Background Women with a vulnerable health status, as determined by a low socioeconomic status and poor lifestyle behaviours, are at risk for adverse pregnancy outcomes. Offering tailored... Show moreBackground Women with a vulnerable health status, as determined by a low socioeconomic status and poor lifestyle behaviours, are at risk for adverse pregnancy outcomes. Offering tailored preconception lifestyle care can significantly help to improve pregnancy outcomes. We hypothesize that so-called 'nudges' can be a successful way of increasing the uptake of preconception lifestyle care. A nudge is a behavioural intervention that supports healthy choices by making them easier to choose. Nudging, however, raises many moral questions. Effectiveness and respect for autonomy are, among other criteria, required for a nudge to be morally permissible. In general, the target group knows best what they find permissible and what would motivate them to change their lifestyle. Therefore, this study - conducted in women with a vulnerable health status - aimed to identify their preferences towards a nudge, provided via a mobile application that aims to help them adopt healthy lifestyle behaviours by offering rewards. Methods We conducted semi-structured interviews with twelve women with a vulnerable health status. A framework approach was used to analyse the data. A thematic content analysis was conducted on five themes: (1) "Usefulness of an app as an integral information source", (2) "Permissibility and effects of offering rewards", (3) "Preferences regarding content", (4) "Preferences regarding type of rewards and system of allocation", and (5) "Barriers". Results Of the 12 participants, 11 deemed an app as integral information source concerning the preconception period useful. None of the participants objected to being nudged i.e., being rewarded for healthy behaviour. All participants stated that they would like the app to contain information on healthy nutrition and 8 participants wanted to know how to get pregnant quickly. Furthermore, participants stated that the freedom to choose the timing and content of the reward would increase the probability of successful behavioural change, and having to pay or contact a healthcare provider to access the app may prevent women using the app. Conclusions These insights into the preferences of women with a vulnerable health status towards nudging will inform the design of an effective app-based nudge. This may help to improve prepregnancy health as investment in health of current and future generations. Show less
The COVID-19 pandemic has a major impact on society, particularly affecting its vulnerable members, including pregnant women and their unborn children. Pregnant mothers reported fear of infection,... Show moreThe COVID-19 pandemic has a major impact on society, particularly affecting its vulnerable members, including pregnant women and their unborn children. Pregnant mothers reported fear of infection, fear of vertical transmission, fear of poor birth and child outcomes, social isolation, uncertainty about their partner's presence during medical appointments and delivery, increased domestic abuse, and other collateral damage, including vaccine hesitancy. Accordingly, pregnant women's known vulnerability for mental health problems has become a concern during the COVID-19 pandemic, also because of the known effects of prenatal stress for the unborn child. The current narrative review provides a historical overview of transgenerational effects of exposure to disasters during pregnancy, and the role of maternal prenatal stress. We place these effects into the perspective of the COVID-19 pandemic. Hereby, we aim to draw attention to the psychological impact of the COVID-19 pandemic on women of reproductive age (15-49 year) and its potential associated short-term and long-term consequences for the health of children who are conceived, carried, and born during this pandemic. Timely detection and intervention during the first 1000 days is essential to reduce the burden of transgenerational effects of the COVID-19 pandemic. Show less
Epigenetic programming is essential for lineage differentiation, embryogenesis and placentation in early pregnancy. In epigenetic association studies, DNA methylation is often examined in DNA... Show moreEpigenetic programming is essential for lineage differentiation, embryogenesis and placentation in early pregnancy. In epigenetic association studies, DNA methylation is often examined in DNA derived from white blood cells, although its validity to other tissues of interest remains questionable. Therefore, we investigated the tissue specificity of epigenome-wide DNA methylation in newborn and placental tissues. Umbilical cord white blood cells (UC-WBC, n = 25), umbilical cord blood mononuclear cells (UC-MNC, n = 10), human umbilical vein endothelial cells (HUVEC, n = 25) and placental tissue (n = 25) were obtained from 36 uncomplicated pregnancies. Genome-wide DNA methylation was measured by the Illumina HumanMethylation450K BeadChip. Using UC-WBC as a reference tissue, we identified 3595 HUVEC tissue-specific differentially methylated regions (tDMRs) and 11,938 placental tDMRs. Functional enrichment analysis showed that HUVEC and placental tDMRs were involved in embryogenesis, vascular development and regulation of gene expression. No tDMRs were identified in UC-MNC. In conclusion, the extensive amount of genome-wide HUVEC and placental tDMRs underlines the relevance of tissue-specific approaches in future epigenetic association studies, or the use of validated representative tissues for a certain disease of interest, if available. To this purpose, we herewith provide a relevant dataset of paired, tissue-specific, genome-wide methylation measurements in newborn tissues. Show less
Windt, M. van der; Kleij, R.M. van der; Snoek, K.M.; Willemsen, S.P.; Dykgraaf, R.H.M.; Laven, J.S.E.; ... ; Steegers-Theunissen, R.P.M. 2020
Background: Periconception lifestyle behaviors affect maternal, paternal, offspring, and transgenerational health outcomes. Previous research in other target populations has shown that personalized... Show moreBackground: Periconception lifestyle behaviors affect maternal, paternal, offspring, and transgenerational health outcomes. Previous research in other target populations has shown that personalized lifestyle interventions, in which face-to-face counseling and eHealth ("blended care") are combined, may effectively target these lifestyle behaviors.Objective: We aimed to assess the effectiveness of a periconceptional lifestyle intervention on the improvement of specific lifestyle components.Methods: A blended periconception lifestyle care approach was developed, combining the outpatient lifestyle counseling service "Healthy Pregnancy" with the eHealth platform "Smarter Pregnancy" (www.smarterpregnancy.co.uk) in which lifestyle was coached for 24 weeks. All couples contemplating pregnancy or already pregnant (<= 12 weeks of gestation) who visited the outpatient clinics of the Department of Obstetrics and Gynecology at the Erasmus University Medical Center (Erasmus MC), Rotterdam, the Netherlands, between June and December 2018, were invited to participate. We measured changes in lifestyle behaviors at weeks 12 and 24 compared with baseline. Generalized estimating equations were used to analyze the changes in lifestyle behaviors over time. Subgroup analyses were performed for women with obesity (BMI >= 30 kg/m(2)), women pregnant at the start of the intervention, and those participating as a couple.Results: A total of 539 women were screened for eligibility, and 450 women and 61 men received the blended periconception intervention. Among the participating women, 58.4% (263/450) were included in the preconception period. Moreover, 78.9% (403/511) of the included participants completed the online lifestyle coaching. At baseline, at least one poor lifestyle behavior was present in most women (379/450, 84.2%) and men (58/61, 95.1%). In the total group, median fruit intake increased from 1.8 to 2.2 pieces/day (P<.001) and median vegetable intake increased from 151 to 165 grams/day (P<.001) after 24 weeks of online coaching. The probability of taking folic acid supplementation among women increased from 0.97 to 1(P<.001), and the probability of consuming alcohol and using tobacco in the total group decreased from 0.25 to 0.19 (P=.002) and from 0.20 to 0.15 (P=.63), respectively. Overall, the program showed the strongest effectiveness for participating couples. Particularly for vegetable and fruit intake, their consumption increased from 158 grams/day and 1.8 pieces/day at baseline to 190 grams/day and 2.7 pieces/day at the end of the intervention, respectively.Conclusions: We succeeded in including most participating women in the preconception period. A high compliance rate was achieved and users demonstrated improvements in several lifestyle components. The blended periconception lifestyle care approach seems to be an effective method to improve lifestyle behaviors. The next step is to further disseminate this approach and to perform a randomized trial to compare the use of blended care with the provision of only eHealth. Additionally, the clinical relevance of these results will need to be substantiated further. Show less
Objective: We aimed to validate a food-frequency questionnaire (FFQ) for Dutch pregnant women, against three 24 h-recalls and blood concentrations of B-vitamins and fatty acids, using the method of... Show moreObjective: We aimed to validate a food-frequency questionnaire (FFQ) for Dutch pregnant women, against three 24 h-recalls and blood concentrations of B-vitamins and fatty acids, using the method of triads. Methods: We included 83 pregnant women from the general population of Rotterdam, the Netherlands, at a median gestational age of 15.6 weeks. Participants completed three non-consecutive 24 h-recalls, and subsequently filled out the 293-item FFQ. Participants provided blood samples from which we analyzed serum folate and vitamin B12, as well as red blood cell folate, linoleic acid, and total saturated, monounsaturated, and polyunsaturated fatty acids. Results: Estimated energy intake did not differ between the FFQ and 24 h-recalls. Deattenuated Pearson's correlation coefficients, between energy-adjusted nutrient intake estimates from the FFQ and the 24 h-recalls, ranged from 0.41 (fat) to 0.88 (fiber) for macronutrients, and were around 0.6 for most micronutrients, except for vitamin E (0.27). Using the triad method, we obtained validity coefficients of 0.86 (95% Confidence Interval (CI) 0.36, 1.00) for serum folate, 0.86 (95% CI 0.18, 1.00) for red blood cell folate, and 1.00 (95% CI 0.42, 1.00) for vitamin B12. Validity coefficients for serum fatty acids ranged from 0.22 to 0.67. Conclusion: This FFQ is a reliable tool for estimating intake of energy, macronutrients, folate and vitamin B12 among women in mid-pregnancy. Show less
BackgroundPreeclampsia is a female-specific risk factor for the development of future cardiovascular disease. Whether early preventive cardiovascular disease risk screenings combined with risk... Show moreBackgroundPreeclampsia is a female-specific risk factor for the development of future cardiovascular disease. Whether early preventive cardiovascular disease risk screenings combined with risk-based lifestyle interventions in women with previous preeclampsia are beneficial and cost-effective is unknown.MethodsA micro-simulation model was developed to assess the life-long impact of preventive cardiovascular screening strategies initiated after women experienced preeclampsia during pregnancy. Screening was started at the age of 30 or 40 years and repeated every five years. Data (initial and follow-up) from women with a history of preeclampsia was used to calculate 10-year cardiovascular disease risk estimates according to Framingham Risk Score. An absolute risk threshold of 2% was evaluated for treatment selection, i.e. lifestyle interventions (e.g. increasing physical activity). Screening benefits were assessed in terms of costs and quality-adjusted-life-years, and incremental cost-effectiveness ratios compared with no screening.ResultsExpected health outcomes for no screening are 27.35 quality-adjusted-life-years and increase to 27.43 quality-adjusted-life-years (screening at 30 years with 2% threshold). The expected costs for no screening are euro9426 and around euro13,881 for screening at 30 years (for a 2% threshold). Preventive screening at 40 years with a 2% threshold has the most favourable incremental cost-effectiveness ratio, i.e. euro34,996/quality-adjusted-life-year, compared with other screening scenarios and no screening.ConclusionsEarly cardiovascular disease risk screening followed by risk-based lifestyle interventions may lead to small long-term health benefits in women with a history of preeclampsia. However, the cost-effectiveness of a lifelong cardiovascular prevention programme starting early after preeclampsia with risk-based lifestyle advice alone is relatively unfavourable. A combination of risk-based lifestyle advice plus medical therapy may be more beneficial. Show less
Objectives Compare the predictive performance of Framingham Risk Score (FRS), Pooled Cohort Equations (PCEs) and Systematic COronary Risk Evaluation (SCORE) model between women with and without a... Show moreObjectives Compare the predictive performance of Framingham Risk Score (FRS), Pooled Cohort Equations (PCEs) and Systematic COronary Risk Evaluation (SCORE) model between women with and without a history of hypertensive disorders of pregnancy (hHDP) and determine the effects of recalibration and refitting on predictive performance. Methods We included 29 751 women, 6302 with hHDP and 17 369 without. We assessed whether models accurately predicted observed 10-year cardiovascular disease (CVD) risk (calibration) and whether they accurately distinguished between women developing CVD during follow-up and not (discrimination), separately for women with and without hHDP. We also recalibrated (updating intercept and slope) and refitted (recalculating coefficients) the models. Results Original FRS and PCEs overpredicted 10-year CVD risks, with expected:observed (E:O) ratios ranging from 1.51 (for FRS in women with hHDP) to 2.29 (for PCEs in women without hHDP), while E:O ratios were close to 1 for SCORE. Overprediction attenuated slightly after recalibration for FRS and PCEs in both hHDP groups. Discrimination was reasonable for all models, with C-statistics ranging from 0.70-0.81 (women with hHDP) and 0.72-0.74 (women without hHDP). C-statistics improved slightly after refitting 0.71-0.83 (with hHDP) and 0.73-0.80 (without hHDP). The E:O ratio of the original PCE model was statistically significantly better in women with hHDP compared with women without hHDP. Conclusions SCORE performed best in terms of both calibration and discrimination, while FRS and PCEs overpredicted risk in women with and without hHDP, but improved after recalibrating and refitting the models. No separate model for women with hHDP seems necessary, despite their higher baseline risk. Show less
AimTo provide a comprehensive overview of cardiovascular disease (CVD) risk prediction models for women and models that include female-specific predictors.MethodsWe performed a systematic review of... Show moreAimTo provide a comprehensive overview of cardiovascular disease (CVD) risk prediction models for women and models that include female-specific predictors.MethodsWe performed a systematic review of CVD risk prediction models for women in the general population by updating a previous review. We searched Medline and Embase up to July 2017 and included studies in which; (a) a new model was developed, (b) an existing model was validated, or (c) a predictor was added to an existing model.ResultsA total of 285 prediction models for women have been developed, of these 160 (56%) were female-specific models, in which a separate model was developed solely in women and 125 (44%) were sex-predictor models. Out of the 160 female-specific models, 2 (1.3%) included one or more female-specific predictors (mostly reproductive risk factors). A total of 591 validations of sex-predictor or female-specific models were identified in 206 papers. Of these, 333 (56%) validations concerned nine models (five versions of Framingham, SCORE, Pooled Cohort Equations and QRISK). The median and pooled C statistics were comparable for sex-predictor and female-specific models. In 260 articles the added value of new predictors to an existing model was described, however in only 3 of these female-specific that no competing interests exist. predictors (reproductive risk factors) were added.ConclusionsThere is an abundance of models for women in the general population. Female-specific and sex-predictor models have similar predictors and performance. Female-specific predictors are rarely included. Further research is needed to assess the added value of female-specific predictors to CVD models for women and provide physicians with a well-performing prediction model for women. Show less
Endocardial cushion defects (ECDs) of the cardiac outflow tract are among the most common congenital heart disease phenotypes. VEGF is essential for endocardial cushion formation and derangements... Show moreEndocardial cushion defects (ECDs) of the cardiac outflow tract are among the most common congenital heart disease phenotypes. VEGF is essential for endocardial cushion formation and derangements in VEGF synthesis lead to ECD. Three functional single nucleotide polymorphisms (SNPs) in the VEGF gene -2578 C>A, -1154 G>A, and -634 G>C play a role in cardiogenesis. In a Dutch case-control family study of triads, 190 case and 317 control children with both parents, we investigated linkage and association between these VEGF SNPs and ECD. Allele frequencies for the three VEGF SNPs were comparable between ECD children and controls. However, VEGF alleles -2578 C and 1154 G were transmitted more frequently to children with ECD (p = 0.003 and p = 0.002), in particular perimembranous ventricular septal defects (p = 0.012 and p = 0.006). The -2578A/-1154A/-634G haplotype was associated with a reduced risk of ECD (OR 0.7: 95% CI, 0.6-1.0) and was significantly less transmitted to children with ECD U) = 0.002). In a Dutch population, we show that the VEGF 2578 C, -1154 G alleles, and the AAG haplotype are associated with ECD. Possible VEGF gene-enviromnent interactions exposures are discussed. (Pediatr Res 67: 23-28, 2010) Show less
