National health registries - a 'goldmine' for studying non-communicable disease occurrence in Norway - the NCDNOR project.

To estimate occurrence of non-communicable diseases (NCDs) over the life-course in the Norwegian population, national health registries are a vital source of information since they fully represent the entire non-institutionalised population. However, as they are mainly established for administrative purposes, more knowledge about how NCDs are recorded in the registries is needed. To establish this, we begin by counting the number of individuals registered annually with one or more NCDs in any of the registries. The study population includes all inhabitants who lived in Norway from 2004 to 2020 (N~6.4m). The NCD outcomes are diabetes, cardiovascular diseases, chronic obstructive lung diseases, cancer and mental disorders/substance use disorders. Further, we included hip fractures in our NCD concept. The data sources used to identify individuals with NCDs, including detailed information on diagnoses in primary and secondary health care and dispensings of prescription drugs, are the Cancer Registry of Norway, The Norwegian Patient Registry, The Norwegian Control and Payment of Health Reimbursement database, and The Norwegian Prescription Database. The number of individuals registered annually with an NCD diagnosis and/or a dispensed NCD drug increased over the study period. Changes over time may reflect changes in disease incidence and prevalence, but also changes in disease-specific guidelines, reimbursement schemes and access to and use of health services. Data from more than one health registry to identify individuals with NCDs are needed since the registries reflect different levels of health care services and therefore may reflect disease severity.

Clustering and trajectories of key noncommunicable disease risk factors in Norway: the NCDNOR project.

Noncommunicable diseases (NCDs) are a leading cause of premature death globally and have common preventable risk factors. In Norway, the NCDNOR-project aims at establishing new knowledge in the prevention of NCDs by combining information from national registries with data from population-based health studies. In the present study, we aimed to harmonize data on key NCD risk factors from the health studies, describe clustering of risk factors using intersection diagrams and latent class analysis, and identify long-term risk factor trajectories using latent class mixed models. The harmonized study sample consisted of 808,732 individuals (1,197,158 participations). Two-thirds were exposed to ≥ 1 NCD risk factor (daily smoking, physical inactivity, obesity, hypertension, hypercholesterolaemia or hypertriglyceridaemia). In individuals exposed to ≥ 2 risk factors (24%), we identified five distinct clusters, all characterized by fewer years of education and lower income compared to individuals exposed to < 2 risk factors. We identified distinct long-term trajectories of smoking intensity, leisure-time physical activity, body mass index, blood pressure, and blood lipids. Individuals in the trajectories tended to differ across sex, education, and body mass index. This provides important insights into the mechanisms by which NCD risk factors can occur and may help the development of interventions aimed at preventing NCDs.

Occupational physical activity and longevity in working men and women in Norway: a prospective cohort study.

BACKGROUND: Studies suggest that high occupational physical activity increases mortality risk. However, it is unclear whether this association is causal or can be explained by a complex network of socioeconomic and behavioural factors. We aimed to examine the association between occupational physical activity and longevity, taking a complex network of confounding variables into account. METHODS: In this prospective cohort study, we linked data from Norwegian population-based health examination surveys, covering all parts of Norway with data from the National Population and Housing Censuses and the Norwegian Cause of Death Registry. 437 378 participants (aged 18-65 years; 48·7% men) self-reported occupational physical activity (mutually exclusive groups: sedentary, walking, walking and lifting, and heavy labour) and were followed up from study entry (between February, 1974, and November, 2002) to death or end of follow-up on Dec 31, 2018, whichever came first. We estimated differences in survival time (death from all causes, cardiovascular disease, and cancer) between occupational physical activity categories using flexible parametric survival models adjusted for confounding factors. FINDINGS: During a median of 28 years (IQR 25-31) from study entry to the end of follow-up, 74 203 (17·0%) of the participants died (all-cause mortality), of which 20 111 (27·1%) of the deaths were due to cardiovascular disease and 29 886 (40·3%) were due to cancer. Crude modelling indicated shorter mean survival times among men in physically active occupations than in those with sedentary occupations. However, this finding was reversed following adjustment for confounding factors (birth cohort, education, income, ethnicity, prevalent cardiovascular disease, smoking, leisure-time physical activity, body-mass index), with estimates suggesting that men in occupations characterised by walking, walking and lifting, and heavy labour had life expectancies equivalent to 0·4 (95% CI -0·1 to 1·0), 0·8 (0·3 to 1·3), and 1·7 (1·2 to 2·3) years longer, respectively, than men in the sedentary referent category. Results for mortality from cardiovascular disease and cancer showed a similar pattern. No clear differences in survival times were observed between occupational physical activity groups in women. INTERPRETATION: Our results suggest that moderate to high occupational physical activity contributes to longevity in men. However, occupational physical activity does not seem to affect longevity in women. These results might inform future physical activity guidelines for public health. FUNDING: The Norwegian Research Council (grant number 249932/F20).

Temporal trends in physical activity levels across more than a decade - a national physical activity surveillance system among Norwegian children and adolescents.

BACKGROUND: There is a scarcity of device measured data on temporal changes in physical activity (PA) in large population-based samples. The purpose of this study is to describe gender and age-group specific temporal trends in device measured PA between 2005, 2011 and 2018 by comparing three nationally representative samples of children and adolescents. METHODS: Norwegian children and adolescents (6, 9 and 15-year-olds) were invited to participate in 2005 (only 9- and 15-year-olds), 2011 and 2018 through cluster sampling (schools primary sampling units). A combined sample of 9500 individuals participated. Physical activity was assessed by hip worn accelerometers, with PA indices including overall PA (counts per minute), moderate-to-vigorous intensity PA (MVPA), and PA guideline adherence (achieving on average ≥ 60 min/day of moderate-to-vigorous PA). Random-effects linear regressions and logistic regressions adjusted for school-level clusters were used to analyse temporal trends. FINDINGS: In total, 8186 of the participating children and adolescents provided valid PA data. Proportions of sufficiently active 6-year-olds were almost identical in 2011 and 2018; boys 95% (95% CI: 92, 97) and 94% (95%CI: 92, 96) and girls 86% (95% CI: 83, 90) and 86% (95% CI: 82, 90). Proportions of sufficiently active 15-year-olds in 2005 and 2018 were 52% (95% CI: 46, 59) and 55% (95% CI: 48, 62) in boys, and 48% (95% CI: 42, 55) and 44% (95% CI: 37, 51) in girls, respectively, resulting from small differences in min/day of MVPA. Among 9-year-old boys and girls, proportions of sufficiently active declined between 2005 and 2018, from 90% (95% CI: 87, 93) to 84% (95% CI: 80, 87)) and 74% (95% CI: 69, 79) to 68% (95% CI: 64, 72), respectively. This resulted from 9.7 min/day less MVPA in boys (95% CI: - 14.8, - 4.7; p < 0.001) and 3.2 min/day less MVPA (95% CI: - 7.0, 0.7; p = 0.106) in girls. CONCLUSIONS: PA levels have been fairly stable between 2005, 2011 and 2018 in Norwegian youth. However, the declining PA level among 9-year-old boys and the low proportion of 15-year-olds sufficiently active is concerning. To evaluate the effect of, and plan for new, PA promoting strategies, it is important to ensure more frequent, systematic, device-based monitoring of population-levels of PA.

Underlying conditions in adults with COVID-19. / Underliggende tilstander hos voksne med covid-19.

BACKGROUND: Cardiovascular diseases, cancer, type-2 diabetes and chronic obstructive pulmonary disease (COPD) were initially noted as the most common diseases among individuals who were hospitalised for COVID-19. However, the evidence base is weak. The objective of this study is to describe how selected diseases were distributed among adults with confirmed COVID-19 (COVID-19 positive tests) and among those hospitalised for COVID-19 compared to the general population. MATERIAL AND METHOD: We used data from the Norwegian Patient Registry, the Norwegian Registry for Primary Health Care and the Norwegian Surveillance System for Communicable Diseases for adults from the age of 20 and older for the period 1 March 2020-13 May 2020. RESULTS: Of all those who tested positive for COVID-19, 7 632 (94 %) were aged 20 years or older, and 1 025 (13.4 %) of these had been hospitalised. Among those hospitalised with COVID-19, there was a higher proportion of individuals with cardiovascular diseases (18.3 % versus 15.6 %), cancer (6.9 % versus 5.4 %), type-2 diabetes (8.6 % versus 5.2 %) and COPD (3.8 % versus 2.7 %) than in the general population as a whole after adjusting for age. The proportion of hospitalised patients with asthma, other chronic respiratory disease, cardiovascular disease, ongoing cancer treatment, complications related to hypertension, obesity and overweight, neurological disorders and cardiac and renal failure was also higher than in the general population. There were few differences between persons who had tested positive for COVID-19 and the general population in terms of underlying conditions. INTERPRETATION: Among those hospitalised for COVID-19, there was a higher proportion of patients with underlying illnesses than in the general population. This may indicate that these patients tend to have a more severe course of disease or that they are more likely to be hospitalised compared to healthy individuals. The results must be interpreted with caution, since the sample of COVID-19 individuals is non-random.

Is the Disease Burden from COPD in Norway Falling off? A Study of Time Trends in Three Different Data Sources.

Background: Less smoking should lead to fewer COPD cases. We aimed at estimating time trends in the prevalence and burden of COPD in Norway from 2001 to 2017. Methods: We used pre-bronchodilator spirometry and other health data from persons aged 40-84 years in three surveys of the Tromsø Study, 2001-2002, 2007-2008 and 2015-2016. We applied spirometry lower limits of normal (LLN) according to Global Lung Initiative 2012. Age-standardized prevalence was determined. We defined COPD as FEV1/FVC

Comparison of smoking-related DNA methylation between newborns from prenatal exposure and adults from personal smoking.

Aim: Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for in utero exposure in newborns is unknown. Materials & methods: We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and personal smoking (16 cohorts, 15907 participants, 2433 current smokers). Results & conclusion: Comparing meta-analyses, we identified numerous signatures specific to newborns along with many shared between newborns and adults. Unique smoking-associated genes in newborns were enriched in xenobiotic metabolism pathways. Our findings may provide insights into specific health impacts of prenatal exposure on offspring.

Leisure-time physical activity before pregnancy and risk of hyperemesis gravidarum: a population-based cohort study.

INTRODUCTION: Women who experience severe nausea and vomiting in early pregnancy are less likely to participate in leisure-time physical activity (LTPA) during pregnancy. Whether LTPA before pregnancy is associated with hyperemesis gravidarum (HG) has not yet been studied. The aim of the study was to estimate associations between prepregnancy LTPA and HG in pregnancy. METHODS: We present data from 37,442 primiparous women with singleton pregnancies enrolled in The Norwegian Mother and Child Cohort Study. Prepregnancy LTPA was self-reported by questionnaire in pregnancy week 17. HG was reported in week 30 and defined as prolonged nausea and vomiting in pregnancy requiring hospitalisation before the 25th gestational week. We estimated the crude and adjusted associations between LTPA and HG using multiple logistic regression. We assessed effect modification by prepregnancy BMI or smoking by stratified analysis and interaction terms. RESULTS: A total of 398 (1.1%) women developed HG. Before pregnancy 56.7% conducted LTPA at least 3 times weekly, while 18.4% of women conducted LTPA less than once a week. Compared to women reporting LTPA 3 to 5 times weekly, women reporting no LTPA before pregnancy had an increased odds of HG (adjusted odds ratio (aOR) 1.69; 95% confidence interval (CI), 1.20 to 2.37). LTPA-HG associations differed by prepregnancy BMI but not by prepregnancy smoking. DISCUSSION: Lack of LTPA before pregnancy was associated with an increased odds of HG. Due to few cases of HG and thereby low statistical power, one need to be cautious when interpreting the results of this study.

Maternal alcohol consumption and offspring DNA methylation: findings from six general population-based birth cohorts.

AIM: Alcohol consumption during pregnancy is sometimes associated with adverse outcomes in offspring, potentially mediated by epigenetic modifications. We aimed to investigate genome-wide DNA methylation in cord blood of newborns exposed to alcohol in utero. MATERIALS & METHODS: We meta-analyzed information from six population-based birth cohorts within the Pregnancy and Childhood Epigenetics consortium. RESULTS: We found no strong evidence of association at either individual CpGs or across larger regions of the genome. CONCLUSION: Our findings suggest no association between maternal alcohol consumption and offspring cord blood DNA methylation. This is in stark contrast to the multiple strong associations previous studies have found for maternal smoking, which is similarly socially patterned. However, it is possible that a combination of a larger sample size, higher doses, different timings of exposure, exploration of a different tissue and a more global assessment of genomic DNA methylation might show evidence of association.

Misclassified exposure in epigenetic mediation analyses. Does DNA methylation mediate effects of smoking on birthweight?

AIMS: Assessing whether epigenetic alterations mediate associations between environmental exposures and health outcomes is increasingly popular. We investigate the impact of exposure misclassification in such investigations. MATERIALS & METHODS: We quantify bias and false-positive rates due to exposure misclassification in mediation analysis and assess the performance of the simulation extrapolation method (SIMEX). We evaluate whether DNA-methylation mediates smoking-birth weight relationship in the Norwegian Mother and Child Study birth cohort. RESULTS: Ignoring exposure misclassification increases type I error in mediation analysis. The direct effect is underestimated and, when the mediator is a biomarker of the exposure, as is true for smoking, the indirect effect is overestimated. CONCLUSION: Misclassification correction plus cautious interpretation are recommended for mediation analyses in the presence of exposure misclassification.

DNA Methylation Score as a Biomarker in Newborns for Sustained Maternal Smoking during Pregnancy.

BACKGROUND: Maternal smoking during pregnancy, especially when sustained, leads to numerous adverse health outcomes in offspring. Pregnant women disproportionately underreport smoking and smokers tend to have lower follow-up rates to repeat questionnaires. Missing, incomplete, or inaccurate data on presence and duration of smoking in pregnancy impairs identification of novel health effects and limits adjustment for smoking in studies of other pregnancy exposures. An objective biomarker in newborns of maternal smoking during pregnancy would be valuable. OBJECTIVES: We developed a biomarker of sustained maternal smoking in pregnancy using common DNA methylation platforms. METHODS: Using a dimension reduction method, we developed and tested a numeric score in newborns to reflect sustained maternal smoking in pregnancy from data on cotinine, a short-term smoking biomarker measured mid-pregnancy, and Illumina450K cord blood DNA methylation from newborns in the Norwegian Mother and Child Cohort Study (MoBa). RESULTS: This score reliably predicted smoking status in the training set (n = 1,057; accuracy = 96%, sensitivity = 80%, specificity = 98%). Sensitivity (58%) was predictably lower in the much smaller test set (n = 221), but accuracy (91%) and specificity (97%) remained high. Reduced birth weight, a well-known effect of maternal smoking, was as strongly related to the score as to cotinine. A three-site score had lower, but acceptable, performance (accuracytrain = 82%, accuracytest = 83%). CONCLUSIONS: Our smoking methylation score represents a promising novel biomarker of sustained maternal smoking during pregnancy easily calculated with Illumina450K or IlluminaEPIC data. It may help identify novel health impacts and improve adjustment for smoking when studying other risk factors with more subtle effects.

Maternal smoking impacts key biological pathways in newborns through epigenetic modification in Utero.

BACKGROUND: Children exposed to maternal smoking during pregnancy exhibit increased risk for many adverse health effects. Maternal smoking influences methylation in newborns at specific CpG sites (CpGs). Here, we extend evaluation of individual CpGs to gene-level and pathway-level analyses among 1062 participants in the Norwegian Mother and Child Cohort Study (MoBa) using the Illumina 450 K platform to measure methylation in newborn DNA and maternal smoking in pregnancy, assessed using the biomarker, plasma cotinine. We used novel implementations of bioinformatics tools to collapse epigenome-wide methylation data into gene- and pathway-level effects to test whether exposure to maternal smoking in utero differentially methylated CpGs in genes enriched in biologic pathways. Unlike most pathway analysis applications, our approach allows replication in an independent cohort. RESULTS: Data on 485,577 CpGs, mapping to a total of 20,199 genes, were used to create gene scores that were tested for association with maternal plasma cotinine levels using Sequence Kernel Association Test (SKAT), and 15 genes were found to be associated (q < 0.25). Six of these 15 genes (GFI1, MYO1G, CYP1A1, RUNX1, LCTL, and AHRR) contained individual CpGs that were differentially methylated with regards to cotinine levels (p < 1.06 × 10-7). Nine of the 15 genes (FCRLA, MIR641, SLC25A24, TRAK1, C1orf180, ITLN2, GLIS1, LRFN1, and MIR451) were associated with cotinine at the gene-level (q < 0.25) but had no genome-wide significant individual CpGs (p > 1.06 × 10-7). Pathway analyses using gene scores resulted in 51 significantly associated pathways, which we tested for replication in an independent cohort (q < 0.05). Of those 32 replicated in an independent cohort, which clustered into six groups. The largest cluster consisted of pathways related to cancer, cell cycle, ERα receptor signaling, and angiogenesis. The second cluster, organized into five smaller pathway groups, related to immune system function, such as T-cell regulation and other white blood cell related pathways. CONCLUSIONS: Here we use novel implementations of bioinformatics tools to determine biological pathways impacted through epigenetic changes in utero by maternal smoking in 1062 participants in the MoBa, and successfully replicate these findings in an independent cohort. The results provide new insight into biological mechanisms that may contribute to adverse health effects from exposure to tobacco smoke in utero.

Cell type specific DNA methylation in cord blood: A 450K-reference data set and cell count-based validation of estimated cell type composition.

Epigenome-wide association studies of prenatal exposure to different environmental factors are becoming increasingly common. These studies are usually performed in umbilical cord blood. Since blood comprises multiple cell types with specific DNA methylation patterns, confounding caused by cellular heterogeneity is a major concern. This can be adjusted for using reference data consisting of DNA methylation signatures in cell types isolated from blood. However, the most commonly used reference data set is based on blood samples from adult males and is not representative of the cell type composition in neonatal cord blood. The aim of this study was to generate a reference data set from cord blood to enable correct adjustment of the cell type composition in samples collected at birth. The purity of the isolated cell types was very high for all samples (>97.1%), and clustering analyses showed distinct grouping of the cell types according to hematopoietic lineage. We explored whether this cord blood and the adult peripheral blood reference data sets impact the estimation of cell type composition in cord blood samples from an independent birth cohort (MoBa, n = 1092). This revealed significant differences for all cell types. Importantly, comparison of the cell type estimates against matched cell counts both in the cord blood reference samples (n = 11) and in another independent birth cohort (Generation R, n = 195), demonstrated moderate to high correlation of the data. This is the first cord blood reference data set with a comprehensive examination of the downstream application of the data through validation of estimated cell types against matched cell counts.

Maternal Age at Delivery Is Associated with an Epigenetic Signature in Both Newborns and Adults.

Offspring of older mothers are at increased risk of adverse birth outcomes, childhood cancers, type 1 diabetes, and neurodevelopmental disorders. The underlying biologic mechanisms for most of these associations remain obscure. One possibility is that maternal aging may produce lasting changes in the epigenetic features of a child's DNA. To test this, we explored the association of mothers' age at pregnancy with methylation in her offspring, using blood samples from 890 Norwegian newborns and measuring DNA methylation at more than 450,000 CpG sites across the genome. We examined replication of a maternal-age finding in an independent group of 1062 Norwegian newborns, and then in 200 US middle-aged women. Older maternal age was significantly associated with reduced methylation at four adjacent CpGs near the 2nd exon of KLHL35 in newborns (p-values ranging from 3x10-6 to 8x10-7). These associations were replicated in the independent set of newborns, and replicated again in women 40 to 60 years after their birth. This study provides the first example of parental age permanently affecting the epigenetic profile of offspring. While the specific functions of the affected gene are unknown, this finding opens the possibility that a mother's age at pregnancy could affect her child's health through epigenetic mechanisms.

Grandmother's smoking when pregnant with the mother and asthma in the grandchild: the Norwegian Mother and Child Cohort Study.

BACKGROUND: A trans-generational influence of prenatal tobacco smoke exposure on asthma development has been proposed but the evidence remains sparse. METHODS: We examined the grandmother's smoking when pregnant with the mother in relation to asthma outcomes in the grandchild (current asthma at 36 months (N=53 169, cases=3013), current asthma at 7 years (N=25 394, cases=1265) and dispensed asthma medications at 7 years in the Norwegian Prescription Database (N=45 607, cases=1787)) within the Norwegian Mother and Child Cohort Study (MoBa). We calculated adjusted RR (adj. RR) and 95% CIs using log binomial regression. RESULTS: A total of 23.5% of mothers reported that their mother smoked when pregnant with them. The grandmother's smoking when pregnant with the mother was positively associated with asthma at 36 months (adj. RR 1.15 (95% CI 1.06 to 1.24)), asthma at 7 years (adj. RR 1.21 (95% CI 1.07 to 1.37)) and dispensed asthma medications at 7 years (adj. RR 1.15 (95% CI 1.04 to 1.26)). This positive association did not differ significantly by the mother's smoking status when pregnant with the child (p values for multiplicative interaction >0.1). CONCLUSIONS: The grandmother's smoking when pregnant with the mother increased the risk of asthma in the grandchild independent of the mother's smoking status. However, given limited information on the grandmother's socioeconomic status, asthma status and other factors, unmeasured confounding may be present.

Prenatal tobacco smoke exposure is associated with childhood DNA CpG methylation.

BACKGROUND: Smoking while pregnant is associated with a myriad of negative health outcomes in the child. Some of the detrimental effects may be due to epigenetic modifications, although few studies have investigated this hypothesis in detail. OBJECTIVES: To characterize site-specific epigenetic modifications conferred by prenatal smoking exposure within asthmatic children. METHODS: Using Illumina HumanMethylation27 microarrays, we estimated the degree of methylation at 27,578 distinct DNA sequences located primarily in gene promoters using whole blood DNA samples from the Childhood Asthma Management Program (CAMP) subset of Asthma BRIDGE childhood asthmatics (n = 527) ages 5-12 with prenatal smoking exposure data available. Using beta-regression, we screened loci for differential methylation related to prenatal smoke exposure, adjusting for gender, age and clinical site, and accounting for multiple comparisons by FDR. RESULTS: Of 27,578 loci evaluated, 22,131 (80%) passed quality control assessment and were analyzed. Sixty-five children (12%) had a history of prenatal smoke exposure. At an FDR of 0.05, we identified 19 CpG loci significantly associated with prenatal smoke, of which two replicated in two independent populations. Exposure was associated with a 2% increase in mean CpG methylation in FRMD4A (p = 0.01) and Cllorf52 (p = 0.001) compared to no exposure. Four additional genes, XPNPEP1, PPEF2, SMPD3 and CRYGN, were nominally associated in at least one replication group. CONCLUSIONS: These data suggest that prenatal exposure to tobacco smoke is associated with reproducible epigenetic changes that persist well into childhood. However, the biological significance of these altered loci remains unknown.

Maternal smoking and DNA methylation in newborns: in utero effect or epigenetic inheritance?

BACKGROUND: Maternal smoking in pregnancy is associated with adverse health outcomes in children, including cancers; underlying mechanisms may include epigenetic modifications. Using Illumina's 450K array, we previously identified differential DNA methylation related to maternal smoking during pregnancy at 26 CpG sites (CpGs) in 10 genes in newborn cord bloods from the Norwegian Mother and Child Cohort Study (MoBa). Whether these methylation signals in newborns reflect in utero exposure only or possibly epigenetic inheritance of smoking-related modifications is unclear. METHODS: We therefore evaluated the impact of the timing of mother's smoking (before or during pregnancy using cotinine measured at 18 weeks gestation), the father's smoking before conception, and the grandmother's smoking during her pregnancy with the mother on methylation at these 26 CpGs in 1,042 MoBa newborns. We used robust linear regression, adjusting for covariates, applying Bonferroni correction. RESULTS: The strongest and only statistically significant associations were observed for sustained smoking by the mother during pregnancy through at least gestational week 18 (P < 1.6 × 10(-5) for all 26 CpGs). We observed no statistically significant differential methylation due to smoking by the mother before pregnancy or that ceased by week 18, father's smoking before conception, or grandmother's smoking while pregnant with the mother. CONCLUSIONS: Differential methylation at these CpGs in newborns seems to reflect sustained in utero exposure rather than epigenetic inheritance. IMPACT: Smoking cessation in early pregnancy may negate effects on methylation. Analyses of maternal smoking during pregnancy and offspring health outcomes, including cancer, limited to ever smoking might miss true associations. Cancer Epidemiol Biomarkers Prev; 23(6); 1007-17. ©2014 AACR.

Changes and tracking of fruit, vegetables and sugar-sweetened beverages intake from 18 months to 7 years in the Norwegian Mother and Child Cohort Study.

BACKGROUND: A few studies have investigated tracking of dietary patterns or nutrient intake in pre-school children, but no studies have been identified examining tracking of sugar-sweetened beverages (SSB), fruit and vegetable intakes in early childhood (1-7 year olds). The purpose of this study was to investigate changes and tracking of intakes of fruit, vegetables and SSB, and association between maternal education and dietary tracking, from 18 months to 7 years of age. METHODS: Longitudinal data from the nation-wide Norwegian Mother and Child Cohort Study, conducted by the Norwegian Institute of Public Health were used, including 9025 children participating at three time points (18 months, 36 months and 7 years). Frequencies of fruit, vegetables and SSB were assessed by questionnaire. Slightly different questions were used at each time point to collect information about intake. Maternal education was categorized into ≤ 12 years, 13-16 years, ≥ 17 years. Cross-tabulation, Spearman's rho and multinomial logistic regression were used for assessing change, tracking and differences by maternal education. RESULTS: Analyses by gender indicated largest changes for intake of fruit and SSB from age 18 months to 7 years. Fair to moderate tracking coefficients (Spearman's rho = 0.23-0.46) for intake of fruit, vegetables and SSB were found and children assigned to low, medium and high frequency of consumption at 18 months continued to be in the same group at age 36 months and 7 years. Children of mothers with low education consumed fruit and vegetables less often and SSB more often compared to children of mothers with high education at 18 months of age. Children with higher educated mothers had lower odds for increasing fruit intake or decreasing SSB intake, compared to children with lower educated mothers showing a stable intake. CONCLUSIONS: The tracking coefficients for intakes were fair to moderate and differences in intakes according to maternal education were found already at age 18 months. This suggests that promotion of healthy dietary behaviours at an early age is important to prevent unfavourable dietary behaviours later in childhood. Moreover, it seems important to target mothers in nutrition interventions for improving dietary habits among children.

Drug exposure: inclusion of dispensed drugs before pregnancy may lead to underestimation of risk associations.

OBJECTIVES: To assess the impact of exposure misclassification on risk associations when using prescription databases as the source for drug exposure in pregnancy by applying results from a validation analysis of exposure classification. STUDY DESIGN AND SETTING: Linkage of data on 27,656 participants in the Norwegian Mother and Child Cohort Study (MoBa) with the Norwegian Prescription Database (NorPD). Exposure to selective serotonin reuptake inhibitors (SSRIs) was defined by dispensed drugs during pregnancy including different time windows before pregnancy. The validity of NorPD data was estimated using self-reported use in MoBa as the reference standard. We applied the results from the validation analysis on data from a Nordic study on SSRI use in pregnancy and risk of persistent pulmonary hypertension in the newborn. RESULTS: Sensitivity increased and specificity decreased when the time window in NorPD was expanded before pregnancy. Using the same time window as in the Nordic study (+90 days before pregnancy), for use in early pregnancy, the odds ratio (OR) corrected for misclassification was 2.6 compared with the OR of 1.6 in the Nordic study. CONCLUSION: Expansion of the time window to include intervals before pregnancy can lead to lower specificity and underestimation of risk associations.