The utility of fetal heart rate deceleration's descending slope in searching for a non-National Institute of Child Health and Human Development parameter for the detection of fetal acidosis.

OBJECTIVE: To identify new parameters predicting fetal acidemia. METHODS: A retrospective case-control study in a cohort of deliveries from a tertiary referral hospital-based cohort deliveries in Zaragoza, Spain between 2018 and 2021 was performed. To predict fetal acidemia, the NICHD categorizations and non-NICHD parameters were analyzed in the electronic fetal monitoring (EFM). Those included total reperfusion time, total deceleration area and the slope of the descending limb of the fetal heart rate of the last deceleration curve. The accuracy of the parameters was evaluated using the specificity for (80%, 85%, 90%, 95%) sensitivity and the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 10 362 deliveries were reviewed, with 224 cases and 278 controls included in the study. The NICHD categorizations showed reasonable discriminatory ability (AUC = 0.727). The non-NICHD parameters measured during the 30-min fetal monitoring, total deceleration area (AUC = 0.807, 95% CI: 0.770, 0.845) and total reperfusion time (AUC = 0.750, 95% CI: 0.707, 0.792), exhibited higher discriminatory ability. The slope of the descending limb of the fetal heart rate of the last deceleration curve had the best AUC value (0.853, 95% CI: 0.816, 0.889). The combination of total deceleration area or total reperfusion time with the slope demonstrated high discriminatory ability (AUC = 0.908, 95% CI: 0.882, 0.933; specificities of 71.6% and 72.7% for a sensitivity of 90%). CONCLUSIONS: The slope of the descending limb of the fetal heart rate of the last deceleration curve is the strongest predictor of fetal acidosis, but its combination with the total reperfusion time shows better clinical utility.

Prostate Cancer and the Mevalonate Pathway.

Antineoplastic therapies for prostate cancer (PCa) have traditionally centered around the androgen receptor (AR) pathway, which has demonstrated a significant role in oncogenesis. Nevertheless, it is becoming progressively apparent that therapeutic strategies must diversify their focus due to the emergence of resistance mechanisms that the tumor employs when subjected to monomolecular treatments. This review illustrates how the dysregulation of the lipid metabolic pathway constitutes a survival strategy adopted by tumors to evade eradication efforts. Integrating this aspect into oncological management could prove valuable in combating PCa.

Interplay of the Mediterranean diet and genetic hypertension risk on blood pressure in European adolescents: Findings from the HELENA study.

Early-life onset of high blood pressure is associated with the development of cardiovascular diseases in adulthood. In adolescents, limited evidence exists regarding the association between adherence to the Mediterranean Diet (MedDiet) and normal blood pressure (BP) levels, as well as its potential to modulate genetic predisposition to HTN. This study investigated the interaction between a MedDiet score and a recently developed HTN-genetic risk score (HTN-GRS) on blood pressure levels in a European adolescent cohort. The MedDiet score was derived from two non-consecutive 24-h dietary recalls and ranged from 0 (indicating low adherence) to 9 (indicating high adherence). Multiple linear regression models, adjusted for covariates, were employed to examine the relationship between the MedDiet score and BP z-scores and to assess the interaction effects between the MedDiet score and HTN-GRS on BP z-scores. MedDiet score showed a negative association with z-systolic BP (SBP) (ß = -0.40, p < 0.001) and z-diastolic BP (DBP) (ß = -0.29, p = 0.001). Additionally, a significant interaction effect was identified between the MedDiet score and HTN-GRS on z-SBP (ß = 0.02, p < 0.001) and z-DBP (ß = 0.02, p < 0.001). The modulatory effect of the MedDiet was more pronounced in females than in males, and HTN-GRS exhibited a stronger influence on DBP than on SBP.   Conclusion: The study suggests that higher adherence to the MedDiet is associated with reduced BP levels in adolescents and provides evidence of a genetic-diet interaction influencing BP in adolescents. What is Known: • Adherence to the Mediterranean diet may reduce BP levels. What is New: • It is the first study to assess the connection between adherence to a Mediterranean diet, a hypertension genetic risk score, and how they interact in influencing blood pressure. • It is conducted within a multicenter cohort of European adolescents.

The body mass index increases the genetic risk scores' ability to predict risk of hepatic damage in European adolescents: The HELENA study.

BACKGROUND: Hepatic disorders are often complex and multifactorial, modulated by genetic and environmental determinants. During the last years, the hepatic disease has been progressively established from early stages in life. The use of genetic risk scores (GRS) to predict the genetic susceptibility to a particular phenotype among youth has gained interest in recent years. Moreover, the alanine aminotransferase (ALT) blood biomarker is often considered as hepatic screening tool, in combination with imaging techniques. The aim of the present study was to develop an ALT-specific GRS to help in the evaluation of hepatic damage risk in European adolescents. METHODS: A total of 972 adolescents (51.3% females), aged 12.5-17.5 years, from the Healthy Lifestyle in Europe by Nutrition in Adolescence study were included in the analyses. The sample incorporated adolescents in all body mass index (BMI) categories and was divided considering healthy/unhealthy ALT levels, using sex-specific cut-off points. From 1212 a priori ALT-related single nucleotide polymorphisms (SNPs) extracted from candidate gene selection, a first screening of 234 SNPs univariately associated was established, selecting seven significant SNPs (p < .05) in the multivariate model. An unweighted GRS (uGRS) was developed by summing the number of reference alleles, and a weighted GRS (wGRS), by multiplying each allele to its estimated coefficient. RESULTS: The uGRS and wGRS were significantly associated with ALT (p < .001). The area under curve was obtained integrating BMI as clinical factor, improving the predictive ability for uGRS (.7039) and wGRS (.7035), using 10-fold internal cross-validation. CONCLUSIONS: Considering BMI status, both GRSs could contribute as complementary tools to help in the early diagnosis of hepatic damage risk in European adolescents.

Development of a genetic risk score to predict the risk of hypertension in European adolescents from the HELENA study.

Introduction: From genome wide association study (GWAS) a large number of single nucleotide polymorphisms (SNPs) have previously been associated with blood pressure (BP) levels. A combination of SNPs, forming a genetic risk score (GRS) could be considered as a useful genetic tool to identify individuals at risk of developing hypertension from early stages in life. Therefore, the aim of our study was to build a GRS being able to predict the genetic predisposition to hypertension (HTN) in European adolescents. Methods: Data were extracted from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study. A total of 869 adolescents (53% female), aged 12.5-17.5, with complete genetic and BP information were included. The sample was divided into altered (≥130 mmHg for systolic and/or ≥80 mmHg for diastolic) or normal BP. Based on the literature, a total of 1.534 SNPs from 57 candidate genes related with BP were selected from the HELENA GWAS database. Results: From 1,534 SNPs available, An initial screening of SNPs univariately associated with HTN (p < 0.10) was established, to finally obtain a number of 16 SNPs significantly associated with HTN (p < 0.05) in the multivariate model. The unweighted GRS (uGRS) and weighted GRS (wGRS) were estimated. To validate the GRSs, the area under the curve (AUC) was explored using ten-fold internal cross-validation for uGRS (0.802) and wGRS (0.777). Further covariates of interest were added to the analyses, obtaining a higher predictive ability (AUC values of uGRS: 0.879; wGRS: 0.881 for BMI z-score). Furthermore, the differences between AUCs obtained with and without the addition of covariates were statistically significant (p < 0.05). Conclusions: Both GRSs, the uGRS and wGRS, could be useful to evaluate the predisposition to hypertension in European adolescents.

Postnatal catch-up growth in term newborns with altered fetal weight patterns. The GROWIN study.

BACKGROUND: Small for gestational age (SGA) perform a postnatal catch-up growth to recover their genetic trajectory. We studied the postnatal catch-up growth pattern of fetuses born with an appropriate-for-gestational-age (AGA) weight but with fetal growth deceleration (FGD) to explore whether they catch up. METHODS: Nine hundred and sixty-six newborns at Villalba University General Hospital (HUGV), were followed from 34 to 37 weeks to birth. Z-scores, adjusted for sex and age, of weight, length, and BMI at 3, 6, 9, and 12 months were calculated. We define catch-up as an increase in z-score greater than 0.67 SD in the growth curves. RESULTS: AGA FGD had lower mean weight and length than AGA non-FGD at all time points; BMI was lower until 3 months. AGA FGD had a lower weight, length, and BMI z-score (until 9, 6 months, and at birth, respectively) than AGA non-FGD. AGA FGD newborns had a significantly increased likelihood of weight catch-up at 3 months (OR 1.79; 95% CI: 1.16, 2.78; p = 0.009) and BMI in all investigated periods (OR 1.90; 95% CI 1.30, 2.78; p < 0.001 at 3 months), compared to AGA non-FGD newborns. CONCLUSIONS: AGA FGD newborns perform catch-up growth, especially in weight and BMI, in the first year of life, compared to AGA non-FGD. IMPACT: Appropriate-for-gestational-age (AGA) newborns with fetal growth deceleration (FGD), between the third trimester of pregnancy and delivery, present a lower weight and height, during the first year of life, compared to AGA non-FGD. Appropriate-for-gestational-age (AGA) newborns with fetal growth deceleration (FGD), between the third trimester of pregnancy and delivery, present a higher likelihood of weight catch-up in the first 3 months of life and of BMI in the first year compared to AGA non-FGD. AGA FGD experienced early weight and BMI catch-up, especially in the first 3 months of life, like SGA. This finding should be considered in the future follow-up.

A multistate model and its standalone tool to predict hospital and ICU occupancy by patients with COVID-19.

Objective: This study aims to build a multistate model and describe a predictive tool for estimating the daily number of intensive care unit (ICU) and hospital beds occupied by patients with coronavirus 2019 disease (COVID-19). Material and methods: The estimation is based on the simulation of patient trajectories using a multistate model where the transition probabilities between states are estimated via competing risks and cure models. The input to the tool includes the dates of COVID-19 diagnosis, admission to hospital, admission to ICU, discharge from ICU and discharge from hospital or death of positive cases from a selected initial date to the current moment. Our tool is validated using 98,496 cases positive for severe acute respiratory coronavirus 2 extracted from the Aragón Healthcare Records Database from July 1, 2020 to February 28, 2021. Results: The tool demonstrates good performance for the 7- and 14-days forecasts using the actual positive cases, and shows good accuracy among three scenarios corresponding to different stages of the pandemic: 1) up-scenario, 2) peak-scenario and 3) down-scenario. Long term predictions (two months) also show good accuracy, while those using Holt-Winters positive case estimates revealed acceptable accuracy to day 14 onwards, with relative errors of 8.8%. Discussion: In the era of the COVID-19 pandemic, hospitals must evolve in a dynamic way. Our prediction tool is designed to predict hospital occupancy to improve healthcare resource management without information about clinical history of patients. Conclusions: Our easy-to-use and freely accessible tool (https://github.com/peterman65) shows good performance and accuracy for forecasting the daily number of hospital and ICU beds required for patients with COVID-19.

Testosterone Recovery after Androgen Deprivation Therapy in Prostate Cancer: Building a Predictive Model.

PURPOSE: To analyze the variability, associated actors, and the design of nomograms for individualized testosterone recovery after cessation of androgen deprivation therapy (ADT). MATERIALS AND METHODS: A longitudinal study was carried out with 208 patients in the period 2003 to 2019. Castrated and normogonadic testosterone levels were defined as 0.5 and 3.5 ng/mL, respectively. The cumulative incidence curve described the recovery of testosterone. Univariate and multivariate analyzes were performed to predict testosterone recovery with candidate prognostic factors prostate-specific antigen at diagnosis, clinical stage, Gleason score from biopsy, age at cessation of ADT, duration of ADT, primary therapy and use of LHRH (luteinizing hormone-releasing hormone) agonists. RESULTS: The median follow-up duration in the study was 80 months (interquartile range, 49-99 mo). Twenty-five percent and 81% of patients did not recover the castrate and normogonadic levels, respectively. Duration of ADT and age at ADT cessation were significant predictors of testosterone recovery. We built two nomograms for testosterone recovery at 12, 24, 36, and 60 months. The castration recovery model had good calibration. The C-index was 0.677, with area under the receiver operating characteristic curve (AUC-ROC) of 0.736, 0.783, 0.782, and 0.780 at 12, 24, 36, and 60 months, respectively. The normogonadic recovery model overestimated the higher values of probability of recovery. The Cindex was 0.683, with AUC values of 0.812, 0.711, 0.708 and 0.693 at 12, 24, 36, and 60 months, respectively. CONCLUSIONS: Depending on the age of the patient and the length of treatment, clinicians may stop ADT and the castrated testosterone level will be maintained or, if the course of treatment has been short, we can estimate if it will return to normogonadic levels.

Personalized Model to Predict Small for Gestational Age at Delivery Using Fetal Biometrics, Maternal Characteristics, and Pregnancy Biomarkers: A Retrospective Cohort Study of Births Assisted at a Spanish Hospital.

Small for gestational age (SGA) is defined as a newborn with a birth weight for gestational age < 10th percentile. Routine third-trimester ultrasound screening for fetal growth assessment has detection rates (DR) from 50 to 80%. For this reason, the addition of other markers is being studied, such as maternal characteristics, biochemical values, and biophysical models, in order to create personalized combinations that can increase the predictive capacity of the ultrasound. With this purpose, this retrospective cohort study of 12,912 cases aims to compare the potential value of third-trimester screening, based on estimated weight percentile (EPW), by universal ultrasound at 35−37 weeks of gestation, with a combined model integrating maternal characteristics and biochemical markers (PAPP-A and ß-HCG) for the prediction of SGA newborns. We observed that DR improved from 58.9% with the EW alone to 63.5% with the predictive model. Moreover, the AUC for the multivariate model was 0.882 (0.873−0.891 95% C.I.), showing a statistically significant difference with EPW alone (AUC 0.864 (95% C.I.: 0.854−0.873)). Although the improvements were modest, contingent detection models appear to be more sensitive than third-trimester ultrasound alone at predicting SGA at delivery.

Statistical characterization of a good biomarker in oncology. / Características bioestadísticas de un buen biomarcador en Oncología.

OBJECTIVE: The  aim of this article is to review and illustrate the attributes that analyze the performance of a predictive model, suchas discrimination, calibration and clinical utility. MATERIAL AND METHODS: To illustrate a biomarkervalidation process, we analyzed 216 patientsrecruited in the Miguel Servet University Hospital Zaragoza, Spain. The outcome of the study was clinicallysignificant prostate cancer (Gleason ≥ 7). A newbiomarker was built using logistic regression modelfrom age, prostate-specific antigen, prostate volumeand digital rectal exam variables. To analyze the discriminationability, the receiver operating characteristiccurve, its area under the curve (AUC), and Youdenindex were estimated. In addition, the calibration wasanalyzed through calibration curve, intercept and slope;and the clinical utility was studied by means of decisionand clinical utility curves. RESULTS: The discrimination ability was good:AUC 0.790 (0.127-0.853 95% C.I.), Youden index cutoffpoint 0.431 (specificity 0.811, sensitivity 0.697).The Intercept was 0 and Slope 1 showing a perfect calibration.Decision curve showed good net benefit in athreshold probability range 25%-80%. Clinical utilitycurve showed that for a 18% cutoff point, a minimum4.5% of CsPCa patients are wrongly classified belowthe cutoff point, saving 18.5% biopsies. CONCLUSIONS: A complete validation process isnecessary to analyze the performance of a biomarkerin oncology, based on their discrimination ability, theconcordance between predicted and actual occurrenceof the outcome, and its applicability in clinical practice.

OBJETIVO: El objetivo principal de esteartículo es revisar e ilustrar las propiedades para analizarel desempeño de un modelo predictivo, que sonla discriminación, calibración y utilidad clínica.MATERIAL Y MÉTODOS: Para ilustrar un procesode validación de biomarcadores, analizamos 216 pacientesreclutados en el Hospital Universitario MiguelServet, Zaragoza, España. El objetivo a predecir en elestudio fue un cáncer de próstata clínicamente significativo(Gleason ≥ 7). Se construyó un nuevo biomarcadorutilizando un modelo de regresión logísticausando la edad, el antígeno prostático específico, elvolumen de la próstata y el tacto rectal como variablespredictoras. Para analizar la capacidad de discriminaciónse estimó la curva característica de funcionamientodel receptor, su área bajo la curva (AUC) y elíndice de Youden. Además, la calibración se analizómediante curva de calibración, intersección y pendiente;y la utilidad clínica se estudió mediante curvasde decisión y utilidad clínica. RESULTADOS: La capacidad de discriminación fuebuena: AUC 0,790 (0,127-0,853 IC del 95%), punto decorte del índice de Youden 0,431 (especificidad 0,811,sensibilidad 0,697). La intersección fue 0 y la pendiente1, mostrando una calibración perfecta. La curva dedecisión muestra un buen beneficio neto en un rangode probabilidad del 25% al 80%. La curva de utilidadclínica mostró que para un punto de corte del 18%, seproduce un mínimo del 4,5% de los pacientes con CsPCaclasificados incorrectamente por debajo del puntode corte, ahorrando un 18,5% de biopsias. CONCLUSIONES: Es necesario un proceso de validacióncompleto para analizar el desempeño de un biomarcadoren oncología, en función de su capacidad dediscriminación, la concordancia entre las prediccionesque proporciona el marcador y la ocurrencia real delevento, y su aplicabilidad en la práctica clínica.

Diagnostic capacity and interobserver variability in FIGO, ACOG, NICE and Chandraharan cardiotocographic guidelines to predict neonatal acidemia.

OBJECTIVE: Despite its routine use in intrapartum care, the technique of fetal cardiotocography has some limitations. The aim of this study is to analyze the predictive capacity and interobserver agreement in the latest versions of four international cardiotocography guidelines: Federation of Gynecology and Obstetrics (FIGO), American College of Obstetrics and Gynecology (ACOG), the National Institute for Health and Care Excellence (NICE) and Chandraharan, used to predict neonatal acidemia. STUDY DESIGN: The last 30 min of 150 cardiotocographic records were analyzed over all the pH ranges and were blindly evaluated by three independent reviewers. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC) were calculated to assess the predictive capacity of each fetal cardiotocographic guideline. The degree of interobserver agreement was evaluated with the Fleiss Kappa coefficient. RESULTS: Observers found fetal cardiotocography guidelines to have a variable sensitivity and specificity. The Chandraharan classification reached the highest sensitivity (78.79%), while ACOG had the highest specificity (95.73%). On average for the three observers, Chandraharan had the highest discrimination capacity for neonatal acidemia, although this was only moderate (AUC 0.66; 95%CI, 0.55-0.77) and did not differ significantly from the remaining guidelines. The degree of agreement among the three observers, assessed according to the Fleiss Kappa coefficient, was generally acceptable or moderate for all items and classifications, being highest with the FIGO classification (ĸ = 0.35; 95%CI, 0.28-0.41) and lowest with the ACOG (ĸ = 0.23; 95%CI, 0.16-0.30). CONCLUSION: Although all the guidelines have a moderate capacity to predict neonatal acidemia, the Chandraharan guideline has the highest capacity. This follows a different approach from the others in that it relies on interpretations of cardiotocographic traces based on fetal physiology. The degree of interobserver agreement is, in general, acceptable for the four guidelines, and is the highest for FIGO.

Total intrapartum fetal reperfusion time (fetal resilience) and neonatal acidemia.

OBJECTIVE: The main objective is to study the predictive capacity of intrapartum total fetal reperfusion (fetal resilience) by itself or in combination with other parameters as a predictor of neonatal acidemia. STUDY DESIGN: A retrospective case-control study was carried out at the Miguel Servet University Hospital (Zaragoza, Spain) on a cohort of 5694 pregnant women between June 2017 and October 2018. Maternal, perinatal, and cardiotocographic records were collected. Two reviewers blindly described the monitors with the American College of Obstetricians and Gynecologists (ACOG) categorizations and parameters and the non-ACOG parameters. Neonatal acidemia was defined as pH <7.10. The parameters analyzed to predict acidemia were evaluated using the sensitivity for specificity 90% value, and the area under the receiver operating characteristic curve. RESULTS: We recorded 192 infants with acidemia, corresponding to a global acidemia rate of 3.4%. Of these, 72 were excluded for lack of criteria, leaving 120 patients with arterial acidemia included in the study and 258 in the control group. The sensitivity (specificity 90%) of detection of acidemia was 42% for the ACOG III categorization (AUC, 0.524: 95% CI, 0.470-0.578), 24% for fetal reperfusion (AUC, 0.704: 95% CI, 0.649-0.759), 27% for total area of decelerations (AUC, 0.717: 95% CI, 0.664-0.771) and 50% for the multivariate model built from total reperfusion time (AUC, 0.826: 95% CI, 0.783-0.869). The total reperfusion time corresponding to a false negative rate of 10% is 23.75 min, with 28% of fetuses above this time. The AUC and sensitivity for a false negative rate of 10% are equivalent for deceleration area and time of reperfusion (p = .504). CONCLUSION: The total reperfusion time (fetal resilience) and total deceleration area are non-ACOG parameters with a good predictive ability for neonatal acidemia, higher than the ACOG III classification and without statistical differences between them. The discrimination ability of total reperfusion time can be improved using a multivariate model. As a cutoff for its use we suggest 23.75 min in 30 min corresponding to an acidemic classification rate of 90%. New parameters in combination with other maternal, obstetrics, or fetal variables, are required for the interpretation of fetal well-being.

Teaching Urology to Undergraduates: A Prospective Survey of What General Practitioners Need to Know.

BACKGROUND: Higher education training in Medicine has considerably evolved in recent years. One of its main goals has been to ensure the training of students as future adequately qualified general practitioners (GPs). Tools need to be developed to evaluate and improve the teaching of Urology at the undergraduate level. Our objective is to identify the knowledge and skills needed in Urology for the real clinical practice of GPs. METHODS: An anonymous self-administered survey was carried out among GPs of Primary Care and Emergencies which sought to evaluate urological knowledge and necessary urological skills. The results of the survey were exported and descriptive statistics were performed using IBM SPSS Statistics version 19.0. RESULTS AND LIMITATIONS: A total of 127 answers were obtained, in which 'Urological infections', 'Renal colic', 'PSA levels and screening for prostate cancer', 'Benign prostatic hyperplasia', 'Hematuria', 'Scrotal pain', 'Prostate cancer diagnosis', 'Bladder cancer diagnosis', 'Urinary incontinence', and 'Erectile dysfunction' were rated as Very high or High formative requirements (>75%). Regarding urological skills, 'Abdominal examination', 'Interpretation of urinalysis', 'Digital rectal examination', 'Genital examination', and 'Transurethral catheterization' were assessed as needing Very high or High training in more than 80% of the surveys. The relevance of urological pathology in clinical practice was viewed as Very high or High in more than 80% of the responses. CONCLUSIONS: This study has shown helpful results to establish a differentiated prioritization of urological knowledge and skills in Primary Care and Emergencies. Efforts should be aimed at optimizing the teaching in Urology within the Degree of Medicine which consistently ensures patients' proper care by future GPs.

Perinatal Adverse Effects in Newborns with Estimated Loss of Weight Percentile between the Third Trimester Ultrasound and Delivery. The GROWIN Study.

Fetal growth restriction has been associated with an increased risk of adverse perinatal outcomes (APOs). We determined the importance of fetal growth detention (FGD) in late gestation for the occurrence of APOs in small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) newborns. For this purpose, we analyzed a retrospective cohort study of 1067 singleton pregnancies. The newborns with higher APOs were SGA non-FGD and SGA FGD in 40.9% and 31.5% of cases, respectively, and we found an association between SGA non-FGD and any APO (OR 2.61; 95% CI: 1.35-4.99; p = 0.004). We did not find an increased APO risk in AGA FGD newborns (OR: 1.13, 95% CI: 0.80, 1.59; p = 0.483), except for cesarean delivery for non-reassuring fetal status (NRFS) with a decrease in percentile cutoff greater than 40 (RR: 2.41, 95% CI: 1.11-5.21) and 50 (RR: 2.93, 95% CI: 1.14-7.54). Conclusions: Newborns with the highest probability of APOs are SGA non-FGDs. AGA FGD newborns do not have a higher incidence of APOs than AGA non-FGDs, although with falls in percentile cutoff over 40, they have an increased risk of cesarean section due to NRFS. Further studies are warranted to detect these newborns who would benefit from close surveillance in late gestation and at delivery.

Prediction of Late-Onset Small for Gestational Age and Fetal Growth Restriction by Fetal Biometry at 35 Weeks and Impact of Ultrasound-Delivery Interval: Comparison of Six Fetal Growth Standards.

Small-for-gestational-age (SGA) infants have been associated with increased risk of adverse perinatal outcomes (APOs). In this work, we assess the predictive ability of the ultrasound-estimated percentile weight (EPW) at 35 weeks of gestational age to predict late-onset SGA and APOs, according to six growth standards, and whether the ultrasound-delivery interval influences the detection rate. To this purpose, we analyze a retrospective cohort study of 9585 singleton pregnancies. EPWs at 35 weeks were calculated to the customized Miguel Servet University Hospital (MSUH) and Figueras standards and the non-customized MSUH, Fetal Medicine Foundation (FMF), INTERGROWTH-21st, and WHO standards. As results of our analysis, for a 10% false positive rate, the detection rates for SGA ranged between 48.9% with the customized Figueras standard (AUC 0.82) and 60.8% with the non-customized FMF standard (AUC 0.87). Detection rates to predict SGA by ultrasound-delivery interval (1-6 weeks) show higher detection rates as intervals decrease. APOs detection rates ranged from 27.0% with FMF to 7.9% with the Figueras standard. In conclusion, the ability of EPW to predict SGA at 35 weeks is good for all standards, and slightly better for non-customized standards. The APO detection rate is significantly greater for non-customized standards.

Development of a Genetic Risk Score to predict the risk of overweight and obesity in European adolescents from the HELENA study.

Obesity is the result of interactions between genes and environmental factors. Since monogenic etiology is only known in some obesity-related genes, a genetic risk score (GRS) could be useful to determine the genetic predisposition to obesity. Therefore, the aim of our study was to build a GRS able to predict genetic predisposition to overweight and obesity in European adolescents. A total of 1069 adolescents (51.3% female), aged 11-19 years participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study were genotyped. The sample was divided in non-overweight (non-OW) and overweight/obesity (OW/OB). From 611 single nucleotide polymorphisms (SNP) available, a first screening of 104 SNPs univariately associated with obesity (p < 0.20) was established selecting 21 significant SNPs (p < 0.05) in the multivariate model. Unweighted GRS (uGRS) was calculated by summing the number of risk alleles and weighted GRS (wGRS) by multiplying the risk alleles to each estimated coefficient. The area under curve (AUC) was calculated in uGRS (0.723) and wGRS (0.734) using tenfold internal cross-validation. Both uGRS and wGRS were significantly associated with body mass index (BMI) (p < .001). Both GRSs could potentially be considered as useful genetic tools to evaluate individual's predisposition to overweight/obesity in European adolescents.

Mediterranean Diet, Screen-Time-Based Sedentary Behavior and Their Interaction Effect on Adiposity in European Adolescents: The HELENA Study.

Childhood obesity is a worldwide epidemic. Mediterranean diet (MD) is inversely associated with childhood obesity, but the interaction with other environmental factors, such screen time, might influence the health benefits of a high MD adherence in adolescents. The aim of the present study was to assess whether an association between MD and screen time exists in European adolescents. Moreover, we also explored whether sedentary time has a modulatory effect on the association between MD and adiposity. Adherence to the MD (24 h recalls), screen time (questionnaire), pubertal development, body mass index (BMI), fat mass index (FMI) and waist circumference (WC) were evaluated in 2053 adolescents (54.7% females), aged 12.5-17.5 years. In females, MD adherence was associated with lower BMI and FMI only when they were exposed to less than 338 min/day of screen time (81.8% of females); MD adherence was also associated with lower WC only when females were exposed to less than 143 min/day of screen time (31.5% of females). No significant MD-screen time interaction was observed in males. In conclusion, screen-time-based sedentary behaviours had a modulatory effect in the association between MD adherence and adiposity in European female adolescents.

Machine Learning Algorithm to Predict Acidemia Using Electronic Fetal Monitoring Recording Parameters.

BACKGROUND: Electronic fetal monitoring (EFM) is the universal method for the surveillance of fetal well-being in intrapartum. Our objective was to predict acidemia from fetal heart signal features using machine learning algorithms. METHODS: A case-control 1:2 study was carried out compromising 378 infants, born in the Miguel Servet University Hospital, Spain. Neonatal acidemia was defined as pH < 7.10. Using EFM recording logistic regression, random forest and neural networks models were built to predict acidemia. Validation of models was performed by means of discrimination, calibration, and clinical utility. RESULTS: Best performance was attained using a random forest model built with 100 trees. The discrimination ability was good, with an area under the Receiver Operating Characteristic curve (AUC) of 0.865. The calibration showed a slight overestimation of acidemia occurrence for probabilities above 0.4. The clinical utility showed that for 33% cutoff point, missing 5% of acidotic cases, 46% of unnecessary cesarean sections could be prevented. Logistic regression and neural networks showed similar discrimination ability but with worse calibration and clinical utility. CONCLUSIONS: The combination of the variables extracted from EFM recording provided a predictive model of acidemia that showed good accuracy and provides a practical tool to prevent unnecessary cesarean sections.

Clinical utility of thrombophilia, anticoagulant treatment, and maternal variables as predictors of placenta-mediated pregnancy complications: an extensive analysis.

Objective: The objective of this study is to analyze the usefulness of thrombophilia and antithrombotic drugs in combination with materno-fetal characteristics to generate a predictive model of placenta-mediated pregnancy complications (PMPC) for counseling treatment.Methods: A retrospective analysis was performed in women with singleton pregnancy that required a thrombophilia study, including 222 patients with unknown cause PMPC and 151 women with no complications at current pregnancy in Hospital Clínico Universitario, Lozano, Blesa, Zaragoza, Spain. Chi-squared and Mann-Whitney test were applied to analyze univariate risk factors. Multivariate analysis was performed using logistic regression model with candidate variables: maternal characteristics, obstetric history, thrombophilia, and treatment with low-molecular-weight heparin (LMWH) and/or with acid acetylsalicylic (ASA). The calibration, discrimination, and best cutoff point for the clinical application of the model was analyzed.Results: Maternal characteristics showed differences in median body mass index (BMI), odds ratio (OR): 0.4, smoking habit, OR: 8.5, and hypertension, OR: 11.4, appearing all of them as risk factors. In our study, a prior pregnancy that ended in a child alive was a protective factor OR: 0.02-0.4, and having a previous preterm child was a strong risk factor OR: 4.2. Thrombophilia was not a risk factor. Patients under LMWH treatment (15%) and/or ASA (6.2%) had better pregnancy outcomes, showing both as protective factors: ASA OR: 0.32 and LMWH OR: 0.16. The model has an AUC value of 0.847, with good calibration. A nomogram and an app is provided for this adjusted model with high discrimination ability in internal validation (AUC = 0.833). Our clinical utility analysis guide us to choose 40% as the best threshold probability.Conclusions: We found risk and protective factors associated with PMPC, but our data were not conclusive to demonstrate its relation with maternal thrombophilia. However, the challenger finding is the clinical utility of antithrombotic drugs as a protective factors in PMPC prevention. It is possible to identify patients with high risk of PMPC through a combined predictive model, for counseling treatment.

Pregestational body mass index, trimester-specific weight gain and total gestational weight gain: how do they influence perinatal outcomes?

OBJECTIVE: To investigate the association between pre-gestational body mass index (BMI), total gestational weight gain (GWG), and/or trimester-specific weight gain (GWGT) with adverse maternal or perinatal outcomes (AMPOs). MATERIALS AND METHODS: Maternal clinical characteristics and pregnancy and perinatal outcomes were used to predict AMPOs. The predictive ability of BMI, GWG, or GWGT for AMPOs was analyzed using the area under the curve (AUC). Logistic regression models in a univariate and multivariate analysis were performed to estimate the odds ratios (OR) and 95% confidence intervals (CI) to predict maternal outcomes (pregnancy-induced hypertension, preeclampsia or gestational diabetes mellitus) and perinatal outcomes (small for gestational age, large for gestational age, 5-min Apgar score, admission to neonatal intensive care unit or umbilical cord pH <7.15). RESULTS: Women with AMPOs (n = 293) were younger with higher rate of nulliparity (p < .001) and with lower height (p = .018) as compared to controls (n = 134). In the univariate study, GWGT in third trimester was associated with double risk of pregnancy-induced hypertension (OR 2.00; 95% CI, 1.01-3.97). Nonetheless, third-trimester GWG and total GWG have a negative relationship with gestational diabetes mellitus OR 0.32 (95% CI, 0.18-0.58) and OR 0.35 (95% CI, 0.21-0.59), respectively. Women with greater overall and in second trimester, GWG have a lower risk of having SGA neonates, OR 0.62 (95% CI, 0.39-0.98) and OR 0.60 (95% CI, 0.37-0.98), respectively. In the multivariate study, pre-gestational BMI is strongly related to the development of preeclampsia and the area under the curve (AUC) of the combination of pre-gestational BMI and total weight gain was 0.832 (95% CI, 0.63-0.81) for preeclampsia and 0.719 (95% CI, 0.71-0.94) for gestational diabetes mellitus. CONCLUSION: Our results suggest than timing of gestational weight gain influence in maternal and perinatal outcomes. Pre-gestational BMI is a determinant of preeclampsia, maternal weight gain in the third trimester is a determinant of pregnancy-induced hypertension and the increase in total GWG reduces the risk of gestational diabetes mellitus and small for gestational age.