No association between long-chain n-3 fatty acid intake during pregnancy and risk of type 1 diabetes in offspring in two large Scandinavian pregnancy cohorts.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether higher dietary intake of marine n-3 fatty acids during pregnancy is associated with a lower risk of type 1 diabetes in children. METHODS: The Danish National Birth Cohort (DNBC) and the Norwegian Mother, Father and Child Cohort Study (MoBa) together include 153,843 mother-child pairs with prospectively collected data on eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake during pregnancy from validated food frequency questionnaires. Type 1 diabetes diagnosis in children (n=634) was ascertained from national diabetes registries. RESULTS: There was no association between the sum of EPA and DHA intake during pregnancy and risk of type 1 diabetes in offspring (pooled HR per g/day of intake: 1.00, 95% CI 0.88, 1.14), with consistent results for both the MoBa and the DNBC. Robustness analyses gave very similar results. CONCLUSIONS/INTERPRETATION: Initiation of a trial of EPA and DHA during pregnancy to prevent type 1 diabetes in offspring should not be prioritised.

Does fluoride exposure affect thyroid function? A systematic review and dose-response meta-analysis.

INTRODUCTION: Fluoride exposure may have various adverse health effects, including affecting thyroid function and disease risk, but the pattern of such relation is still uncertain. METHODS: We systematically searched human studies assessing the relation between fluoride exposure and thyroid function and disease. We compared the highest versus the lowest fluoride category across these studies, and we performed a one-stage dose-response meta-analysis for aggregated data to explore the shape of the association. RESULTS: Most retrieved studies (27 of which with a cross-sectional design) were conducted in Asia and in children, assessing fluoride exposure through its concentrations in drinking water, urine, serum, or dietary intake. Twenty-four studies reported data on thyroid function by measuring thyroid-related hormones in blood (mainly thyroid-stimulating-hormone - TSH), 9 reported data on thyroid disease, and 4 on thyroid volume. By comparing the highest versus the lowest fluoride categories, overall mean TSH difference was 1.05 µIU/mL. Dose-response curve showed no change in TSH concentrations in the lowest water fluoride exposure range, while the hormone levels started to linearly increase around 2.5 mg/L, also dependending on the risk of bias of the included studies. The association between biomarkers of fluoride exposure and TSH was also positive, with little evidence of a threshold. Evidence for an association between fluoride exposure and blood concentrations of thyroid hormones was less evident, though there was an indication of inverse association with triiodothyronine. For thyroid disease, the few available studies suggested a positive association with goiter and with hypothyroidism in both children and adults. CONCLUSIONS: Overall, exposure to high-fluoride drinking water appears to non-linearly affect thyroid function and increase TSH release in children, starting above a threshold of exposure, and to increase the risk of some thyroid diseases.

Postpartum pelvic organ prolapse and pelvic floor muscle training: secondary analysis of a randomized controlled trial of primiparous women.

INTRODUCTION AND HYPOTHESIS: Pelvic floor dysfunction is common after childbirth. We hypothesize that physiotherapist-guided pelvic floor muscle training (PFMT) is effective regarding pelvic organ prolapse (POP) symptoms during the first postpartum year. METHODS: This was a secondary analysis from a randomized controlled trial (RCT), carried out at a physiotherapy clinic, Reykjavik. Participants were eighty-four primiparous women with a singleton delivery. They were screened for eligibility 6-13 weeks postpartum. Women in a training group conducted 12 weekly individual sessions with a physiotherapist within an RCT, starting on average 9 weeks postpartum. Outcomes were assessed after the last session (short term) and at approximately 12 months postpartum (long term). The control group received no instructions after the initial assessment. Main outcome measures were self-evaluated POP symptoms by the Australian Pelvic Floor Questionnaire. RESULTS: Forty-one and 43 women were in the training and control groups, respectively. At recruitment, 17 (42.5%) of the training group and 15 (37%) of the control group reported prolapse symptoms (p = 0.6). Five (13%) from the training group and nine (21%) controls were bothered by the symptoms (p = 0.3). There was a gradual decrease in the number of women with symptoms and no significant short-term (p = 0.08) or long-term (p = 0.6) differences between the groups regarding rates of women with POP symptoms. The difference between groups regarding bother in the short (p = 0.3) or longer term (p = 0.4) was not significant. Repeated-measures analyses using Proc Genmod in SAS did not indicate a significant effect of the intervention over time (p > 0.05). CONCLUSIONS: There was an overall decrease in postpartum symptoms of POP and bother during the first year. Physiotherapist-led PFMT did not change the outcomes. CLINICAL TRIAL REGISTRATION: The trial was registered 30 March 2015 at https://register. CLINICALTRIALS: gov (NCT02682212). Initial participant enrollment was on 16 March 2016 and reported following CONSORT guidelines for randomized controlled trials.

Growth Rate in Childhood and Adolescence and the Risk of Breast and Prostate Cancer: A Population-Based Study.

Growth rate is regulated by hormonal pathways that might affect early cancer development. We explored the association between rate of growth in height from ages 8 to 13 years (childhood) and from age 13 to attainment of adult height (adolescence), as measured at study entry, and the risk of breast or prostate cancer. Participants were 2,037 Icelanders born during 1915-1935, who took part in the Reykjavik Study, established in 1967. Height measurements were obtained from school records and at study entry. We used multivariable Cox regression models to calculate hazard ratios with 95% confidence intervals of breast and prostate cancer by rates of growth in tertiles. During a mean follow-up of 66 years (women) and 64 years (men), 117 women were diagnosed with breast cancer and 118 men with prostate cancer (45 with advanced disease). Women in the highest growth-rate tertile in adolescence had a higher risk of breast cancer (hazard ratio = 2.4, 95% confidence interval: 1.3, 4.3) compared with women in the lowest tertile. A suggestive inverse association was observed for highest adolescent growth rate in men and advanced prostate cancer: hazard ratio = 0.4, 95% confidence interval: 0.2, 1.0. Rapid growth, particularly in adolescence may affect cancer risk later in life.

Maternal acrylamide exposure during pregnancy and fetal growth: A systematic review and dose-response meta-analysis of epidemiological studies.

BACKGROUND: Acrylamide is a food contaminant linked to developmental toxicity in animals and possibly in humans. OBJECTIVES: We performed a systematic review and dose-response meta-analysis of epidemiological studies evaluating the relationship between maternal acrylamide exposure during pregnancy and the risk of being small for gestational age (SGA) and birth weight, birth head circumference and birth length. METHODS: We performed the literature search in PubMed, Scopus, and Web of Science, until June 6th, 2022. Studies carried out in mother-newborn pairs, assessing maternal acrylamide exposure during pregnancy, either via dietary assessments or biomarkers i.e., hemoglobin adducts of acrylamide (AA-Hb) and glycidamide (GA-Hb), and evaluating birth outcomes were included. We employed a random-effects model to assess the pooled effect estimates and their 95% confidence intervals (CI) for the association between acrylamide exposure and birth outcomes. Risk of Bias for Nutrition Observational Studies tool was used for bias assessment. RESULTS: Out of 169 records identified, five original studies were eligible, including 53,870 mother-newborn pairs in total. Means were 21.9 µg/day for estimated dietary acrylamide exposure (3 studies), and 18.4 and 14.9 pmol/g for AA-Hb and GA-Hb, respectively (2 studies). Higher risk of SGA and lower birth weight and head circumference were observed in the highest quartile of AA-Hb [odds ratio (OR): 1.20 (95% CI: 1.08; 1.33); mean difference (MD): -131 g (95% CI: -204; -58) and -0.31 cm (95% CI: -0.58; -0.04), respectively], and GA-Hb [OR: 1.36 (95% CI: 1.13; 1.64), MD: -161 g (95% CI: -271; -52); and MD: -0.38 cm (95% CI: -0.66; -0.10), respectively], whereas a lower birth length was observed only in the highest quartile of GA-Hb (MD: -0.85 cm (95% CI: -1.38; -0.33). Results from the dose-response meta-analysis between increasing maternal acrylamide exposure during pregnancy and birth weight showed no clear evidence of a deviation from linearity. CONCLUSIONS: Overall, our findings strengthen the evidence of an adverse effect of maternal acrylamide exposure during pregnancy on fetal growth. These results encourage to increase preventive actions towards lowering acrylamide exposure in the population.

[Correlation between intake of fish or supplements containing omega-3 fatty acids and early pregnancy plasma concentrations.]

INTRODUCTION: Long-chain polyunsaturated omega-3 fatty acids are considered important for fetal development, but previous studies suggest suboptimal intake in part of pregnant women in Iceland. The study aim was to evaluate intake of food and supplements containing omega-3 fatty acids, among pregnant women in Iceland and correlations to fatty acid composition in plasma. MATERIALS AND METHODS: Subjects were 853 pregnant women attending their 11-14 weeks ultrasound appointment. Information on intake of food and supplements containing long-chain omega-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) as well as background was obtained by a questionnaire. Blood samples were collected for analysis of plasma fatty acids. Correlation was evaluated using the Spearman correlation. RESULTS: Median intake of lean fish was 1.3 times per week, while fatty fish was consumed once monthly. About 50% of the women took omega-3 containing supplements daily. Higher intake of both fish and omega-3 containing supplements was reflected in higher omega-3 plasma levels (r=0.37 p<0.001). A positive correlation was seen between intake of cod liver oil/capsules (r=0.23, p=0.001), omega-3 oil/capsules (r=0.20, p=0.001) and plasma concentration of omega-3. However, no correlation was seen between intake of a maternal multivitamin containing omega-3 and corresponding plasma concentration (r=0.03, p=0.98). CONCLUSION: Intake of food and supplements containing omega-3 fatty acids was reflected in plasma concentration, except for an Icelandic maternal multivitamin. One third of the women followed the recommendation of eating fish at least twice weekly. About 50% had a daily intake of supplements containing omega-3 fatty acids.

Higher Alkylresorcinol Concentrations, a Consequence of Whole-Grain Intake, are Inversely Associated with Gestational Diabetes Mellitus in Iceland.

BACKGROUND: A diet rich in whole grains may provide benefits for pregnant women due to whole grains' high nutritional value and dietary fiber content. OBJECTIVES: To study the associations of whole-grain consumption, as well as the plasma alkylresorcinol concentration, a whole-grain consumption biomarker, in early pregnancy with gestational diabetes mellitus (GDM) diagnoses. METHODS: Subjects were women from the prospective study Pregnant Women in Iceland II (PREWICE II; n = 853) who attended their ultrasound appointment in gestational weeks 11-14 during the period from October 2017 to March 2018. During that visit, whole-grain consumption was estimated using a diet screening questionnaire, and blood samples were collected for analysis of plasma alkylresorcinols (ARs). Information on GDM diagnoses was later extracted from medical records. Multivariate log-binomial regression was used to evaluate the association of dietary whole-grain and AR concentrations with GDM. RESULTS: In total, 14.9% of the women adhered to the national food-based dietary guidelines (n = 127), which recommend 2 portions of whole grains daily. GDM was diagnosed in 127 women (14.9%). The frequency of whole-grain consumption was lower in women who were later diagnosed with GDM compared to the women without GDM (median, 5 times/week vs. 6 times/week, respectively; P = 0.02). This difference was reflected in the lower median concentration of total AR in women diagnosed with GDM (163 nmol/L vs. 209 nmol/L, respectively; P < 0.01). The quartile with the highest concentrations of AR had a RR of 0.50 (95% CI: 0.27-0.90) of being diagnosed with GDM, in comparison to the lowest quartile. There was a significant dose response in the GDM risk with higher AR levels. CONCLUSIONS: We found that a higher consumption of whole grains, reflected both by reported consumption according to the FFQ and AR biomarkers, was associated with a decreased risk of receiving a GDM diagnosis.

Cross-sectional study of early postpartum pelvic floor dysfunction and related bother in primiparous women 6-10 weeks postpartum.

INTRODUCTION AND HYPOTHESIS: To study the prevalence of pelvic floor dysfunction and related bother in primiparous women 6-10 weeks postpartum, comparing vaginal and cesarean delivery. METHODS: Cross-sectional study of 721 mothers with singleton births in Reykjavik, Iceland, 2015 to 2017, using an electronic questionnaire. Information on urinary and anal incontinence, pelvic organ prolapse and sexual dysfunction with related bother (trouble, nuisance, worry, annoyance) was collected. Main outcome measures were prevalence of pelvic floor dysfunction and related bother. RESULTS: The overall prevalence of urinary and anal incontinence was 48% and 60%, respectively. Bother regarding urinary symptoms was experienced by 27% and for anal symptoms by 56%. Pelvic organ prolapse was noted by 29%, with less than half finding this bothersome. Fifty-five percent were sexually active, of whom 66% reported coital pain. Of all the women, 48% considered sexual issues bothersome. Urinary incontinence and pelvic organ prolapse were more prevalent in women who delivered vaginally compared to cesarean section, but no differences were observed for anal incontinence and coital pain. Compared to women with BMI < 25, obesity was a predictor for urinary incontinence after vaginal delivery (OR 1.94; 95% CI 1.20-3.14). Birthweight > 50th percentile was predictive for urgency incontinence after vaginal delivery (OR 1.53; 95% CI 1.05-2.21). Episiotomy predicted more anal incontinence (OR 2.19; 95% CI 1.30-3.67). No associations between maternal and delivery characteristics were found for pelvic floor dysfunction after cesarean section. CONCLUSIONS: Bothersome pelvic floor dysfunction symptoms are prevalent among first-time mothers in the immediate postpartum period.

Sodium Intake during Pregnancy, but Not Other Diet Recommendations Aimed at Preventing Cardiovascular Disease, Is Positively Related to Risk of Hypertensive Disorders of Pregnancy.

BACKGROUND: The role of diet on hypertensive disorders of pregnancy (HDPs), including preeclampsia and gestational hypertension (GHTN), remains unclear. OBJECTIVES: We evaluated whether adherence during pregnancy to dietary recommendations that reduce cardiovascular disease (CVD) in the general population is related to the risk of HDPs. METHODS: We followed 66,651 singleton pregnancies from 62,774 women participating in the Danish National Birth Cohort. Diet was assessed during week of gestation 25 with an FFQ from which we created 2 dietary pattern scores: 1) AHA, based on the diet recommendations from the AHA 2020 Strategic Impact Goals; and 2) the Dietary Approaches to Stop Hypertension (DASH) diet. Cases of HDPs were identified through linkage with the Danish National Patient Registry. RRs and 95% CIs of HDPs were estimated by increasing quintiles of adherence to the AHA and DASH scores using log-Poisson regression models with generalized estimating equations-to account for repeated pregnancies per woman-while adjusting for potential confounders. RESULTS: We identified 1809 cases of HDPs: n = 1310 preeclampsia (n = 300 severe preeclampsia) and n = 499 cases of GHTN. Greater adherence to AHA or DASH scores was not related to the risk of HDPs. However, when each component of the scores was separately evaluated, there were positive linear relations of sodium intake with HDPs (P-linearity < 0.01). Women with the highest sodium intake [median 3.70 g/d (range: 3.52, 7.52 g/d)] had 54% (95% CI:16%, 104%) higher risk of GHTN and 20% (95% CI:1%, 42%) higher risk of preeclampsia than women with the lowest intake [median 2.60 g/d (range: 0.83, 2.79 g/d)]. In addition, intake of whole grains was positively related to the risk of GHTN but not to preeclampsia ( P-heterogeneity = 0.002). CONCLUSION: Sodium intake during pregnancy, but no other diet recommendations to prevent CVD among nonpregnant adults, is positively related to the occurrence of HDPs among pregnant Danish women.

Can postpartum pelvic floor muscle training reduce urinary and anal incontinence?: An assessor-blinded randomized controlled trial.

BACKGROUND: Pelvic floor dysfunction, including urinary and anal incontinence, is a common postpartum complaint and likely to reduce quality of life. OBJECTIVE: To study the effects of individualized physical therapist-guided pelvic floor muscle training in the early postpartum period on urinary and anal incontinence and related bother, as well as pelvic floor muscle strength and endurance. MATERIALS AND METHODS: This was an assessor-blinded, parallel-group, randomized controlled trial evaluating effects of pelvic floor muscle training by a physical therapist on the rate of urinary and/or anal leakage (primary outcomes); related bother and muscle strength and endurance in the pelvic floor were secondary outcomes. Between 2016 and 2017, primiparous women giving birth at Landspitali University Hospital in Reykjavik, Iceland, were screened for eligibilty 6-10 weeks after childbirth. Of those identified as urinary incontinent, 95 were invited to participate, of whom 84 agreed. The intervention, starting at ∼9 weeks postpartum consisted of 12 weekly sessions with a physical therapist, after which the main outcomes were assessed (endpoint, ∼6 months postpartum). Additional follow-up was conducted at ∼12 months postpartum. The control group received no instructions after the initial assessment. The Fisher exact test was used to test differences in the proportion of women with urinary and anal incontinence between the intervention and control groups, and independent-sample t tests were used for mean differences in muscle strength and endurance. Significance levels were set as α = 0.05. RESULTS: A total of 41 and 43 women were randomized to the intervention and control groups, respectively. Three participants and 1 participant withdrew from these respective groups. Measurement variables and main delivery outcomes were not different at recruitment. At the endpoint, urinary incontinence was less frequent in the intervention group, with 21 participants (57%) still symptomatic, compared to 31 controls (82%) (P = .03), as was bladder-related bother with 10 participants (27%) in the intervention vs 23 (60%) in the control group (P = .005). Anal incontinence was not influenced by pelvic floor muscle training (P = .33), nor was bowel-related bother (P = .82). The mean differences between groups in measured pelvic floor muscle strength changes at endpoint was 5 hPa (95% confidence interval, 2-8; P = .003), and for pelvic floor muscle endurance changes, 50 hPa/s (95% confidence interval, 23-77; P = .001), both in favor of the intervention group. The mean between-group differences for anal sphincter strength changes was 10 hPa (95% confidence interval, 2-18; P = .01) and for anal sphincter endurance changes 95 hPa/s (95% confidence interval, 16-173; P = .02), both in favor of the intervention. At the follow-up visit 12 months postpartum, no differences were observed between the groups regarding rates of urinary and anal incontinence and related bother. Pelvic floor- and anal muscle strength and endurance favoring the intervention group were maintained. CONCLUSION: Postpartum pelvic floor mucle training decreased the rate of urinary incontinence and related bother 6 months postpartum and increased muscle strength and endurance.

Childhood overweight and obesity and the risk of depression across the lifespan.

BACKGROUND: Obesity has been longitudinally associated with depression but only few studies take a life course approach. This longitudinal study investigates whether being overweight or obese at age 8 and 13 years is associated with depressive symptoms more than 60 years later and whether this association is independent of late-life body mass index (BMI). We also investigated the association of being overweight/obese at age 8 or 13 years with ever having major depressive disorder (lifetime MDD). METHOD: This analysis is based on a sub-sample of 889 AGES-Reykjavik participants with measured BMI data from early life. Late-life depressive symptoms were measured with the Geriatric Depression Scale (GDS) and lifetime MDD was assessed at late-life using the Mini International Neuropsychiatric Interview. Logistic regression analysis was used to estimate the relationships between BMI (continuous and categorical) at age 8 or 13 years, and late-life depressive symptoms (measured as GDS ≥ 5) or lifetime MDD, adjusted for sex, education, physical activity, smoking status and alcohol use. In a separate model, additional adjustments were made for late-life BMI. RESULTS: One hundred and one subjects (11%) had depressive symptoms at late-life (GDS ≥ 5), and 39 subjects (4.4%) had lifetime MDD. Being overweight or obese at age 8 or 13 years was not associated with higher depressive symptoms during late-life, irrespective of late-life BMI. Being overweight or obese at age 8 years, but not age 13 years was associated with an increased risk of lifetime MDD (Odds Ratio (OR) (95% confidence interval [CI]) for age 8 = 4.03[1.16-13.96]P = 0.03 and age 13 = 2.65[0.69-10.26] P = 0.16, respectively). CONCLUSION: Being overweight in childhood was associated with increased odds of lifetime MDD, although the magnitude of the risk is uncertain given the small numbers of participants with lifetime MDD. No clear association was observed between childhood and adolescent overweight/obesity and late-life depressive symptoms irrespective of late life BMI.

Examining the Effect of Fish Oil Supplementation in Chinese Pregnant Women on Gestation Duration and Risk of Preterm Delivery.

BACKGROUND: Intervention studies have shown that long-chain (LC) n-3 PUFA intake can prolong gestation but the dose-time-effect relations remain unresolved. OBJECTIVES: We examined the effect on gestation duration of 2 doses of supplemental LC n-3 PUFAs. METHODS: We undertook a 3-group parallel randomized controlled trial in areas of China with low (median: 2.1 g/d) and higher (14.3 g/d) fish intake. Unselected women (median: age, 26.2 y; BMI, 20. kg/m2) were randomly assigned at midgestation to take four 0.72-g identical gelatin capsules per day until the last day of the preterm period (<259 days of gestation), when they were asked to stop. Capsules contained fish oil [high fish oil (HFO) group (60% w/w LC n-3 PUFAs)], a 1:3 mixture of fish oil to olive oil [low fish oil (LFO) group (20%)], or olive oil [control (CON) group (0%)], providing 2.0, 0.5, and 0 g/d of LC n-3 PUFAs, respectively. Habitual fish intake was recorded at baseline. Hazard rate ratios (HRRs) for spontaneous delivery <259 days of gestation and <273 days of gestation across groups were estimated by Cox regression. RESULTS: Among 5531 women randomly assigned, 92.5% were included in analyses (1706/1825, 1695/1851, and 1717/1855, respectively). The groups were similar with respect to hazard rates <259 days of gestation [HRR: 1.04 (95% CI: 0.70, 1.53) for LFO compared with CON and 0.90 (95% CI: 0.60, 1.35) for HFO compared with CON], hazard rates <273 days of gestation [HRR: 1.00 (95% CI: 0.86, 1.18) and 0.91 (95% CI: 0.77, 1.07), respectively], and mean gestation durations [differences: 0.2 d (95% CI: -0.5, 0.8) and 0.6 d (95% CI: -0.06, 1.2), respectively]. Inspection of pregnancy survival curves suggested that LC n-3 PUFAs delayed delivery in low fish consumers by 5-10 d and that this effect ceased rapidly after stopping taking the capsules. CONCLUSION: This trial could not substantiate that fish oil prevents preterm birth in Chinese women, possibly because statistical power was too low. This trial was registered at clinicaltrials.gov as NCT02770456.

Development of a dietary screening questionnaire to predict excessive weight gain in pregnancy.

Excessive gestational weight gain (GWG) is a risk factor for several adverse pregnancy outcomes, including macrosomia. Diet is one of the few modifiable risk factors identified. However, most dietary assessment methods are impractical for use in maternal care. This study evaluated whether a short dietary screening questionnaire could be used as a predictor of excessive GWG in a cohort of Icelandic women. The dietary data were collected in gestational weeks 11-14, using a 40-item food frequency screening questionnaire. The dietary data were transformed into 13 predefined dietary risk factors for an inadequate diet. Stepwise backward elimination was used to identify a reduced set of factors that best predicted excessive GWG. This set of variables was then used to calculate a combined dietary risk score (range 0-5). Information regarding outcomes, GWG (n = 1,326) and birth weight (n = 1,651), was extracted from maternal hospital records. In total, 36% had excessive GWG (Icelandic criteria), and 5% of infants were macrosomic (≥4,500 g). A high dietary risk score (characterized by a nonvaried diet, nonadequate frequency of consumption of fruits/vegetables, dairy, and whole grain intake, and excessive intake of sugar/artificially sweetened beverages and dairy) was associated with a higher risk of excessive GWG. Women with a high (≥4) versus low (≤2) risk score had higher risk of excessive GWG (relative risk = 1.23, 95% confidence interval, CI [1.002, 1.50]) and higher odds of delivering a macrosomic offspring (odds ratio = 2.20, 95% CI [1.14, 4.25]). The results indicate that asking simple questions about women's dietary intake early in pregnancy could identify women who should be prioritized for further dietary counselling and support.

Lack of Association Between Maternal or Neonatal Vitamin D Status and Risk of Childhood Type 1 Diabetes: A Scandinavian Case-Cohort Study.

Studies on vitamin D status during pregnancy and risk of type 1 diabetes mellitus (T1D) lack consistency and are limited by small sample sizes or single measures of 25-hydroxyvitamin D (25(OH)D). We investigated whether average maternal 25(OH)D plasma concentrations during pregnancy are associated with risk of childhood T1D. In a case-cohort design, we identified 459 children with T1D and a random sample (n = 1,561) from the Danish National Birth Cohort (n = 97,127) and Norwegian Mother and Child Cohort Study (n = 113,053). Participants were born between 1996 and 2009. The primary exposure was the estimated average 25(OH)D concentration, based on serial samples from the first trimester until delivery and on umbilical cord plasma. We estimated hazard ratios using weighted Cox regression adjusting for multiple confounders. The adjusted hazard ratio for T1D per 10-nmol/L increase in the estimated average 25(OH)D concentration was 1.00 (95% confidence interval: 0.90, 1.10). Results were consistent in both cohorts, in multiple sensitivity analyses, and when we analyzed mid-pregnancy or cord blood separately. In conclusion, our large study demonstrated that normal variation in maternal or neonatal 25(OH)D is unlikely to have a clinically important effect on risk of childhood T1D.

Relative validity of a web-based food frequency questionnaire for Danish adolescents.

BACKGROUND: With increased focus on dietary intake among youth and risk of diseases later in life, it is of importance, prior to assessing diet-disease relationships, to examine the validity of the dietary assessment tool. This study's objective was to evaluate the relative validity of a self-administered web-based FFQ among Danish children aged 12 to 15 years. METHODS: From a nested sub-cohort within the Danish National Birth Cohort, 124 adolescents participated. Four weeks after completion of the FFQ, adolescents were invited to complete three telephone-based 24HRs; administered 4 weeks apart. Mean or median intakes of nutrients and food groups estimated from the FFQ were compared with the mean of 3x24HRs. To assess the level of ranking we calculated the proportion of correctly classified into the same quartile, and the proportion of misclassified (into the opposite quartile). Spearman's correlation coefficients and de-attenuated coefficients were calculated to assess agreement between the FFQ and 24HRs. RESULTS: The mean percentage of all food groups, for adolescents classified into the same and opposite quartile was 35 and 7.5%, respectively. Mean Spearman's correlation was 0.28 for food groups and 0.35 for nutrients, respectively. Adjustment for energy and within-person variation in the 24HRs had little effect on the magnitude of the correlations for food groups and nutrients. We found overestimation by the FFQ compared with the 24HRs for fish, fruits, vegetables, oils and dressing and underestimation by the FFQ for meat/poultry and sweets. Median intake of beverages, dairy, bread, cereals, the mean total energy and carbohydrate intake did not differ significantly between the two methods. CONCLUSION: The relative validity of the FFQ compared with the 3x24HRs showed that the ranking ability differed across food groups and nutrients with best ranking for estimated intake of dairy, fruits, and oils and dressing. Larger variation was observed for fish, sweets and vegetables. For nutrients, the ranking ability was acceptable for fatty acids and iron. When evaluating estimates from the FFQ among Danish adolescents these findings should be considered.

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.

Impact of Road Traffic Pollution on Pre-eclampsia and Pregnancy-induced Hypertensive Disorders.

BACKGROUND: Road traffic is a major source of air pollution and noise. Both exposures have been associated with hypertension in adults, but pregnant women have been less studied. METHODS: We examined single and joint effects of ambient air pollution and road traffic noise on pre-eclampsia and pregnancy-induced hypertensive disorders among 72,745 singleton pregnancies (1997-2002) from the Danish National Birth Cohort with complete covariate data and residential address history from conception until live born birth. Nitrogen dioxide (NO2) and noise from road traffic (Lden) were modeled at all addresses. Outcome and covariate data were derived from registries, hospital records, and questionnaires. RESULTS: A 10-µg/m increase in NO2 exposure during first trimester was associated with increased risk of pre-eclampsia (n = 1,880, adjusted odds ratio = 1.07 [95% confidence interval = 1.01, 1.14]) and pregnancy-induced hypertensive disorders (n = 2,430, adjusted odds ratio = 1.07 [1.01, 1.13]). A 10 dB higher road traffic noise was also associated with increased risk of pre-eclampsia (1.10 [1.02, 1.18]) and pregnancy-induced hypertensive disorders (1.08 [1.02, 1.15]). For both exposures, the associations were strongest for mild pre-eclampsia (n = 1,393) and early-onset pre-eclampsia (n = 671), whereas higher risk for severe pre-eclampsia (n = 487) was not evident. In mutually adjusted models, estimates for both exposures decreased and only the association between NO2 and mild pre-eclampsia remained. CONCLUSIONS: Road traffic may increase the risk of pre-eclampsia and hypertensive disorders in pregnancy through exposure to both ambient air pollution and noise, although associations with the two exposures were generally not found to be independent of one another. See video abstract, http://links.lww.com/EDE/B112.

Dietary supplement use in the older population of Iceland and association with mortality.

Dietary supplements are often used by the elderly to improve their nutritional status. However, intake above the recommended dietary levels may be detrimental, and uncertainty exists on the potential health benefits of supplementation in this population. The aim of this study was to describe supplement use among Icelandic older adults and to assess its association with total mortality and CVD-related mortality. This study used data from the Age Gene/Environment Susceptibility-Reykjavik study, which recruited 5764 participants aged 66-98 years in 2002-2006. Intake of vitamins and minerals from dietary supplements was estimated from interviews. Hazard ratios (HR) for mortality were estimated in multivariate analyses with follow-up ending in 2009. The results showed that most (77 %) of the participants used supplements. Overall, the consumption of vitamins and minerals from supplements was moderate although 22 and 14 % of users exceeded the upper recommended intake levels for vitamin B6 and Zn, respectively. Supplement users followed in general a healthier lifestyle than non-users. There were 1221 deaths including 525 CVD-related deaths during the follow-up period. When comparing multivitamin users with non-users in multivariable models, no associations with total mortality (HR 0·91; 95 % CI: 0·77, 1·08) or CVD-related mortality (HR 0·91; 95 % CI 0·70, 1·18) were observed. In conclusion, users of supplements generally lead healthier lifestyles than non-users and supplements did not confer any added advantage or harm relative to mortality risk. However, the intake of vitamin B6 and Zn from dietary supplements exceeded the recommended daily intake for almost a quarter of the supplement users.

Plasma Concentrations of Ferritin in Early Pregnancy Are Associated with Risk of Gestational Diabetes Mellitus in Women in the Danish National Birth Cohort.

BACKGROUND: Evidence from experimental studies has demonstrated that higher than normal iron concentrations can lead to pancreatic ß cell dysfunction and impaired glucose metabolism. Studies on body iron stores in early pregnancy and subsequent gestational diabetes mellitus (GDM) risk are sparse. OBJECTIVE: Our objective was to determine whether biomarkers of body iron stores measured in early pregnancy are associated with GDM risk. METHODS: A case-control study of 350 GDM cases and 349 non-GDM controls was conducted in participants from the Danish National Birth Cohort. Blood was collected at a mean ± SD gestational age of 9.4 ± 3.2 wk. Plasma biomarkers of iron stores, including ferritin and soluble transferrin receptor (sTfR), were measured. Logistic regression was used to estimate the OR of GDM associated with quintiles of plasma biomarkers of body iron stores, controlling for maternal age, family history of diabetes, exercise in pregnancy, parity, and prepregnancy body mass index (BMI). RESULTS: Cases were older (mean ± SD age: 32.2 ± 4.3 compared with 29.9 ± 4.2 y) and had a higher BMI (in kg/m(2); mean ± SD: 28.7 ± 6.0 compared with 24.1 ± 4.6) than controls. Plasma concentrations of both ferritin and sTfR in early pregnancy were significantly higher in GDM cases than in controls [means ± SDs: 80.6 ± 56.0 compared with 71.8 ± 50.1 µg/L (P = 0.03) and 1.5 ± 0.7 compared with 1.4 ± 0.6 mg/L (P = 0.002) for ferritin and sTfR, respectively]. Ferritin was positively and significantly associated with GDM risk even after adjustment for major risk factors of GDM, including prepregnancy BMI. ORs across increasing quintiles of ferritin were 1.00 (reference), 1.25 (95% CI: 0.70, 2.22), 1.89 (95% CI: 1.06, 3.37), 0.82 (95% CI: 0.46, 1.48), and 2.34 (95% CI: 1.30, 4.21) (P-linear trend = 0.02). CONCLUSION: These findings suggest that plasma ferritin measured in early pregnancy is significantly and positively associated with GDM risk.

Maternal thyroid function in pregnancy may program offspring blood pressure, but not adiposity at 20 y of age.

BACKGROUND: Experimental evidence exists indicating that maternal thyroid hormones during pregnancy may affect the metabolic set point and cardio-vascular function in the offspring. The objective of this study was to investigate the association between maternal thyroid function in week 30 of gestation and offspring adiposity and blood pressure at 20 y. METHODS: The study was based on the follow up of a Danish birth cohort from 1988 to 1989 (n = 965). A blood sample was drawn from the pregnant women in week 30 of gestation (N = 877). In 2008-2009, the offspring were followed up with self-reported anthropometrics (N = 645) and a clinically measured blood pressure (N = 425). Multiple linear regressions were used to estimate the association between maternal thyroid function and offspring BMI, waist circumference, and blood pressure. RESULTS: Offspring of subclinical hypothyroid women had higher systolic blood pressure (adjusted difference = 3.6, 95% confidence interval: 0.2, 7.0 mmHg) and a tendency toward higher diastolic blood pressure (adjusted difference = 2.3, 95% confidence interval: -0.2, 4.9 mmHg) compared to offspring of euthyroid women. No association was found with offspring BMI and waist circumference. CONCLUSION: Maternal thyroid function during third trimester of pregnancy may affect long-term blood pressure in the offspring.