cases and controls (Mann‐Whitney P = .46). There was a possible association in the NIMA HLA‐DQB1*03:01subgroup with later T1D (aOR 3.89, 95%CI 1.05‐14.4). MMc in cord blood was not significantly associated with MMc at T1D diagnosis. Conclusions: Our findings did not support the hypothesis that the degree of MMc in cord blood predict T1D risk. The potential subgroup association with T1D risk should be replicated in a larger cohort. acceptedVersion