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Structured AbstractObjectiveIt has been hypothesized that SARS-CoV-2 infection in children can increase risk of developing type 1 diabetes.Research Design and MethodsWe undertook a prospective analysis based on all children in Denmark where we investigated the association between SARS-CoV-2 infection and subsequent risk of type 1 diabetes, using information from several different national Danish registers. Denmark had one of the highest test-rates per capita in the world during the pandemic.ResultsWe did not observe a higher risk of a first time diagnosis of type 1 diabetes in children 30 days or more after a positive SARS-CoV-2 test, compared to children with a history of only negative SARS-CoV-2 tests (Hazard ratio 0.85, 95% CI 0.70, 1.04).ConclusionsOur data do not support that SARS-CoV-2 infection is associated with type 1 diabetes, or that type 1 diabetes should be a special focus after a SARS-CoV-2 infection in children.Article HighlightsWhy did we undertake this study?Studies have shown an association between SARS-CoV-2 infection and subsequent risk of type 1 diabetes, supporting the possibility of a viral etiology in type 1 diabetes and adding to concerns regarding adverse health consequences of COVID-19.What is the specific question(s) we wanted to answer?Is the risk of new onset type 1 diabetes increased among children in the period after SARS-CoV-2 infection?What did we find?We estimated the relative risk of being diagnosed with type 1 diabetes after a positive compared to a negative SARS-CoV-2 test, to 0.85 (95% CI 0.70, 1.04).What are the implications of our findings?Our data do not support an association between SARS-CoV-2 infection and subsequent risk of type 1 diabetes among children.Twitter SummaryA study based on all children in Denmark does not show any association between #SarsCoV2 infection and subsequent risk of #Type1Diabetes among persons < 18 years. #Type1Diabetes should not be a special focus after a #SarsCoV2 infection in children.

Background Previous epidemiological studies have found positive associations between maternal infections and childhood leukaemia; however, evidence from prospective cohort studies is scarce. We aimed to examine the associations using large-scale prospective data. Methods Data were pooled from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA (recruitment 1950s-2000s). Primary outcomes were any childhood leukaemia and acute lymphoblastic leukaemia (ALL); secondary outcomes were acute myeloid leukaemia (AML) and any childhood cancer. Exposures included maternal self-reported infections [influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections and urinary tract infection (including cystitis)] and infection-associated symptoms (fever and diarrhoea) during pregnancy. Covariate-adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using multilevel Cox models. Results Among 312 879 children with a median follow-up of 13.6 years, 167 leukaemias, including 129 ALL and 33 AML, were identified. Maternal urinary tract infection was associated with increased risk of any leukaemia [HR (95% CI) 1.68 (1.10–2.58)] and subtypes ALL [1.49 (0.87–2.56)] and AML [2.70 ([0.93–7.86)], but not with any cancer [1.13 (0.85–1.51)]. Respiratory tract infection was associated with increased risk of any leukaemia [1.57 (1.06–2.34)], ALL [1.43 (0.94–2.19)], AML [2.37 (1.10–5.12)] and any cancer [1.33 (1.09–1.63)]; influenza-like illness showed a similar pattern but with less precise estimates. There was no evidence of a link between other infections and any outcomes. Conclusions Urinary tract and respiratory tract infections during pregnancy may be associated with childhood leukaemia, but the absolute risk is small given the rarity of the outcome.

Experimental evidence suggests that perinatal light imprinting of circadian clocks and systems may affect downstream physiology and cancer risk in later life. For humans, the predominant circadian stimulus is the daily light-dark cycle. Herein, we explore associations between perinatal photoperiod characteristics (photoperiod: duration of daylight as determined by time-of-year and location) and childhood cancer risk. We use pooled data on 182,856 mothers and babies from prospective birth cohorts in six countries (Australia, Denmark, Israel, Norway, UK, USA) within the International Childhood Cancer Cohort Consortium (I4C). Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In line with predicted differential dose–responses, restricted cubic splines indicate a potential non-linear, non-monotonic relationship between perinatal mean daily photoperiod (0–24 h) and childhood cancer risk. In a restricted analysis of 154,121 individuals who experienced third trimester photoperiods exclusively within the 8–16-h range, the relative risk of developing childhood cancer decreased by 9% with every hour increase in third trimester mean daily photoperiod [HR: 0.91 (95%CIs: 0.84–0.99)]. In conclusion, in this first study of perinatal photoperiod and childhood cancer, we detected an inverse [“protective”] linear association between third trimester mean daily photoperiod and childhood cancer risk in the 8–16-h set of the total study population. Limited statistical power impeded the investigation of risks with individuals exposed to more extreme photoperiods. Future studies are needed to confirm differential photoperiod-associated risks and further investigations into the hypothesized circadian imprinting mechanism are warranted.

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

Background: Folate prevents neural tube defects and may play a role in some neurodevelopmental disorders. Objectives: We investigated whether higher intakes of periconceptional or midpregnancy folate, as recommended, were associated with a reduced risk of offspring cerebral palsy (CP). Methods: We included participants from the Nordic collaboration cohort consisting of mother-child dyads in the Danish National Birth Cohort and the Norwegian Mother, Father, and Child Cohort Study [combined as MOthers and BAbies in Norway and Denmark (MOBAND-CP)]. A total of 190,989 live-born children surviving the first year of life were included. Missing covariate data were multiply imputed. Our exposures were defined as any or no folic acid supplementation in gestational weeks (GWs) -4 to 8 (periconceptional), 9 to 12, and -4 to 12, and supplemental, dietary, and total folate during midpregnancy (GWs 22-25). CP overall and the unilateral and bilateral spastic subtypes, as well as CP with low or moderate/high gross motor function impairments, were our outcomes of interest. Results: Periconceptional folic acid supplementation was not associated with CP [adjusted odds ratio (aOR), 1.02; 95% CI: 0.82-1.28]. However, supplementation in GWs 9 to 12 was associated with a reduced risk of CP (aOR, 0.74; 95% CI: 0.57-0.96), and inverse associations were indicated for both the unilateral (aOR, 0.68; 95% CI: 0.46-1.02) and bilateral (aOR, 0.70; 95% CI: 0.49-1.02) spastic subtypes, although the associations were not statistically significant. Supplemental or dietary folate in midpregnancy alone were not associated with CP. Strong inverse associations were observed with low gross motor function impairment (aOR, 0.49; 95% CI: 0.29-0.83), while for unilateral CP the aOR was 0.63 (95% CI: 0.34-1.22) for intakes of ≥500 compared to ≤199 dietary folate equivalents/day during midpregnancy. Conclusions: Our findings suggest that folate intakes in GWs 9 to 12 and midpregnancy were associated with lower risks of CP, while no association was observed for periconceptional supplementation.

Lactation is associated with a lower risk of subsequent cardiometabolic disease among parous women; however, the underlying mechanisms are unknown. Further, the potential protective effects of lactation on cardiometabolic risk markers at mid-life among high-risk women with past gestational diabetes (GDM) are not established. Using data from the Diabetes & Women’s Health Study (2012–2014; n = 577), a longitudinal cohort of women with past GDM from the Danish National Birth Cohort (1996–2002), we assessed associations of cumulative lactation duration (none

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 (

Author(s): Hinkle, Stefanie N; Rawal, Shristi; Bjerregaard, Anne Ahrendt; Halldorsson, Thor I; Li, Mengying; Ley, Sylvia H; Wu, Jing; Zhu, Yeyi; Chen, Liwei; Liu, Aiyi; Grunnet, Louise Groth; Rahman, Mohammad L; Kampmann, Freja Bach; Mills, James L; Olsen, Sjurdur F; Zhang, Cuilin | Abstract: BackgroundArtificially sweetened beverages (ASBs) are commonly consumed and recommended for individuals at high risk for cardiometabolic diseases; however, the health effects of ASBs remain contradictory. Given that cross-sectional analyses are subject to reverse causation, prospective studies with long-term follow-up are needed to evaluate associations between ASBs and cardiometabolic health, especially among high-risk individuals.ObjectiveThe aim of this study was to examine associations of ASB intake and cardiometabolic health among high-risk women with prior gestational diabetes mellitus (GDM).MethodsWe included 607 women with GDM from the Danish National Birth Cohort (DNBC; 1996-2002) who completed a clinical exam 9-16 y after the DNBC pregnancy for the Diabetes a Women's Health (DWH) Study (2012-2014). We assessed ASB intake using FFQs completed during the DNBC pregnancy and at the DWH Study clinical exam. We examined cardiometabolic outcomes at the DWH clinical exam. We estimated percentage differences in continuous cardiometabolic markers and RRs for clinical endpoints in association with ASB intake both during pregnancy and at follow-up adjusted for prepregnancy BMI, diet, and lifestyle factors. Sensitivity analyses to account for reverse causation were performed.ResultsIn pregnancy and at follow-up, 30.4% and 36.4% of women regularly (≥2 servings/wk) consumed ASB, respectively. Consumption of ASBs, both during pregnancy and at follow-up, was associated with higher glycated hemoglobin (HbA1c), insulin, HOMA-IR, triglycerides, liver fat, and adiposity and with lower HDL at follow-up. After adjustment for covariates, particularly prepregnancy BMI, the majority of associations between ASB intake in pregnancy and outcomes at follow-up became null with the exception of HbA1c. ASB intake at follow-up (≥1 serving/d compared with l1 serving/mo) was associated with higher HbA1c (6.5%; 95% CI: 1.9, 11.3; P-trend = 0.007); however, associations were not upheld in sensitivity analyses for reverse causation.ConclusionsAmong Danish women with a history of GDM, ASB intake was not significantly associated with cardiometabolic profiles.

Objective: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes.Design: Individual level meta‐analysis, which reduces heterogeneity across studies.Setting: A consortium of eight population‐based studies (seven European and one US) comprising 72 694 participants.Methods: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking, and alcohol intake) were used to test associations between self‐reported LTPA at either early (8–18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta‐analyses.Main outcome measures: Birth weight, large‐for‐gestational age (LGA), macrosomia, small‐for‐gestational age (SGA), % body fat, and ponderal index at birth.Results: Late, but not early, gestation maternal moderate to vigorous physical activity (MVPA), vigorous activity, and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia, and ponderal index, without heterogeneity (all: I2 = 0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95% CI: 0.94, 0.98), respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA.Conclusions: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA.Tweetable abstract: In an individual participant meta‐analysis, late pregnancy moderate to vigorous physical activity modestly reduced birth size outcomes.

Offspring of women with gestational diabetes mellitus (GDM) exhibit a high risk of developing type 2 diabetes later in life, potentially as a result of developmental programming by epigenetic mechanisms (1,2). We read with great interest the meta-analysis by Howe et al. (3) integrating results of differential cord blood DNA methylation changes from seven epigenome-wide association studies (EWAS) including in total 3,677 mother-newborn pairs. Pregnancies complicated with GDM were associated with significantly lower cord blood methylation levels within the promoter region of the OR2L13 gene, as well as within the gene body of the CYP2E1 gene (3). At single CpG site levels, the authors reported GDM to be associated with differential methylations at six distinct CpG sites (3). As pointed out by Howe et al., replication of EWAS analyses is extremely important due to 1 ) high risk of confounders; 2 ) in general, small absolute methylation differences; and 3 ) analytical uncertainties related to multiple comparisons and adjustment for cell …

The prevalence of GDM is on the rise in relation to an increase in predisposing maternal characteristics. The increase is more marked with application of IADPSG-WHO 2013 criteria [1], with very high rates in special populations [2]. Lifestyle modifications are the first step in the management of GDM and medical nutrition therapy is an essential component of it. Maternal diet should provide adequate energy intake to promote maternal and fetal health, help achieve glycemic goals and be culturally appropriate and individualized [3]. DRI for normal weight pregnant women should be taken into account: provide no increase in energy requirement during the first trimester, + 340 kcal/day in the second trimester and + 452 kcal/day in the third; provide > = 175 g carbohydrate/day, 71 g protein/day and 28 g fiber/day; and have an acceptable energy macronutrient distribution range (45–65% of energy from carbohydrates, 20–35% of energy from fat, 10–35% of energy from protein). However, little is known about the characteristics of diets consumed by women with GDM. We aimed to characterize the dietary intake of women with GDM in usual clinical care.

ObjectiveNut intake has been associated with reduced cardiometabolic risk, but few studies have examined its association with renal function. We examined associations between nut intake and renal function among women with previous gestational diabetes mellitus (GDM), a population with an increased risk for renal dysfunction.Design and methodsThis study included 607 women with a history of GDM who participated in the Diabetes & Women's Health Study (2012-2014) follow-up clinical examination in Denmark. At the clinic, biospecimens were collected, and habitual intake of nuts (9 types) in the past year was assessed using a food frequency questionnaire. A total of 330 women free of major chronic diseases were included in the analysis. Total nut intake was classified as none (≤1 serving/month), monthly (2-3 servings/month), weekly (1-6 servings/week), and daily (≥1 serving/day). One serving was defined as 28 g. Renal function markers included estimated glomerular rate (eGFR) and urinary albumin-to-creatinine ratio (UACR), calculated based on plasma creatinine (mg/dL), and urinary albumin (mg/L), and creatinine (mg/dL) measurements, respectively. We estimated percent differences with 95% confidence intervals for each outcome by nut intake, adjusted for current body mass index, age, physical activity, energy intake, alcohol consumption, and vegetables intake.ResultsWe observed a nonlinear association between total nut intake and UACR with lowest UACR values among women with weekly intake. Compared to women with weekly intake (n=222), the adjusted UACR values were higher by 86% [95% confidence interval: 15%, 202%], 24% [-1%, 54%], and 117% [22%, 288%] among women with no (n=13), monthly (n=86), and daily (n=9) intake, respectively. Compared to weekly consumers, daily nut consumers also had 9% [0%, 19%] significantly higher eGFR values, but eGFR values were similar among women with no and monthly intake.ConclusionModerate nut consumption may be beneficial to kidney health among women with prior GDM.

IntroductionDietary changes in pregnancy may be a marker for later pregnancy complications. This study aims to investigate if there is a difference in the proportion of women who experience specific pregnancy related complications vs those who do not, in relation to specific dietary changes made during pregnancy.Materials and methodsWithin the Danish National Birth Cohort, established during 1996 and 2003, dietary changes from 70,053 pregnancies were assessed in gestational week (GW) 25 using two open-ended questions (q1 and q2) on aversions or preferences appended to a 350-item food frequency questionnaire; “did you stop(q1) or start(q2) consuming a specific food during pregnancy?” After restricting to the firstborn child enrolled, born at term (GW 37 + 1–42 + 0) with a birth weight between 1,0 and 6,0 kilograms, excluding multiple pregnancies and abortions, dietary change answers from 55,087 women were coded into 65 food groups. Using chi-X2 test, we compared proportions of women with and without three pregnancy complications: preeclampsia (obtained via linkage to the Danish National Patient Registry), children born small-for-gestational-age (SGA, < 10th percentile) or children born large-for-gestational-age (LGA, > 90th percentile) with respect to their answers about aversions/preferences.ResultsAmong the 55,087 women, 49% and 31% reported any aversions or preferences, respectively. Most frequent were women reporting aversion of alcohol (22.7%) or coffee (15.4%), and preference of milk products (7.9%) or fruits and berries (6.9%), which were selected a priori for analyses. 8.3% of women experienced preeclampsia, and 9.7% and 9.3% of children were characterizes as being born SGA or LGA, respectively. Compared with no dietary change: avoiding alcohol or coffee was associated with smaller proportion of SGA (10% vs 8%, p = 0.01 and 10% vs 7%, p < 0.0001) and avoiding coffee was also associated with greater proportion of LGA (9% vs 11%, p = 0.01). Increasing milk products or fruit/berries was associated with smaller proportions of SGA (14% vs 10% in both conditions, p < 0.009). No significant association in reported aversions/preferences was detected for preeclampsia.DiscussionThe results lead to additional questions, such as “Why do women who increase consumption of milk products or fruits/berries tend to deliver SGA infants and why do women who stop drinking coffee tend to deliver LGA infants?” The presented results and further analyses are important to public health initiatives for optimizing maternal nutrition with long-term influence to offspring Health.

Introduction:By October 2002, a little more than 100,000 women in their early pregnancies had been recruited in the Danish National Birth Cohort (DNBC), for long-term follow-up of themselves and their offspring. The overall purpose of DNBC is the establishment of a research database comprising information on exposures and other factors during pregnancy and early life that can be linked to health-related phenomena occurring throughout life. More than 90,000 live-born children are followed by questionnaires and registry linkages, and more than 500 peer-reviewed articles have so far been published from DNBC.The latest completed assessment in the children recorded diet and physical activity at age 14. Our group was responsible for the development and implementation of the questionnaire in DNBC. We report on its development; on selected data; and on their potential utility for research.Materials and methods:The questionnaire was an on-line food-frequency questionnaire (FFQ) comprising 158 food items. It was a substantially modified version of the questionnaire developed for the offspring of Nurses’ Health Study 2 participants (GUTS) adapted to the Danish food culture.Results:Mean BMI was 19, and 9.1% of boys and 8.3% of girls were overweight (n = the first 20,814 completed questionnaire). For boys and girls, respectively, estimated mean (SD) intakes were: Energy 9.3 (3.5) and 10.4 (3.9) MJ/d; Protein 15.7 (2.4) and 15.8 (2.5) E%; Fat 32.1 (4.6) and 32.6 (4.5) E%; Carbohydrate 52.2 (5.3) and 51.5 (5.3) E%; Sugar 7.8 (4.1) and 7.1 (3.8) E%; Fruits 213 (208) and 253 (222) g/d; Vegetables 201 (142) and 240 (163) g/d; Fish 96 (108) and 94 (107) g/w; Meat 792 (415) and 694 (381) g/week; and Sugar-sweetened beverages 1.2 (1.3) and 0.8 (1.1) L/week.Considerable variability was observed. E.g., for sugar-sweetened beverages, the highest quarter consumed more than 1.4 and the lowest less than 0.32 L/week; for fish, the corresponding figures were 120 and 30 g/week, respectively. We observed substantial gradients across sociodemographic groups.Discussion:Our data revealed a considerable variability in dietary intake in DNBC, with substantial sociodemographic gradients. These results point to an important and unique potential for prevention and future research. DNBC is the largest database worldwide of its kind with extensive information on dietary exposures in pregnancy (1) as well as during adolescence.

Fish oil supplementation has been shown to delay spontaneous delivery, but the levels and clinical significance remain uncertain. We examined the association between plasma fatty acids quantified in pregnancy and subsequent risk of early preterm birth.In a case-control design nested in the Danish National Birth Cohort, we identified 376 early preterm cases (34 gestational weeks, excluding preeclampsia cases) and 348 random controls. Plasma eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA% of total fatty acids), were measured twice in pregnancy, at gestation weeks 9 and 25 (medians). Odds ratios and 95% confidence intervals (CI's) for associations between EPA+DHA and early preterm risk were estimated by logistic regression, adjusted for the woman's age, height, pre-pregnancy BMI, parity, smoking, and socioeconomic factors. Hypotheses and analytical plan were defined and archived a priori.Analysis using restricted cubic splines of the mean of 1st and 2nd sample measurements showed a strong and significant non-linear association (p 0.0001) in which the risk of early preterm birth steeply increased when EPA+DHA concentrations were lower than 2% and flattened out at higher levels. Women in the lowest quintile (EPA+DHA 1.6%) had 10.27 times (95% confidence interval 6.80-15.79, p 0.0001) increased risk, and women in the second lowest quintile had 2.86 (95% CI 1.79-4.59, p 0.0001) times increased risk, when compared to women in the three aggregated highest quintiles (EPA+DHA ≥ 1.8%).Low plasma concentration of EPA and DHA during pregnancy is a strong risk factor for subsequent early preterm birth in Danish women.

Individuals born small have an increased risk for developing type 2 diabetes. Altered food preferences in these subjects seem to play a role; however, limited evidence is available on the association between being born small-for-gestational-age (SGA) at term and food intake in adolescence. Alterations in leptin, ghrelin and dopamine levels are suggested mechanisms linking SGA with later food intake. From a large prospective Danish National Birth Cohort, we compared dietary intake of adolescents being born SGA with normal-for-gestational-age (NGA) adolescents. Intake of foods and nutrients was assessed by a validated food frequency questionnaire in a subsample of 15,607 14-year-old individuals born at term. SGA was defined by birth weight (BW) n = 1470) and NGA as BW between 10 and 90th percentile (n = 14,137) according to sex and gestational age-specific BW standard curves. Girls born SGA had a 7% (95% CI: 3–12%, P = 0.002) higher intake of added sugar and a 2–8% lower intake of dietary fibre, vegetables, polyunsaturated fatty acids, and total n−6, compared with NGA girls (P < 0.05). Adjusting for parental socio-occupational status, maternal smoking and diet in pregnancy did not substantially change the differences in dietary intake, except from dietary fibre, which were no longer statistically significant. No significant differences in dietary intake between SGA and NGA boys were found. In summary, girls born SGA had an unfavourable dietary intake compared with NGA girls. These differences persisted after controlling for potential confounders, thus supporting a fetal programming effect on dietary intake in girls born SGA at term. However, residual confounding by other factors operating early in childhood cannot be excluded.

The "delayed infection hypothesis" states that a paucity of infections in early childhood may lead to higher risks of childhood leukemia (CL), especially acute lymphoblastic leukemia (ALL). Using prospectively collected data from six population-based birth cohorts we studied the association between birth order (a proxy for pathogen exposure) and CL. We explored whether other birth or parental characteristics modify this association. With 2.2 × 106 person-years of follow-up, 185 CL and 136 ALL cases were ascertained. In Cox proportional hazards models, increasing birth order (continuous) was inversely associated with CL and ALL; hazard ratios (HR) = 0.88, 95% confidence interval (CI): (0.77-0.99) and 0.85: (0.73-0.99), respectively. Being later-born was associated with similarly reduced hazards of CL and ALL compared to being first-born; HRs = 0.78: 95% CI: 0.58-1.05 and 0.73: 0.52-1.03, respectively. Successive birth orders were associated with decreased CL and ALL risks (P for trend 0.047 and 0.055, respectively). Multivariable adjustment somewhat attenuated the associations. We found statistically significant and borderline interactions between birth weight (p = 0.024) and paternal age (p = 0.067), respectively, in associations between being later-born and CL, with the lowest risk observed for children born at

BACKGROUND: High glycemic index (GI) and glycemic load (GL) as indicators of carbohydrate quality and quantity have been found to increase risk of metabolic outcomes in adults. Whether carbohydrate quality may influence metabolic programming already in early life is unknown. We examined the association of maternal GI and GL with offspring body mass index (BMI) in the first 7 years of life among 68,471 mother-offspring dyads from the Danish National Birth Cohort (DNBC). In a sub-cohort of offspring with clinical data (n = 1234) that included 608 dyads exposed to gestational diabetes mellitus (GDM), we also examined the relation to metabolic health at 9-16 years.METHODS: Maternal GI and GL were quantified using a mid-pregnancy food frequency questionnaire. We used birth weight and length to calculate offspring's ponderal index. Age- and sex-specific BMI z scores at 5 mo, 12 mo, and 7 y were standardized against WHO reference data. In the clinical cohort, we quantified body composition, HOMA-IR, and HOMA-B. We used multivariable mixed linear and Poisson regression to model the associations.RESULTS: Median (IQR) of GI and GL were 83 (63-111) and 241 (180-333) g/day, respectively. We found that GI (Q4 vs. Q1:1.09, 95%CI: 1.03, 1.15) and GL (Q4 vs. Q1:1.10, 95%CI: 1.05, 1.16) modestly increased the relative risk of large-for gestational age (LGA). In the clinical sub-cohort, we observed a potential increase in offspring HOMA-IR, adiposity, and metabolic syndrome z score with higher maternal GI and GI. These associations were stronger among the GDM-exposed offspring, but the CI included the null value.CONCLUSION: We found associations of GI and GL in pregnancy with offspring LGA. Potential long-term benefits to offspring exposed to GDM need to be confirmed in larger, well-powered studies.

Objective Fetal exposure to gestational diabetes mellitus (GDM) increases the risk of metabolic diseases in the offspring. Leptin, adiponectin, and fibroblast growth factor 21 (FGF21) may play potential roles in the underlying disease mechanisms. We investigated the impact of fetal exposure to GDM on leptin, adiponectin, and FGF21 concentrations and their associations with measures of adiposity and metabolic traits during childhood/adolescence. Design and methods The follow-up study included 504 GDM and 540 control offspring aged 9–16 from the Danish National Birth Cohort. Anthropometric measurements, fasting blood samples, puberty status and fat percentages by dual-energy X-ray absorptiometry were examined. Serum concentrations of leptin, adiponectin, and FGF21 were measured by validated immune assays. Results GDM offspring had 38% (95% CI: 22–55%) higher leptin, 0.6 mg/L (95% CI: −1.2, −0.04 mg/L) lower adiponectin, and 32% (95% CI: −47%, −12%) lower FGF21 concentrations than control offspring (P P = 0.06) and significantly lower FGF21 concentrations (P = 0.006). When accounting for offspring BMI z-score, GDM exposure had no significant independent effect on leptin or adiponectin concentrations, whereas FGF21 was still significant. In univariate analyses, leptin and adiponectin were associated with fasting insulin, HOMA-IR, and adiposity, and FGF21 with total fat percentage. Conclusions GDM offspring had higher leptin, lower adiponectin and FGF21 concentrations than control offspring. Elevated leptin and decreased adiponectin concentrations associated with adverse metabolic traits and were most likely driven by higher obesity prevalence among GDM offspring. The functional implications of decreased FGF21 concentrations among GDM offspring need to be further explored.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common pregnancy complication which has substantial short- and long-term adverse health implications for women and their children. However, large-scale studies on genetic risk loci for GDM remain sparse. METHODS: We conducted a case-control study among 2,636 GDM cases and 6,086 non GDM controls from the Nurses’ Health Study II (NHSII) and the Danish National Birth Cohort (DNBC). One hundred and twelve susceptibility genetic variants confirmed by genome-wide association studies for type 2 diabetes (T2D) were selected and measured. A weighted genetic risk score (GRS) was created based on variants that were significantly associated with risk of GDM after correcting for false discovery rate (FDR). RESULTS: For the first time, we identified eight variants associated with GDM, namely rs7957197 (HNF1A), rs10814916 (GLIS3), rs3802177 (SLC30A8), rs9379084 (RREB1), rs34872471 (TCF7L2), rs7903146 (TCF7L2), rs11787792 (GPSM1), and rs7041847 (GLIS3). Additionally, we confirmed three variants, rs10830963 (MTNR1B), rs1387153 (MTNR1B), and rs4506565 (TCF7L2), that were previously significantly associated with GDM risk. Furthermore, compared to participants in the first (lowest) quartile of weighted GRS based on these 11 SNPs, the odds ratios of GDM were 1.07 (95% CI: 0.93, 1.22), 1.23 (95% CI 1.07, 1.41), and 1.53 (95% CI 1.34, 1.74) in the second, third, and fourth (highest) quartile, respectively. The significant positive associations between the weighted GRS and risk of GDM persisted across most of the strata of major risk factors for GDM including family history of type 2 diabetes, smoking status, body mass index, and age. CONCLUSION: In this large-scale case-control study with women from two independent populations, eight novel GDM SNPs were identified, which offers potential to improve our understanding on GDM etiology, particularly biological mechanisms related to beta cell function.

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.

Shortened telomere length is a marker of cell damage and is associated with oxidative stress, chronic inflammation and metabolic disease. We hypothesised that the offspring of women with gestational diabetes mellitus (GDM) with increased risk of cardiovascular and metabolic diseases might exhibit shorter telomere length. We investigated telomere length in 439 GDM and 469 control group offspring, aged between 9 and 16 years, recruited from the Danish National Birth Cohort. Relative telomere length was measured in peripheral blood DNA (n = 908) using a quantitative PCR approach. Multivariate regression analysis was used to investigate the association between mothers’ GDM status and telomere length in the offspring. Female offspring had longer telomeres than males. Offspring of mothers with GDM had significantly shorter telomere length than control offspring, but this difference was observed only in girls. There was a negative association between telomere length and GDM exposure among the female offspring (14% shorter telomeres, p = 0.003) following adjustment for the age of the offspring. Telomere length in female offspring was negatively associated with fasting insulin levels and HOMA-IR (p = 0.03). Maternal age, smoking, gestational age, birthweight and the offspring’s anthropometric characteristics were not associated with telomere length (p ≥ 0.1). The 9- to 16-year-old girls of mothers with GDM had shorter telomeres than those from the control population. Further studies are needed to understand the extent to which shortened telomere length predicts and/or contributes to the increased risk of disease later in life among the offspring of women with GDM.

Background Vitamin D may play a pivotal role in regulating insulin secretion and insulin sensitivity. However, the effect of vitamin D intake, either from the diet or from supplements, on the development of gestational diabetes mellitus (GDM) remains unclear. We prospectively examined the association of prepregnancy habitual intake of vitamin D from diet and supplements with the risk of incident GDM in a well-established cohort. Methods The present study was performed on 21 356 singleton pregnancies from 15 225 women in the Nurses’ Health Study II cohort. Diet information, including vitamin D intake from food sources and supplements, was assessed in 1991 and every 4 years thereafter by validated food frequency questionnaires. Log-binomial models with generalized estimating equations were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results During 10 years of follow-up, 865 incident GDM cases were documented. After adjustment for age, parity, race/ethnicity, family history of diabetes, dietary and lifestyle factors, and body mass index, the RRs (95% CIs) of GDM risk associated with supplemental vitamin D intake of 0, 1–399, and ≥400 IU/day were 1.00 (reference), 0.80 (0.67–0.96), and 0.71 (0.56–0.90), respectively (Ptrend = 0.002). Dietary and total vitamin D intakes were also inversely associated with GDM risk, but the associations were not statistically significant. Conclusions Prepregnancy supplemental vitamin D intake was significantly and inversely associated with risk of GDM. This study indicates potential benefits of increasing vitamin D intake from supplements in the prevention of GDM in women of reproductive age.

Background: Road traffic is a main source of air pollution and noise. Both exposures have been associated with type 2 diabetes, but associations with gestational diabetes mellitus (GDM) have been studied less. Objectives: We aimed to examine single and joint associations of exposure to air pollution and road traffic noise on GDM in a prospective cohort. Methods: We identified GDM cases from self-reports and hospital records, using two different criteria, among 72,745 singleton pregnancies (1997–2002) from the Danish National Birth Cohort. We modeled nitrogen dioxide (NO2) and noise from road traffic (Lden) exposure at all pregnancy addresses. Results: According to the two diagnostic criteria: the Danish clinical guidelines, which was our main outcome, and the WHO standard during recruitment period, a total of 565 and 210 women, respectively, had GDM. For both exposures no risk was evident for the common Danish criterion of GDM. A 10-μg/m3 increase in NO2 exposure during first trimester was, however, associated with an increased risk of WHO-GDM (adjusted odds ratio (OR)=1.24; 95% confidence interval (CI): 1.03, 1.49). The corresponding OR associated with a 10-dB higher road traffic noise level was 1.15 (0.94 to 1.18). In mutually adjusted models the OR for NO2 remained similar 1.22 (0.98, 1.53) whereas that for road traffic noise decreased to 1.03 (0.80, 1.32). Significant associations were also observed for exposure averaged over the 2nd and 3rd trimesters and the full pregnancy. Conclusions: No risk was evident for the common Danish criterion of GDM. NO2 was associated with higher risk for GDM according to the WHO criterion, which might be due to selection bias. Keywords: Air pollution, Environment, Gestational diabetes mellitus, Noise, Pregnancy, Traffic

Background: It has been suggested that prenatal exposure to n-3 long-chain fatty acids protects against asthma and other allergy-related diseases later in childhood. The extent to which fish intake in pregnancy protects against child asthma and rhinitis symptoms remains unclear. We aimed to assess whether fish and seafood consumption in pregnancy is associated with childhood wheeze, asthma and allergic rhinitis. Methods: We pooled individual data from 60 774 mother-child pairs participating in 18 European and US birth cohort studies. Information on wheeze, asthma and allergic rhinitis prevalence was collected using validated questionnaires. The time periods of interest were: infancy (0-2 years), preschool age (3-4 years), and school age (5-8 years). We used multivariable generalized models to assess associations of fish and seafood (other than fish) consumption during pregnancy with child respiratory outcomes in cohort-specific analyses, with subsequent random-effects meta-analyses. Results: The median fish consumption during pregnancy ranged from 0.44 times/week in The Netherlands to 4.46 times/week in Spain. Maternal fish intake during pregnancy was not associated with offspring wheeze symptoms in any age group nor with the risk of child asthma [adjusted meta-analysis relative risk (RR) per 1-time/week = 1.01, 95% confidence interval 0.97-1.05)] and allergic rhinitis at school age (RR = 1.01, 0.99-1.03). These results were consistently found in further analyses by type of fish and seafood consumption and in sensitivity analyses. Conclusion: We found no evidence supporting a protective association of fish and seafood consumption during pregnancy with offspring symptoms of wheeze, asthma and allergic rhinitis from infancy to mid childhood. This work was supported by the European Community’s Seventh Framework Program [EU- FP7- HEALTH-2009-single-stage-241604]. Details of funding per cohort are available at IJE online.

Background: Refined grains, a major source of dietary carbohydrates, have been related to impaired glucose homeostasis and obesity. Emerging animal data suggest that in utero exposure to dietary refined carbohydrates may predispose offspring to an obese phenotype, indicating a potential role for nutritional programming in the early origins of obesity, but intergenerational human data are lacking.Objective: We prospectively investigated refined-grain intake during pregnancy in association with offspring growth through age 7 y among high-risk children born to women with gestational diabetes mellitus (GDM).Design: The analysis included 918 mother-singleton child dyads from the Danish National Birth Cohort. Offspring body mass index z scores (BMIZs) were calculated by using weight and length or height measured at birth, 5 and 12 mo, and 7 y. Overweight or obesity was defined by WHO cutoffs. Linear and Poisson regressions were used, with adjustment for maternal demographic, lifestyle, and dietary factors.Results: Refined-grain intake during pregnancy was positively associated with offspring BMIZ (adjusted β per serving increase per day: 0.09; 95% CI: 0.02, 0.15) and risk of overweight or obesity at age 7 y [adjusted RR (aRR) comparing the highest with the lowest quartile: 1.80; 95% CI: 1.09, 2.98; P-trend = 0.032]. The association appeared to be more pronounced among children who were breastfed

Introduction The Danish National Birth Cohort (DNBC) contains comprehensive information on diet, lifestyle, constitutional and other major characteristics of women during pregnancy. It provides a unique source for studies on health consequences of gestational diabetes mellitus. Our aim was to identify and validate the gestational diabetes mellitus cases in the cohort. Material and methods We extracted clinical information from hospital records for 1609 pregnancies included in the Danish National Birth Cohort with a diagnosis of diabetes during or before pregnancy registered in the Danish National Patient Register and/or from a Danish National Birth Cohort interview during pregnancy. We further validated the diagnosis of gestational diabetes mellitus in 2126 randomly selected pregnancies from the entire Danish National Birth Cohort. From the individual hospital records, an expert panel evaluated gestational diabetes mellitus status based on results from oral glucose tolerance tests, fasting blood glucose and Hb1c values, as well as diagnoses made by local obstetricians. Results The audit categorized 783 pregnancies as gestational diabetes mellitus, corresponding to 0.89% of the 87 792 pregnancies for which a pregnancy interview for self-reported diabetes in pregnancy was available. From the randomly selected group the combined information from register and interviews could correctly identify 96% (95% CI 80-99.9%) of all cases in the entire Danish National Birth Cohort population. Positive predictive value, however, was only 59% (56-61%). Conclusions The combined use of data from register and interview provided a high sensitivity for gestational diabetes mellitus diagnosis. The low positive predictive value, however, suggests that systematic validation by hospital record review is essential not to underestimate the health consequences of gestational diabetes mellitus in future studies.

Offspring of obese mothers have increased risk of developing obesity and related short- and long-term disease. The cause is multifactorial and may partly be explained by the unfavorable intrauterine environment. Intervention during pregnancy leading to a healthier lifestyle among obese may alter this.To assess the effect of lifestyle intervention on markers of maternal metabolism and inflammation in 'the TOP (Treatment of Obese Pregnant Women) study', a randomized controlled trial.In the TOP-study 425 participants with body mass index ⩾30 kg/mMedian levels of hsCRP in gestational week 28-30 were lower in each of the intervention groups (8.3 mg/l in PA+D group, P=0.03; and 8.8 mg/l in PA group, P=0.02) versus the control group (11.5 mg/l). Obtaining 11 000 steps per day as aimed for resulted in a 21% lower hsCRP compared to non-compliant women. Women reporting high carbohydrate intake had around 30% higher hsCRP concentrations in late gestation than women reporting the lowest intake. There were no differences in lipid profile or any of the metabolic markers in gestational week 28-30 when comparing the intervention and control groups.Lifestyle intervention in obese women can reduce hsCRP representing a marker of inflammation during pregnancy. The effect may partly be mediated by more physical activity and partly by changes in intake of carbohydrates and the glycaemic load.

Dietary long-chain n-3 PUFA (n-3 LCPUFA) in infancy may have long-term effects on lifestyle disease risk. The present follow-up study investigated whether maternal fish oil (FO) supplementation during lactation affected growth and blood pressure in adolescents and whether the effects differed between boys and girls. Mother–infant pairs (n 103) completed a randomised controlled trial with FO (1·5 g/d n-3 LCPUFA) or olive oil (OO) supplements during the first 4 months of lactation; forty-seven mother–infant pairs with high fish intake were followed-up for 4 months as the reference group. We also followed-up 100 children with assessment of growth, blood pressure, diet by FFQ and physical activity by 7-d accelerometry at 13·5 (sd 0·4) years of age. Dried whole-blood fatty acid composition was analysed in a subgroup (n 49). At 13 years of age, whole-blood n-3 LCPUFA, diet, physical activity and body composition did not differ between the three groups. The children from the FO group were 3·4 (95 % CI 0·2, 6·6) cm shorter (P=0·035) than those from the OO group, and tended to have less advanced puberty (P=0·068), which explained the difference in height. There was a sex-specific effect on diastolic blood pressure (Psex×group=0·020), which was driven by a 3·9 (95 % CI 0·2, 7·5) mmHg higher diastolic blood pressure in the FO compared with the OO group among boys only (P=0·041). Our results indicate that early n-3 LCPUFA intake may reduce height in early adolescence due to a delay in pubertal maturation and increase blood pressure specifically in boys, thereby tending to counteract existing sex differences.

OBJECTIVE We examined the association of lactation duration with incident type 2 diabetes among women with a history of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS We monitored 4,372 women with a history of GDM participating in the Nurses’ Health Study II for incident type 2 diabetes over 25 years up to 2017. Lactation history was obtained through follow-up questionnaires to calculate lactation duration. Follow-up blood samples were collected from a subset of these women at median age of 58 years through the Diabetes & Women’s Health Study. RESULTS We documented 873 incident cases of type 2 diabetes during 87,411 person-years of follow-up. Longer duration of lactation was associated with lower risk of type 2 diabetes for both total lactation (hazard ratio 1.05 [95% CI 0.83–1.34] for up to 6 months, 0.91 [0.72–1.16] for 6–12 months, 0.85 [0.67–1.06] for 12–24 months, and 0.73 [0.57–0.93] for >24 months, compared with 0 months; P-trend = 0.003) and exclusive breastfeeding (P-trend = 0.002) after adjustment for age, ethnicity, family history of diabetes, parity, age at first birth, smoking, diet quality, physical activity, and prepregnancy BMI. Longer duration of lactation was also associated with lower HbA1c, fasting plasma insulin, and C-peptide concentrations among women without type 2 diabetes at follow-up (all adjusted P-trend ≤0.04). CONCLUSIONS Longer duration of lactation is associated with a lower risk of type 2 diabetes and a favorable glucose metabolic biomarker profile among women with a history of GDM. The underlying mechanisms and impact on diabetes complications, morbidity, and mortality remain to be determined.

Supplemental Digital Content is available in the text., Background: Road traffic is a major source of air pollution and noise. Both exposures may contribute to increased blood pressure and metabolic disease; however, few studies have examined these relationships in children. Objectives: We aimed to investigate whether long-term exposures to air pollution and noise from road traffic were associated with increased blood pressure and insulin resistance in children. Methods: Cardiometabolic outcomes were derived from a follow-up examination of 629 children (10–15 years old) enrolled in the Danish National Birth Cohort. We evaluated associations with prenatal and postnatal residential exposure to nitrogen dioxide (NO2) and noise from road traffic (Lden) using historical addresses and linear regression models. Results: A 10-unit increase in postnatal exposure to NO2 and Lden was associated with a 0.31 (−0.87, 1.48) and 0.18 (−0.61, 0.96) mmHg changes in diastolic blood pressure, respectively. In contrast, both exposures were associated with decreased systolic blood pressure. After adjustment and mutual adjustment for NO2, exposure to Lden was associated with a statistical significant decrease in systolic blood pressure both during prenatal and postnatal life, but the majority of the associations evaluated did not reach statistical significance. Inverse associations were observed for plasma fasting glucose, insulin, and HOMA of insulin resistance for both exposures, exposure windows, before and after adjustment. Conclusions: The findings do not support evidence of associations between long-term exposures to air pollution and road traffic noise, increased blood pressure, and a metabolic profile characteristic of increased risk for glucose intolerance or type 2 diabetes later in life.

Publisher's version (útgefin grein), Background: The Developmental Origins of Health and Disease (DOHaD) hypothesis postulates that exposures during early life, such as maternal dietary intake during pregnancy, may have a lifelong impact on the individual's susceptibility to diseases. The individual's own lifestyle habits are obviously an additional factor, but we have only limited knowledge regarding how it may interact with prenatal exposures in determining later disease. To gain further insight into these potentially complex relationships, we examined the longitudinal association between maternal diet quality during pregnancy and diet quality in early adolescence in a contemporary cohort. Methods and findings: From 1996 to 2003, the Danish National Birth Cohort (DNBC) was established. Women from across the country were enrolled, and dietary intake in midpregnancy was assessed concurrently with a 360-item food frequency questionnaire (FFQ) (https://www.dnbc.dk/-/ media/arkiv/projekt-sites/dnbc/kodeboeger/dnbc-food-frequency-questionnaire/dnbc-foodfrequency- questionnaire-pdf.pdf?la=en). During 2013-2018, dietary intake was assessed at age 14 years with a 150-item FFQ (https://www.dnbc.dk/-/media/arkiv/projekt-sites/dnbc/ kodeboeger/ffq-14/dnbc-ffq-14-english-translation.pdf?la=en) in the DNBC children. Among the 19,582 mother-offspring pairs included in the analyses, the mean age (±standard deviation [SD]) was 30.7 (±4.1) years and 14.0 (±0.0) years for mothers and offspring, respectively. The majority of both mothers (67%) and offspring (76%) were classified as normal weight. For both questionnaires, a Healthy Eating Index (HEI) was developed as an indicator for diet quality based on current Danish Food-Based Dietary Guidelines (FBDG) including eight components: fruits and vegetables, fish, dietary fibres, red meat, saturated fatty acids (SFAs), sodium, sugar-sweetened beverages (SSBs), and added sugar. The HEI score was divided into quartiles; individuals in the highest quartile represented those with the most optimal diet. The maternal HEI score was correlated positively with offspring HEI score (Pearson r = 0.22, p < 0.001). A log-linear binomial model was used to estimate the relative risk of the offspring being in the highest quartile of HEI at age 14 years if the mother was ranked in quartile 4 during pregnancy. Results showed that offspring born to mothers who were in the highest HEI quartile during pregnancy were more likely themselves to be located in the highest HEI quartile at age 14 years (risk ratio [RR]: 2.1, 95% confidence interval [CI]: 2.0, 2.3, p < 0.001). Adjusting for maternal prepregnancy body mass index (BMI), parity, education, alcohol intake, physical activity, smoking, and breastfeeding, as well as offspring total energy intake and sex, did not influence the effect estimates. The limitations of our study include that some attrition bias towards more healthy participants was observed when comparing participants with nonparticipants. Bias in the FFQ method may also have resulted in underrepresentation of adolescents with poorer diet quality. Conclusions: In this study using data from a large national birth cohort, we observed that maternal diet quality during pregnancy was associated with diet quality of the offspring at age 14 years. These findings indicate the importance of separating early dietary exposures from later dietary exposures when studying dietary aetiologies of diseases postulated to have developmental origins such as, for instance, obesity or asthma in observational settings., SFO received the Awards. This work was supported by grants from The Danish Council for Strategic Research, now Innovation Fund Denmark [09-067124 (Centre for Fetal Programming)] and [09-075611]; and by Nordea-fonden (https:// nordeafonden.dk/) [02-2013-2014]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Objective To summarize the published evidence regarding the association between maternal infection during pregnancy and childhood leukemia. Study design In this systematic review and meta-analysis (PROSPERO number, CRD42018087289), we searched PubMed and Embase to identify relevant studies. We included human studies that reported associations of at least one measure of maternal infection during pregnancy with acute lymphoblastic leukemia (ALL) or all childhood leukemias in the offspring. One reviewer extracted the data first using a standardized form, and the second reviewer independently checked the data for accuracy. Two reviewers used the Newcastle-Ottawa Scale to assess the quality of included studies. We conducted random effects meta-analyses to pool the ORs of specific type of infection on ALL and childhood leukemia. Results This review included 20 studies (ALL, n = 15; childhood leukemia, n = 14) reported in 32 articles. Most (>65%) included studies reported a positive association between infection variables and ALL or childhood leukemia. Among specific types of infection, we found that influenza during pregnancy was associated with higher risk of ALL (pooled OR, 3.64; 95% CI, 1.34-9.90) and childhood leukemia (pooled OR, 1.77; 95% CI, 1.01-3.11). Varicella (pooled OR, 10.19; 95% CI, 1.98-52.39) and rubella (pooled OR, 2.79; 95% CI, 1.16-6.71) infections were also associated with higher childhood leukemia risk. Conclusions Our findings suggest that maternal infection during pregnancy may be associated with a higher risk of childhood leukemia.

OBJECTIVES: Women with gestational diabetes (GDM) are at increased risk for renal complications later in life. Nut intake has been associated with reduced cardiometabolic risk, but few studies have examined its association with renal function. We examined associations of nut intake and renal function among women with prior GDM. METHODS: We studied 330 women from the Danish National Birth Cohort (1996–2002) with a GDM pregnancy who participated in a clinical exam 9 to 16 years after the index pregnancy as part of the Diabetes & Women's Health Study (2012–2014) and were free of major chronic diseases at follow-up. Habitual past year intake of nine types of nuts was ascertained at follow-up using a food frequency questionnaire. Total nut intake was classified as none (1 serving/d). Estimated glomerular filtration rate (eGFR) via CKD-EPI equation and urine albumin-to-creatinine ratio (UACR) were calculated based on serum creatinine (mg/dL) and urine albumin (mg/L), and creatinine (mg/dL) measurements respectively. We estimated % differences with 95% confidence intervals (CI) in these outcomes by nut intake adjusted for current body mass index, age, physical activity, energy intake, and dietary variables. We explored possible non-linear relations using restricted cubic splines. RESULTS: A significant non-linear U-shaped association was detected between total nut consumption and UACR (P = 0.001) with lowest UACR levels among women with weekly consumption. Compared to women with weekly intake (n = 222), adjusted UACR levels were 86% [95% CI: 15%, 200%] and 23% [−1%, 54%] higher among women with no or monthly nut intake, respectively, while UACR levels were 118% [22%, 286%] higher among women with daily intake. Compared to weekly consumers, adjusted eGFR levels were 9% [0%, 19%] higher among daily consumers. CONCLUSIONS: Moderate nut consumption may be beneficial to kidney health among women with prior GDM. FUNDING SOURCES: Intramural Research Program of the NICHD, March of Dimes Birth Defects Foundation, Innovation Fund Denmark, Health Foundation, Heart Foundation, EU, Danish Diabetes Academy supported by Novo Nordisk Foundation, and NIH Building Interdisciplinary Research Careers in Women's Health Program.

Background and Aim: Training in advanced carbohydrate counting improves glycemic control in type 1 diabetes and type 2 diabetes. We aimed to investigate, whether a course in advanced carbohydrate counting reduced intake of carbohydrates and glycemic index of carbohydrates in persons with basal-bolus insulin treated type 2 diabetes. Material and Methods: We conducted a 24-week open-label, randomized controlled study in 79 participants with basal-bolus insulin treated type 2 diabetes. Participants were randomized 1:1 into two groups. ABC group received 6-hour training in advanced carbohydrate counting and use of an automated bolus calculator. MC group also received 6-hour training in advanced carbohydrate counting but was trained in manual calculation of insulin bolus. Diet composition and intake of macronutrients were assessed at baseline, week 12 and week 24 using a validated electronic food frequencies questionnaire. Results: Baseline characteristics were similar between groups (mean age 62.5 ± 9.6 years, mean HbA1C 72 ± 11 mmol/mol, mean diabetes duration 18.7 ± 7.6 years, mean BMI 33 ± 6 kg/m2). Mean energy intake was significantly reduced in the ABC group from baseline to week 24 (P=0.03), primarily due to significantly reduced intake of carbohydrates in form of cereals (P=0.005). No significant changes in energy intake were seen in the MC group (P=0.62). Further, glycemic index of ingested carbohydrates was reduced significantly in the ABC group (P=0.03), but not in the MC group (P=0.09). As previously reported HbA1c had decreased significantly by 9.0 mmol/mol in both groups at week 24. There were no significant changes in BMI throughout the study. Conclusion: Advanced carbohydrate counting with the use of an automated bolus calculator may help to reduce energy intake and glycemic index of ingested carbohydrates in basal-bolus insulin treated type 2 diabetes. Disclosure M.B. Christensen: None. T.I. Halldorsson: None. A. Gotfredsen: None. E. Hommel: None. P. Gæde: None. S.F. Olsen: None. K. Nørgaard: Advisory Panel; Self; Abbott, Medtronic, Novo Nordisk A/S. Speaker's Bureau; Self; Bayer US, Medtronic, Roche Diabetes Care, Rubin Medical, Sanofi, Zealand Pharma A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Funding Roche A/S

Background: Offspring of mothers with gestational diabetes mellitus (GDM) are at increased risk of developing metabolic diseases. Adipokines such as adiponectin and leptin may be involved in the underlying mechanisms. Fibroblast growth factor 21 (FGF-21) has recently been identified as a potent metabolic regulator. Therefore, we investigated the impact of fetal exposure to GDM on adiponectin, leptin and FGF-21 levels and their associations with metabolic and adiposity traits during adolescence. Methods: A prospective study comparing 502 offspring of GDM exposed mothers and 535 offspring of non-exposed mothers. During a clinical exam of offspring, aged 9-16 years old, metabolic traits were measured and fasting blood samples collected and assayed for serum concentrations of leptin, adiponectin and FGF-21. Results: GDM exposed offspring had 34% (95% CI: 18-51%) higher leptin levels, and 34% (95% CI: -48, -15%) lower FGF-21 concentrations than non-exposed offspring (p Conclusion: GDM exposed offspring had higher leptin and lower FGF-21 concentrations than non-exposed controls, but this was driven by higher prevalence of adiposity among GDM offspring. The differential adipokine concentration does not seem to be the major driver behind the dysmetabolic phenotype among GDM offspring. Disclosure F.B. Kampmann: None. A. Thuesen: None. L. Hjort: None. M. Bjerre: None. J. Frystyk: None. I. Tetens: None. A.A. Bjerregaard: None. J.E. Chavarro: None. S.F. Olsen: None. P. Damm: Advisory Panel; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S. A.A. Vaag: Employee; Self; AstraZeneca. L. Grunnet: None. Funding Danish Council for Strategic Research; Innovation Fund, Denmark (09-067124, 11-115923); Novo Nordisk Foundation (NNF160C0022518); Danish Diabetes Academy

Background: Women with prior gestational diabetes (GDM) are at exceptionally high risk for type 2 diabetes (T2D). Yet, little is known about genetic determinants for the progression to T2D from GDM. Further, inference from existing data is hindered by small sample size. In a large study based on two independent populations, we examined a genetic risk score (GRS) for T2D in relation to the progression risk. Methods: This study included white women in the Diabetes and Women’s Health Study, which followed women with GDM from the Nurses’ Health Study II (NHSII, N = 1998) and the Danish National Birth Cohort (DNBC, N = 550). A GRS of T2D was calculated using 59 T2D SNPs (GRS59) from genome-wide association studies in European populations. GRS scores for beta-cell function (GRSBC) and insulin resistance (GRSIR) were derived based on subsets of these SNPs. The relative risks (RRs) of progression to T2D were estimated using log-binomial regression. RRs from the two cohorts were meta-analyzed using fixed effects models. Results: During the study follow-ups of more than 10 years after the index pregnancy, 416 (20.8%) in NHSII and 155 (28.2%) women in DNBC developed T2D. GRS59 was positively related to the risk of progression to T2D. RRs (95% CI) for increasing quartiles of GRS59 were 1.00, 0.99 (0.79, 1.23), 1.26 (1.03, 1.55), and 1.25 (1.01, 1.53), respectively (p-trend = 0.008). The associations were significantly stronger among lean (pre-pregnant BMI < 25 kg/m2) than overweight or obese women (p-interaction < 0.001). Further, GRSIR, but not GRSBC, was related to the risk of T2D. RRs (95% CI) for increasing quartiles of GRSIR were 1.00, 1.25 (1.02, 1.55), 1.32 (1.07, 1.64), and 1.29 (1.05, 1.58), respectively (p-trend = 0.02). The results were generally consistent across the two cohorts. Conclusion: In this large prospective study of women with prior GDM, greater GRS of T2D, especially GRS of insulin resistance, was associated with greater risk of progression to T2D. Disclosure M. Li: None. M.L. Rahman: None. J. Wu: None. M. Ding: None. J.E. Chavarro: None. Y. Lin: None. S.H. Ley: None. L. Grunnet: None. S. Hinkle: None. A. Thuesen: None. E. Yeung: None. R.E. Gore-Langton: None. S.J. Sherman: None. L. Hjort: None. F.B. Kampmann: None. P. Damm: Advisory Panel; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S. F. Tekola-Ayele: None. A. Liu: None. J. Mills: None. A.A. Vaag: Employee; Self; AstraZeneca. S.F. Olsen: None. F. Hu: None. C. Zhang: None. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health; March of Dimes Birth Defects Foundation; Innovation Fund Denmark; Health Foundation; Heart Foundation; European Union

Parental occupational exposures to pesticides, animals and organic dust have been associated with an increased risk of childhood cancer based mostly on case–control studies. We prospectively evaluated parental occupational exposures and risk of childhood leukemia and central nervous system (CNS) tumors in the International Childhood Cancer Cohort Consortium. We pooled data on 329,658 participants from birth cohorts in five countries (Australia, Denmark, Israel, Norway and United Kingdom). Parental occupational exposures during pregnancy were estimated by linking International Standard Classification of Occupations-1988 job codes to the ALOHA+ job exposure matrix. Risk of childhood (