Nicolai A. Lund-Blix

Infant Feeding in Relation to Islet Autoimmunity and Type 1 Diabetes in Genetically Susceptible Children: The MIDIA Study

OBJECTIVE We aimed to study the association of breast-feeding duration and age at the introduction of solid foods with the risk of islet autoimmunity and type 1 diabetes in genetically susceptible children. RESEARCH DESIGN AND METHODS Newborns were recruited from the Norwegian general population during 2001–2007. After genetic screening of nearly 50,000 newborns, 908 children with the high-risk HLA genotype were followed up with blood samples and questionnaires at age 3, 6, 9, and 12 months and then annually. Complete infant diet data were available for 726 children. RESULTS Any breast-feeding for 12 months or longer predicted a decreased risk of developing type 1 diabetes compared with any breast-feeding for less than 12 months before and after adjusting for having a first-degree relative with type 1 diabetes, vitamin D supplementation, maternal education, sex, and delivery type (hazard ratio 0.37 [95% CI 0.15–0.93]). Any breast-feeding for 12 months or longer was not associated with islet autoimmunity but predicted a lower risk of progression from islet autoimmunity to type 1 diabetes (hazard ratio 0.35 [95% CI 0.13–0.94]). Duration of full breast-feeding was not significantly associated with the risk of islet autoimmunity or type 1 diabetes nor was age at introduction of solid foods or breast-feeding at the time of introduction of any solid foods. CONCLUSIONS These results suggest that breast-feeding for 12 months or longer predict a lower risk of progression from islet autoimmunity to type 1 diabetes among genetically predisposed children.

Infant Feeding and Risk of Type 1 Diabetes in Two Large Scandinavian Birth Cohorts

OBJECTIVE Our aim was to study the relation between the duration of full and any breastfeeding and risk of type 1 diabetes. RESEARCH DESIGN AND METHODS We included two population-based cohorts of children followed from birth (1996–2009) to 2014 (Denmark) or 2015 (Norway). We analyzed data from a total of 155,392 children participating in the Norwegian Mother and Child Cohort Study (MoBa) and the Danish National Birth Cohort (DNBC). Parents reported infant dietary practices when their child was 6 and 18 months old. The outcome was clinical type 1 diabetes, ascertained from nationwide childhood diabetes registries. Hazard ratios (HRs) were estimated using Cox regression. RESULTS Type 1 diabetes was identified in 504 children during follow-up, and the incidence of type 1 diabetes per 100,000 person-years was 30.5 in the Norwegian cohort and 23.5 in the Danish cohort. Children who were never breastfed had a twofold increased risk of type 1 diabetes compared with those who were breastfed (HR 2.29 [95% CI 1.14–4.61] for no breastfeeding vs. any breastfeeding for ≥12 months). Among those who were breastfed, however, the incidence of type 1 diabetes was independent of duration of both full breastfeeding (HR per month 0.99 [95% CI 0.97–1.01]) and any breastfeeding (0.97 [0.92–1.03]). CONCLUSIONS Suggestive evidence supports the contention that breastfeeding reduces the risk of type 1 diabetes. Among those who were breastfed, however, no evidence indicated that prolonging full or any breastfeeding was associated with a reduced risk of type 1 diabetes.

Breast-feeding and Infant Hospitalization for Infections: Large Cohort and Sibling Analysis

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 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.

Vitamin A and D intake in pregnancy, infant supplementation, and asthma development: the Norwegian Mother and Child Cohort

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.

Paternal and maternal obesity but not gestational weight gain is associated with type 1 diabetes

Abstract Background Our objective was to examine the associations of parental body mass index (BMI) and maternal gestational weight gain with childhood-onset type 1 diabetes. Comparing the associations of maternal and paternal BMI with type 1 diabetes in the offspring will provide further insight into the role of unmeasured confounding by characteristics linked to BMI in both parents. Methods We studied 132 331 children participating in the Norwegian Mother and Child Cohort Study (MoBa) and the Danish National Birth Cohort (DNBC) who were born between February 1998 and July 2009. Exposures of interest included parental BMI and maternal gestational weight gain obtained by maternal report. We used Cox-proportional hazards regression to examine the risk of type 1 diabetes (n=499 cases), which was ascertained by national childhood diabetes registers. Results The incidence of type 1 diabetes was 32.7 per 100 000 person-years in MoBa and 28.5 per 100 000 person-years in DNBC. Both maternal pre-pregnancy obesity, adjusted hazard ratio (HR) 1.41 [95% confidence interval (CI): 1.06, 1.89] and paternal obesity, adjusted HR 1.51 (95% CI: 1.11, 2.04), were associated with childhood-onset type 1 diabetes. The associations were similar after mutual adjustment. In contrast, maternal total gestational weight gain was not associated with childhood-onset type 1 diabetes, adjusted HR 1.00 (95% CI: 0.99, 1.02) per kilogram increase. Conclusions Our study suggests that the association between maternal obesity and childhood-onset type 1 diabetes is not likely explained by intrauterine mechanisms, but possibly rather by unknown environmental factors influencing BMI in the family.

Prenatal iron exposure and childhood type 1 diabetes

Iron overload due to environmental or genetic causes have been associated diabetes. We hypothesized that prenatal iron exposure is associated with higher risk of childhood type 1 diabetes. In the Norwegian Mother and Child cohort study (n = 94,209 pregnancies, n = 373 developed type 1 diabetes) the incidence of type 1 diabetes was higher in children exposed to maternal iron supplementation than unexposed (36.8/100,000/year compared to 28.6/100,000/year, adjusted hazard ratio 1.33, 95%CI: 1.06–1.67). Cord plasma biomarkers of high iron status were non-significantly associated with higher risk of type 1 diabetes (ferritin OR = 1.05 [95%CI: 0.99–1.13] per 50 mg/L increase; soluble transferrin receptor: OR = 0.91 [95%CI: 0.81–1.01] per 0.5 mg/L increase). Maternal but not fetal HFE genotypes causing high/intermediate iron stores were associated with offspring diabetes (odds ratio: 1.45, 95%CI: 1.04, 2.02). Maternal anaemia or non-iron dietary supplements did not significantly predict type 1 diabetes. Perinatal iron exposures were not associated with cord blood DNA genome-wide methylation, but fetal HFE genotype was associated with differential fetal methylation near HFE. Maternal cytokines in mid-pregnancy of the pro-inflammatory M1 pathway differed by maternal iron supplements and HFE genotype. Our results suggest that exposure to iron during pregnancy may be a risk factor for type 1 diabetes in the offspring.

Plasma phospholipid pentadecanoic acid, EPA, and DHA, and the frequency of dairy and fish product intake in young children

Background There is a lack of studies comparing dietary assessment methods with the biomarkers of fatty acids in children. Objective The objective was to evaluate the suitability of a food frequency questionnaire (FFQ) to rank young children according to their intake of dairy and fish products by comparing food frequency estimates to the plasma phospholipid fatty acids pentadecanoic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Design Cross-sectional data for the present study were derived from the prospective cohort ‘Environmental Triggers of Type 1 Diabetes Study’. Infants were recruited from the Norwegian general population during 2001–2007. One hundred and ten (age 3–10 years) children had sufficient volumes of plasma and FFQ filled in within 2 months from blood sampling and were included in this evaluation study. The quantitative determination of plasma phospholipid fatty acids was done by fatty acid methyl ester analysis. The association between the frequency of dairy and fish product intake and the plasma phospholipid fatty acids was assessed by a Spearman correlation analysis and by investigating whether participants were classified into the same quartiles of distribution. Results Significant correlations were found between pentadecanoic acid and the intake frequency of total dairy products (r=0.29), total fat dairy products (r=0.39), and cheese products (r=0.36). EPA and DHA were significantly correlated with the intake frequency of oily fish (r=0.26 and 0.37, respectively) and cod liver/fish oil supplements (r=0.47 for EPA and r=0.50 DHA). To a large extent, the FFQ was able to classify individuals into the same quartile as the relevant fatty acid biomarker. Conclusions The present study suggests that, when using the plasma phospholipid fatty acids pentadecanoic acid, EPA, and DHA as biomarkers, the FFQ used in young children showed a moderate capability to rank the intake frequency of dairy products with a high-fat content and cod liver/fish oil supplements.