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Background: Gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) share many pathophysiological factors including genetics, but whether epigenetic marks are shared is unknown. We aimed to test whether a DNA methylation risk score (MRS) for T2DM was associated with GDM across ancestry and GDM criteria., Methods: In two independent pregnancy cohorts, EPIPREG (n = 480) and EPIDG (n = 32), DNA methylation in peripheral blood leukocytes was measured at a gestational age of 28 ± 2. We constructed an MRS in EPIPREG and EPIDG based on CpG hits from a published epigenome-wide association study (EWAS) of T2DM., Results: With mixed models logistic regression of EPIPREG and EPIDG, MRS for T2DM was associated with GDM: odd ratio (OR)[95% CI]: 1.3 [1.1-1.8], P = 0.002 for the unadjusted model, and 1.4 [1.1-1.7], P = 0.00014 for a model adjusted by age, pre-pregnant BMI, family history of diabetes and smoking status. Also, we found 6 CpGs through a meta-analysis (cg14020176, cg22650271, cg14870271, cg27243685, cg06378491, cg25130381) associated with GDM, and some of their methylation quantitative loci (mQTLs) were related to T2DM and GDM., Conclusion: For the first time, we show that DNA methylation marks for T2DM are also associated with GDM, suggesting shared epigenetic mechanisms between GDM and T2DM., (© 2024. The Author(s).)

Background: We aimed to evaluate the impact of recommending supplementation to pregnant women with serum ferritin (SF) < 20 µg/L in early pregnancy on use of supplements, and to explore which factors were associated with changes in iron status by different iron indicators to 14 weeks postpartum., Methods: A multi-ethnic population-based cohort study of 573 pregnant women examined at mean gestational week (GW) 15 (enrolment), at mean GW 28 and at the postpartum visit (mean 14 weeks after delivery). Women with SF < 20 µg/L at enrolment were recommended 30-50 mg iron supplementation and supplement use was assessed at all visits. Change of SF, soluble transferrin receptor and total body iron from enrolment to postpartum were calculated by subtracting the concentrations at the postpartum visit from that at enrolment. Linear and logistic regression analyses were performed to assess associations between use of supplements in GW 28 and changes in iron status and postpartum iron deficiency/anaemia. Change of iron status was categorized into 'steady low', 'improvement', 'deterioration', and 'steady high' based on SF status at enrolment and postpartum. Multinomial logistic regression analyses were performed to identify factors associated with change of iron status., Results: At enrolment, 44% had SF < 20 µg/L. Among these women (78% non-Western European origin), use of supplements increased from 25% (enrolment) to 65% (GW 28). Use of supplements in GW 28 was associated with improved iron levels by all three indicators (p < 0.05) and with haemoglobin concentration (p < 0.001) from enrolment to postpartum, and with lower odds of postpartum iron deficiency by SF and TBI (p < 0.05). Factors positively associated with 'steady low' were: use of supplements, postpartum haemorrhage, an unhealthy dietary pattern and South Asian ethnicity (p ≤ 0.01 for all); with 'deterioration': postpartum haemorrhage, an unhealthy dietary pattern, primiparity and no use of supplements (p < 0.01 for all), and with 'improvement': use of supplements, multiparity and South Asian ethnicity (p < 0.03 for all)., Conclusions: Both supplement use and iron status improved from enrolment to the postpartum visit among women recommended supplementation. Dietary pattern, use of supplements, ethnicity, parity and postpartum haemorrhage were identified as factors associated with change in iron status., (© 2023. The Author(s).)

Background: To describe ethnic differences in concentrations of lipids and lipoproteins, and their changes, during pregnancy to postpartum., Methods: This was a population-based cohort study conducted in primary antenatal care in Norway. The participants (n = 806) were healthy, pregnant women, 59% were ethnic minorities. Outcomes were triglycerides, total cholesterol, HDL- and LDL-cholesterol, analysed from fasting blood samples drawn at gestational age (weeks) 15, 28 and 14 weeks postpartum. We performed linear regression models and linear mixed models to explore the total effect of ethnicity on the outcomes, adjusting for gestational age /week postpartum, maternal age and education. The analyses are corrected for multiple testing using the Bonferroni correction., Results: At gestational age 15, triglyceride concentrations were lower in women of African origin (1.03 mmol/mol (95% CI: 0.90, 1.16)) and higher in women of South Asian (primarily Pakistan and Sri Lanka) origin (1.42 mmol/mol (1.35, 1.49)) and East Asian (primarily Vietnam, Philippines and Thailand) origin (1.58 mmol/mol (1.43, 1.73)) compared with Western Europeans (1.26 mmol/mol (1.20, 1.32)). Women of Asian and African origin had a smaller increase in triglycerides, LDL- and total cholesterol from gestational age 15 to 28. At gestational age 28, LDL-cholesterol levels were lowest among East Asians (3.03 mmol/mol (2.72, 3.34)) compared with Western Europeans (3.62 mmol/mol (3.50, 3.74)). Triglycerides and HDL-cholesterol were lower postpartum than at gestational age 15 in all groups, but the concentration of LDL-cholesterol was higher, except in Africans. South and East Asian women had lower HDL-cholesterol and higher triglycerides postpartum, while African women had lower triglycerides than Western Europeans., Conclusion: We found significant differences in the concentrations of lipids and lipoproteins and their changes during pregnancy and the early postpartum period related to ethnic origin., (© 2022. The Author(s).)

Background: There is still no worldwide agreement on the best diagnostic thresholds to define gestational diabetes (GDM) or the optimal approach for identifying women with GDM. Should all pregnant women perform an oral glucose tolerance test (OGTT) or can easily available maternal characteristics, such as age, BMI and ethnicity, indicate which women to test? The aim of this study was to assess the prevalence of GDM by three diagnostic criteria and the predictive accuracy of commonly used risk factors., Methods: We merged data from four Norwegian cohorts (2002-2013), encompassing 2981 women with complete results from a universally offered OGTT. Prevalences were estimated based on the following diagnostic criteria: 1999 WHO (fasting plasma glucose (FPG) ≥7.0 or 2-h glucose ≥7.8 mmol/L), 2013 WHO (FPG ≥5.1 or 2-h glucose ≥8.5 mmol/L), and 2017 Norwegian (FPG ≥5.3 or 2-h glucose ≥9 mmol/L). Multiple logistic regression models examined associations between GDM and maternal factors. We applied the 2013 WHO and 2017 Norwegian criteria to evaluate the performance of different thresholds of age and BMI., Results: The prevalence of GDM was 10.7, 16.9 and 10.3%, applying the 1999 WHO, 2013 WHO, and the 2017 Norwegian criteria, respectively, but was higher for women with non-European background when compared to European women (14.5 vs 10.2%, 37.7 vs 13.8% and 27.0 vs 7.8%). While advancing age and elevated BMI increased the risk of GDM, no risk factors, isolated or in combination, could identify more than 80% of women with GDM by the latter two diagnostic criteria, unless at least 70-80% of women were offered an OGTT. Using the 2017 Norwegian criteria, the combination "age≥25 years or BMI≥25 kg/m 2 " achieved the highest sensitivity (96.5%) with an OGTT required for 93% of European women. The predictive accuracy of risk factors for identifying GDM was even lower for non-European women., Conclusions: The prevalence of GDM was similar using the 1999 WHO and 2017 Norwegian criteria, but substantially higher with the 2013 WHO criteria, in particular for ethnic non-European women. Using clinical risk factors such as age and BMI is a poor pre-diagnostic screening method, as this approach failed to identify a substantial proportion of women with GDM unless at least 70-80% were tested., (© 2021. The Author(s).)

Background: Chronic fatigue syndrome (CFS) is defined according to subjective symptoms only, and several conflicting case definition exist. Previous research has discovered certain biological alterations. The aim of the present study was to explore possible subgroups based on biological markers within a widely defined cohort of adolescent CFS patients and investigate to what extent eventual subgroups are associated with other variables., Methods: The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL) has previously performed detailed investigation of immunological, autonomic, neuroendocrine, cognitive and sensory processing functions in an adolescent group of CFS patients recruited according to wide diagnostic criteria. In the present study, hierarchical cluster analyses (Ward's method) were performed using representative variables from all these domains. Associations between clusters and constitutional factors (including candidate genetic markers), diagnostic criteria, subjective symptoms and prognosis were explored by standard statistical methods., Results: A total of 116 patients (26.7% males, mean age 15.4 years) were included. The final cluster analyses revealed six clusters labelled pain tolerant & good cognitions, restored HPA dynamics, orthostatic intolerance, low-grade inflammation, pain intolerant & poor cognitions, and high vagal (parasympathetic) activity, respectively. There was substantial overlap between clusters. The pain intolerant & poor cognitions-cluster was associated with low functional abilities and quality of life, and adherence to the Canada 2003 diagnostic criteria for CFS. No other statistically significant cluster associations were discovered., Conclusion: Within a widely defined cohort of adolescent CFS patients, clusters could be delineated, but no distinct subgroups could be identified. Associations between clusters and constitutional factors, subjective symptoms and prognosis were scarce. These results question the clinical usefulness of searching for CFS subgroups, as well as the validity of the most "narrow" CFS diagnostic criteria., Trial Registration: Clinical Trials NCT01040429.

Background: Epigenetic clocks have been recognized for their precise prediction of chronological age, age-related diseases, and all-cause mortality. Existing epigenetic clocks are based on CpGs from the Illumina HumanMethylation450 BeadChip (450 K) which has now been replaced by the latest platform, Illumina MethylationEPIC BeadChip (EPIC). Thus, it remains unclear to what extent EPIC contributes to increased precision and accuracy in the prediction of chronological age., Results: We developed three blood-based epigenetic clocks for human adults using EPIC-based DNA methylation (DNAm) data from the Norwegian Mother, Father and Child Cohort Study (MoBa) and the Gene Expression Omnibus (GEO) public repository: 1) an Adult Blood-based EPIC Clock (ABEC) trained on DNAm data from MoBa (n = 1592, age-span: 19 to 59 years), 2) an extended ABEC (eABEC) trained on DNAm data from MoBa and GEO (n = 2227, age-span: 18 to 88 years), and 3) a common ABEC (cABEC) trained on the same training set as eABEC but restricted to CpGs common to 450 K and EPIC. Our clocks showed high precision (Pearson correlation between chronological and epigenetic age (r) > 0.94) in independent cohorts, including GSE111165 (n = 15), GSE115278 (n = 108), GSE132203 (n = 795), and the Epigenetics in Pregnancy (EPIPREG) study of the STORK Groruddalen Cohort (n = 470). This high precision is unlikely due to the use of EPIC, but rather due to the large sample size of the training set., Conclusions: Our ABECs predicted adults' chronological age precisely in independent cohorts. As EPIC is now the dominant platform for measuring DNAm, these clocks will be useful in further predictions of chronological age, age-related diseases, and mortality.

Background: Childhood obesity is a worldwide health challenge and risk factor for adult life obesity, which predisposes to development of type 2 diabetes and cardiovascular diseases. However, also thinness in early life has been related to these diseases, especially if followed by fat gain. In European countries, susceptibility to cardio-metabolic diseases varies considerably between ethnic groups. We investigated ethnic differences in overweight and thinness in a multi-ethnic, population-based cohort of preschool children in Norway, and associations with maternal and early postnatal factors., Methods: Participants were children aged 4-5 years (n = 570) drawn from the population-based STORK Groruddalen cohort of healthy women and offspring followed from early pregnancy. Ethnic groups were: European (n = 298), South Asian (n = 154), and Middle East/North African (n = 118). Children's growth data were provided from routine visits at local Child Health Clinics. Weight status was defined by the International Obesity Task Force. Using multinomial logistic regression analysis, we explored ethnic differences in overweight and thinness, and associations with maternal-, pre, - and postnatal factors., Results: Children of Middle East/North African origin had higher prevalence of overweight (22.0%) compared to European (12.8%) children, and in adjusted logistic regression analysis almost the double risk (OR 1.98; 95%CI: 1.08-3.63). Prevalence was lower in children of South Asian origin (5.2%). Children with South Asian background had higher prevalence of thinness (26.0%) compared to ethnic Europeans (10.4%), and the double risk (OR 2.20; 95%CI: 1.25-3.87) in adjusted models. Applying newly suggested BMI adjustments in South Asian children, taking into account their relatively increased adiposity, markedly increased the prevalence of overweight, and decreased the prevalence of thinness in this subgroup. Birthweight and maternal prepregnant overweight were strongly, positively associated with overweight, and inversely associated with thinness. Lower maternal age was associated with overweight only., Conclusions: In a multi-ethnic cohort we found strikingly different patterns of overweight and thinness among children of different ethnic groups at age 4-5 years, and a strong association between maternal BMI and their children's weight status. More knowledge is needed on what characterizes and what promotes healthy growth patterns in multi-ethnic populations.

Background: Peri-conceptional use of folic acid supplements is recommended to prevent neural tube defects. Correct supplement use seems to be less common among ethnic minorities. We examined ethnic differences in folic acid supplement use before and during pregnancy and possible effect modification by education or planning of pregnancy., Methods: The participants were 811 healthy pregnant women from a population-based cohort study in Oslo, Norway in 2008-2010. Ethnicity was categorized to five groups (European, Middle Eastern, South Asian, East Asian, African). Data on folic acid supplement use were obtained from hospital records and remaining data by a questionnaire. Logistic regression analyses were adjusted for age, parity, planning of pregnancy, education and Norwegian language skills., Results: Before pregnancy, 30.1% of European women and 7.1 to 13.6% of women in the other ethnic groups used folic acid supplements (p < 0.001). The adjusted odds ratio (OR) for supplement use was 0.55 (95% confidence interval 0.31; 0.96) for South Asian and 0.42 (95% confidence interval 0.19; 0.94) for Middle Eastern women compared with European women. During pregnancy, supplement use was most common in European women (65.7%) and least common in Middle Eastern (29.4%) and African women (29.0%) (p < 0.001). Compared with European women, all other ethnic groups had lower adjusted odds (OR 0.30 to 0.50, p < 0.05 for all) for supplement use among women with high school or less education, but not among more educated women. Planning of pregnancy did not modify the association between ethnicity and supplement use., Conclusions: Few women used folic acid supplements before pregnancy. Educational level modified the association between ethnicity and supplement use during pregnancy. Public health campaigns should focus on increasing awareness especially in ethnic minority groups with low educational level.

Background: Physical activity may reduce the risk of adverse pregnancy outcomes; however, compared to non-pregnant women, a lower proportion of pregnant women meet the physical activity guidelines. Our objectives were to explore overall changes and ethnic differences in objectively recorded moderate-to-vigorous intensity physical activity (MVPA) during pregnancy and postpartum and to investigate the associations with objective and perceived access to recreational areas., Methods: We analysed 1,467 person-observations from 709 women in a multi-ethnic population-based cohort, with MVPA data recorded with the SenseWear™ Pro(3) Armband in early pregnancy (mean gestational week (GW) 15), mid-pregnancy (mean GW 28) and postpartum (mean postpartum week 14). MVPA was limited to bouts ≥10 min. Women were nested within 56 neighbourhoods defined by postal code area. We derived neighbourhood-level objective access to recreational areas (good vs limited) by geographic information systems. We collected information about perceived access (high vs low perception) to recreational areas in early pregnancy. We treated ethnicity, objective and perceived access as explanatory variables in separate models based on linear mixed effects regression analyses., Results: Overall, MVPA dropped between early and mid-pregnancy, followed by an increase postpartum. Western women performed more MVPA than women in other ethnic groups across time points, but the differences increased postpartum. Women residing in neighbourhoods with good objective access to recreational areas accumulated on average nine additional MVPA minutes/day (p < 0.01) compared with women in neighbourhoods with limited access. Women with perceptions of high access to recreational areas accumulated on average five additional MVPA minutes/day (p < 0.01) compared with women with perceptions of low access. After mutual adjustments, perceived and objective access to recreational areas remained significantly associated with MVPA. The association between MVPA and access to recreational areas did not differ by time point, ethnic group or socio-economic position., Conclusions: In all ethnic groups, we observed a decline in MVPA between early and mid-pregnancy. However, at both time points during pregnancy, and especially three months postpartum, Western women were more physically active than ethnic minority women. In all ethnic groups, and at all three time points, both objective and perceived access to recreational areas were positively associated with MVPA levels.

Background: To investigate ethnic differences in vitamin D levels during pregnancy, assess risk factors for vitamin D deficiency and explore the effect of vitamin D supplementation in women with deficiency in early pregnancy., Methods: This is a population-based, multiethnic cohort study of pregnant women attending Child Health Clinics for antenatal care in Oslo, Norway. Serum-25-hydroxyvitamin D [25(OH)D] was measured in 748 pregnant women (59% ethnic minorities) at gestational weeks (GW) 15 (SD:3.6) and 28 (1.4). Women with 25(OH)D <37 nmol/L at GW 15 were for ethical reasons recommended vitamin D3 supplementation. Main outcome measure was 25(OH)D, and linear regression models were performed., Results: Severe deficiency (25(OH)D <25 nmol/L) was found at GW 15 in 45% of women from South Asia, 40% from the Middle East and 26% from Sub-Saharan Africa, compared to 2.5% in women from East Asia and 1.3% of women from Western Europe. Women from South Asia, the Middle East and Sub-Saharan Africa had mean values that were -28 (95 % CI:-33, -23), -24 (-29, -18) and -20 (-27, -13) nmol/L lower than in Western women, respectively. Ethnicity, education, season and intake of vitamin D were independently associated with 25(OH)D. At GW 28, the mean 25(OH)D had increased from 23 (SD:7.8) to 47 (27) nmol/L (p < 0.01) in women who were recommended vitamin D supplementation, with small or no change in women with sufficient vitamin D levels at baseline., Conclusions: Vitamin D deficiency was prevalent among South Asian, Middle Eastern and African women. The serum levels of 25(OH)D increased significantly from GW 15 to 28 in vitamin D deficient women who received a recommendation for supplementation. This recommendation of vitamin D supplementation increased vitamin D levels in deficient women.

Background: Maternal glucose and lipid levels are associated with neonatal anthropometry of the offspring, also independently of maternal body mass index (BMI). Gestational weight gain, however, is often not accounted for. The objective was to explore whether the effects of maternal glucose and lipid levels on offspring's birth weight and subcutaneous fat were independent of early pregnancy BMI and mid-gestational weight gain., Methods: In a population-based, multi-ethnic, prospective cohort of 699 women and their offspring, maternal anthropometrics were collected in gestational week 15 and 28. Maternal fasting plasma lipids, fasting and 2-hour glucose post 75 g glucose load, were collected in gestational week 28. Maternal risk factors were standardized using z-scores. Outcomes were neonatal birth weight and sum of skinfolds in four different regions., Results: Mean (standard deviation) birth weight was 3491 ± 498 g and mean sum of skinfolds was 18.2 ± 3.9 mm. Maternal fasting glucose and HDL-cholesterol were predictors of birth weight, and fasting and 2-hour glucose were predictors of neonatal sum of skinfolds, independently of weight gain as well as early pregnancy BMI, gestational week at inclusion, maternal age, parity, smoking status, ethnic origin, gestational age and offspring's sex. However, weight gain was the strongest independent predictor of both birth weight and neonatal sum of skinfolds, with a 0.21 kg/week increased weight gain giving a 110.7 (95% confidence interval 76.6-144.9) g heavier neonate, and with 0.72 (0.38-1.06) mm larger sum of skinfolds. The effect size of mother's early pregnancy BMI on birth weight was higher in non-Europeans than in Europeans., Conclusions: Maternal fasting glucose and HDL-cholesterol were predictors of offspring's birth weight, and fasting and 2-hour glucose were predictors of neonatal sum of skinfolds, independently of weight gain. Mid-gestational weight gain was a stronger predictor of both birth weight and neonatal sum of skinfolds than early pregnancy BMI, maternal glucose and lipid levels.

Background: Depression in pregnancy increases the risk of complications for mother and child. Few studies are done in ethnic minorities. We wanted to identify the prevalence of depression in pregnancy and associations with ethnicity and other risk factors., Method: Population-based, prospective cohort of 749 pregnant women (59% ethnic minorities) attending primary antenatal care during early pregnancy in Oslo between 2008 and 2010. Questionnaires covering demographics, health problems and psychosocial factors were collected through interviews. Depression in pregnancy was defined as a sum score ≥ 10 by the Edinburgh Postnatal Depression Scale (EPDS) at gestational week 28., Results: The crude prevalence of depression was; Western Europeans: 8.6% (95% CI: 5.45-11.75), Middle Easterners: 19.5% (12.19-26.81), South Asians: 17.5% (12.08-22.92), and other groups: 11.3% (6.09-16.51). Median EPDS score was 6 in Middle Easterners and 3 in all other groups. Middle Easterners (OR = 2.81; 95% CI (1.29-6.15)) and South Asians (2.72 (1.35-5.48)) had significantly higher risk for depression than other minorities and Western Europeans in logistic regression models. When adjusting for socioeconomic position and family structure, the ORs were reduced by 16-18% (OR = 2.44 (1.07-5.57) and 2.25 (1.07-4.72). Other significant risk factors were the number of recent adverse life events, self-reported history of depression and poor subjective health three months before conception., Conclusion: The prevalence of depression in pregnancy was higher in ethnic minorities from the Middle East and South Asia. The increased risk persisted after adjustment for risk factors.