Person:

Olsen, Sjurdur

Asthma is a heterogeneous outcome and how the condition should be measured to best capture clinically relevant disease in epidemiologic studies remains unclear. We compared three methods of measuring asthma in the Danish National Birth Cohort (n>50.000). When the children were 7 years old, the prevalence of asthma was estimated from a self-administered questionnaire using parental report of doctor diagnoses, ICD-10 diagnoses from a population-based hospitalization registry, and data on anti-asthmatic medication from a population-based prescription registry. We assessed the agreement between the methods using kappa statistics. Highest prevalence of asthma was found using the prescription registry (32.2%) followed by the self-report (12.0%) and the hospitalization registry (6.6%). We found a substantial non-overlap between the methods (kappa = 0.21–0.38). When all three methods were combined the asthma prevalence was 3.6%. In conclusion, self-reported asthma, ICD-10 diagnoses from a hospitalization registry and data on anti-asthmatic medication use from a prescription registry lead to different prevalences of asthma in the same cohort of children. The non-overlap between the methods may be due to different abilities of the methods to identify cases with different phenotypes, in which case they should be treated as separate outcomes in future aetiological studies.

Vitamin D deficiency during pregnancy has been associated with the development of several adverse health outcomes, e.g., pre-eclampsia, gestational diabetes mellitus, preterm delivery, low birth weight, birth length, and bone mineral content. The aims of the present study were to estimate the intake and sources of vitamin D in Danish pregnant women and to examine potential determinants of vitamin D intake of the recommended level (10 µg per day). In 68,447 Danish pregnant women the mean ± SD for vitamin D intake was 9.23 ± 5.60 µg per day (diet: 3.56 ± 2.05 µg per day, supplements: 5.67 ± 5.20 µg per day). 67.6% of the women reported use of vitamin D supplements but only 36.9% reported use of vitamin D supplements of at least 10 µg. Supplements were the primary source of vitamin D for the two higher quartiles of total vitamin D intake, with diet being the primary source for the two lower quartiles. Determinants of sufficient total vitamin D intake were: high maternal age, nulliparity, non-smoking, and filling out of the Food Frequency Questionnaire (FFQ) during summer or fall. We propose that clinicians encourage vitamin D supplementation among pregnant women, with special focus on vulnerable groups such as the young, smokers and multiparous women, in order to improve maternal and fetal health both during and after pregnancy.

Background: Past evidence has suggested a role of artificial sweeteners in allergic disease; yet, the evidence has been inconsistent and unclear. Objective: To examine relation of intake of artificially-sweetened beverages during pregnancy with child asthma and allergic rhinitis at 18 months and 7 years. Methods: We analyzed data from 60,466 women enrolled during pregnancy in the prospective longitudinal Danish National Birth Cohort between 1996 and 2003. At the 25th week of gestation we administered a validated Food Frequency Questionnaire which asked in detail about intake of artificially-sweetened soft drinks. At 18 months, we evaluated child asthma using interview data. We also assessed asthma and allergic rhinitis through a questionnaire at age 7 and by using national registries. Current asthma was defined as self-reported asthma diagnosis and wheeze in the past 12 months. We examined the relation between intake of artificially-sweetened soft drinks and child allergic disease outcomes and present here odds ratios with 95% CI comparing daily vs. no intake. Results: At 18 months, we found that mothers who consumed more artificially-sweetened non-carbonated soft drinks were 1.23 (95% CI: 1.13, 1.33) times more likely to report a child asthma diagnosis compared to non-consumers. Similar results were found for child wheeze. Consumers of artificially-sweetened carbonated drinks were more likely to have a child asthma diagnosis in the patient (1.30, 95% CI: 1.01, 1.66) and medication (1.13, 95% CI: 0.98, 1.29) registry, as well as self-reported allergic rhinitis (1.31, 95% CI: 0.98, 1.74) during the first 7 years of follow-up. We found no associations for sugar-sweetened soft drinks. Conclusion: Carbonated artificially-sweetened soft drinks were associated with registry-based asthma and self-reported allergic rhinitis, while early childhood outcomes were related to non-carbonated soft drinks. These results suggest that consumption of artificially-sweetened soft drinks during pregnancy may play a role in offspring allergic disease development.

Background: Past studies suggest that maternal vitamin D intake during pregnancy may protect against child wheeze but studies on asthma are limited. Our objective was to examine the relation between intake of vitamin D in mid-pregnancy and child asthma and allergic rhinitis at 18 months and 7 years. Methods: We examined data from 44,825 women enrolled during pregnancy in the longitudinal Danish National Birth Cohort (1996–2002). We estimated vitamin D intake from diet and supplements based on information from a validated food frequency questionnaire completed in gestational week 25. At 18 months, we evaluated child asthma using data from phone interviews. We assessed asthma and allergic rhinitis by self-report at age 7 and asthma by using records from national registries. Current asthma at age 7 was defined as lifetime asthma diagnosis and wheeze in the past 12 months. We calculated multivariable risk ratios with 95% CIs comparing highest vs. lowest quintile of vitamin D intake in relation to child allergic disease outcomes. Results: The median (5%-95%ile) intake of total vitamin D was 11.7(3.0-19.4) μg/day (68% from supplements). In multivariable analysis, mothers in the highest (vs. lowest) quintile of total vitamin D intake were less likely to have children classified with current asthma at 7 years (Q5 vs. Q1: 0.74, 95% CI: 0.56, 0.96, P = 0.02) and they were less likely to have children admitted to the hospital due to asthma (Q5 vs. Q1: 0.80, 95% CI: 0.64, 1.00, P = 0.05). We found no associations with child asthma at 18 months or with allergic rhinitis at 7 years. Conclusions: Our findings suggest a weak inverse relationship between high total vitamin D and asthma outcomes in later, but not early, childhood. The data did not suggest a clear threshold of vitamin D intake above which risk of asthma was reduced.

Background: Previous findings suggest that developmental exposures to persistent organochlorine pollutants (POPs) may be detrimental for the development of the immune system in the offspring. Whether these suspected immunoregulatory effects persist beyond early childhood remains unclear. Objectives: The objective of this study was to evaluate the association between maternal serum concentrations of POPs and the risk of asthma in offspring after 20 years of follow-up. Methods: A birth cohort with 965 women was formed in 1988–1989 in Aarhus, Denmark. Concentrations of six polychlorinated biphenyls (PCBs) (congeners 118, 138, 153, 156, 170, 180), hexachlorobenzene (HCB), and dichlorodiphenyldichloroethylene (p,p´-DDE) were quantified in maternal serum (n = 872) collected in gestation week 30. Information about offspring use of asthma medications was obtained from the Danish Registry of Medicinal Product Statistics. Results: Maternal serum concentrations of HCB and dioxin-like PCB-118 were positively associated with offspring asthma medication use after 20 years of follow-up (p for trend < 0.05). Compared with subjects in the first tertile of maternal concentration, those in the third tertile of PCB-118 had an adjusted hazard ratio (HR) of 1.90 (95% CI: 1.12, 3.23). For HCB the HR for the third versus the first tertile of maternal concentration was 1.92 (95% CI: 1.15, 3.21). Weak positive associations were also estimated for PCB-156 and the non-dioxin-like PCBs (PCBs 138, 153, 170, 180). No associations were found for p,p´-DDE. Conclusions: Maternal concentrations of PCB-118 and HCB were associated with increased risk of asthma in offspring followed through 20 years of age. Citation: Hansen S, Strøm M, Olsen SF, Maslova E, Rantakokko P, Kiviranta H, Rytter D, Bech BH, Hansen LV, Halldorsson TI. 2014. Maternal concentrations of persistent organochlorine pollutants and the risk of asthma in offspring: results from a prospective cohort with 20 years of follow-up. Environ Health Perspect 122:93–99; http://dx.doi.org/10.1289/ehp.1206397

Objective: To examine the relation between the protein:carbohydrate (P/C) ratio and added sugar intake in pregnancy and gestational weight gain (GWG). Design: A prebirth cohort including 103 119 pregnancies enrolled between 1996 and 2003. Setting: All women in Denmark were eligible to participate if they spoke Danish and were planning to carry to term.The pregnant women were recruited and enrolled during their first antenatal visit (6–10 weeks of gestation). Participants: Participants included women with live-born singletons and complete data on dietary intake and GWG, leaving 46 262 women for the analysis. Exposure Macronutrient intake was quantified using a validated food frequency questionnaire administered in the 25th week of gestation. The P/C ratio and added sugar intake were examined in quintiles. Primary outcome measures GWG was based on self-reported weight in gestational weeks 12 and 30 and defined as gain in g/week. We used multivariable linear regression, including adjusting for pre-pregnancy body mass index, to calculate relative change in GWG and 95% CI. Results: Average GWG was 471(224) g/week. The adjusted weight gain was 16 g/week lower (95% CI 9 to 22, p for trend <0.001) in the highest (Q5) versus lowest (Q1) quintile of the P/C ratio (∼3% average reduction across the entire pregnancy). Weight gain for those with >20%E vs <12%E from protein was 36 g/week lower (95% CI 20 to 53, p for trend <0.0001; ∼8% average reduction). A high P/C ratio was inversely related to intake of added sugars. Added sugar consumption was strongly associated with GWG (Q5 vs Q1: 34, 95% CI 28 to 40 g/week, p for trend <0.0001). Conclusions: A high P/C ratio was associated with reduced GWG. This association appeared to be partly driven by a decrease in intake of added sugar. These results are consistent with randomised trials in non-pregnant participants. A dietary intervention targeting an increased P/C ratio with emphasis on reducing added sugar can contribute to reducing excessive GWG.

Higher maternal and biomarker levels of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) have been associated with improved perinatal outcomes and may also influence offspring metabolic health. Past studies were not powered to examine metabolic outcomes and few have specifically targeted metabolically vulnerable populations. We examined the associations of prenatal n-3 LCPUFA status with markers of metabolic health in early and mid-childhood in the full population as well as stratified by maternal glucose tolerance. Our data consisted of 1418 mother–child dyads from Project Viva, a longitudinal, prospective pre-birth cohort enrolled in eastern Massachusetts. We assessed maternal dietary intake of fish and n-3 LCPUFA in mid-pregnancy using a validated food frequency questionnaire. N-3 LCPUFA levels were quantified in maternal second trimester and umbilical cord plasma using liquid-gas chromatography. We assessed offspring anthropometry, adiposity, and blood pressure at early (median age: 3.2 years) and mid-childhood (median age: 7.7 years); and assayed blood samples collected at these visits for metabolic biomarkers. We report here multivariable effect estimates and 95% CI. Early childhood BMI z-score was on average 0.46 (1.03) units and waist circumference 51.3 (3.7) cm. At mid-childhood these measures were 0.39 (1.00) units and 60.0 (8.3) cm, respectively. Higher cord plasma DHA levels were associated with lower BMI z-score ((Q)uartile 4 vs. Q1: −0.21, 95% CI: −0.38, −0.03), waist circumference (Q4 vs. Q1: −0.63, 95% CI: −1.27, 0.00 cm), and leptin levels (Q4 vs. Q1: −0.36, 95% CI: −0.77, 0.05 ng/mL) in early childhood. These associations were strongest and reached significance in offspring of women with isolated hyperglycemia vs. better or worse glycemic status. Higher maternal DHA + EPA (Q4 vs. Q1: −1.59, 95% CI: −2.80, −0.38 μg/mL) and fish (≥3 vs. 0 portions/week: −2.18, 95% CI: −3.90, −0.47 μg/mL) intake was related to lower adiponectin in early childhood. None of these associations persisted with mid-childhood outcomes. We did not find associations with any of the other outcomes. This study supports early and possibly transient effects of prenatal n-3 LCPUFA status on anthropometric measures and adipokine levels. It also raises the possibility that offspring of women with isolated hyperglycemia derive the most benefits from higher n-3 LCPUFA status.

Background: Results from 2 cohort studies in Scotland established in the 1940s and 1950s (Aberdeen and Motherwell) suggested that a high protein diet during pregnancy might adversely influence offspring blood pressure at adult age. Our objective was to examine this association in the Danish Fetal Origins Cohort (DaFO88). Methods and Results: This was a prospective birth cohort of 965 women who gave birth in 1988–1989 in Aarhus, Denmark, and whose offspring (n=434) participated in a clinical examination ≈20 years later. Macronutrient intake was assessed in gestational week 30. Multivariable adjusted linear regression was used to examine the relation between higher maternal protein intake, at the expense of carbohydrates, and offspring blood pressure (isocaloric substitution). Main analyses were adjusted for mother's age during pregnancy, prepregnancy body mass index, parity, smoking during pregnancy, educational level, and offspring's sex. The mean total energy intake was 8.7 MJ/day (SD 2.3 MJ/day). The mean energy from carbohydrate, fat, and protein intake was 51, 31, and 16 of total energy, respectively. The results showed that after adjustment, higher maternal protein intake was associated with slightly higher offspring diastolic blood pressure (highest compared with the lowest quintile of protein intake: ∆=2.4 mm Hg; 95% CI 0.4–4.4; P=0.03 for trend). Similar differences, although not significant, were found for systolic blood pressure (∆=2.6 mm Hg; 95% CI −0.0 to 5.3; P=0.08 for trend). Conclusions: Higher maternal dietary protein intake at the expense of carbohydrates was associated with a modest increase in offspring blood pressure in young adulthood.