Dorte Rytter

Prenatal Exposure to Perfluorooctanoate and Risk of Overweight at 20 Years of Age: A Prospective Cohort Study

Background: Perfluoroalkyl acids are persistent compounds used in various industrial -applications. Of these compounds, perfluorooctanoate (PFOA) is currently detected in humans worldwide. A recent study on low-dose developmental exposure to PFOA in mice reported increased weight and elevated biomarkers of adiposity in postpubertal female offspring. Objective: We examined whether the findings of increased weight in postpubertal female mice could be replicated in humans. Methods: A prospective cohort of 665 Danish pregnant women was recruited in 1988–1989 with offspring follow-up at 20 years. PFOA was measured in serum from gestational week 30. Offspring body mass index (BMI) and waist circumference were recorded at follow-up (n = 665), and biomarkers of adiposity were quantified in a subset (n = 422) of participants. Results: After adjusting for covariates, including maternal pre-pregnancy BMI, smoking, education, and birth weight, in utero exposure to PFOA was positively associated with anthropometry at 20 years in female but not male offspring. Adjusted relative risks comparing the highest with lowest quartile (median: 5.8 vs. 2.3 ng/mL) of maternal PFOA concentration were 3.1 [95% confidence interval (CI): 1.4, 6.9] for overweight or obese (BMI ≥ 25 kg/m2) and 3.0 (95% CI: 1.3, 6.8) for waist circumference > 88 cm among female offspring. This corresponded to estimated increases of 1.6 kg/m2 (95% CI: 0.6, 2.6) and 4.3 cm (95% CI: 1.4, 7.3) in average BMI and waist circumference, respectively. In addition, maternal PFOA concentrations were positively associated with serum insulin and leptin levels and inversely associated with adiponectin levels in female offspring. Similar associations were observed for males, although point estimates were less precise because of fewer observations. Maternal perfluorooctane sulfonate (PFOS), perfluorooctane sulfonamide (PFOSA), and perfluorononanoate (PFNA) concentrations were not independently associated with offspring anthropometry at 20 years. Conclusions: Our findings on the effects of low-dose developmental exposures to PFOA are in line with experimental results suggesting obesogenic effects in female offspring at 20 years of age.

Intake of fish oil during pregnancy and adiposity in 19-y-old offspring: follow-up on a randomized controlled trial

BACKGROUND It is well established that obesity tends to track from early childhood into adult life. Studies in experimental animals have suggested that changes in the peri- and early postnatal intake of n-3 (omega-3) polyunsaturated acids can affect the development of obesity in adult life. OBJECTIVE The aim of the current study was to investigate the effect of daily supplementation with 2.7 g long-chain n-3 fatty acids during the third trimester of pregnancy on adiposity in 19-y-old offspring. DESIGN The study was based on follow-up of a randomized controlled trial from 1990, in which 533 pregnant women were randomly assigned to receive fish oil, olive oil, or no oil. At ≈19 y of age, the offspring of subjects from the randomized controlled trial were invited to undergo a physical examination, including anthropometric measurements and fasting blood sampling. The blood sample was analyzed for insulin, glucose, glycated hemoglobin, leptin, adiponectin, insulin-like growth factor I, and high-sensitivity C-reactive protein. Multiple linear regression modeling, adjusted for sex, smoking, and parental overweight, was used to estimate the effect of fish oil relative to that of olive oil on BMI (in kg/m(2)), waist circumference, and biochemical measures. RESULTS A total of 243 of the offspring were followed up. We found no difference between the fish-oil and olive oil groups in BMI (0.13; -0.92, 1.17) or waist circumference (0.7 cm; -2.1, 3.4 cm). Overall, results of the biochemical analyses supported the finding of no difference between the groups. CONCLUSION We detected no effect of fish-oil supplementation during pregnancy on offspring adiposity in adolescence.

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

Maternal protein intake during pregnancy and offspring overweight 20 y later

BACKGROUND Animal studies have shown that protein intake in pregnancy may influence offspring fat metabolism and adiposity. The macronutrient ratio in human pregnancy appears to be important for offspring glucose tolerance; however, less is known about the influence on offspring adiposity. OBJECTIVE We examined the relation between maternal dietary protein intake during pregnancy and offspring anthropometric measures and biomarkers of adiposity and glucose metabolism. DESIGN We used a prospective cohort of 965 Danish pregnant women recruited in 1988-1989 with offspring follow-up at 19-21 y. Macronutrient intake was collected in gestational week 30, and we divided protein according to its source (animal and vegetable including cereals). Offspring body mass index (BMI; in kg/m(2)) and waist circumference were recorded at follow-up (n = 695-697), and biomarkers were quantified in a subset (n = 443) of participants. We used multivariable linear and log-binomial regression to calculate effect estimates and 95% CIs for a 1:1-g substitution of carbohydrates for protein. RESULTS Offspring mean (±SD) BMI was 22.1 ± 3.3 and 22.8 ± 2.9 for women and men, respectively. The prevalence of overweight (BMI ≥25) was 16.9% for women and 19.1% for men. We showed that a 1:1-g substitution of animal protein for carbohydrates increased risk of BMI ≥25 in female [quartile 4 compared with quartile 1: risk ratio (RR): 3.36; 95% CI: 1.52, 7.42] and male (quartile 4 compared with quartile 1: RR: 2.22; 95% CI: 0.92, 5.35) offspring. These results appeared to be accounted for by protein from meat sources. The results could not be explained by postnatal risk factors. CONCLUSIONS Protein from animal sources, primarily meat products, consumed during pregnancy may increase risk of overweight in offspring; this association appeared to be stronger for female offspring. Because of the lack of information on postnatal exposure in this cohort, these results are hypothesis-generating and need to be replicated in other cohorts.

Dietary glycemic index during pregnancy is associated with biomarkers of the metabolic syndrome in offspring at age 20 years.

Objective Growing evidence indicates that metabolic syndrome is rooted in fetal life with a potential key role of nutrition during pregnancy. The objective of the study was to assess the possible associations between the dietary glycemic index (GI) and glycemic load (GL) during pregnancy and biomarkers of the metabolic syndrome in young adult offspring. Methods Dietary GI and GL were assessed by questionnaires and interviews in gestation week 30 and offspring were clinically examined at the age of 20 years. Analyses based on 428 mother-offspring dyads were adjusted for maternal smoking during pregnancy, height, pre-pregnancy body mass index (BMI), education, energy intake, and the offspring’s ambient level of physical activity. In addition, possible confounding by gestational diabetes mellitus was taken into account. Outcome Measures Waist circumference, blood pressure, HOMA insulin resistance (HOMA-IR) and plasma levels of fasting glucose, triglycerides, HDL cholesterol, LDL cholesterol, total cholesterol, insulin, and leptin were measured in the offspring. Results Significant associations were found between dietary GI in pregnancy and HOMA-IR (the relative increase in HOMA-IR per 10 units’ GI increase was 1.09 [95% CI: 1.01, 1.16], p = 0.02), insulin (1.09 [95% CI: 1.02, 1.16], p = 0.01) and leptin (1.21 [95% CI: 1.06, 1.38], p = 0.01) in the offspring; whereas no associations were detected for GL. Conclusions Our data suggests that high dietary GI in pregnancy may affect levels of markers for the metabolic syndrome in young adult offspring in a potentially harmful direction.

No association between the intake of marine n-3 PUFA during the second trimester of pregnancy and factors associated with cardiometabolic risk in the 20-year-old offspring.

The intake of marine n-3 PUFA has been shown to decrease the risk of CVD in a number of studies. Since the development of CVD is often a lifelong process, marine n-3 PUFA intake early in life may also affect the development of later CVD. The aim of the present study was to investigate the association between maternal intake of marine n-3 PUFA during the second trimester of pregnancy and factors associated with cardiometabolic risk in the 20-year-old offspring. The study was based on the follow-up of the offspring of a Danish pregnancy cohort who participated in a study conducted from 1988 to 1989. A total of 965 pregnant women were originally included in the cohort and detailed information about the intake of marine n-3 PUFA during the second trimester was collected. In 2008-9, the offspring were invited to participate in a clinical examination including anthropometric, blood pressure (BP) and short-term heart rate variability measurements. Also, a fasting venous blood sample was drawn from them. Multiple linear regression modelling, using the lowest quintile of marine n-3 PUFA intake as the reference, was used to estimate the association with all outcomes. A total of 443 offspring participated in the clinical examination. No association between the intake of marine n-3 PUFA during the second trimester of pregnancy and offspring adiposity, glucose metabolism, BP or lipid profile was found. In conclusion, no association between the intake of marine n-3 PUFA during the second trimester of pregnancy and the factors associated with cardiometabolic risk in the 20-year-old offspring could be detected.

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.

Gestational weight gain in normal weight women and offspring cardio-metabolic risk factors at 20 years of age

Objective:Limited knowledge exists on the long-term implications of maternal gestational weight gain (GWG) on offspring health. Our objective was to examine whether high GWG in normal weight women is associated with adult offspring cardio-metabolic risk factors.Methods:We used a cohort of 308 Danish women who gave birth in 1988–89 and whose offspring participated in a clinical examination at 20 years of age. Main outcome measures were offspring body mass index (BMI), waist circumference, weight-regulating hormones, blood lipids and glucose metabolism. Associations were assessed using multivariable linear and logistic regression models.Results:A weak positive association was observed between GWG during the first 30 weeks and offspring anthropometry. Each 1-kg increase in maternal GWG was associated with 0.1-kg m−2 higher (95% confidence interval (CI): 0.01, 0.2) offspring BMI and 10% (95% CI: 0.1%, 20%) higher odds of offspring overweight at the age of 20 years, with similar associations observed in both sexes. However, sex differences were observed for the association between maternal GWG and specific cardio-metabolic risk factors. Hence, a 1-kg increase in GWG was associated with 3.4% (95% CI; 0.8, 6.0%) higher homeostasis model assessment-estimated insulin resistance (HOMA-IR), 3.7% (95% CI: 1.4%, 6.2%) higher insulin and 10.7% (95% CI: 5.7%, 15.9%) higher leptin levels in male offspring. These associations were not observed in females, which may partly be explained by more frequent reports of dieting and physical exercise at follow-up among female offspring.Conclusions:In normal-weight women, high GWG may have modest long-term implications on offspring cardio-metabolic risk factors at adult age.

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.

The effect of maternal fish oil supplementation during the last trimester of pregnancy on blood pressure, heart rate and heart rate variability in the 19-year-old offspring

Studies in experimental animals and human subjects have suggested that intake of n-3 fatty acids in early life can affect cardiovascular risk factors in adult life. Therefore, the aim of the present study was to investigate the effect of fish oil (FO) supplementation during the third trimester of pregnancy on blood pressure (BP), heart rate (HR) and HR variability (HRV) in the 19-year-old offspring. The study was based on follow-up of a randomised, controlled trial from 1990, in which 533 pregnant women were randomised to FO, olive oil (OO) or no oil (NO) during the last trimester of pregnancy. The offspring was invited to a physical examination including BP, HR and HRV measurements. A subgroup consisting of the offspring of mothers with a low baseline fish intake also had 24 h HRV determined. The OO group was used as reference and multiple linear regression modelling was used to compare the FO and OO groups. A total of 180 of the offspring from the FO and OO groups agreed to participate in the study (45%). The adjusted difference between the FO and OO groups was 2 (95% CI -1, 4) mmHg in systolic and 1 (95% CI 0, 3) mmHg in diastolic BP. The difference in HR was 1 (95% CI -2, 4). Also, HRV indices did not differ significantly between groups. Hence, FO supplementation during late pregnancy was not associated with offspring BP, HR and HRV during adolescence.