Epigenetic modifications in the ferroptosis pathway in cord blood cells from newborns of smoking mothers and their influence on fetal growth.

Maternal smoking during pregnancy increases oxidative stress and decreases antioxidant capacity in newborns. Uncontrolled oxidative stress plays a role in fetal development disorders and in adverse perinatal outcomes. In order to identify molecular pathways involved in low fetal growth, epigenetic modifications in newborns of smoking and non-smoking mothers were examined. Low birth weight newborns of mothers who smoked more than 10 cigarettes per day during the first trimester of pregnancy and normal birth weight newborns of mothers who did not smoke during pregnancy were included in the study. DNA was extracted from umbilical cord blood of term newborns. 125 differentially methylated regions were identified by MeDIP-Seq. Functional analysis revealed several pathways, such as ferroptosis, that were enriched in differentially methylated genes after prenatal smoke exposure. GPX4 and PCBP1 were found to be hypermethylated and associated with low fetal growth. These epigenetic modifications in ferroptosis pathway genes in newborns of smoking mothers can potentially contribute to intrauterine growth restriction through the induction of cell death via lipid peroxidation of cell membranes. The identification of epigenetic modifications in the ferroptosis pathway sheds light on the potential mechanisms underlying the pathophysiology of low birth weight in infants born to smoking mothers.

Identification of miRNAs Involved in Foetal Growth Restriction Due to Maternal Smoking during Pregnancy.

INTRODUCTION: Smoking during pregnancy is associated with reduced foetal growth, amongst other effects. Epigenetic modification in the foetus and placenta during embryonic development as a result of changes in the function of miRNAs is one of the pathophysiological mechanisms responsible for this. This dysregulation may be due to environmental changes or toxins such as tobacco. OBJECTIVE: To study the impact of smoking during pregnancy and its role in intrauterine growth restriction via hypermethylated miRNAs. MATERIALS AND METHODS: The differences in methylation patterns for miRNAs in umbilical cord blood from low-birth-weight newborns of smoking mothers were compared with those from normal-weight newborns using MedIP-seq (StarArray). RESULTS: Seven hypermethylated miRNAs were identified in the epigenetic study of cord blood from low-birth-weight newborns of smoking mothers in our sample. The miRNAs found to be hypermethylated were: MIR7-1, MIR3918, MIR1244-1, MIR4721, MIR25, MIR93, MIR3656. CONCLUSION: Intrauterine exposure to tobacco induces hypermethylation-mediated miRNA silencing in low-birth-weight newborns by modifying the expression of factors involved in vascular development, growth, and adaptation to hypoxia.

Detection of Adverse Perinatal Outcomes at Term Delivery Using Ultrasound Estimated Percentile Weight at 35 Weeks of Gestation: Comparison of Five Fetal Growth Standards.

OBJECTIVE: To assess the predictive ability of the ultrasound estimated percentile weight (EPW) at 35 weeks of pregnancy to predict adverse perinatal outcomes (APOs) at term delivery according to 5 fetal growth standards, including population, population-customized, and international references. METHODS: This was a retrospective cohort study of 9,585 singleton pregnancies. Maternal clinical characteristics, fetal ultrasound data obtained at 35 weeks and pregnancy and perinatal outcomes were used to calculate EPWs to predict APOs according to: the customized and noncustomized (NC) Miguel Servet University Hospital (MSUH), the customized Figueras, the NC INTERGROWTH-21st, and the NC World Health Organization (WHO) international standards. APOs were defined as the occurrence of cesarean or instrumental delivery for nonreassuring fetal status, 5-min Apgar score < 7, arterial cord blood pH <7.10, or stillbirth. The predictive ability of EPW for APOs was analyzed using the area under the curve (AUC), and sensitivities were calculated for different false-positive rates (FPRs). RESULTS: For a 10% FPR, detection rates for total APOs ranged between 12.7% with the customized MSUH (AUC 0.52; 95% CI 0.50-0.55) and 14.4% with the NC MSUH standard (AUC 0.55; 95% CI 0.53-0.57) for EPW by ultrasound; and from 22.0% with the customized MSUH standard (AUC 0.60; 95% CI 0.58-0.63) to 27.8% with the NC WHO (AUC 0.65; 95% CI 0.63-0.68) for EPW at delivery. CONCLUSIONS: The predictive capacity of the EPW for APOS is limited and similar, by both ultrasound and at delivery, for the 5 growth standards, without significant differences between customized and NC standards.

Is it too late to quit? Premature placental aging and smoking / ¿Demasiado tarde para dejarlo? Envejecimiento placentario prematuro y tabaquismo

Objetive: The aim of this study was to determine the relationship between being smoker, ex-smoker or passive smoker and the risk of developing a placental Grannum-grade- III and the interval of time necessary between stop smoking and becomepregnant. Material and methods: A retrospective case-control analysis was performed for women with singleton pregnancy that had ultrasound in the third trimester, establishing two groups according to the classification of placental aging purposed by Grannum: Grannum grade III and Grannum grade I-II. In both groups,maternal characteristics and perinatal outcomes were studied, and also the risk of placental premature aging in pregnant smokers, ex-smokers and passive smokers. Results: Being smokers (p < 0.01) or suffer from a hypertensive disorder (p = 0.01)is associated with a higher risk of premature placental aging. Smokers who quit during early pregnancy and passive smokers behave like smokers,withno significant differences between them. We have also studied ex-smokers and the period of time between quit and became pregnant and the findings show a decrease of six times risk of to develop a Grannum grade III placenta for women who retires from smoke more than a year beforepregnancy. Conclusions: The main causes of developing a premature aging of the placenta are being a smoker and developing a hypertensive disorder. Smoking cessation should occur before becoming pregnant, ideally more than 18 months earlier, in order to avoid placentalabnormalities

Objetivo: el objetivo de este estudio fue determinar la relación entre ser fumadora, exfumadora o fumadora pasiva y el riesgo de desarrollar una placenta Grannum grado III y el intervalo de tiempo necesario entre dejar de fumar y quedarembarazada. Material y métodos: se realizó un análisis retrospectivo de casos y controles para mujeres con embarazos únicos a las que se realizó una ecografía en el tercer trimestre, estableciendo dos grupos según la clasificación de envejecimiento placentario propuesta por Grannum: Grannum grado III y Grannum grado I-II. En ambos grupos, se estudiaron las características maternas y los resultados perinatales, así como el riesgo de envejecimiento prematuro de placenta en mujeres embarazadas fumadoras, exfumadoras y fumadoraspasivas. Resultados: ser fumador (p < 0,01) o padecer un trastorno hipertensivo (p = 0,01) se asocia con mayor riesgo de envejecimiento prematuro de placenta. Las fumadoras que abandonan el hábito al inicio del embarazo y las fumadoras pasivas se comportan como fumadoras, sin diferencias significativas entre ellas. Asimismo se ha estudiado a las exfumadoras y el período de tiempo entre dejar de fumar y quedar embarazada y los hallazgos muestran un riesgo seis veces menor de desarrollar una placenta de grado III de Grannum en mujeres que abandonaron el hábito más de doce meses antes de quedar gestantes. Conclusiones: las principales causas de desarrollar envejecimiento prematuro de placenta son ser fumadora y desarrollar un trastorno hipertensivo. El abandono del hábito tabáquico debe producirse antes de quedar embarazada, idealmente más de 18 meses antes, para evitar anormalidades placentarias

Diagnóstico prenatal y repercusiones perinatales de la persistencia de vena cava superior izquierda. Serie de casos y revisión bibliográfica / Prenatal diagnosis and perinatal results of the persistent left superior vena cava. Cases series and literature review

Resumen Objetivo Describir las anomalías asociadas y las repercusiones perinatales de la persistencia de la vena cava superior izquierda en el feto y revisar la bibliografía. Materiales y métodos Estudio descriptivo, transversal y retrospectivo efectuado de enero de 2009 a diciembre 2012 en la Unidad de Diagnóstico Prenatal del Departamento de Obstetricia y Ginecología del Hospital Universitario Miguel Servet de Zaragoza, España. El estudio incluyó a todos los fetos con diagnóstico prenatal de persistencia de la vena cava superior izquierda establecido durante los controles gestacionales ecográficos. Resultados Se diagnosticaron 21 casos de persistencia de la vena cava superior izquierda entre las 20 y 35 semanas de embarazo. El 29% de los casos se detectó en la ecografía de las 20 semanas; 9 casos (43%) tuvieron anomalías cardiacas o extracardiacas asociadas y en 2 casos (10%) se encontró, además, trisomía 21, ambos con anomalías cardiacas asociadas. En 4 casos (19%) no hubo vena cava superior derecha. En los casos aislados la evolución fue favorable. Conclusiones Puesto que la persistencia de la vena cava superior izquierda se asocia, frecuentemente, con anomalías cardiacas y extracardiacas está justificada la ecografía morfológica fetal detallada y una ecocardiografía con posterior seguimiento antenatal. Si es aislada, la evolución obstétrica y el pronóstico perinatal serán favorables, como ha sucedido en los casos de persistencia de la vena cava superior izquierda aislados, con ausencia de vena cava superior derecha.

Abstract Objective To describe the associated anomalies and perinatal results in fetuses diagnosed with persistence of the left superior vena cava and to conduct a review of the literature. Materials and methods A descriptive, cross-sectional, retrospective study conducted between January 2009 and December 2012 in the Prenatal Diagnostic Unit of the Obstetrics and Gynecology Department at the Miguel Servet University Hospital in Zaragoza, Spain. The study included all fetuses with prenatal diagnosis of persistence of the left superior vena cava performed during gestational ultrasound controls in that period. Results 21 cases of persistence of the left superior vena cava were diagnosed between 20 and 35 weeks. Only 29% of the cases were detected on ultrasound at 20 weeks. 9 cases (43%) had associated cardiac or extracardiac anomalies and two cases (10%) associated trisomy 21, both with associated cardiac anomalies. In 4 cases (19%) there was an absence of right superior vena cava. In isolated cases, the evolution was favorable. Conclusions The presence of persistence of the left superior vena cava is frequently associated with cardiac and extracardiac abnormalities, so in the case of diagnosis, detailed fetal morphological ultrasound and echocardiogram are justified with subsequent antenatal follow-up. In the case of being isolated, it has an obstetric evolution and a favorable perinatal prognosis, results that were also presented in isolated persistence of the left superior vena cava cases with absence of right superior vena cava.

Prenatal diagnosis of umbilical cord cyst: Clinical significance and prognosis.

OBJECTIVE: Clarify the prognosis of the prenatal ultrasound diagnosis of umbilical cord cysts at any gestation trimester and to assess the ultrasound findings and chromosomal alterations associated to this entity. MATERIALS AND METHODS: Between 2003 and 2015 a multicenter study was carried out, collecting, in five centers in Spain, the associated findings and perinatal outcomes of 27 cases of umbilical cord cysts, regardless of gestational age of diagnosis. A bibliographic review was conducted to identify previous studies in order to compare them with our data. RESULTS: In our sample, the prognosis of this finding and the neonatal outcome, when isolated, is favorable, regardless of gestational age at diagnosis, multiple or unique presentation or vanishing or persistent cysts. CONCLUSIONS: It is important to properly assess the umbilical cord cyst and when is diagnosed, it is recommended to conduct a meticulous ultrasound examination searching for other associated malformations. In our study the prognosis of this finding seems to be favorable when isolated. Also, there is no relation between prognosis and gestation weeks at diagnosis. On the other hand, when we find this entity with associated anomalies, it is recommended to assess the need to carry out a karyotype.

Are congenital malformations more frequent in fetuses with intrahepatic persistent right umbilical vein? A comparative study.

OBJECTIVE: Persistent right umbilical vein (PRUV) is a vascular anomaly where the right umbilical vein remains as the only conduit that returns oxygenated blood to the fetus. It has classically been described as associated with numerous defects. We distinguish the intrahepatic variant (better prognosis) and the extrahepatic variant (associated with worse prognosis). The objective of this study was to compare rates of congenital malformations in fetuses with intrahepatic PRUV (I-PRUV) versus singleton pregnancies without risk factors. MATERIALS AND METHODS: A multicenter, crossover design, comparative study was performed between 2003 and 2013 on fetuses diagnosed with I-PRUV (n=56), and singleton pregnancies without congenital malformation risk factors (n=4050). RESULTS: Fifty-six cases of I-PRUV were diagnosed (incidence 1:770). A statistically significant association between I-PRUV and the presence of congenital malformations (odds ratio 4.321; 95% confidence interval 2.15-8.69) was found. This positive association was only observed with genitourinary malformations (odds ratio 3.038; 95% confidence interval 1.08-8.56). CONCLUSION: Our rate of malformations associated with I-PRUV (17.9%) is similar to previously published rates. I-PRUV has shown a significant increase in the rate of associated malformations, although this association has only been found to be statistically significant in the genitourinary system. Noteworthy is the fact that this comparative study has not pointed to a significant increase in the congenital heart malformation rate. Diagnosis of isolated I-PRUV does not carry a worse prognosis.

[Split hand-foot: sonographic detection at 12 weeks]. / Ectrodactilia: detección ecográfica a las 12 semanas.

Split hand-foot malformation is a rare disorder inherited in an autosomal dominant pattern with variable expression. Inour case, it was detected early by ultrasound in the twelfth week of gestation. The sonographic findings were bilateral split hands and feet. No other alterations were observed in the rest of the systematic assessment of the foetal anatomy. The pathological findings were consistent with the sonographic diagnosis. Prenatal diagnosis by corionic villus sampling was performed and voluntary termination of gestation decided.

Diagnóstico prenatal de catarata congénita / Prenatal diagnosis of congenital cataract

La catarata congénita (CC) es una patología poco frecuente en nuestro medio frente a los países en desarrollo donde constituye la etiología más frecuente de ceguera infantil. La prevención de deterioro visual debido a esta patología es parte del programa de la OMS cuyo objetivo es la eliminación de ceguera evitable en el año 2020. Presentamos el caso de una gestante en la que el diagnóstico prenatal se realizó en la ecografía morfológica. Si somos capaces de realizar este diagnóstico podremos evitar el deterioro precoz de la función visual del recién nacido. Así, la identificación de ambos cristalinos debe de formar parte de las estructuras a reconocer de forma obligada en la ecografía morfológica.

Congenital cataract is a rare disease in our environment opposite developing countries where it is the most frequent etiology of childhood blindness. Prevention of visual impairment due to this pathology is a part of the WHO programme whose objective is the elimination of avoidable blindness by the year 2020. We present the case of a pregnant woman that prenatal diagnosis was made on mid- trimester ultrasound. If we are able to perform this diagnosis, we will be able to prevent early deterioration of visual function of the newborn. Thus, identification of both crystalline should be part of the structures to recognize in the mid- trimester ultrasound.