Susanne Hansen

HPV DETECTION IN CHILDREN PRIOR TO SEXUAL DEBUT

Knowledge of the epidemiology of infection with human papillomavirus (HPV) in childhood is important, since HPV infection early in life could represent a risk factor for later development of anogenital cancer. A random sample of Danish children aged 0 to 17 years was tested for the presence of HPV in the anal region and the oral cavity by the polymerase chain reaction using a consensus HPV L1 primer. Only 4 of 249 anal beta‐globin‐positive samples and one of 392 oral beta‐globin‐positive samples were HPV‐positive. All HPV‐positive samples were of unknown types. We conclude that the prevalence of anogenital HPV infection in childhood is very low indeed and that the oral cavity does not seem to act as a reservoir for HPV infection in childhood. This indicates that anogenital types of HPV are not transmitted to any measureable degree by non‐sexual routes and further supports the notion that HPV infection takes place mainly later in life. Int. J. Cancer73:621–624, 1997.

A comparison of three methods to measure asthma in epidemiologic studies: results from the Danish National Birth Cohort.

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.

Maternal Concentrations of Persistent Organochlorine Pollutants and the Risk of Asthma in Offspring: Results from a Prospective Cohort with 20 Years of Follow-up

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

Growth and obesity through the first 7 y of life in association with levels of maternal glycemia during pregnancy: a prospective cohort study

BACKGROUND Given the long-term adverse sequelae of childhood obesity, identification of early life factors related to fetal growth and childhood obesity is warranted. Investigation on growth and obesity in early life in association with intrauterine exposure to maternal hyperglycemia, a common metabolic pregnancy complication, is of public health significance and clinical implications. OBJECTIVE We investigated the association of fasting plasma glucose (FPG) concentrations during pregnancy with offspring growth and risk of overweight/obesity through age 7 y, after adjustment for confounders, including maternal prepregnancy obesity status. DESIGN FPG concentrations at 28 gestational weeks (IQR: 22-32 wk) were extracted from medical records for 661 pregnancies complicated by gestational diabetes mellitus in the Danish National Birth Cohort (1996-2002). Offsprings ponderal index was derived from birth weight and length; age- and sex-specific body mass index (BMI) z scores at 5 mo, 12 mo, and 7 y were calculated based on WHO reference data. Relations between FPG and offspring growth and obesity were assessed by linear and Poisson regression with robust standard errors, adjusting for maternal prepregnancy BMI and sociodemographic and perinatal factors. RESULTS At birth, maternal FPG during pregnancy was significantly associated with offspring ponderal index (β = 0.46; 95% CI: 0.14, 0.78 per 1-mmol/L increase) and risk of macrosomia (birth weight >4000 g) (RR = 1.21; 95% CI: 1.07, 1.38 per 1-mmol/L increase). At 7 y, higher maternal FPG concentrations were significantly associated with increased BMI z scores (β = 0.20; 95% CI: 0.04, 0.36) and elevated risk of overweight/obesity (RR = 1.21; 95% CI: 1.01, 1.50). Additional adjustment for birth weight and childhood lifestyle factors did not appreciably alter results. No associations were observed at 5 or 12 mo. CONCLUSION Among women with gestational diabetes mellitus, maternal FPG concentrations during pregnancy were significantly and positively associated with offspring birth size and overweight/obesity risk at 7 y, adjusting for maternal prepregnancy BMI.

Predicted vitamin D status in mid-pregnancy and child allergic disease

Vitamin D deficiency in pregnancy may be a risk factor for child allergic disease. However, less is known about disease risk across different levels of vitamin D.

Fish oil supplementation during pregnancy and allergic respiratory disease in the adult offspring

Background: Maternal supplementation with long‐chain n‐3 polyunsaturated fatty acids can have immunologic effects on the developing fetus through several anti‐inflammatory pathways. However, there is limited knowledge of the long‐term programming effects. Objective: In a randomized controlled trial from 1990 with 24 years of follow‐up, our aim was to determine whether supplementation with 2.7 g of long‐chain n‐3 polyunsaturated fatty acids in pregnancy can reduce the risk of asthma in offspring and allergic respiratory disease. Methods: The randomized controlled trial included 533 women who were randomly assigned to receive fish oil during the third trimester of pregnancy, olive oil, or no oil in the ratio 2:1:1. The offspring were followed in a mandatory national prescription register, with complete follow‐up for prescriptions related to the treatment of asthma and allergic rhinitis as primary outcomes. Furthermore, the offspring were invited to complete a questionnaire (74% participated) and attend a clinical examination (47% participated) at age 18 to 19 years. Results: In intention‐to‐treat analyses the probability of having had asthma medication prescribed was significantly reduced in the fish oil group compared with the olive oil group (hazard ratio, 0.54, 95% CI, 0.32‐0.90; P = .02). The probability of having had allergic rhinitis medication prescribed was also reduced in the fish oil group compared with the olive oil group (hazard ratio, 0.70, 95% CI, 0.47‐1.05; P = .09), but the difference was not statistically significant. Self‐reported information collected at age 18 to 19 years supported these findings. No associations were detected with respect to lung function outcomes or allergic sensitization at 18 to 19 years of age. Conclusion: Maternal supplementation with fish oil might have prophylactic potential for long‐term prevention of asthma in offspring.

The long-term programming effect of maternal 25-hydroxyvitamin D in pregnancy on allergic airway disease and lung function in offspring after 20 to 25 years of follow-up

BACKGROUND High prenatal vitamin D status has been linked to decreased risk of atopic diseases in early childhood, but whether such relations persist until adulthood has not been explored. OBJECTIVE We sought to examine the association between maternal 25-hydryxovitamin D (25[OH]D) concentrations and outcomes of allergic airway disease and lung function in offspring with 20 to 25 years of follow-up. METHODS In a prospective birth cohort with 965 pregnant women enrolled in 1988-1989, maternal 25(OH)D concentrations were quantified in serum from gestational week 30 (n = 850 [88%]). Offspring were followed in nationwide registries with complete follow-up to the age of 25 years (n = 850 [100%]). Additionally, at age 20 years, outcomes of allergic airway disease and lung function were assessed in a subset of offspring by using blood samples and spirometry (n = 410 [45%]) and a questionnaire (n = 641 [70%]). RESULTS Exposure to a high maternal 25(OH)D concentration (≥125 nmol/L) was associated with an increased risk of asthma hospitalizations in offspring (hazard ratio [HR], 1.81; 95% CI, 0.78-4.16) during 25 years of follow-up compared with the reference group (75-<125 nmol/L). Furthermore, there were lower risks of asthma hospitalizations (HR, 0.29; 95% CI, 0.08-1.02) and asthma medication use (HR, 0.58; 95% CI, 0.35-0.95) in those exposed to a low maternal 25(OH)D concentration (<50 nmol/L). In a reduced set of participants, we found no associations between maternal 25(OH)D concentrations and offspring allergen-specific IgE, total IgE, and eosinophil cationic protein levels; self-reported doctors diagnosis of asthma or hay fever; or lung function at 20 years of age. CONCLUSIONS Our study does not provide support for a protective effect of a high maternal 25(OH)D concentration on outcomes of allergic airway disease and lung function at 20 to 25 years of age. In contrast, a high maternal 25(OH)D concentration might be associated with an increased risk of allergic diseases in offspring.

Prenatal exposure to persistent organic pollutants and offspring allergic sensitization and lung function at 20 years of age.

Prenatal exposures to persistent organic pollutants (POPs) have been associated with asthma medication use and self‐reported symptoms, but associations with lung function and allergic sensitization have been minimally explored. The aim of the study was to examine the associations between prenatal exposures to POPs and allergic sensitization and lung function in 20‐year‐old offspring.

Adiposity, Dysmetabolic Traits and Earlier Onset of Female Puberty in Adolescent Offspring of Women With Gestational Diabetes Mellitus: A Clinical Study Within the Danish National Birth Cohort

OBJECTIVE Offspring of pregnancies affected by gestational diabetes mellitus (GDM) are at increased risk of the development of type 2 diabetes. However, the extent to which these dysmetabolic traits may be due to offspring and/or maternal adiposity is unknown. We examined body composition and associated cardiometabolic traits in 561 9- to 16-year-old offspring of mothers with GDM and 597 control offspring. RESEARCH DESIGN AND METHODS We measured anthropometric characteristics; puberty status; blood pressure; and fasting glucose, insulin, C-peptide, and lipid levels; and conducted a DEXA scan in a subset of the cohort. Differences in the outcomes between offspring of mothers with GDM and control subjects were examined using linear and logistic regression models. RESULTS After adjustment for age and sex, offspring of mothers with GDM displayed higher weight, BMI, waist-to-hip ratio (WHR), systolic blood pressure, and resting heart rate and lower height. Offspring of mothers with GDM had higher total and abdominal fat percentages and lower muscle mass percentages, but these differences disappeared after correction for offspring BMI. The offspring of mothers with GDM displayed higher fasting plasma glucose, insulin, C-peptide, HOMA-insulin resistance (IR), and plasma triglyceride levels, whereas fasting plasma HDL cholesterol levels were decreased. Female offspring of mothers with GDM had an earlier onset of puberty than control offspring. Offspring of mothers with GDM had significantly higher BMI, WHR, fasting glucose, and HOMA-IR levels after adjustment for maternal prepregnancy BMI, and glucose and HOMA-IR remained elevated in the offspring of mothers with GDM after correction for both maternal and offspring BMIs. CONCLUSIONS In summary, adolescent offspring of women with GDM show increased adiposity, an adverse cardiometabolic profile, and earlier onset of puberty among girls. Increased fasting glucose and HOMA-IR levels among the offspring of mothers with GDM may be explained by the programming effects of hyperglycemia in pregnancy.

Maternal protein intake in pregnancy and offspring metabolic health at age 9–16 y: results from a Danish cohort of gestational diabetes mellitus pregnancies and controls

Background: Recent years have seen strong tendencies toward high-protein diets. However, the implications of higher protein intake, especially during developmentally sensitive periods, are poorly understood. Conversely, evidence on the long-term developmental consequences of low protein intake in free-living populations remains limited.Objective: We examined the association of protein intake in pregnancy with offspring metabolic health at age 9-16 y in a longitudinal cohort that oversampled pregnancies with gestational diabetes mellitus (GDM).Design: Six hundred eight women with an index pregnancy affected by gestational diabetes mellitus and 626 controls enrolled in the Danish National Birth Cohort were used for the analysis. Protein (total, animal, vegetable) intake was assessed by using a food-frequency questionnaire in gestational week 25. The offspring underwent a clinical examination including fasting blood samples and a dual-energy X-ray absorptiometry scan (subset of 650) from which metabolic outcomes were derived. Multivariable analyses were conducted applying a 1:1 substitution of carbohydrates for protein.Results: The mean ± SD protein intake in pregnancy was 93 ± 15 g/d (16% ± 3% of energy) in GDM-exposed women and 90 ± 14 g/d (16% ± 2% of energy) in control women. There were overall no associations between maternal protein intake and offspring fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR). We found that maternal total protein intake was associated with a tendency for a higher abdominal fat mass percentage (quartile 4 compared with quartile 1: 0.40 SD; 95% CI: -0.03, 0.83 SD; P = 0.07) in GDM-exposed offspring and a tendency for a higher total fat mass percentage among male offspring (quartile 4 compared with quartile 1: 0.33 SD; 95% CI: -0.01, 0.66 SD; P = 0.06), but a small sample size may have compromised the precision of the effect estimates. GDM-exposed offspring of mothers with a protein intake in the lowest decile (≤12.5% of energy compared with >12.5% of energy) had lower fasting insulin (ratio of geometric means: 0.82; 95% CI: 0.68, 0.99; P = 0.04) and a tendency toward lower HOMA-IR (ratio of geometric means: 0.82; 95% CI: 0.66, 1.02; P = 0.07), but there was no evidence of associations with body composition. Male offspring seemed to derive a similar benefit from a maternal low protein intake as did GDM-exposed offspring.Conclusions: Overall, our results provide little support for an association of maternal protein intake in pregnancy with measures of offspring metabolic health. Further studies in larger cohorts are needed to determine whether low maternal protein intake in pregnancy may improve glucose homeostasis in GDM-exposed and male offspring.