Telomere length as biomarker of nutritional therapy for prevention of type 2 diabetes mellitus development in patients with coronary heart disease: CORDIOPREV randomised controlled trial.

BACKGROUND: Telomere Length (TL), a marker of cellular aging, holds promise as a biomarker to elucidate the molecular mechanism of diabetes. This study aimed to investigate whether shorter telomeres are associated with a higher risk of type 2 diabetes mellitus (T2DM) incidence in patients with coronary heart disease; and to determine whether the most suitable dietary patterns, particularly a Mediterranean diet or a low-fat diet, can mitigate the development of diabetes in these patients after a follow-up period of five years. METHODS: The CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study) was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20-75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive two healthy diets. Clinical investigators were masked to treatment assignment; participants were not. Quantitative-PCR was used to assess TL measurements. FINDINGS: 1002 patients (59.5 ± 8.7 years and 82.5% men) were enrolled into Mediterranean diet (n = 502) or a low-fat diet (n = 500) groups. In this analysis, we included all 462 patients who did not have T2DM at baseline. Among them, 107 patients developed T2DM after a median of 60 months. Cox regression analyses showed that patients at risk of short telomeres (TL < percentile 20th) are more likely to experience T2DM than those at no risk of short telomeres (HR 1.65, p-value 0.023). In terms of diet, patients at high risk of short telomeres had a higher risk of T2DM incidence after consuming a low-fat diet compared to patients at no risk of short telomeres (HR 2.43, 95CI% 1.26 to 4.69, p-value 0.008), while no differences were observed in the Mediterranean diet group. CONCLUSION: Patients with shorter TL presented a higher risk of developing T2DM. This association could be mitigated with a specific dietary pattern, in our case a Mediterranean diet, to prevent T2DM in patients with coronary heart disease. TRIAL REGISTRATION: Clinicaltrials.gov number NCT00924937.

Hepatitis C and cigarette smoking behavior: Themes from focus groups.

INTRODUCTION: People with chronic hepatitis C virus (HCV; PWHC) use cigarettes at a much higher prevalence than other individuals, and smoking can exacerbate the harms specifically related to HCV (e.g., hepatocellular carcinoma). Little is known about factors related to cigarette use among PWHC. This study examined focus group data to explore beliefs and behaviors related to cigarette use among PWHC. METHODS: Qualitative data from two focus groups of PWHC reporting current cigarette smoking (n=15, 60% male) were collected using a semi-structured interview guide. Participants were asked about reasons for smoking, barriers to quitting smoking, and the relationship of HCV to smoking. Focus groups were transcribed verbatim and coded in NVivo 12. Four coders examined themes that arose in the focus groups. Common themes are described and supported with quotes. RESULTS: Reasons for smoking included addiction to cigarettes, stress, substituting cigarettes for other drugs, and social norms, while reasons for quitting included health and being free from the use of all drugs. Barriers to quitting included concerns about coping with stress, weight gain, and having a lack of support for and education about quitting. Many participants believed there was a link between smoking and HCV and discussed smoking in relation to the stress of an HCV diagnosis. CONCLUSIONS: Participants identified both HCV-related and non-HCV-related aspects of cigarette smoking and cessation-related behaviors that could be targeted in cessation treatment. More research is needed to identify the best treatment approaches that reduce the significant medical consequences of cigarette use among PWHC. IMPLICATIONS: People with chronic hepatitis C virus (HCV; PWHC) smoke cigarettes at a high prevalence, yet little is known about their smoking behaviors. Moreover, there are no cessation treatments targeting PWHC. This is the first study to collect focus group data from PWHC who smoke in order to identify reasons for cigarette use (HCV-related and non-HCV-related), and motivators and barriers to quitting cigarettes. PWHC report using cigarettes to cope with the stress of an HCV diagnosis and to celebrate HCV cure. These findings suggest there are specific times during the HCV care continuum where providers can aid with cessation efforts.

New Approaches to the Management of Cardiovascular Risk Associated with Sleep Respiratory Disorders in Pediatric Patients.

Exposure to risk factors in youth can exacerbate the development of future cardiovascular disease (CVD). Obstructive sleep apnea (OSA), characterized by repetitive episodes of airway obstructions, could trigger said CVD acting as a modifiable risk factor. Measurements from echocardiography have shown impairments in the anatomy and function of the heart related to the severity of OSA. Therefore, the aim of this review was to propose a new clinical approach to the management of cardiovascular risk (CVR) in children based on treating OSA. The review includes studies assessing echocardiographic parameters for cardiac function and structure in pediatric OSA diagnosed using the apnea-hypopnea index (AHI) ≥ 1/h using polysomnography (PSG) and conducted within a year. Based on the reviewed evidence, in addition to PSG, echocardiography should be considered in OSA children in order to indicate the need for treatment and to reduce their future CVR. A follow-up echocardiography after treatment could be performed if impairments in the anatomy and function were found. Prioritizing parameters intimately connected to comorbidity could propel more effective patient-centered care. In conclusion, a reevaluation of pediatric OSA strategies should be considered, emphasizing comorbidity-related parameters in the cardiovascular field. Further studies are needed to assess this approach, potentially leading to enhanced protocols for more effective pediatric OSA treatment and CVR prevention.

Double Transverse Foramina-An Anatomical Basis for Possible Vertebrobasilar Insufficiency Risk and Vertebral Artery Injury.

Cervical vertebrae may exhibit the anomalous presence of a double transverse foramen (DTF) that may impact the anatomy of related structures that traverse the cervical region, such as the vertebral artery (VA). This retrospective anatomical study utilized CT angiography cervical scans to examine the prevalence of DTF, VA, and TF areas. The subjects were separated into two groups: normal TF (NTF group; 26 males and 21 females) and double TF (DTF group; 21 males and 24 females). The males presented significantly higher TF area values (30.31 ± 4.52 mm2) than the females (27.48 ± 1.69 mm2) in the NTF group (p = 0.006). The sex differences disappeared when a DTF was present (p = 0.662). There were no differences in the VA area values between the sexes in both the NTF and DTF groups (p = 0.184). No significant differences in the VA area values between males of the NTF and DTF groups (p = 0.485) were noted. The DTF subjects presented an increased VA/TF area ratio than the NTF subjects (p < 0.001). This study showed that DTF presence reduced the TF area. In contrast, the VA area did not change despite the decreasing TF area. This might be an anatomical risk for transient vertebrobasilar insufficiency in subjects with DTF, especially in females, because VA space in the TF is less in DTF subjects than in NTF subjects. This may lead to easy VA compression in DTF subjects following neck trauma.

Innovative approaches to accurately assess the effectiveness of biocide-based treatments to fight biodeterioration of Cultural Heritage monuments.

The development of diagnostic methods to accurately assess the effects of treatments on lithobiont colonization remains a challenge for the conservation of Cultural Heritage monuments. In this study, we tested the efficacy of biocide-based treatments on microbial colonization of a dolostone quarry, in the short and long-term, using a dual analytical strategy. We applied a metabarcoding approach to characterize fungal and bacterial communities over time, integrated with microscopy techniques to analyze the interactions of microorganisms with the substrate and evaluate the effectiveness. These communities were dominated by the bacterial phyla Actinobacteriota, Proteobacteria and Cyanobacteria, and the fungal order Verrucariales, which include taxa previously reported as biodeteriogenic agents and observed here associated with biodeterioration processes. Following the treatments, changes over time in the abundance profiles depend on taxa. While Cyanobacteriales, Cytophagales and Verrucariales decreased in abundance, other groups, such as Solirubrobacteriales, Thermomicrobiales and Pleosporales increased. These patterns could be related not only to the specific effects of the biocide on the different taxa, but also to different recolonization abilities of those organisms. The different susceptibility to treatments could be associated with the inherent cellular properties of different taxa, but differences in biocide penetration to endolithic microhabitats could be involved. Our results demonstrate the importance of both removing epilithic colonization and applying biocides to act against endolithic forms. Recolonization processes could also explain some of the taxon-dependent responses, especially in the long-term. Taxa showing resistance, and those benefiting from nutrient accumulation in the form of cellular debris following treatments, may have an advantage in colonizing treated areas, pointing to the need for long-term monitoring of a wide range of taxa. This study highlights the potential utility of combining metabarcoding and microscopy to analyze the effects of treatments and design appropriate strategies to combat biodeterioration and establish preventive conservation protocols.

Impact of obstructive sleep apnea in cardiovascular risk in the pediatric population: A systematic review.

While the association of obstructive sleep apnea (OSA) with an increased cardiovascular risk (CVR) in the adult population is well known, there is insufficient evidence to affirm something similar in the pediatric population. On the other hand, adenotonsillectomy has been shown to be an effective treatment. Our objective was to evaluate the association of sleep respiratory disorders in children with increased CVR and the impact of adenotonsillectomy in the literature. To this aim, a literature search was conducted, between 2002 to the present. After carrying out a systematic review, the following results were provided: thoracic echocardiography after surgery found improvements in terms of cardiac function and structure; blood pressure (BP) measurement, verified a tendency to higher BP values in the OSA pediatric population, which improved after surgery; different biomarkers of CVR, were increased in OSA patients and improved after treatment and finally; some studies found endothelial dysfunction in pediatric OSA, a measurement of vascular system function, was reversible with adenotonsillectomy. Increases in BP parameters, biological markers related to CVR and alterations in cardiac function structure, have been reported in pediatric patients with OSA. At least, some of these parameters would be reversible after adenotonsillectomy, reflecting a possible reduction in CVR.

A Rare Case of Kikuchi-Fujimoto Disease.

Kikuchi-Fujimoto disease (KFD) is an autoimmune condition that is more common in females and occurs in the third decade of life. The condition is usually benign and self-resolving and is characterized by fever, cervical lymphadenopathy, night sweats, myalgia, and rashes. The disease can be misdiagnosed as reactive follicular hyperplasia, tuberculous lymphadenitis, systemic lupus erythematosus, and malignant lymphoma. The diagnosis of KFD involves the excision of the affected lymph node. Although there is no specific treatment for the disease, usually symptomatic and supportive measures are effective; however, steroids and immunosuppressive therapies are considered in more severe cases. The disease lasts for around one to four months. The neurological complications include cerebellar ataxia, meningoencephalitis, and aseptic meningitis. Here, we describe the case of a 36-year-old male who presented with complaints of fever, malaise chills, anorexia, and fatigue associated with a tender right axillary lymph node. The patient underwent a biopsy which confirmed KFD and responded well to supportive therapy.

Effects of Gestational Intermittent Hypoxia on Placental Morphology and Fetal Development in a Murine Model of Sleep Apnea.

Obstructive sleep apnea (OSA) during pregnancy is characterized by episodes of intermittent hypoxia (IH) during sleep, resulting in adverse health outcomes for mother and offspring. Despite a prevalence of 8-20% in pregnant women, this disorder is often underdiagnosed.We have developed a murine model of gestational OSA to study IH effects on pregnant mothers, placentas, fetuses, and offspring. One group of pregnant rats was exposed to IH during the last 2 weeks of gestation (GIH). One day before the delivery date, a cesarean section was performed. Other group of pregnant rats was allowed to give birth at term to study offspring's evolution.Preliminary results showed no significant weight differences in mothers and fetuses. However, the weight of GIH male offspring was significantly lower than the controls at 14 days (p < 0.01). The morphological study of the placentas showed an increase in fetal capillary branching, expansion of maternal blood spaces, and number of cells of the external trophectoderm in the tissues from GIH-exposed mothers. Additionally, the placentas from the experimental males were enlarged (p < 0.05). Further studies are needed to follow the long-term evolution of these changes to relate the histological findings of the placentas with functional development of the offspring in adulthood.

Intermittent Hypoxia and Diet-Induced Obesity on the Intestinal Wall Morphology in a Murine Model of Sleep Apnea.

This work analyzes the impact of two conditions, intermittent hypoxia exposure and high-fat diet in rats as models of sleep apnea. We studied the autonomic activity and histological structure of the rat jejunum and whether the overlapping of both conditions, as often observed in patients, induces more deleterious effects on the intestinal barrier. We found alterations in jejunum wall histology, predominantly in HF rats, based on increased crypt depth and submucosal thickness, as well as decreased muscularis propria thickness. These alterations were maintained with the IH and HF overlap. An increase in the number and size of goblet cells in the villi and crypts and the infiltration of eosinophils and lymphocytes in the lamina propria suggest an inflammatory status, confirmed by the increase in plasma CRP levels in all experimental groups. Regarding the CAs analysis, IH, alone or combined with HF, causes a preferential accumulation of NE in the catecholaminergic nerve fibers of the jejunum. In contrast, serotonin increases in all three experimental conditions, with the highest level in the HF group. It remains to be elucidated whether the alterations found in the present work could affect the permeability of the intestinal barrier, promoting sleep apnea-induced morbidities.

Diagnosis and Treatment of Sleep Apnea in Children: A Future Perspective Is Needed.

Obstructive sleep apnea (OSA) in children is a prevalent, but still, today, underdiagnosed illness, which consists of repetitive episodes of upper airway obstruction during sleep with important repercussions for sleep quality. OSA has relevant consequences in the pediatric population, mainly in the metabolic, cardiovascular (CV), and neurological spheres. However, contrary to adults, advances in diagnostic and therapeutic management have been scarce in the last few years despite the increasing scientific evidence of the deleterious consequences of pediatric OSA. The problem of underdiagnosis and the lack of response to treatment in some groups make an update to the management of OSA in children necessary. Probably, the heterogeneity of OSA is not well represented by the classical clinical presentation and severity parameters (apnea/hypopnea index (AHI)), and new strategies are required. A specific and consensus definition should be established. Additionally, the role of simplified methods in the diagnosis algorithm should be considered. Finally, the search for new biomarkers for risk stratification is needed in this population. In conclusion, new paradigms based on personalized medicine should be implemented in this population.

Far UV narrowband mirrors tuned at H Lyman α.

Imaging at H Ly-α (121.6 nm), among other spectral lines in the short far UV (FUV), is of high interest for astrophysics, solar, and atmosphere physics, since this spectral line is ubiquitously present in space observations. However, the lack of efficient narrowband coatings has mostly prevented such observations. Present and future space observatories like GLIDE and the IR/O/UV NASA concept, among other applications, can benefit from the development of efficient narrowband coatings at Ly-α. The current state of the art of narrowband FUV coatings lacks performance and stability for coatings that peak at wavelengths shorter than ∼135 nm. We report highly reflective AlF3/LaF3 narrowband mirrors at Ly-α prepared by thermal evaporation, with, to our knowledge, the highest reflectance (over 80%) of a narrowband multilayer at such a short wavelength obtained so far. We also report a remarkable reflectance after several months of storage in different environments, including relative humidity levels above 50%. For astrophysics targets in which Ly-α may mask a close spectral line, such as in the search for biomarkers, we present the first coating in the short FUV for imaging at the OI doublet (130.4 and 135.6 nm), with the additional requirement of rejecting the intense Ly-α, which might mask the OI observations. Additionally, we present coatings with the symmetric design, aimed to observe at Ly-α, and reject the strong OI geocoronal emission, that could be of interest for atmosphere observations.

Analysis of the Ischemia-Modified Albumin as a Potential Biomarker for Cardiovascular Damage in Obstructive Sleep Apnea Patients with Acute Coronary Syndrome.

Obstructive sleep apnea (OSA) has been identified as a cardiovascular (CV) risk factor. The potential of OSA promoting the synthesis of CV biomarkers in acute coronary syndrome (ACS) is unknown. Ischemia-modified albumin (IMA) has been identified as a specific CV biomarker. The aim of this study was to evaluate the role of IMA as a potential biomarker for determining the impact of OSA in ACS patients. A total of 925 patients (15.5% women, age: 59 years, body mass index: 28.8 kg/m2) from the ISAACC study (NCT01335087) were included. During hospitalization for ACS, a sleep study for OSA diagnosis was performed and blood samples extraction for IMA determination were obtained. IMA values were significantly higher in severe OSA (median (IQR), 33.7 (17.2-60.3) U/L) and moderate (32.8 (16.9-58.8) U/L) than in mild/no OSA (27.7 (11.8-48.6) U/L) (p = 0.002). IMA levels were very weakly related to apnea-hypopnea index (AHI) as well as hospital and intensive care unit stay, although they only maintained a significant relationship with days of hospital stay after adjusting for sex, age and BMI (ß = 0.410, p = 0.013). The results of the present study would suggest a potentially weaker role of OSA in the synthesis of the CV risk biomarker IMA in patients with ACS than in primary prevention.

Sex differences in cardiovascular and disease-related features in axial spondyloarthritis. A multicenter study of 912 patients.

OBJECTIVES: To determine the potential impact of sex-specific disease-related characteristics on cardiovascular (CV) disease in axial spondyloarthritis (axSpA). METHODS: Cross-sectional study of the Spanish AtheSpAin cohort to study CV disease in axSpA. Data on carotid ultrasound and CV disease and disease-related features were collected. RESULTS: 611 men and 301 women were recruited. Classic CV risk factors were significantly less prevalent in women, who also showed a lower frequency of carotid plaques (p = 0.001), lower carotid intima-media thickness (IMT) values ​​(p<0.001) and CV events (p = 0.008). However, after adjustment for classic CV risk factors, only the differences with respect to carotid IMT remained statistically significant. Women showed higher ESR at diagnosis (p = 0.038), and more active disease (ASDAS, p = 0.012, and BASDAI, p<0.001). They had shorter disease duration (p<0.001), lower prevalence of psoriasis (p = 0.008), less structural damage (mSASSS, p<0.001), and less mobility limitation (BASMI, p = 0.033). To establish whether these findings could lead to sex differences in CV disease burden, we compared the prevalence of carotid plaques in men and women with the same level of CV risk stratified according to the Systematic Coronary Risk Evaluation (SCORE). Men included in the low-moderate CV risk SCORE category had more carotid plaques (p = 0.050), along with longer disease duration (p = 0.004), higher mSASSS (p = 0.001) and psoriasis (p = 0.023). In contrast, in the high-very high-risk SCORE category, carotid plaques were observed more frequently in women (p = 0.028), who were characterized as having worse BASFI (p = 0.011), BASDAI (p<0.001) and ASDAS (p = 0.027). CONCLUSION: Disease-related features may influence the expression of atherosclerosis in patients with axSpA. This may be especially applicable to women at high CV risk, characterized by greater disease severity and more severe subclinical atherosclerosis than men, suggesting a stronger interaction between disease activity and atherosclerosis in women with axSpA.

Comunidades Compasivas: intervención comunitaria para la preven-ción del duelo complicado. Modelo implantado por Madrid Salud / Compassionate Communities: Community intervention for the prevention of complicated grief. Model implemented by Madrid Salud

Objetivo: Fortalecer la capacidad de las personas para afrontar y acompañar las situaciones de duelo desde el modelo de Comunidades Compasivas a través de una perspectiva comunitaria. Metodología: Diseño de dos ejes de intervención: sensibilización y formación a la población y profesionales, y desarrollo de espacios grupales dirigidos a prevenir el duelo complicado. Resultado: Se ha realizado un diagnóstico de la ciudad de Madrid. Se han realizado 60 formaciones dirigidas al personal de Madrid Salud y 32 a profesionales entidades del entorno comunitario. Se han realizado 327 sensibilizaciones en torno al final de la vida y el duelo (5.873 personas). Se ha establecido contacto con 283 recursos públicos y 158 recursos privados a lo largo del año. Por último, se han llevado a cabo un total de 15 Espacios Grupales de Acompañamiento al Duelo. Conclusiones: El modelo de comunidades compasivas de la ciudad de Madrid ha conseguido fortalecer las capacidades de la ciudadanía de Madrid para el cuidado colectivo a través de las diferentes actividades de sensibilización e impactar en el fortalecimiento profesional y sensibilidad de los profesionales de la salud en relación con los conceptos clave del proyecto, generando así una comunidad compasiva (AU)

Objective:The main objective of the Compassionate Communities project in the city of Madrid is to strengthen people’s ability to face and accompany grief situations through a community perspective. Methodology: Design of two intervention axes: sensitization and training of the population and professionals, and development of group spaces aimed at preventing complicated grief. Result: A diagnosis of the city of Madrid has been carried out. Sixty trainings have been carried out for Madrid Salud staff and 32 for professionals and community organizations. There have been 327 sensitizations about the end of life and bereavement (5,873 people). Contact was established with 283 public resources and 158 private resources throughout the year. Finally, a total of 15 Group Spaces for Grieving Support have been carried out. Conclusions: The compassionate communities model of the city of Madrid has managed to strengthen the capacities of the citizens of Madrid for collective care through the different awareness-raising activities and to impact on the professional strengthening and sensitivity of health professionals in relation to the key concepts of the project, thus generating a compassionate community (AU)

Facilitating Factors and Barriers in the Return to Work of Working Women Survivors of Breast Cancer: A Qualitative Study.

Several studies have identified the main barriers and facilitators that breast cancer survivors experience in the return to work (RTW). The authors conducted a qualitative study using focus group discussions with a group of female non-metastatic breast cancer survivors (n = 6), a group of health professionals from different medical specialties (n = 8), and a third group of company managers mainly composed of human resources managers (n = 7). The study was carried out between March and December 2021 in Zaragoza (Spain). Transcripts were analyzed using inductive content analysis to identify work-related barriers and facilitators and coded by the research team. Barriers identified included physical and cognitive symptoms, psychosocial problems, lack of knowledge and coordination (health professional, patients, and managers), legal vacuum, physical change, time constraints, work characteristics (lower skilled jobs), unsupportive supervisors and coworkers, family problems and self-demand. Facilitators included family and work support, physical activity and rehabilitation, personalized attention, interdisciplinary collaboration, legal advice for workers, knowledge about breast cancer in companies, positive aspects of work, elaboration of protocols for RTW in women with breast cancer. RTW in working women with breast cancer requires a personalized and holistic view that includes the perspectives of patients, healthcare professionals and company managers.

Association between missense variants of uncertain significance in the CHEK2 gene and hereditary breast cancer: a cosegregation and bioinformatics analysis.

Inherited mutations in the CHEK2 gene have been associated with an increased lifetime risk of developing breast cancer (BC). We aim to identify in the study population the prevalence of mutations in the CHEK2 gene in diagnosed BC patients, evaluate the phenotypic characteristics of the tumor and family history, and predict the deleteriousness of the variants of uncertain significance (VUS). A genetic study was performed, from May 2016 to April 2020, in 396 patients diagnosed with BC at the University Hospital Lozano Blesa of Zaragoza, Spain. Patients with a genetic variant in the CHEK2 gene were selected for the study. We performed a descriptive analysis of the clinical variables, a bibliographic review of the variants, and a cosegregation study when possible. Moreover, an in-depth bioinformatics analysis of CHEK2 VUS was carried out. We identified nine genetic variants in the CHEK2 gene in 10 patients (two pathogenic variants and seven VUS). This supposes a prevalence of 0.75% and 1.77%, respectively. In all cases, there was a family history of BC in first- and/or second-degree relatives. We carried out a cosegregation study in two families, being positive in one of them. The bioinformatics analyses predicted the pathogenicity of six of the VUS. In conclusion, CHEK2 mutations have been associated with an increased risk for BC. This risk is well-established for foundation variants. However, the risk assessment for other variants is unclear. The incorporation of bioinformatics analysis provided supporting evidence of the pathogenicity of VUS.

Prevalence of High Blood Pressure in Pediatric Patients with Sleep-Disordered Breathing, Reversibility after Treatment: The KIDS TRIAL Study Protocol.

Current data support an increase in the prevalence of high blood pressure (HBP) in pediatric patients with sleep-disordered breathing (SDB). Adeno-tonsillectomy has been shown to be an effective treatment for most patients. Our objective was to determine the prevalence of HBP in pediatric patients with SDB and the impact of adeno-tonsillectomy with a multicenter, longitudinal, and prospective study that included 286 children referred for suspected SDB. The diagnosis of SDB was established by polysomnography (PSG) and the diagnosis of HBP by 24-h ambulatory blood pressure monitoring (ABPM). In patients without SDB and SDB without treatment indication, these tests were repeated six months after the baseline visit. For patients with medical treatment for SDB, the tests were repeated six months after the treatment initiation. Finally, in patients with surgery indication, ABPM was performed just before surgical treatment and ABPM and PSG six months after the intervention. The study contributes to elucidating the association between SDB and HBP in pediatric patients. Moreover, it contributes to determining if intervention with adeno-tonsillectomy is associated with BP reduction. The results have direct implications for the management of SDB, providing essential information on treatment indications for existing clinical guidelines. NCT03696654.

The Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) Trial to Avoid Adverse Perinatal Outcomes: Protocol for a Multicenter, Open-Label, Randomized Controlled Trial.

BACKGROUND: Fetal smallness affects 10% of pregnancies. Small fetuses are at a higher risk of adverse outcomes. Their management using estimated fetal weight and feto-maternal Doppler has a high sensitivity for adverse outcomes; however, more than 60% of fetuses are electively delivered at 37 to 38 weeks. On the other hand, classification using angiogenic factors seems to have a lower false-positive rate. Here, we present a protocol for the Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) trial, which compares the use of angiogenic factors and Doppler to manage small fetuses at term. OBJECTIVE: The primary objective is to demonstrate that classification based on angiogenic factors is not inferior to estimated fetal weight and Doppler at detecting fetuses at risk of adverse perinatal outcomes. METHODS: This is a multicenter, open-label, randomized controlled trial conducted in 20 hospitals across Spain. A total of 1030 singleton pregnancies with an estimated fetal weight ≤10th percentile at 36+0 to 37+6 weeks+days will be recruited and randomly allocated to either the control or the intervention group. In the control group, standard Doppler-based management will be used. In the intervention group, cases with a soluble fms-like tyrosine kinase to placental growth factor ratio ≥38 will be classified as having fetal growth restriction; otherwise, they will be classified as being small for gestational age. In both arms, the fetal growth restriction group will be delivered at ≥37 weeks and the small for gestational age group at ≥40 weeks. We will assess differences between the groups by calculating the relative risk, the absolute difference between incidences, and their 95% CIs. RESULTS: Recruitment for this study started on September 28, 2020. The study results are expected to be published in peer-reviewed journals and disseminated at international conferences in early 2023. CONCLUSIONS: The angiogenic factor-based protocol may reduce the number of pregnancies classified as having fetal growth restriction without worsening perinatal outcomes. Moreover, reducing the number of unnecessary labor inductions would reduce costs and the risks derived from possible iatrogenic complications. Additionally, fewer inductions would lower the rate of early-term neonates, thus improving neonatal outcomes and potentially reducing long-term infant morbidities. TRIAL REGISTRATION: ClinicalTrials.gov NCT04502823; https://clinicaltrials.gov/ct2/show/NCT04502823. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37452.