How to Integrate Personalized Medicine into Prevention? Recommendations from the Personalized Prevention of Chronic Diseases (PRECeDI) Consortium.

Medical practitioners are increasingly adopting a personalized medicine (PM) approach involving individually tailored patient care. The Personalized Prevention of Chronic Diseases (PRECeDI) consortium project, funded within the Marie Sklodowska Curie Action (MSCA) Research and Innovation Staff Exchange (RISE) scheme, had fostered collaboration on PM research and training with special emphasis on the prevention of chronic diseases. From 2014 to 2018, the PRECeDI consortium trained 50 staff members on personalized prevention of chronic diseases through training and research. The acquisition of skills from researchers came from dedicated secondments from academic and nonacademic institutions aimed at training on several research topics related to personalized prevention of cancer and cardiovascular and neurodegenerative diseases. In detail, 5 research domains were addressed: (1) identification and validation of biomarkers for the primary prevention of cardiovascular diseases, secondary prevention of Alzheimer disease, and tertiary prevention of head and neck cancer; (2) economic evaluation of genomic applications; (3) ethical-legal and policy issues surrounding PM; (4) sociotechnical analysis of the pros and cons of informing healthy individuals on their genome; and (5) identification of organizational models for the provision of predictive genetic testing. Based on the results of the research carried out by the PRECeDI consortium, in November 2018, a set of recommendations for policy makers, scientists, and industry has been issued, with the main goal to foster the integration of PM approaches in the field of chronic disease prevention.

Effects of a simple educational intervention in well-baby clinics on women's knowledge about and intake of folic acid supplements in the periconceptional period: a controlled trial.

OBJECTIVE: To test the hypothesis that a concise intervention to promote the preconception use of folic acid (FA) supplements among mothers who visit a well-baby clinic (WBC) for the 6-month check-up of their youngest child is effective. Effectiveness was measured as intention to use or actual use of FA supplements before a next pregnancy among women who expected to be pregnant within 0-12 months. DESIGN: Controlled intervention study with independent samples of intervention and control mothers. The intervention took place at the 6-month visit. A post-intervention measurement was done in the intervention group and a comparable measurement in the control group at the 11-month check-up visit. SETTING: The intervention, verbal and in writing, was implemented in four Dutch WBC and given by the WBC physician to the mothers who visited the WBC. SUBJECTS: All mothers visiting the WBC were eligible for inclusion, unless they were unable to complete a questionnaire. The intervention group consisted of 198 (68 %) mothers recruited from 291 6-month intervention visits and the control group of 215 (84%) mothers recruited from 255 11-month normal visits. RESULTS: In mothers who expected to be pregnant within 0-12 months, the proportion using or intending to use FA was 65% in the intervention group (n 49) v. 42% in the control group (n 43; difference 23%, 95% CI 4, 43%, P<0·05). CONCLUSIONS: Health education intervention at the 6-month WBC visit is an effective means to promote the use of FA supplements or the intention to do so.

Prevention of congenital malformations and other adverse pregnancy outcomes with 4.0 mg of folic acid: community-based randomized clinical trial in Italy and the Netherlands.

BACKGROUND: In 2010 a Cochrane review confirmed that folic acid (FA) supplementation prevents the first- and second-time occurrence of neural tube defects (NTDs). At present some evidence from observational studies supports the hypothesis that FA supplementation can reduce the risk of all congenital malformations (CMs) or the risk of a specific and selected group of them, namely cardiac defects and oral clefts. Furthermore, the effects on the prevention of prematurity, foetal growth retardation and pre-eclampsia are unclear.Although the most common recommendation is to take 0.4 mg/day, the problem of the most appropriate dose of FA is still open.The aim of this project is to assess the effect a higher dose of peri-conceptional FA supplementation on reducing the occurrence of all CMs. Other aims include the promotion of pre-conceptional counselling, comparing rates of selected CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age, abruptio placentae. METHODS/DESIGN: This project is a joint effort by research groups in Italy and the Netherlands. Women of childbearing age, who intend to become pregnant within 12 months are eligible for the studies. Women are randomly assigned to receive 4 mg of FA (treatment in study) or 0.4 mg of FA (referent treatment) daily. Information on pregnancy outcomes are derived from women-and-physician information.We foresee to analyze the data considering all the adverse outcomes of pregnancy taken together in a global end point (e.g.: CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age). A total of about 1,000 pregnancies need to be evaluated to detect an absolute reduction of the frequency of 8%. Since the sample size needed for studying outcomes separately is large, this project also promotes an international prospective meta-analysis. DISCUSSION: The rationale of these randomized clinical trials (RCTs) is the hypothesis that a higher intake of FA is related to a higher risk reduction of NTDs, other CMs and other adverse pregnancy outcomes. Our hope is that these trials will act as catalysers, and lead to other large RCTs studying the effects of this supplementation on CMs and other infant and maternal outcomes. TRIAL REGISTRATION: Italian trial: ClinicalTrials.gov Identifier: NCT01244347.Dutch trial: Dutch Trial Register ID: NTR3161.

Factors associated with not using folic acid supplements preconceptionally.

OBJECTIVE: Neural tube defects are among the most common birth defects worldwide. Folic acid intake from one month before to three months after conception reduces the likelihood of neural tube defects by at least 50%. Since 1995, several campaigns have been organised in the Netherlands which resulted in 51% of pregnant women using folic acid supplements during the entire recommended period in the northern part of the Netherlands in 2005. Our research question was to gain insight into the current prevalence and factors associated with inadequate pregnancy-related use of folic acid supplements. DESIGN: Data from the DELIVER study were used, which is a population-based cohort study. SETTING: Twenty midwifery practices across the Netherlands in 2009 and 2010. SUBJECTS: In total 5975 pregnant women completed a questionnaire covering items on sociodemographic and lifestyle factors, including folic acid intake. RESULTS: Of our study population, 55·5% (3318/5975) used folic acid supplements before conception. Several sociodemographic and lifestyle factors were associated with no preconception use of folic acid, of which non-Western ethnicity and not having a partner had the largest effect size. CONCLUSIONS: In the Netherlands, the folic acid intake before conception is suboptimal and has not improved over recent years. Fortification of staple foods with folic acid should be reconsidered as it would provide a more effective means of ensuring an adequate intake, especially for those groups of women who are unlikely to plan their pregnancies or to receive or respond to health promotion messages.

Challenges in the care for consanguineous couples: an exploratory interview study among general practitioners and midwives.

BACKGROUND: It is often suggested that an effort must be made to increase awareness among consanguineous couples of their reproductive risk, and to refer them for genetic counseling if needed. Primary care professionals are considered most appropriate for addressing the subject and identifying couples at risk during consultations in their practice. This Dutch study aims to explore the experiences, attitudes and beliefs of such professionals regarding their care for consanguineous couples. METHODS: Sixteen semi-structured interviews were conducted with midwives and general practitioners. RESULTS: Although most primary care professionals considered it their task to inform couples about the risks of consanguinity, during consultations the topic was generally only briefly touched upon and quickly abandoned. Important reasons for this were professionals' beliefs about religious and social values of couples, their low perception of the couples' reproductive risk and expected limited feasibility of referral. Feelings of embarrassment regarding addressing consanguinity did not seem to play a significant role. CONCLUSIONS: Primary care professional beliefs about their clients' religious and social values, their attitudes toward the risk, and perceived limited options for referral seem to conflict with the professional norm to address the topic of consanguinity.

[Peri-pregnancy folic acid supplementation must be improved]. / Foliumzuursuppletiebeleid bij zwangerschap werkt, maar moet beter.

The correct usage of folic acid (FA) supplements to prevent neural tube defects (NTDs) increased from 28% in 1996 to 50% in 2005 and remained stable until 2009. Recent data from national birth defect registries show a decrease of NTD prevalence from 13.2 (per 10,000) in 1997 to 8.3 in 2005 and stabilization up to 2009. It is estimated that between 2005 and 2009 FA supplementation prevented 583 NTD cases. The medical costs thus averted are € 75 M. If the correct usage of FA were to be increased to 70%, another 34 cases per year could be prevented. Part of the gain from continued prevention and other averted costs should be invested beforehand in the promotion of FA supplement usage.

Attitudes of general practitioners and midwives towards ethnicity-based haemoglobinopathy-carrier screening.

Haemoglobinopathies (HbP) are severe autosomal recessive disorders with high prevalence among certain ethnic groups. World Health Organisation (WHO) advises implementing screening programmes for risk groups. Research in the Netherlands has shown that general practitioners and midwives do not perceive ethnicity as a risk factor for HbP. Moreover, registration of ethnicity is a controversial societal issue, which may complicate the introduction of a national preconception or antenatal carrier screening programme. This study investigates attitudes, intention and behaviour of general practitioners and midwives towards ethnicity-based HbP-carrier screening in general. A structured questionnaire based on the Theory of Planned Behaviour was sent by mail to a random selection of 2100 general practitioners and 1800 primary care midwives. Response was 35% (midwives 44.2%; GPs 27.6%). Although 45% of respondents thought that offering a carrier test on the basis of ethnicity alone should become national policy, it is currently not carried out. The main factor explaining lack of intention towards ethnicity-based HbP-carrier screening was subjective norm, the perception that their peers do not think they should offer screening (52.2% variance explained). If ethnicity-based HbP-carrier screening would become national policy, most professionals report that they would carry this out. Most respondents favoured ethnicity registration for health purposes. As most practitioners look for role models among peers, debate among general practitioners and midwives should be encouraged when new policy is to be developed, articulating the voices of colleagues who already actively offer HbP-carrier screening. Moreover, primary care professionals and professional organisations need support of policy at national level.

Genetic educational needs and the role of genetics in primary care: a focus group study with multiple perspectives.

BACKGROUND: Available evidence suggests that improvements in genetics education are needed to prepare primary care providers for the impact of ongoing rapid advances in genomics. Postgraduate (physician training) and master (midwifery training) programmes in primary care and public health are failing to meet these perceived educational needs. The aim of this study was to explore the role of genetics in primary care (i.e. family medicine and midwifery care) and the need for education in this area as perceived by primary care providers, patient advocacy groups and clinical genetics professionals. METHODS: Forty-four participants took part in three types of focus groups: mono-disciplinary groups of general practitioners and midwives, respectively and multidisciplinary groups composed of a diverse set of experts. The focus group sessions were audio-taped, transcribed verbatim and analysed using content analysis. Recurrent themes were identified. RESULTS: Four themes emerged regarding the educational needs and the role of genetics in primary care: (1) genetics knowledge, (2) family history, (3) ethical dilemmas and psychosocial effects in relation to genetics and (4) insight into the organisation and role of clinical genetics services. These themes reflect a shift in the role of genetics in primary care with implications for education. Although all focus group participants acknowledged the importance of genetics education, general practitioners felt this need more urgently than midwives and more strongly emphasized their perceived knowledge deficiencies. CONCLUSION: The responsibilities of primary care providers with regard to genetics require further study. The results of this study will help to develop effective genetics education strategies to improve primary care providers' competencies in this area. More research into the educational priorities in genetics is needed to design courses that are suitable for postgraduate and master programmes for general practitioners and midwives.

Validation of self-reported folic acid use in a multiethnic population: results of the Amsterdam Born Children and their Development study.

OBJECTIVE: To assess folic acid supplementation rates and validate the self-reporting of folic acid supplement use among pregnant women in a multiethnic cohort. DESIGN: Secondary analysis of a prospective cohort study. SETTING: Self-reported folic acid supplement use in the Amsterdam Born Children and their Development study cohort was compared with serum folate concentrations using non-parametric trend analysis and linear and logistic regression. SUBJECTS: A total of 4234 pregnant women of various ethnic backgrounds. RESULTS: Serum folate levels showed a significant positive linear trend as reported use of folic acid increased (P < 0·001), which was supported by linear regression (r = 0·49). Odds of having low serum folate concentration decreased with reported early start of folic acid intake. Young, multiparous or non-Western women reported less pre-conception folic acid intake. Non-Western women showed lower serum folate concentrations. The overall rate of over-reporting, i.e. serum folate concentrations ≤20 nmol/l while reporting the use of folic acid supplements, was 20·7 %. Women of Surinamese and Moroccan ancestry had higher odds of over-reporting (OR = 2·3; 95 % CI 1·5, 3·5 and OR = 2·3; 95 % CI 1·3, 4·0, respectively). The odds for Surinamese women remained significant after adjusting for the onset of supplement use, parity and age (OR = 1·7; 95 % CI 1·1, 2·6). CONCLUSIONS: Although self-reporting is a valid method for assessing folic acid supplement use in a multiethnic population, some participants do over-report. Surinamese and possibly Moroccan women appear to over-report more often. Rates of supplementation are low, especially in non-Western women. This suggests the need for intensifying current campaigns or perhaps even additional advice to start or continue to use folic acid post-conceptionally.

Influence of educational level on determinants of folic acid use.

In The Netherlands, periconceptional folic acid use to prevent neural tube defects was promoted through a national 'Folic Acid Campaign'. In two regions, a local campaign supplemented the national campaign to increase the chances of reaching women with low socio-economic status (SES). A framework of outcome criteria, defined as awareness knowledge, perceived safety, attitudes and subjective norms, was developed to evaluate the effectiveness of the two local campaigns. Data were gathered by means of two cross-sectional studies conducted just before and 1 year after the campaigns took place. Before the campaigns were conducted, there were already differences in all effect criteria and folic acid use between women of different educational levels, mostly in favour of women with a high level of education. Although both educational campaigns appeared to have a positive impact on all outcome criteria, they failed to reduce the existing differences in these outcome criteria between women of different educational levels. Folic acid use can be promoted effectively by mass media campaigns, certainly in a large group of women with no prior knowledge of the health benefits associated with periconceptional folic acid use. However, in order to achieve more equal health outcomes among women of low and high SES, it seems that more tailored interventions for women of low SES are needed.