Unlocking the genomic landscape: Results of the Beyond 1 Million Genomes (B1MG) pilot in Belgium towards Genomic Data Infrastructure (GDI).

Genomic medicine has great potential to offer insights into how humans' genetic variation can affect their health, prevention options and treatment responses. The Beyond 1 Million Genomes (B1MG) project was kicked off in 2020 with the aim of building a federated network of genomic data in Europe, in which Belgium took part as a piloting country. B1MG developed a framework to enable all interested countries to self-evaluate the level of maturity of national genomic medicine practices following a common matrix, called Maturity Level Model (MLM), that contained 49 indicators across eight domains: I. Governance and strategy; II. Investment and economic model; III. Ethics, legislation and policy; IV. Public awareness and acceptance; V. Workforce skills and organisation; VI. Clinical organisation, infrastructure and tools; VII. Clinical genomics guidelines and infrastructure; and VIII. Data management, standards and infrastructure. The ongoing Genomic Data Infrastructure (GDI) project aims to capitalise on the experience of B1MG piloting countries and their MLM results. In this paper, we present the qualitative and quantitative outcomes of B1MG MLM assessment in Belgium and discuss their relevance to GDI. The insights gained from this study can be helpful for steering future policy directions and interventions on genomics in Belgium and beyond.

Contextual factors influencing the equitable implementation of precision medicine in routine cancer care in Belgium.

BACKGROUND: Precision medicine represents a paradigm shift in health systems, moving from a one-size-fits-all approach to a more individualized form of care, spanning multiple scientific disciplines including drug discovery, genomics, and health communication. This study aims to explore the contextual factors influencing the equitable implementation of precision medicine in Belgium for incorporating precision medicine into routine cancer care within the Belgian health system. METHODS: As part of a foresight study, our approach evaluates critical factors affecting the implementation of precision oncology. The study scrutinizes contextual, i.e. demographic, economic, societal, technological, environmental, and political/policy-related (DESTEP) factors, identified through a comprehensive literature review and validated by a multidisciplinary group at the Belgian Cancer Center, Sciensano. An expert survey further assesses the importance and likelihood of these factors, illuminating potential barriers and facilitators to implementation. RESULTS: Based on the expert survey, five key elements (rising cancer rates, dedicated healthcare reimbursement budgets, increasing healthcare expenditures, advanced information technology solutions for data transfer, and demand for high-quality data) are expected to influence the equitable implementation of precision medicine in routine cancer care in Belgium in the future. CONCLUSIONS: This work contributes to the knowledge base on precision medicine in Belgium and public health foresight, exploring the implementation challenges and suggesting solutions with an emphasis on the importance of comparative analyses of health systems, evaluation of health technology assessment methods, and the exploration of ethical issues in data privacy and equity.

Prioritizing health information for national health reporting - a Delphi study of the Joint Action on Health Information (InfAct).

BACKGROUND: Health information (HI) strategies exist in several EU Member States, however, they mainly focus on technical issues and improving governance rather than on content-related priority setting. There is also little research available about national prioritization processes underlying HI development for policy support in the EU. The aim of this study was to broaden the knowledge base on HI prioritization strategies and to encourage expert exchange towards good practice models. A specific focus was put on HI produced for national health reporting, this being a crucial tool for policy advice. METHODS: We conducted a literature search to identify published and grey literature on national HI prioritization. This was followed by a two-round Policy Delphi study, where we explored which processes and methods exist in EU Member States and associated countries for the prioritization of HI collection. In the first round, information about these processes was gathered in semi-structured questions; in the second round, participants were asked to rank the identified approaches for desirability and feasibility. The survey was conducted online; participants were recruited from the membership of the Joint Action on Health Information (InfAct - Information for Action). RESULTS: 119 experts were contacted, representing 40 InfAct partner institutions in 28 EU Member States and associated countries. Of these, 28 experts responded fully or partially to the first round, and six to the second round. In the first round, more than half of the respondents reported the existence of structured HI prioritization processes in their countries. To prioritize HI, a clear preference was given in the second round for a formal, horizontal process which includes different experts and stakeholders. National public health institutes were named desirable key stakeholders in this process, and also desirable and feasible coordinators for stakeholder coordination. CONCLUSION: Health information prioritization methods and procedures reflect the heterogeneity of national public health systems in European countries. Mapping, sharing and ranking prioritization methods and procedures for "good practices" provides a meaningful basis for expert knowledge exchange on HI development. We recommend to make this process part of a future sustainable EU health information system and to use the information gathered in this project to initiate the development of a guidance "Good Practice HI Prioritization" among EU Member States and associated countries.

Developing a tool to monitor knowledge translation in the health system: results from an international Delphi study.

BACKGROUND: It is generally accepted that evidence-informed decision making contributes to better health system performance and health outcomes, yet we are lacking benchmarks to monitor the impact of national health information systems (HIS) in policy and practice. Hence in this study, we have aimed to identify criteria for monitoring Knowledge Translation (KT) capacity within countries. METHODS: We conducted a web-based Delphi with over 120 public health professionals from 45 countries to reach agreement on criteria to monitor KT at the level of national HIS. Public health professionals participated in three survey rounds, in which they ranked 85 preselected criteria and could suggest additional criteria. RESULTS: Experts working in national (public) health agencies and statistical offices, as well as in health policy and care agreed on 29 criteria which constitute the Health Information (HI)-Impact Index. The criteria cover four essential domains of evaluation: the production of high-quality evidence, broad access and dissemination, stakeholder engagement and knowledge integration across sectors and in civil society. The HI-Impact Index was pretested by officials working in ministries of health and public health agencies in eight countries; they found the tool acceptable and user-friendly. CONCLUSIONS: The HI-Impact Index provides benchmarks to monitor KT so that countries can assess whether high-quality evidence can be easily accessed and used by the relevant stakeholders in health policy and practice, by civil society and across sectors. Next steps include further refining the procedure for conducting the assessment in routine, and sharing experiences from HIS evaluations using the HI-Impact Index.

Innovative use of data sources: a cross-sectional study of data linkage and artificial intelligence practices across European countries.

BACKGROUND: The availability of data generated from different sources is increasing with the possibility to link these data sources with each other. However, linked administrative data can be complex to use and may require advanced expertise and skills in statistical analysis. The main objectives of this study were to describe the current use of data linkage at the individual level and artificial intelligence (AI) in routine public health activities, to identify the related estimated health indicators (i.e., outcome and intervention indicators) and health determinants of non-communicable diseases and the obstacles to linking different data sources. METHOD: We performed a survey across European countries to explore the current practices applied by national institutes of public health, health information and statistics for innovative use of data sources (i.e., the use of data linkage and/or AI). RESULTS: The use of data linkage and AI at national institutes of public health, health information and statistics in Europe varies. The majority of European countries use data linkage in routine by applying a deterministic method or a combination of two types of linkages (i.e., deterministic & probabilistic) for public health surveillance and research purposes. The use of AI to estimate health indicators is not frequent at national institutes of public health, health information and statistics. Using linked data, 46 health outcome indicators, 34 health determinants and 23 health intervention indicators were estimated in routine. The complex data regulation laws, lack of human resources, skills and problems with data governance, were reported by European countries as obstacles to routine data linkage for public health surveillance and research. CONCLUSIONS: Our results highlight that the majority of European countries have integrated data linkage in their routine public health activities but only a few use AI. A sustainable national health information system and a robust data governance framework allowing to link different data sources are essential to support evidence-informed health policy development. Building analytical capacity and raising awareness of the added value of data linkage in national institutes is necessary for improving the use of linked data in order to improve the quality of public health surveillance and monitoring activities.

How can we monitor the impact of national health information systems? Results from a scoping review.

BACKGROUND: National health information (HI) systems provide data on population health, the determinants of health and health system performance within countries. The evaluation of these systems has traditionally focused on statistical practices and procedures, and not on data use or reuse for policy and practice. This limits the capacity to assess the impact of HI systems on healthcare provision, management and policy-making. On the other hand, the field of Knowledge Translation (KT) has developed frameworks to guide evidence into practice. METHODS: A scoping review of the KT literature to identify the essential mechanisms and determinants of KT that could help monitor the impact of HI systems. RESULTS: We examined 79 publications and we identified over 100 different KT frameworks but none of these were focused on HI systems per se. There were specific recommendations on disseminating evidence to stakeholders at the institutional and organizational level, and on sustaining the use of evidence in practice and the broader community setting. CONCLUSIONS: We developed a new model, the HI-Impact framework, in which four domains are essential for mapping the impact of national HI systems: (i) HI Evidence Quality, (ii) HI System Responsiveness, (iii) Stakeholder Engagement and (iv) Knowledge Integration. A comprehensive impact assessment of HI systems requires addressing the use of HI in public health decision-making, health service delivery and in other sectors which might have not been considered previously. Monitoring Stakeholder Engagement and Knowledge Integration certifies that the use of HI in all policies is an explicit point of assessment.

Epidemiology of late preterm and early term births - An international perspective.

Late preterm (34-36 weeks of gestational age (GA)), and early term (37-38 weeks GA) birth rates among singleton live births vary from 3% to 6% and from 15% to 31%, respectively, across countries, although data from low- and middle-income countries are sparse. Countries with high preterm birth rates are more likely to have high early term birth rates; many risk factors are shared, including pregnancy complications (hypertension, diabetes), medical practices (provider-initiated delivery, assisted reproduction), maternal socio-demographic and lifestyle characteristics and environmental factors. Exceptions include nulliparity and inflammation which increase risks for preterm, but not early term birth. Birth before 39 weeks GA is associated with adverse child health outcomes across a wide range of settings. International rate variations suggest that reductions in early delivery are achievable; implementation of best practice guidelines for obstetrical interventions and public health policies targeting population risk factors could contribute to prevention of both late preterm and early term births.

Quantifying the burden of stillbirths before 28 weeks of completed gestational age in high-income countries: a population-based study of 19 European countries.

BACKGROUND: International comparisons of stillbirth allow assessment of variations in clinical practice to reduce mortality. Currently, such comparisons include only stillbirths from 28 or more completed weeks of gestational age, which underestimates the true burden of stillbirth. With increased registration of early stillbirths in high-income countries, we assessed the reliability of including stillbirths before 28 completed weeks in such comparisons. METHODS: In this population-based study, we used national cohort data from 19 European countries participating in the Euro-Peristat project on livebirths and stillbirths from 22 completed weeks of gestation in 2004, 2010, and 2015. We excluded countries without national data for stillbirths by gestational age in these periods, or where data available were not comparable between 2004 and 2015. We also excluded those countries with fewer than 10 000 births per year because the proportion of stillbirths at 22 weeks to less than 28 weeks of gestation is small. We calculated pooled stillbirth rates using a random-effects model and changes in rates between 2004 and 2015 using risk ratios (RR) by gestational age and country. FINDINGS: Stillbirths at 22 weeks to less than 28 weeks of gestation accounted for 32% of all stillbirths in 2015. The pooled stillbirth rate at 24 weeks to less than 28 weeks declined from 0·97 to 0·70 per 1000 births from 2004 to 2015, a reduction of 25% (RR 0·75, 95% CI 0·65-0·85). The pooled stillbirth rate at 22 weeks to less than 24 weeks of gestation in 2015 was 0·53 per 1000 births and did not significantly changed over time (RR 0·97, 95% CI 0·80-1·16) although changes varied widely between countries (RRs 0·62-2·09). Wide variation in the percentage of all births occurring at 22 weeks to less than 24 weeks of gestation suggest international differences in ascertainment. INTERPRETATION: Present definitions used for international comparisons exclude a third of stillbirths. International consistency of reporting stillbirths at 24 weeks to less than 28 weeks suggests these deaths should be included in routinely reported comparisons. This addition would have a major impact, acknowledging the burden of perinatal death to families, and making international assessments more informative for clinical practice and policy. Ascertainment of fetal deaths at 22 weeks to less than 24 weeks should be stabilised so that all stillbirths from 22 completed weeks of gestation onwards can be reliably compared. FUNDING: EU Union under the framework of the Health Programme and the Bridge Health Project.

Are risk factors for preterm and early-term live singleton birth the same? A population-based study in France.

OBJECTIVES: To investigate whether risk factors for preterm (<37 weeks gestation) and early-term birth (37 and 38 weeks gestation) are similar. DESIGN: Nationally representative cross-sectional study of births. SETTING: France in 2010. PARTICIPANTS: Live singleton births (n=14 326). PRIMARY AND SECONDARY OUTCOME MEASURES: Preterm and early-term birth rates overall and by mode of delivery (spontaneous and indicated). Risk factors were maternal sociodemographic characteristics, previous preterm birth, height, prepregnancy body mass index (BMI) and smoking, assessed using multinomial regression models with full-term births 39 weeks and over as the reference group. RESULTS: There were 5.5% preterm and 22.5% early-term births. Common risk factors were: a previous preterm delivery (adjusted relative risk ratio (aRRR) 8.2 (95% CI 6.2 to 10.7) and aRRR 2.4 (95% CI 2.0 to 3.0), respectively), short stature, underweight (overall and in spontaneous deliveries), obesity (in indicated deliveries only), a low educational level and Sub-Saharan African origin. In contrast, primiparity was a risk factor only for preterm birth, aRRR 1.8 (95% CI 1.5 to 2.2), while higher parity was associated with greater risk of early-term birth. CONCLUSIONS: Most population-level risk factors were common to both preterm and early-term birth with the exception of primiparity, and BMI which differed by mode of onset of delivery. Our results suggest that preterm and early-term birth share similar aetiologies and thus potentially common strategies for prevention.

International variations in the gestational age distribution of births: an ecological study in 34 high-income countries.

Background: Few studies have investigated international variations in the gestational age (GA) distribution of births. While preterm births (22-36 weeks GA) and early term births (37-38 weeks) are at greater risk of adverse health outcomes compared to full term births (39-40 weeks), it is not known if countries with high preterm birth rates also have high early term birth rates. We examined rate associations between preterm and early term births and mean term GA by mode of delivery onset. Methods: We used routine aggregate data on the GA distribution of singleton live births from up to 34 high-income countries/regions in 1996, 2000, 2004, 2008 and 2010 to study preterm and early term births overall and by spontaneous or indicated onset. Pearson correlation coefficients were adjusted for clustering in time trend analyses. Results: Preterm and early term births ranged from 4.1% to 8.2% (median 5.5%) and 15.6% to 30.8% (median 22.2%) of live births in 2010, respectively. Countries with higher preterm birth rates in 2004-2010 had higher early term birth rates (r > 0.50, P < 0.01) and changes over time were strongly correlated overall (adjusted-r = 0.55, P < 0.01) and by mode of onset. Conclusion: Positive associations between preterm and early term birth rates suggest that common risk factors could underpin shifts in the GA distribution. Targeting modifiable population risk factors for delivery before 39 weeks GA may provide a useful preterm birth prevention paradigm.

Can the Apgar Score be Used for International Comparisons of Newborn Health?

BACKGROUND: The Apgar score has been shown to be predictive of neonatal mortality in clinical and population studies, but has not been used for international comparisons. We examined population-level distributions in Apgar scores and associations with neonatal mortality in Europe. METHODS: Aggregate data on the 5 minute Apgar score for live births and neonatal mortality rates from countries participating in the Euro-Peristat project in 2004 and 2010 were analysed. Country level associations between the Apgar score and neonatal mortality were assessed using the Spearman rank correlation coefficient. RESULTS: Twenty-three countries or regions provided data on Apgar at 5 minutes, covering 2 183 472 live births. Scores <7 ranged from 0.3% to 2.4% across countries in 2004 and 2010 and were correlated over time (ρ = 0.88, P < 0.01). There were large differences in healthy baby scores: scores of 10 ranged from 8.8% to 92.7% whereas scores of 9 or 10 ranged from 72.9% to 96.8%. Countries more likely to score 10 s, as opposed to 9 s, for healthy babies had lower proportions of Apgar <7 (ρ = -0.43, P = 0.04). Neonatal mortality rates were weakly correlated with Apgar score <7 (ρ = -0.06, P = 0.61), but differences over time in these two indicators were correlated (ρ =0.56, P = 0.02). CONCLUSIONS: Large variations in the distribution of Apgar scores likely due to national scoring practices make the Apgar score an unsuitable indicator for benchmarking newborn health across countries. However, country-level trends over time in the Apgar score may reflect real changes and merit further investigation.

Temporal Trends in Late Preterm and Early Term Birth Rates in 6 High-Income Countries in North America and Europe and Association With Clinician-Initiated Obstetric Interventions.

IMPORTANCE: Clinicians have been urged to delay the use of obstetric interventions (eg, labor induction, cesarean delivery) until 39 weeks or later in the absence of maternal or fetal indications for intervention. OBJECTIVE: To describe recent trends in late preterm and early term birth rates in 6 high-income countries and assess association with use of clinician-initiated obstetric interventions. DESIGN: Retrospective analysis of singleton live births from 2006 to the latest available year (ranging from 2010 to 2015) in Canada, Denmark, Finland, Norway, Sweden, and the United States. EXPOSURES: Use of clinician-initiated obstetric intervention (either labor induction or prelabor cesarean delivery) during delivery. MAIN OUTCOMES AND MEASURES: Annual country-specific late preterm (34-36 weeks) and early term (37-38 weeks) birth rates. RESULTS: The study population included 2,415,432 Canadian births in 2006-2014 (4.8% late preterm; 25.3% early term); 305,947 Danish births in 2006-2010 (3.6% late preterm; 18.8% early term); 571,937 Finnish births in 2006-2015 (3.3% late preterm; 16.8% early term); 468,954 Norwegian births in 2006-2013 (3.8% late preterm; 17.2% early term); 737,754 Swedish births in 2006-2012 (3.6% late preterm; 18.7% early term); and 25,788,558 US births in 2006-2014 (6.0% late preterm; 26.9% early term). Late preterm birth rates decreased in Norway (3.9% to 3.5%) and the United States (6.8% to 5.7%). Early term birth rates decreased in Norway (17.6% to 16.8%), Sweden (19.4% to 18.5%), and the United States (30.2% to 24.4%). In the United States, early term birth rates decreased from 33.0% in 2006 to 21.1% in 2014 among births with clinician-initiated obstetric intervention, and from 29.7% in 2006 to 27.1% in 2014 among births without clinician-initiated obstetric intervention. Rates of clinician-initiated obstetric intervention increased among late preterm births in Canada (28.0% to 37.9%), Denmark (22.2% to 25.0%), and Finland (25.1% to 38.5%), and among early term births in Denmark (38.4% to 43.8%) and Finland (29.8% to 40.1%). CONCLUSIONS AND RELEVANCE: Between 2006 and 2014, late preterm and early term birth rates decreased in the United States, and an association was observed between early term birth rates and decreasing clinician-initiated obstetric interventions. Late preterm births also decreased in Norway, and early term births decreased in Norway and Sweden. Clinician-initiated obstetric interventions increased in some countries but no association was found with rates of late preterm or early term birth.

Association of PNC, BC, and PM2.5 measured at a central monitoring site with blood pressure in a predominantly near highway population.

Elevated blood pressure is an indicator of cardiovascular stress and increased risk of cardiovascular-related morbidity and mortality. There is emerging evidence suggesting air pollutants, including particulate matter (PM), could promote hypertension, thereby increasing cardiovascular disease risk. Repeated measurement analyses were conducted to examine the associations of three types of PM with systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) in 220 participants, (mean age=58.5 years) from the Community Assessment of Freeway Exposure and Health study (CAFEH), most of whom live near a major highway. Ambient levels of air pollutants including particle number concentration (PNC; a measure of ultrafine particle (UFP) concentration), fine PM (PM2.5, Particle diameter<2.5 µm), and black carbon (BC) were measured at a central site<7 km from the study areas. Central sites are good at capturing short-term temporal trends in pollution associated with meteorological changes over regional areas. Linear mixed-effect models that accounted for repeated measures within one person were used to examine the associations between blood pressure variables and daily average of ambient PNC, PM2.5, or BC, controlling for demographic characteristics and major confounders including temperature. Our PNC model predicted that a higher PNC of 10,000 particles/cm3 was associated with higher DBP of 2.40 mmHg (p=0.03), independent of other factors in the model. There were no significant associations for PM2.5 or BC. Post hoc subgroup analyses by obesity status showed that positive associations of DBP with PNC were more pronounced among obese individuals than non-obese individuals. These results suggested that PNC levels are associated with increased blood pressure, which may contribute to cardiovascular disease risk. More research is needed to assess the relationship between PNC and blood pressure and to address possible residual confounding.

What contributes to disparities in the preterm birth rate in European countries?

PURPOSE OF REVIEW: In countries with comparable levels of development and healthcare systems, preterm birth rates vary markedly--a range from 5 to 10% among live births in Europe. This review seeks to identify the most likely sources of heterogeneity in preterm birth rates, which could explain differences between European countries. RECENT FINDINGS: Multiple risk factors impact on preterm birth. Recent studies reported on measurement issues, population characteristics, reproductive health policies as well as medical practices, including those related to subfertility treatments and indicated deliveries, which affect preterm birth rates and trends in high-income countries. We showed wide variation in population characteristics, including multiple pregnancies, maternal age, BMI, smoking, and percentage of migrants in European countries. SUMMARY: Many potentially modifiable population factors (BMI, smoking, and environmental exposures) as well as health system factors (practices related to indicated preterm deliveries) play a role in determining preterm birth risk. More knowledge about how these factors contribute to low and stable preterm birth rates in some countries is needed for shaping future policy. It is also important to clarify the potential contribution of artifactual differences owing to measurement.

Varying gestational age patterns in cesarean delivery: an international comparison.

BACKGROUND: While international variations in overall cesarean delivery rates are well documented, less information is available for clinical sub-groups. Cesarean data presented by subgroups can be used to evaluate uptake of cesarean reduction policies or to monitor delivery practices for high and low risk pregnancies based on new scientific evidence. We studied differences and patterns in cesarean delivery rates by multiplicity and gestational age in Europe and the United States. METHODS: This study used routine aggregate data from 17 European countries and the United States on the number of singleton and multiple live births with cesarean versus vaginal delivery by week of gestation in 2008. Overall and gestation-specific cesarean delivery rates were analyzed. We computed rate differences to compare mode of delivery (cesarean vs vaginal birth) between selected gestational age groups and studied associations between rates in these subgroups namely: very preterm (26-31 weeks GA), moderate preterm (32-36 weeks GA), near term (37-38 weeks GA), term (39-41 weeks GA) and post-term (42+ weeks GA) births, using Spearman's rank tests. RESULTS: High variations in cesarean rates for singletons and multiples were observed everywhere. Rates for singletons varied from 15% in The Netherlands and Slovenia, to over 30% in the US and Germany. In singletons, rates were highest for very preterm births and declined to a nadir at 40 weeks of gestation, ranging from 8.0% in Sweden and Norway, to 22.5% in the US. These patterns differed across countries; the average rate difference between very preterm and term births was 43 percentage points, but ranged from 14% to 61%. High variations in rate differences were also observed for near term versus term births. For multiples, rates declined by gestational age in some countries, whereas in others rates were similar across all weeks of gestation. Countries' overall cesarean rates were highly correlated with gestation-specific subgroup rates, except for very preterm births. CONCLUSIONS: Gestational age patterns in cesarean delivery were heterogeneous across countries; these differences highlight areas where consensus on best practices is lacking and could be used in developing strategies to reduce cesareans.