Effectiveness of a Step Counter Smartband and Midwife Counseling Intervention on Gestational Weight Gain and Physical Activity in Pregnant Women With Obesity (Pas and Pes Study): Randomized Controlled Trial

Background: Women who are pregnant and have obesity and excessive gestational weight gain (GWG) present a higher risk of maternal and perinatal complications. The use of mobile apps and a wristband during pregnancy may contribute to promoting healthy lifestyles and, thus, improving maternal and neonatal health. Objective: This study aims to evaluate the effectiveness of a complex digital health intervention, using a smartband and app with midwife counseling, on GWG and physical activity (PA) in women who are pregnant and have obesity and analyze its impact on maternal and perinatal outcomes. In addition, we aim to study the frequency of use, usability, and satisfaction with the mobile apps used by the women in the intervention group. Methods: A parallel, 2-arm, randomized controlled trial was conducted. A total of 150 women who were pregnant and had obesity were included. The intervention group received a complex combined digital intervention. The intervention was delivered with a smartband (Mi Band 2) linked to the app Mi Fit to measure PA and the Hangouts app with the midwife to provide personal health information. The control group received usual care. The validated Spanish versions of the International Physical Activity Questionnaire-Short Form and the System Usability Scale were used. Satisfaction was measured on a 1- to 5-point Likert scale. Results: We analyzed 120 women, of whom 30 (25%) were withdrawn because of the COVID-19 pandemic. The median GWG in the intervention group was 7.0 (IQR 4-11) kg versus 9.3 (IQR 5.9-13.3) kg in the control group (P=.04). The adjusted mean GWG per week was 0.5 (95% CI 0.4-0.6) kg per week in the control group and 0.3 (95% CI 0.3-0.4) kg per week in the intervention group (df=0.1, 95% CI −0.2 to 0.03; P=.008). During the 35 and 37 gestational weeks, women in the intervention group had higher mean PA than women in the control group (1980 metabolic equivalents of tasks-minutes per week vs 1386 metabolic equivalents of tasks-minutes per week, respectively; P=.01). No differences were observed between the study groups in the incidence of maternal and perinatal outcomes. In the intervention group, 61% (36/59) of the women who were pregnant used the smartband daily, and 75% (44/59) evaluated the usability of the Mi Fit app as excellent. All women in the intervention group used the Hangouts app at least once a week. The mean of the satisfaction scale with the health counseling app and midwife support was 4.8/5 (SD 0.6) points. Conclusions: The use of a complex mobile health intervention was associated with adequate GWG, which was lower in the intervention group than in the control group. In addition, we observed that the intervention group had increases in PA. No differences were observed in maternal perinatal complications. Trial Registration: ClinicalTrials.gov NCT03706872; https://www.clinicaltrials.gov/ct2/show/NCT03706872 JMIR Mhealth Uhealth 2022;10(2):e2888

Circadian clock gene variants and their link with chronotype, chrononutrition, sleeping patterns and obesity in the European prospective investigation into cancer and nutrition (EPIC) study

Background & aims: The circadian clock is involved in the control of daily rhythms and is related to the individual's chronotype, i.e., the morningness-eveneningness preference. Knowledge is limited on the relationship between circadian genes, chronotype, sleeping patterns, chronutrition and obesity. The aim was to explore these associations within the EPIC-Spain cohort study. Methods: There were 3183 subjects with information on twelve genetic variants of six genes (PER1, PER2, PER3, CRY1, NR1D1, CLOCK). Their association was evaluated with: chronotype and sleeping duration/ quality (assessed by questionnaires), chrononutrition (number of meals and timing of intake assessed by a diet history), and also anthropometric measures of obesity at early and late adulthood (in two points in time), such as weight and waist circumference (assessed by physical measurements). Multivariable logistic and linear regression as well as additive genetic models were applied. Odds ratios (ORs), b coefficients, and p-values corrected for multiple comparisons were estimated. Genetic risk scores (GRS) were built to test gene-outcome associations further. Results: At nominal significance level, the variant rs2735611 (PER1 gene) was associated with a 11.6% decrease in long-term weight gain (per-allele b beta - -0.12), whereas three CLOCK gene variants (rs12649507, rs3749474 and rs4864548), were associated with a similar to 20% decrease in waist circumference gain (per-allele beta similar to -0.19). These and other associations with body measures did not hold after multiple testing correction, except waist-to-hip ratio and rs1801260, rs2070062 and rs4580704 (CLOCK gene). Associations with chrononutrition variables, chronotype and sleep duration/quality failed to reach statistical significance. Conversely, a weighted GRS was associated with the evening/late chronotype and with all other outcomes (p < 0.05). The chronotype-GRS was associated with an increased overweight/ obesity risk (vs normal weight) in both early and late adulthood (OR = 2.2; p = 0.004, and OR = 2.1; p = 0.02, respectively). Conclusion: Genetic variants of some circadian clock genes could explain the link between genetic susceptibility to the individual's chronotype and obesity risk

Mycotoxin Exposure and Renal Cell Carcinoma Risk: An Association Study in the EPIC European Cohort

Background: Mycotoxins have been suggested to contribute to a spectrum of adverse health effects in humans, including at low concentrations. The recognition of these food contaminants being carcinogenic, as co-occurring rather than as singularly present, has emerged from recent research. The aim of this study was to assess the potential associations of single and multiple mycotoxin exposures with renal cell carcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Food questionnaire data from the EPIC cohort were matched to mycotoxin food occurrence data compiled by the European Food Safety Authority (EFSA) from European Member States to assess long-term dietary mycotoxin exposures, and to associate these with the risk of renal cell carcinoma (RCC, n = 911 cases) in 450,112 EPIC participants. Potential confounding factors were taken into account. Analyses were conducted using Cox's proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (95% CIs) with mycotoxin exposures expressed as mu g/kg body weight/day. Results: Demographic characteristics differed between the RCC cases and non-cases for body mass index, age, alcohol intake at recruitment, and other dietary factors. In addition, the mycotoxin exposure distributions showed that a large proportion of the EPIC population was exposed to some of the main mycotoxins present in European foods such as deoxynivalenol (DON) and derivatives, fumonisins, Fusarium toxins, Alternaria toxins, and total mycotoxins. Nevertheless, no statistically significant associations were observed between the studied mycotoxins and mycotoxin groups, and the risk of RCC development. Conclusions: These results show an absence of statistically significant associations between long-term dietary mycotoxin exposures and RCC risk. However, these results need to be validated in other cohorts and preferably using repeated dietary exposure measurements. In addition, more occurrence data of, e.g., citrinin and fumonisins in different food commodities and countries in the EFSA database are a prerequisite to establish a greater degree of certainty

Associations between Fatty Acid Intakes and Plasma Phospholipid Fatty Acid Concentrations in the European Prospective Investigation into Cancer and Nutrition

Background: The aim of this study is to determine the correlations between dietary fatty acid (FA) intakes and plasma phospholipid (PL) FA levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: The dietary intake of 60 individual FAs was estimated using centre-specific validated dietary questionnaires. Plasma PL FA concentrations of these FAs were measured in non-fasting venous plasma samples in nested case-control studies within the EPIC cohort (n = 4923, using only non-cases). Spearman rank correlations were calculated to determine associations between FA intakes and plasma PL FA levels. Results: Correlations between FA intakes and circulating levels were low to moderately high (-0.233 and 0.554). Moderate positive correlations were found for total long-chain n-3 poly-unsaturated FA (PUFA) (r = 0.354) with the highest (r = 0.406) for n-3 PUFA docosahexaenoic acid (DHA). Moderate positive correlations were also found for the non-endogenously synthesized trans-FA (r = 0.461 for total trans-FA C16-18; r = 0.479 for industrial trans-FA (elaidic acid)). Conclusions: Our findings indicate that dietary FA intakes might influence the plasma PL FA status to a certain extent for several specific FAs. The stronger positive correlations for health-enhancing long-chain PUFAs and the health-deteriorating trans-FA that are not endogenously produced are valuable for future cancer prevention public health interventions

Menstrual And Reproductive Factors, Hormone Use, And Risk Of Pancreatic Cancer: Analysis From The International Pancreatic Cancer Case-control Consortium (Panc4)

Objectives: We aimed to evaluate the relation between menstrual and reproductive factors, exogenous hormones, and risk of pancreatic cancer (PC). Methods: Eleven case-control studies within the International Pancreatic Cancer Case-control Consortium took part in the present study, including in total 2838 case and 4748 control women. Pooled estimates of odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using a 2-step logistic regression model and adjusting for relevant covariates. Results: An inverse OR was observed in women who reported having had hysterectomy (ORyesvs.no, 0.78; 95% CI, 0.67-0.91), remaining significant in postmenopausal women and never-smoking women, adjusted for potential PC confounders. A mutually adjusted model with the joint effect for hormone replacement therapy (HRT) and hysterectomy showed significant inverse associations with PC in women who reported having had hysterectomy with HRT use (OR, 0.64; 95% CI, 0.48-0.84). Conclusions: Our large pooled analysis suggests that women who have had a hysterectomy may have reduced risk of PC. However, we cannot rule out that the reduced risk could be due to factors or indications for having had a hysterectomy. Further investigation of risk according to HRT use and reason for hysterectomy may be necessary

Reproductive and hormonal factors and risk of renal cell carcinoma among women in the European Prospective Investigation into Cancer and Nutrition

PurposeThe incidence of small intestinal cancer (SIC) is increasing, however, its aetiology remains unclear due to a lack of data from large-scale prospective cohorts. We examined modifiable risk factors in relation to SIC overall and by histological subtype.MethodsWe analysed 450,107 participants enrolled in the European Prospective Investigation into Cancer and Nutrition cohort. Cox proportional hazards models were used to estimate univariable and multivariable hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsDuring an average of 14.1 years of follow-up, 160 incident SICs (62 carcinoids, 51 adenocarcinomas) were identified. Whilst univariable models revealed a positive association for current versus never smokers and SIC (HR, 95% CI: 1.77, 1.21-2.60), this association attenuated in multivariable models. In energy-adjusted models, there was an inverse association across vegetable intake tertiles for SIC overall (HRT3vsT1, 95% CI: 0.48, 0.32-0.71, p-trend: < 0.001) and for carcinoids (HRT3vsT1, 95% CI: 0.44, 0.24-0.82, p-trend: 0.01); however, these attenuated in multivariable models. Total fat was also inversely associated with total SIC and both subtypes but only in the second tertile (SIC univariable HRT2vsT1, 95% CI: 0.57, 0.38-0.84; SIC multivariable HRT2vsT1, 95% CI: 0.55, 0.37-0.81). Physical activity, intake of alcohol, red or processed meat, dairy products, or fibre were not associated with SIC.ConclusionThese exploratory analyses found limited evidence for a role of modifiable risk factors in SIC aetiology. However, sample size was limited, particularly for histologic subtypes; therefore, larger studies are needed to delineate these associations and robustly identify risk factors for SIC

Reproductive and hormonal factors and risk of renal cell carcinoma among women in the European Prospective Investigation into Cancer and Nutrition

Background - Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology. Materials & Methods - We investigated associations of age at menarche and age at menopause, pregnancy-related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Results - During 15 years of follow-up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. Conclusion - Our results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology

Dietary and lifestyle determinants of acrylamide and glycidamide hemoglobin adducts in non-smoking postmenopausal women from the EPIC cohort

Purpose Acrylamide was classified as 'probably carcinogenic' to humans in 1994 by the International Agency for Research on Cancer. In 2002, public health concern increased when acrylamide was identified in starchy, plant-based foods, processed at high temperatures. The purpose of this study was to identify which food groups and lifestyle variables were determinants of hemoglobin adduct concentrations of acrylamide (HbAA) and glycidamide (HbGA) in 801 non-smoking postmenopausal women from eight countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods Biomarkers of internal exposure were measured in red blood cells (collected at baseline) by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) . In this cross-sectional analysis, four dependent variables were evaluated: HbAA, HbGA, sum of total adducts (HbAA + HbGA), and their ratio (HbGA/HbAA). Simple and multiple regression analyses were used to identify determinants of the four outcome variables. All dependent variables (except HbGA/HbAA) and all independent variables were log-transformed (log2) to improve normality. Median (25th-75th percentile) HbAA and HbGA adduct levels were 41.3 (32.8-53.1) pmol/g Hb and 34.2 (25.4-46.9) pmol/g Hb, respectively. Results The main food group determinants of HbAA, HbGA, and HbAA + HbGA were biscuits, crackers, and dry cakes. Alcohol intake and body mass index were identified as the principal determinants of HbGA/HbAA. The total percent variation in HbAA, HbGA, HbAA + HbGA, and HbGA/HbAA explained in this study was 30, 26, 29, and 13 %, respectively. Conclusions Dietary and lifestyle factors explain a moderate proportion of acrylamide adduct variation in non-smoking postmenopausal women from the EPIC cohort

A comparison of complementary measures of vitamin B6 status, function, and metabolism in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Background: Vitamin B6 insufficiency has been linked to increased risk of cancer and other chronic diseases. The circulating concentration of pyridoxal 5'-phosphate (PLP) is a commonly used measure of vitamin B6 status. Ratios of substrates indicating PLP coenzymatic function and metabolism may be useful complementary measures to further explore the role of vitamin B6 in health. Objectives: We explored the sensitivity of 5 outcomes, namely PLP concentration, homocysteine:cysteine (Hcy:Cys), cystathionine:cysteine (Cysta:Cys), the 3´-hydroxykynurenine ratio (HKr), and the 4-pyridoxic acid ratio (PAr) to vitamin B6 intake as well as personal and lifestyle characteristics. Medthods: Dietary intake and biomarker data were collected from participants from 3 nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC). Bayesian regression models assessed the associations of the 5 biomarker outcomes with vitamin B6 intake and personal and lifestyle covariates. Analogous models examined the relations of Hcy:Cys, Cysta:Cys, and HKr with PLP. Results: In total, 4608 participants were included in the analyses. Vitamin B6 intake was most strongly associated with PLP, moderately associated with Hcy:Cys, Cysta:Cys, and HKr, and not associated with PAr (fold change in marker given a doubling of vitamin B6 intake: PLP 1.60 [95% credible interval (CrI): 1.50, 1.71]; Hcy:Cys 0.87 [95% CrI: 0.84, 0.90]; Cysta:Cys 0.89 [95% CrI: 0.84, 0.94]; HKr 0.88 [95% CrI: 0.85, 0.91]; PAr 1.00 [95% CrI: 0.95, 1.05]). PAr was most sensitive to age, and HKr was least sensitive to BMI and alcohol intake. Sex and menopause status were strongly associated with all 5 markers. Conclusions: We found that 5 different markers, capturing different aspects of vitamin B6-related biological processes, varied in their associations with vitamin B6 intake and personal and lifestyle predictors

Predicting circulating CA125 levels among healthy premenopausal women

Background: Cancer antigen 125 (CA125) is the most promising ovarian cancer screening biomarker to date. Multiple studies reported CA125 levels vary by personal characteristics, which could inform personalized CA125 thresholds. However, this has not been well described in premenopausal women. Methods: We evaluated predictors of CA125 levels among 815 premenopausal women from the New England Case Control Study (NEC). We developed linear and dichotomous (≥35 U/mL) CA125 prediction models and externally validated an abridged model restricting to available predictors among 473 premenopausal women in the European Prospective Investigation into Cancer and Nutrition Study (EPIC). Results: The final linear CA125 prediction model included age, race, tubal ligation, endometriosis, menstrual phase at blood draw, and fibroids, which explained 7% of the total variance of CA125. The correlation between observed and predicted CA125 levels based on the abridged model (including age, race, and menstrual phase at blood draw) had similar correlation coefficients in NEC (r = 0.22) and in EPIC (r = 0.22). The dichotomous CA125 prediction model included age, tubal ligation, endometriosis, prior personal cancer diagnosis, family history of ovarian cancer, number of miscarriages, menstrual phase at blood draw, and smoking status with AUC of 0.83. The abridged dichotomous model (including age, number of miscarriages, menstrual phase at blood draw, and smoking status) showed similar AUCs in NEC (0.73) and in EPIC (0.78). Conclusions: We identified a combination of factors associated with CA125 levels in premenopausal women. Impact: Our model could be valuable in identifying healthy women likely to have elevated CA125 and consequently improve its specificity for ovarian cancer screening