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Objectives: Infections in early childhood have been associated with risk of celiac disease (CD) and type 1 diabetes (T1D). We investigated whether this is driven by susceptibility genes for autoimmune disease by comparing infection frequency by genetic susceptibility variants for CD or T1D., Methods: We genotyped 373 controls and 384 children who developed CD or T1D in the population-based Norwegian Mother, Father and Child Cohort study (MoBa) study for human leukocyte antigen (HLA)-DQ, FUT2, SH2B3, and PTPN22, and calculated a weighted non-HLA genetic risk score (GRS) for CD and T1D based on over 40 SNPs. Parents reported infections in questionnaires when children were 6 and 18 months old. We used negative binomial regression to estimate incidence rate ratio (IRR) for infections by genotype., Results: HLA genotypes for CD and T1D or non-HLA GRS for T1D were not associated with infections. The non-HLA GRS for CD was associated with a nonsignificantly lower frequency of infections (aIRR: 0.95, 95% CI: 0.87-1.03 per weighted allele score), and significantly so when restricting to healthy controls (aIRR: 0.89, 0.81-0.99). Participants homozygous for rs601338(A;A) at FUT2, often referred to as nonsecretors, had a nonsignificantly lower risk of infections (aIRR: 0.91, 95% CI: 0.83-1.01). SH2B3 and PTPN22 genotypes were not associated with infections. The association between infections and risk of CD (OR: 1.15 per five infections) was strengthened after adjustment for HLA genotype and non-HLA GRS (OR: 1.24)., Conclusions: HLA variants and non-HLA GRS conferring susceptibility for CD were not associated with increased risk of infections in early childhood and is unlikely to drive the observed association between infections and risk of CD or T1D in many studies., (© 2023 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

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-DQB103:01, 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.

Objectives: Breast-feeding may protect against infections, but its optimal duration remains controversial. We aimed to study the association of the duration of full and any breast-feeding with infections the first 18 months of life., Methods: The Norwegian Mother and Child study (MoBa) is a prospective birth cohort which recruited expecting mothers giving birth from 2000 to 2009. We analyzed data from the full cohort (n = 70,511) and sibling sets (n = 21,220) with parental report of breast-feeding and infections. The main outcome measures were the relative risks (RRs) for hospitalization for infections from 0 to 18 months by age at introduction of complementary foods and duration of any breast-feeding., Results: Although we found some evidence for an overall association between longer duration of full breast-feeding and lower risk of hospitalizations for infections, 7.3% of breast-fed children who received complementary foods at 4 to 6 months of age compared to 7.7% of those receiving complementary foods after 6 months were hospitalized (adjusted RR 0.95, 95% confidence interval 0.88-1.03). Higher risk of hospitalization was observed in those breast-fed 6 months or less (10.0%) compared to ≥12 months (7.6%, adjusted RR 1.22, 95% confidence interval 1.14-1.31), but with similar risks for 6 to 11 months versus ≥12 months. Matched sibling analyses, minimizing the confounding from shared maternal factors, showed nonsignificant associations and were generally weaker compared with the cohort analyses., Conclusions: Our results support the recommendation to fully breast-feed for 4 months and to continue breast-feeding beyond 6 months, and suggest that protection against infections is limited to the first 12 months.

Objectives: Infections in pregnancy are common, may affect fetal development, and have been linked to offspring autoimmunity. We aimed to determine whether maternal infections, the use of antibiotics, and use of paracetamol in pregnancy are associated with the risk of offspring celiac disease (CD)., Methods: The nationwide Norwegian Mother and Child Cohort Study includes 84,274 children born in the period from 2000 to 2009 with prospectively collected questionnaire data on maternal infections and medication use in pregnancy. CD was identified through questionnaires and the Norwegian Patient Register. Logistic regression yielded odds ratios adjusted for age and sex (aORs)., Results: During a median follow-up of 8.5 years, 617 children (0.7%) were diagnosed with CD. The aOR for offspring CD per increase in number of maternal infections was 1.07 (95% confidence interval [CI] = 1.01-1.13), but not significantly increased for categories 1 infection (1.01 [95% CI = 0.82-1.25]) and ≥2 infections (1.22 [95% CI = 1.00-1.49]) versus no infection. We found the same pattern for respiratory tract infections, but not for gastrointestinal infections. The aORs were broadly consistent across pregnancy periods of exposure. The use of antibiotics and paracetamol was, compared with no use, not associated with offspring CD (aOR = 1.16 [95% CI = 0.94-1.43] and aOR = 1.13 [95% CI = 0.96-1.33], respectively; P values for trend >0.2)., Conclusions: In this large pregnancy cohort we found no clear association between maternal infections in pregnancy and offspring CD, but considering the marginal significance in some of our results maternal infections cannot be ruled out as a risk factor. Reassuringly for both parents-to-be and clinicians, the use of antibiotics and paracetamol in pregnancy was not a significant risk factor.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease, where destruction of beta-cells causes insulin deficiency. The incidence of T1DM has increased in the last decades and cannot entirely be explained by genetic predisposition. Several environmental factors are suggested to promote T1DM, like early childhood enteroviral infections and nutritional factors, but the evidence is inconclusive. Prenatal and early life exposure to environmental pollutants like phthalates, bisphenol A, perfluorinated compounds, PCBs, dioxins, toxicants, and air pollutants can have negative effects on the developing immune system, resulting in asthma-like symptoms and increased susceptibility to childhood infections. In this review the associations between environmental chemical exposure and T1DM development is summarized. Although information on environmental chemicals as possible triggers for T1DM is sparse, we conclude that it is plausible that environmental chemicals can contribute to T1DM development via impaired pancreatic beta-cell and immune-cell functions and immunomodulation. Several environmental factors and chemicals could act together to trigger T1DM development in genetically susceptible individuals, possibly via hormonal or epigenetic alterations. Further observational T1DM cohort studies and animal exposure experiments are encouraged.

Objective: To study differences in ultrasound-based compared to menstrual-based term estimation in women with type 1 diabetes., Design: Nationwide register study., Setting: Norway., Population: Deliveries in Norway 1999-2004 by women registered in the Norwegian Childhood Diabetes Registry (n = 342) and the background population (n = 307 248), with data on both ultrasound-based and menstrual-based gestational age notified in the Birth Registry of Norway. Births with major malformations were excluded., Methods: Linkage of two nationwide registries, the Medical Birth Registry of Norway and the Norwegian Childhood Diabetes Registry., Main Outcome Measures: Estimated gestational age at delivery based on routine second trimester ultrasound measurements and last menstrual period., Results: In women with type 1 diabetes, the distribution of gestational age at delivery was shifted considerably towards a lower gestational age when using second trimester ultrasound data for estimation, compared with last menstrual period data. The difference between the two estimation methods was larger among women with type 1 diabetes, although also evident in the general population. One in four women with diabetes and a certain last menstrual period date had their ultrasound-calculated term postponed 1 week or more, while one in 10 had it postponed 2 weeks or more. Corresponding numbers in the background population were one in five and one in 20., Conclusions: We found a systematic postponement of ultrasound-based compared with menstrual-based term estimation in women with type 1 diabetes. Relying solely on routine ultrasound-based term calculation for delivery decision may imply a risk of going beyond an optimal pregnancy length., (© 2014 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objectives: The aim of this study was to describe the occurrence of clinically diagnosed coeliac disease in children ages 0 to 12 years in Norway, including regional variation and coexisting type 1 diabetes mellitus, thyroid disease, and Down syndrome., Methods: The Norwegian Patient Register (NPR) contains individual-level hospital data from 2008 onward. Small-bowel biopsies for establishing the coeliac disease diagnosis are only performed at public hospitals reporting to the NPR. Data on all hospital contacts during 2008-2011 when a diagnosis of coeliac disease was registered were retrieved from the NPR for patients born between 1999 and 2011, allowing estimation of the proportion registered with coeliac disease at ages 0 to 12 years in a cohort study., Results: A total of 3006 individuals (58.2% girls) were recorded as having coeliac disease among 797,360 children, corresponding to a proportion of 3.8/1000 (95% confidence interval [CI] 3.7-3.9/1000) children, 4.5 (CI 4.3-4.7) among girls and 3.1 (CI 2.9-3.3/1000) among boys (P < 0.001). The proportion increased with age up to approximately 6 years and was 5.0/1000 (CI 4.5-5.6) at the age of 12 years, and was slightly higher in the south/west (3.9/1000) as compared to the middle/north (3.5/1000) regions of Norway (P = 0.013). A total of 214 of 3006 (7.1%) patients with coeliac disease were registered with coexisting conditions: type 1 diabetes mellitus (n = 142, 4.7%), Down syndrome (n = 47, 1.6%), or thyroid disease (n = 41, 1.4%)., Conclusions: In this first nationwide study of clinically diagnosed coeliac disease in Norwegian children, we found a high occurrence, comparable with that in Sweden. Comorbidity was common, but routine screening of high-risk groups contributed to a limited number of cases.

Objective: To estimate the risk of congenital anomalies in offspring of women with type 1 diabetes in Norway during recent years., Design: Nationwide population-based study using the Medical Birth Registry of Norway and the Norwegian type 1 Diabetes Registry., Setting: All birth clinics in Norway., Participants: All births in Norway during 1999-2004 (N = 350,961), of which 1,583 were births by a mother registered with pregestational type 1 diabetes., Main Outcome Measure: Congenital anomalies, excluding minor anomalies according to the EUROCAT system., Results: Anomalies were registered in 5.7% of offspring of women with type 1 diabetes, and in 2.9% among the background population (odds ratio 2.1, 95% CI: 1.7-2.6). Cardiovascular anomalies were registered in 3.2% in the diabetes group and 0.94% in the background population (odds ratio 3.5, 95% CI: 2.7-4.7). Results were similar when restricted to women identified with type 1 diabetes through the Diabetes Registry., Conclusions: Women in Norway with type 1 diabetes experience a significantly higher risk of congenital anomalies in their babies compared with the background population.