Prediction of low birth weight with hypoglycemia in glucose tolerance test.

OBJECTIVE: Determine the value of the combination of fasting glucose less than the 10th percentile (FG < p10) during 75 gram oral glucose tolerance test (75g OGTT) with maternal characteristics to predict low birth weight (LBW) established by Intergrowth-21st tables. METHODS: Prospective cohort study of pregnant women who was underwent 75g OGTT between 24 and 28.6 weeks. The 10th percentile fasting glucose of the population was determined at 65 mg/dL and women with risk factors that could modify fetal weight, including those related to intrauterine growth restriction, were excluded. Two groups were formed: group FG < p10 and group with normal fasting glucose. The main finding was the diagnosis of LBW. The association between FG < p10, maternal characteristics and LBW was established by multivariate logistic regression. The predictive performance of the models constructed was evaluated by receiver operating characteristic (ROC) curve and area under the curve (AUC) analysis. RESULTS: 349 women were eligible for study, of whom 66 (18.91%) had FG < p10; neonates in this group had lower birth weights (2947.28 g and 3138.26 g, p = 0.001), higher frequencies of LBW (25% and 6.81%, p < 0.001) and of weights < 2500 g in term births (8.6% and 2.3%, p = 0.034). The basal prediction model consisted of nulliparity by achieving an AUC of 60%, while the addition of FG < p10 resulted in the significant improvement of the previous model (AUC 72%, DeLong: p = 0.005). CONCLUSIONS: In pregnant women without factors that could modify fetal weight, the predictive model created by combining FG < p10 during 75g OGTT with nulliparity was significantly associated with increased risk of LBW. REGISTRATION: ClinicalTrials.gov: NCT04144595.

Analysis of HPV Integrations in Mexican Pre-Tumoral Cervical Lesions Reveal Centromere-Enriched Breakpoints and Abundant Unspecific HPV Regions.

Human papillomavirus (HPV) DNA integration is a crucial event in cervical carcinogenesis. However, scarce studies have focused on studying HPV integration (HPVint) in early-stage cervical lesions. Using HPV capture followed by sequencing, we investigated HPVint in pre-tumor cervical lesions. Employing a novel pipeline, we analyzed reads containing direct evidence of the integration breakpoint. We observed multiple HPV infections in most of the samples (92%) with a median integration rate of 0.06% relative to HPV mapped reads corresponding to two or more sequence breakages. Unlike cancer studies, most integrations events were unique (supported by one read), consistent with the lack of clonal selection. Congruent to other studies, we found that breakpoints could occur, practically, in any part of the viral genome. We noted that L1 had a higher frequency of rupture integration (25%). Based on host genome integration frequencies, we found previously reported integration sites in cancer for genes like FHIT, CSMD1, and LRP1B and putatively many new ones such as those exemplified in CSMD3, ROBO2, and SETD3. Similar host integrations regions and genes were observed in diverse HPV types within many genes and even equivalent integration positions in different samples and HPV types. Interestingly, we noted an enrichment of integrations in most centromeres, suggesting a possible mechanism where HPV exploits this structural machinery to facilitate integration. Supported by previous findings, overall, our analysis provides novel information and insights about HPVint.

Prediction of low birth weight with hypoglycemia in glucose tolerance test / Predicción de bajo peso al nacer con hipoglucemia en la prueba de tolerancia a la glucosa

ABSTRACT OBJECTIVE: Determine the value of the combination of fasting glucose less than the 10th percentile (FG < p10) during 75 gram oral glucose tolerance test (75g OGTT) with maternal characteristics to predict low birth weight (LBW) established by Intergrowth-21st tables. METHODS: Prospective cohort study of pregnant women who was underwent 75g OGTT between 24 and 28.6 weeks. The 10th percentile fasting glucose of the population was determined at 65 mg/dL and women with risk factors that could modify fetal weight, including those related to intrauterine growth restriction, were excluded. Two groups were formed: group FG < p10 and group with normal fasting glucose. The main finding was the diagnosis of LBW. The association between FG < p10, maternal characteristics and LBW was established by multivariate logistic regression. The predictive performance of the models constructed was evaluated by receiver operating characteristic (ROC) curve and area under the curve (AUC) analysis. RESULTS: 349 women were eligible for study, of whom 66 (18.91%) had FG < p10; neonates in this group had lower birth weights (2947.28 g and 3138.26 g, p = 0.001), higher frequencies of LBW (25% and 6.81%, p < 0.001) and of weights < 2500 g in term births (8.6% and 2.3%, p = 0.034). The basal prediction model consisted of nulliparity by achieving an AUC of 60%, while the addition of FG < p10 resulted in the significant improvement of the previous model (AUC 72%, DeLong: p = 0.005). CONCLUSIONS: In pregnant women without factors that could modify fetal weight, the predictive model created by combining FG < p10 during 75g OGTT with nulliparity was significantly associated with increased risk of LBW. REGISTRATION: ClinicalTrials.gov: NCT04144595.

RESUMEN OBJETIVO: Determinar el valor de la combinación de la glucosa en ayunas menor que el percentil 10 (GA < p10) durante la prueba de tolerancia oral a la glucosa con 75 gramos (PTG-75g) con características maternas para predecir bajo peso al nacer (BPN) establecido mediante tablas de Intergrowth-21st. MÉTODOS: Estudio de cohorte prospectivo de mujeres embarazadas que se realizaron PTG-75g entre las 24 y 28.6 semanas. Se determinó el percentil 10 de glucosa en ayunas de la población en 65 mg/dL y fueron excluidas aquellas mujeres con factores de riesgo que pudieran modificar el peso fetal incluyendo los relacionados con la restricción del crecimiento intrauterino. Se formaron dos grupos: grupo GA < p10 y grupo con glucosa en ayunas normal. El hallazgo principal fue el diagnóstico de BPN. La asociación entre GA < p10, características maternas y BPN se estableció mediante regresión logística multivariante. El desempeño predictivo de los modelos construidos fue evaluado por el análisis de la curva característica operativa del receptor (ROC) y del área bajo la curva (ABC). RESULTADOS: Fueron elegibles para estudio 349 mujeres, de las cuales 66 (18,91%) tuvieron GA < p10; los neonatos de este grupo tuvieron pesos al nacer más bajos (2947.28 g y 3138.26 g, p = 0,001), frecuencias más altas de BPN (25% y 6,81%, p < 0,001) y de pesos < 2500 g en nacimientos de término (8,6% y 2,3%, p = 0,034). El modelo basal de predicción consistió en nuliparidad al lograr un ABC del 60%, mientras que al añadir la GA < p10 se obtuvo la mejora significativa del modelo previo (ABC 72%, DeLong: p = 0,005). CONCLUSIONES: En mujeres embarazadas sin factores que pudieran modificar el peso fetal, el modelo predictivo creado combinando GA < p10 durante la PTG-75g con nuliparidad estuvo asociado significativamente con riesgo incrementado de BPN. REGISTRO: ClinicalTrials.gov: NCT04144595.

Multiple HPV Infections and Viral Load Association in Persistent Cervical Lesions in Mexican Women.

Persistent high-risk human papillomavirus (HR-HPV) infections play a major role in the development of invasive cervical cancer (CC), and screening for such infections is in many countries the primary method of detecting and preventing CC. HPV typing can be used for triage and risk stratification of women with atypical squamous cells of undetermined significance (ASC-US)/low-grade cervical lesions (LSIL), though the current clinical practice in Mexico is to diagnose CC or its preceding conditions mainly via histology and HR-HPV detection. Additional information regarding these HPV infections, such as viral load and co-infecting agents, might also be useful for diagnosing, predicting, and evaluating the possible consequences of the infection and of its prevention by vaccination. The goal of this follow-up hospital case study was to determine if HPV types, multiple HPV infections, and viral loads were associated with infection persistence and the cervical lesion grade. A total of 294 cervical cytology samples drawn from patients with gynecological alterations were used in this study. HPV types were identified by real-time PCR DNA analysis. A subset of HPV-positive patients was reevaluated to identify persistent infections. We identified HPV types 16, 18, and 39 as the most prevalent. One hundred five of the patients (59%) were infected with more than one type of HPV. The types of HPV associated with multiple HPV infections were 16, 18, and 39. In the follow-up samples, 38% of patients had not cleared the initially detected HPV infection, and these were considered persistent. We found here an association between multiple HPV infections and high viral loads with and infection persistence. Our findings suggest there are benefits in ascertaining viral load and multiple HPV infections status of HR-HPV infections for predicting the risk of persistence, a requirement for developing CC. These findings contribute to our understanding of HPV epidemiology and may allow screening programs to better assess the cancer-developing risks associated with individual HR-HPV infections.