Angiogenic imbalance in maternal and cord blood is associated with neonatal birth weight and head circumference in pregnancies with major fetal congenital heart defect.

OBJECTIVES: To ascertain whether abnormalities in neonatal head circumference and/or body weight are associated with levels of angiogenic/antiangiogenic factors in the maternal and cord blood of pregnancies with a congenital heart defect (CHD) and to assess whether the specific type of CHD influences this association. METHODS: This was a multicenter case-control study of women carrying a fetus with major CHD. Recruitment was carried out between June 2010 and July 2018 at four tertiary care hospitals in Spain. Maternal venous blood was drawn at study inclusion and at delivery. Cord blood samples were obtained at birth when possible. Placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) were measured in maternal and cord blood. Biomarker concentrations in the maternal blood were expressed as multiples of the median (MoM). RESULTS: PlGF, sFlt-1 and sEng levels were measured in the maternal blood in 237 cases with CHD and 260 healthy controls, and in the cord blood in 150 cases and 56 controls. Compared with controls, median PlGF MoM in maternal blood was significantly lower in the CHD group (0.959 vs 1.022; P < 0.0001), while median sFlt-1/PlGF ratio MoM was significantly higher (1.032 vs 0.974; P = 0.0085) and no difference was observed in sEng MoM (0.981 vs 1.011; P = 0.4673). Levels of sFlt-1 and sEng were significantly higher in cord blood obtained from fetuses with CHD compared to controls (mean ± standard error of the mean, 447 ± 51 vs 264 ± 20 pg/mL; P = 0.0470 and 8.30 ± 0.92 vs 5.69 ± 0.34 ng/mL; P = 0.0430, respectively). Concentrations of sFlt-1 and the sFlt-1/PlGF ratio in the maternal blood at study inclusion were associated negatively with birth weight and head circumference in the CHD group. The type of CHD anomaly (valvular, conotruncal or left ventricular outflow tract obstruction) did not appear to alter these findings. CONCLUSIONS: Pregnancies with fetal CHD have an antiangiogenic profile in maternal and cord blood. This imbalance is adversely associated with neonatal head circumference and birth weight. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Malformación arteriovenosa uterina. Un reto diagnóstico y terapéutico / Uterine arteriovenous malformation: A diagnostic and therapeutic challenge

Introducción: Las malformaciones arteriovenosas uterinas (MAVU) generalmente se presentan como sangrado vaginal en mujeres en edad fértil. Los antecedentes obstétricos o quirúrgicos uterinos y la ecografía son clave para la sospecha de esta dolencia. Existen múltiples tratamientos disponibles tanto médicos como quirúrgicos, con efectividad diversa. Material y métodos: Analizamos el proceso diagnóstico y terapéutico de 3 pacientes con episodios de metrorragias y antecedentes obstétricos o cirugías uterinas que presentaban MAVU. Resultados: En los 3 casos analizados, se realizó tratamiento médico como primera elección. Tras el fracaso del tratamiento médico mediante gestágenos orales, metilergometrina o ácido tranexámico, se realizó embolización transarterial con oclusión del nido o punto de la fístula. Conclusiones: Con base en nuestra experiencia, debido a la demora entre el diagnóstico y la amplia variedad de tratamientos de las MAVU, la embolización supraselectiva podría valorarse como uno de los tratamientos con mayor tasa de eficacia en un perfil de paciente que habitualmente no ha completado su deseo genésico. Aunque los resultados a corto plazo parece que no afectan a la fertilidad, sería importante realizar un seguimiento prospectivo de estas pacientes en lo que respecta a la consecución de nueva gestación o recidiva de MAVU.(AU)

Introduction: Uterine arteriovenous malformations (UAVM) usually present as vaginal bleeding in women of childbearing age. Obstetric or uterine surgical history and ultrasound are key when suspecting this pathology. There are multiple treatments available, including medical surgery or interventional radiology with different effectiveness. Material and methods: We analysed the diagnosis and management of three patients with episodes of vaginal bleeding and obstetric history, or uterine surgeries with a MAVU diagnosis. Results: In the three cases analysed, medical treatment was provided as first line treatment. After the failure of medical treatment with oral gestagens, methylergometrine, or tranexamic acid, transarterial embolization was performed with occlusion of the nidus or fistula point. Conclusions: Based on our experience, due to the delay between diagnosis and the wide variety of MAVU treatments, supraselective embolization could be assessed as one of the treatments with the highest rate of efficacy in a patient profile that has usually not fulfilled their reproductive desire. Although the short-term results do not seem to affect fertility, it is important to prospectively follow-up these patients regarding achievement of a new pregnancy or recurrence of MAVU.(AU)

Obstetric perinatal and maternal outcomes of monochorionic diamniotic twins following assisted reproductive techniques. Retrospective observational study / Resultados obstétricos perinatales y maternales en gemelos monocoriales diamnióticos conseguidos mediante técnicas de reproducción asistida. Estudio observacional retrospectivo

Introduction: Multiple and specifically monochorionic diamniotic (MCDA) pregnancies are related to maternal and foetal complications. The aim of this study is to evaluate obstetric and perinatal outcomes of MCDA after assisted reproductive techniques (ART). Methods: This is a case-control study comparing 23 MCDA twin pregnancies after ART (ART-MCDA) and 75 spontaneous MCDA (sMCDA). Maternal, obstetric, foetal, and perinatal outcomes variables including maternal age, prematurity, TTTS, sIUGR, TAPS, PROM, and neonatal weight were compared. Results: mean maternal age is higher in the ART-MCDA pregnancies, 38.0±.6 (OR=1.32(1.13–1.53)). Neonates weighing between 1500 and 2500g are more frequent in the sMCDA group and those weighing >2500g in the ART group (OR=0.47(0.22–0.97)). Foetuses born at between 32 and 37 weeks are more frequent in sMCDA pregnancies and those born >37 in the TRA group (OR=0.27(0.09–0.80)). These differences are lost when we adjust the results by maternal age. There were no differences in maternal, obstetric, or foetal complications. Conclusions: ART-MCDA are not associated with a higher number of maternal, obstetric or foetal complications if they are adjusted by maternal age. When they are not adjusted by maternal age, there would be better outcomes such as premature and neonatal weight in the ART group.(AU)

Antecedentes: El incremento de las técnicas de reproducción asistida (TRA) ha supuesto un aumento de las gestaciones gemelares en general, pero también de las monocoriales biamnióticas (MCBA), que se asocian a diversas complicaciones maternofetales. Estas complicaciones están bien estudiadas en gestaciones espontáneas, pero no en aquellas conseguidas mediante una TRA. Objetivo: Comparar la incidencia de complicaciones maternas, fetales, obstétricas y perinatales en gestaciones MCBA conseguidas de forma espontánea frente a aquellas conseguidas mediante TRA. Materiales y métodos: Estudio de casos-controles retrospectivo. Se han analizado 98 gestaciones gemelares MCBA controladas en la Unidad de Medicina Materno-Fetal del Servicio de Obstetricia del Hospital La Paz de Madrid entre los años 2015 y 2020. Resultados: La media de edad de las madres de las gestaciones MCBA conseguidas mediante TRA es mayor (OR=1,32 [1,13-1,53]). Los recién nacidos de peso entre 1.500-2.500g son más frecuentes en las gestaciones MCBA conseguidas de forma espontánea y los de >2.500g en las de TRA (OR=0,47 [0,22–0,97]). Los recién nacidos entre las 32-37 semanas son más frecuentes en las gestaciones gemelares MCBA espontáneas y los recién nacidos de >37 semanas en las de TRA (OR=0,27 [0,09-0,80]). Cuando estos resultados se ajustan por la edad materna dejan de ser estadísticamente significativos. Conclusiones: Las TRA no conllevan un aumento de las complicaciones en las gestaciones MCBA cuando se ajustan los resultados por la edad materna. Si no se ajustasen por la edad materna, las gestaciones MCBA conseguidas mediante TRA tendrían mejores resultados, con menos prematuridad y mayor peso del neonato.(AU)

Hernia diafragmática congénita en la gestación gemelar / Congenital diaphragmatic hernia in twin gestation

La hernia diafragmática congénita (HDC) en un feto de una gestación gemelar es una situación extremadamente infrecuente y de difícil manejo. La cirugía fetal no parece una opción válida debido al alto riesgo de rotura prematura de membranas y/o parto prematuro. La interrupción fetal selectiva debe hacerse antes de la semana 22, y tampoco está exenta de riesgos. El manejo expectante se asocia a la prematuridad y a fetos de bajo peso característicos de una gestación gemelar. Por tanto, el asesoramiento a los padres por parte de un equipo multidisciplinar es crucial en la toma de decisiones. La cesárea programada a término parece ser la vía más razonable en estos casos, sobre todo si es el segundo gemelo el afecto por HDC. Se presentan 6 casos de gestaciones gemelares bicoriales con uno de los fetos afecto de HDC con diferentes manejos y evoluciones obstétricas.(AU)

Congenital diaphragmatic hernia (CDH) in a twin gestation foetus is an extremely infrequent and difficult situation to manage. Foetal surgery does not seem to be an option due to the high risk of premature rupture of membranes and/or preterm delivery. Selective foetal termination must be done before 22 weeks and is also not without risk. Expectant management is associated with prematurity and low weight foetuses characteristic of twin gestation. Therefore, parental counselling by a multidisciplinary team is crucial in decision making. Programmed caesarean section at term seems to be the most reasonable route in these cases, especially if the second twin is affected by CDH. Six cases of bicornuate twin gestations with one of the foetuses affected by CDH are presented, with different management and obstetric outcomes.(AU)

Cómo reestructurar una Sección de Medicina Fetal en tiempos de pandemia COVID-19. Medidas de seguridad y limpieza de los equipos ecográficos / How to organize a Fetal Medicine Unit in the context of COVID-19 pandemic. Safe measures for obstetric scans and equipment cleaning

En situación de pandemia, los tres principios básicos en la atención sanitaria son priorizar los recursos, mantener el confinamiento del paciente para evitar la transmisión comunitaria y el colapso sanitario, y reducir la asistencia no prioritaria con el fin de evitar la exposición del paciente y de salvaguardar la salud del profesional sanitario. El control antenatal debe mantenerse durante el periodo de crisis sanitaria, independientemente del estado de alerta COVID-19. La ecografía obstétrica es una prueba fundamental para la toma de decisiones clínicas durante el embarazo, con un impacto en el manejo del binomio madre-feto y en el resultado perinatal, por lo que se ha de garantizar su realización. Con el fin de reducir las visitas presenciales al mínimo número posible, estas se intentarán organizar teniendo en cuenta los controles ecográficos establecidos. Basados en la evidencia científica y en las principales guías nacionales e internacionales, hemos elaborado este documento que incluye las principales recomendaciones para el cuidado antenatal de la gestante en el contexto de la pandemia por SARS-CoV-2. En él se recoge cómo debe reestructurarse una Sección de Medicina Fetal ante esta nueva situación, qué medidas de seguridad deben seguirse para la realización de las exploraciones ecográficas y técnicas invasivas, y de qué modo debe procederse para la limpieza y desinfección de los equipos ecográficos. Estas recomendaciones deberán adaptarse a los diferentes medios teniendo en cuenta la infraestructura del centro y sus recursos

During a pandemic, the three basic principles are. to prioritize medical resources, ensure patients' lockdown in order to avoid community transmission and prevent healthcare collapse, and keep the number of visits to an absolute minimum to avoid patient exposure and safeguard healthcare workers. Antenatal care must be maintained during a health crisis, regardless of the COVID-19 state of alert. Routine and specialist obstetric ultrasound scans are essential for clinical decision-making during pregnancy, as it has a direct impact on the management of mothers and fetuses and on the perinatal outcome. In an attempt to minimize in-person visits, these will be organized according to the established ultrasound schedule. Based on scientific evidence, and on existing main national and international guidelines, this document has been prepared, in which proposals and options are provided for managing pregnant women in the context of the SARS-CoV-2 pandemic. It includes how a Fetal Medicine Unit facing this health crisis should be restructured, what safety measures should be followed in the performance of obstetric scans and invasive procedures, and how ultrasound rooms, equipment and transducers should be cleaned and disinfected. These recommendations should be adapted to different units based on their resources and infrastructure

Genetic predisposition to fetal and neonatal cancer.

BACKGROUND: Neonatal tumors represent an extremely rare and heterogeneous disease with an unknown etiology. Due to its early onset, it has been proposed that genetic factors could play a critical role; however, germline genetic analysis is not usually performed in neonatal cancer patients PATIENTS AND METHODS: To improve the identification of cancer genetic predisposition syndromes, we retrospectively review clinical characteristics in 45 patients with confirmed tumor diagnosis before 28 days of age, and we carried out germline genetic analysis in 20 patients using next-generation sequencing and directed sequencing. RESULTS: The genetic studies did not find any germline mutation except patients diagnosed with bilateral retinoblastoma who harbored RB1 germline mutations. CONCLUSIONS: Our results suggest that genetic factors have almost no higher impact in most neonatal tumors. However, since the heterogeneity of the tumors and the small sample size analyzed, we recommend complementary and centralized germline studies to discard the early onset as an additional criterion to take into account to improve the identification of cancer genetic predisposition syndromes in neonates.

[How to organize a Fetal Medicine Unit in the context of COVID-19 pandemic. Safe measures for obstetric scans and equipment cleaning]. / Cómo reestructurar una Sección de Medicina Fetal en tiempos de pandemia COVID-19. Medidas de seguridad y limpieza de los equipos ecográficos.

During a pandemic, the three basic principles are. to prioritize medical resources, ensure patients' lockdown in order to avoid community transmission and prevent healthcare collapse, and keep the number of visits to an absolute minimum to avoid patient exposure and safeguard healthcare workers. Antenatal care must be maintained during a health crisis, regardless of the COVID-19 state of alert. Routine and specialist obstetric ultrasound scans are essential for clinical decision-making during pregnancy, as it has a direct impact on the management of mothers and fetuses and on the perinatal outcome. In an attempt to minimize in-person visits, these will be organized according to the established ultrasound schedule. Based on scientific evidence, and on existing main national and international guidelines, this document has been prepared, in which proposals and options are provided for managing pregnant women in the context of the SARS-CoV-2 pandemic. It includes how a Fetal Medicine Unit facing this health crisis should be restructured, what safety measures should be followed in the performance of obstetric scans and invasive procedures, and how ultrasound rooms, equipment and transducers should be cleaned and disinfected. These recommendations should be adapted to different units based on their resources and infrastructure.

Feasibility, tolerability, and safety of hysterosalpingo-foam sonography (hyfosy). multicenter, prospective Spanish study.

OBJECTIVE: To determine the feasibility,tolerability, and safety of the ultrasound assessment of tubal patency using foam as contrast. METHODS: This was a prospective multicenter study of 915 infertile nulliparous women scheduled for sonohysterosalpingography with foam instillation (HYFOSY) for tubal patency testing as a part of the fertility workup. Clinical and sonographic data were recorded into a web-shared database. Tubal patency, cervical catheterization, pain during the procedure and post-procedural complications were collected. Patients reported discomfort or pain experienced during the procedure with a visual analogue scale (VAS) score. RESULTS: Nine hundred fifteen women were included in the final analysis. Median age was 34 (range, 21-45) years and median body mass index was 23 (range, 16-41) kg/m2. Of 839 women, only 8(0.95 %) cases were abandoned due to impossibility of introducing the intracervical catheter. Most of the cervical os were easily cannulated with either paediatric nasogastric probes or special catheter for intrauterine insemination / sonohysterosalpingography 688/914(75.3 %). With a median instillation of 4 mL (range 1-16) of foam, both tubes were identified in 649/875 (70.9 %) patients, while unilateral patency was observed in 190/875 (20.8 %). Only 36/875 (3.9 %) of the women had bilateral tubal obstruction. The median VAS score for perception of pain during HyFoSy examination was 2 (range 0-10), and only 17 (1.9 %) of women reported severe pain (VAS ≥ 7). Pain was unrelated to tubal patency or tubal blockage. Unexpectedly, difficult cervical catheterizations that needed tenaculum, were more likely associated with mild pain during procedure [nasogastric probe group 176/289 (70.9 %) vs. insemination catheter group 166/399 (41.6 %) vs. tenaculum group 190/218(87.2 %) p < 0.001]. Finally, among 915 patients, we only noticed 3 (0.32 %) complications of the technique: two vasovagal episodes and a mild urinary infection. CONCLUSION: HYFOSY is a feasible, well-tolerated and safe technique for the evaluation of tubal patency in infertile women.

Cómo reestructurar una Sección de Medicina Fetal en tiempos de pandemia COVID-19. Medidas de seguridad y limpieza de los equipos ecográficos / How to organize a Fetal Medicine Unit in the context of COVID-19 pandemic. Safe measures for obstetric scans and equipment cleaning

En situación de pandemia, los tres principios básicos en la atención sanitaria son priorizar los recursos, mantener el confinamiento del paciente para evitar la transmisión comunitaria y el colapso sanitario, y reducir la asistencia no prioritaria con el fin de evitar la exposición del paciente y de salvaguardar la salud del profesional sanitario. El control antenatal debe mantenerse durante el periodo de crisis sanitaria, independientemente del estado de alerta COVID-19. La ecografía obstétrica es una prueba fundamental para la toma de decisiones clínicas durante el embarazo, con un impacto en el manejo del binomio madre-feto y en el resultado perinatal, por lo que se ha de garantizar su realización. Con el fin de reducir las visitas presenciales al mínimo número posible, estas se intentarán organizar teniendo en cuenta los controles ecográficos establecidos. Basados en la evidencia científica y en las principales guías nacionales e internacionales, hemos elaborado este documento que incluye las principales recomendaciones para el cuidado antenatal de la gestante en el contexto de la pandemia por SARS-CoV-2. En él se recoge cómo debe reestructurarse una Sección de Medicina Fetal ante esta nueva situación, qué medidas de seguridad deben seguirse para la realización de las exploraciones ecográficas y técnicas invasivas, y de qué modo debe procederse para la limpieza y desinfección de los equipos ecográficos. Estas recomendaciones deberán adaptarse a los diferentes medios teniendo en cuenta la infraestructura del centro y sus recursos

During a pandemic, the three basic principles are. to prioritize medical resources, ensure patients’ lockdown in order to avoid community transmission and prevent healthcare collapse, and keep the number of visits to an absolute minimum to avoid patient exposure and safeguard healthcare workers. Antenatal care must be maintained during a health crisis, regardless of the COVID-19 state of alert. Routine and specialist obstetric ultrasound scans are essential for clinical decision-making during pregnancy, as it has a direct impact on the management of mothers and fetuses and on the perinatal outcome. In an attempt to minimize in-person visits, these will be organized according to the established ultrasound schedule. Based on scientific evidence, and on existing main national and international guidelines, this document has been prepared, in which proposals and options are provided for managing pregnant women in the context of the SARS-CoV-2 pandemic. It includes how a Fetal Medicine Unit facing this health crisis should be restructured, what safety measures should be followed in the performance of obstetric scans and invasive procedures, and how ultrasound rooms, equipment and transducers should be cleaned and disinfected. These recommendations should be adapted to different units based on their resources and infrastructure

Multicenter prospective clinical study to evaluate children short-term neurodevelopmental outcome in congenital heart disease (children NEURO-HEART): study protocol.

BACKGROUND: Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns. While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. METHODS: Eligible participants are women presenting at 20 to < 37 weeks of gestation carrying a fetus with CHD. Maternal/neonatal recordings are performed at regular intervals, from the fetal period to 24 months of age, and include: placental and fetal hemodynamics, fetal brain magnetic resonance imaging (MRI), functional echocardiography, cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers. Neurodevelopmental assessment is planned at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. Target recruitment is at least 150 cases classified in three groups according to three main severe CHD groups: transposition of great arteries (TGA), Tetralogy of Fallot (TOF) and Left Ventricular Outflow Tract Obstruction (LVOTO). DISCUSSION: The results of NEURO-HEART study will provide the most comprehensive knowledge until date of children's neurologic prognosis in CHD and will have the potential for developing future clinical decisive tools and improving preventive strategies in CHD. TRIAL REGISTRATION: NCT02996630 , on 4th December 2016 (retrospectively registered).

[Study of pulmonary hypertension and long-term respiratory clinic in children with congenital diaphragmatic hernia]. / Estudio de la hipertensión pulmonar y la clínica respiratoria a largo plazo en los niños con hernia diafragmática congénita.

INTRODUCTION AND OBJECTIVES: The aim of this study is to identify respiratory clinic and pulmonary arterial hypertension (PAH) in congenital diaphragmatic hernia (CDH) and whether these could be predicted by prenatal measures. MATERIAL AND METHODS: We studied fetal ultrasound: Observed/expected Lung to Head Ratio (O/E LHR) and classified patients according to their outcome (group 1: O/E LHR <25%, group 2: 26-35%, group 3: 36-45%, group 4: >55%) as well as the severity of PAH (group 0: non-PAH, group 1: mild, group 2: moderate, group 3: severe) in echocardiograms at birth, 1st, 6th, 12th and 24 months of life. We also evaluated gestational age, weight, bronchodilator treatment and number of hospital admissions. RESULTS: 58 patients with CDH, 13 without prenatal diagnosis. 36 patients out of 45 had O/E LHR calculated at 22.4 ± 5.8 weeks. O/E LHR had significant association with the severity of PAH at birth and in the 1st, 6th, 12th and 24th months (p <0.05). At 6 months, only 30.4% had PAH without any association with a higher risk of hospital admission [OR 1.07 (0.11-10.1)] and only three patients (5.1%) required bronchodilator treatment. CONCLUSION: In CDH, PAH and the respiratory clinic improve over time, being uncommon the need for treatment as of the 6th month. O/E LHR predicts the presence and severity of PAH in short and long term.

INTRODUCCION Y OBJETIVOS: Nuestro objetivo es estudiar la presencia en hernia diafragmática congénita (HDC) de clínica respiratoria e hipertensión pulmonar (HTP) a largo plazo y si estas pueden predecirse prenatalmente. MATERIAL Y METODOS: Estudiamos en ecografía fetal: Lung to Head Ratio observado/esperado (LHR O/E) y clasificamos a los pacientes según su resultado (grupo 1: LHR O/E <25%, grupo 2: 26-35%, grupo 3: 36-45%, grupo 4: >55%) así como la gravedad de HTP (grupo 0: no HTP, grupo 1: leve, grupo 2: moderada, grupo 3: grave) en los ecocardiogramas al nacimiento, 1º, 6º, 12º y 24º meses de vida. Estudiamos también edad gestacional, peso, tratamiento broncodilatador y número de ingresos hospitalarios. RESULTADOS: Se identificaron 58 pacientes con HDC, 13 de ellos sin diagnóstico prenatal. De los 45 restantes, 36 tenían calculado el LHR O/E registrado a las 22,4 ± 5,8 semanas. El LHR O/E se relacionó significativamente con la gravedad de la HTP al nacimiento y en los meses 1º, 6º, 12º y 24º (p <0,05). A los 6 meses únicamente el 30,4% presentaban HTP sin que ello asociara más riesgo de ingresos hospitalarios [OR 1,07 (0,11-10,1)] y siendo solo n = 3 (5,1%) los que precisaban algún tipo de tratamiento broncodilatador. CONCLUSION: En HDC, la HTP y la clínica respiratoria mejoran con el tiempo, siendo infrecuente la necesidad de tratamiento a partir del 6º mes. El LHR O/E predice la presencia y gravedad de HTP a corto y largo plazo.

Estudio de la hipertensión pulmonar y la clínica respiratoria a largo plazo en los niños con hernia diafragmática congénita / Study of pulmonary hypertension and long-term respiratory clinic in children with congenital diaphragmatic hernia

Introducción y objetivos. Nuestro objetivo es estudiar la presencia en hernia diafragmática congénita (HDC) de clínica respiratoria e hipertensión pulmonar (HTP) a largo plazo y si estas pueden predecirse prenatalmente. Material y métodos. Estudiamos en ecografía fetal: Lung to Head Ratio observado/esperado (LHR O/E) y clasificamos a los pacientes según su resultado (grupo 1: LHR O/E 55%) así como la gravedad de HTP (grupo 0: no HTP, grupo 1: leve, grupo 2: moderada, grupo 3: grave) en los ecocardiogramas al nacimiento, 1º, 6º, 12º y 24º meses de vida. Estudiamos también edad gestacional, peso, tratamiento broncodilatador y número de ingresos hospitalarios. Resultados. Se identificaron 58 pacientes con HDC, 13 de ellos sin diagnóstico prenatal. De los 45 restantes, 36 tenían calculado el LHR O/E registrado a las 22,4 ± 5,8 semanas. El LHR O/E se relacionó significativamente con la gravedad de la HTP al nacimiento y en los meses 1º, 6º, 12º y 24º (p < 0,05). A los 6 meses únicamente el 30,4% presentaban HTP sin que ello asociara más riesgo de ingresos hospitalarios [OR 1,07 (0,11-10,1)] y siendo solo n = 3 (5,1%) los que precisaban algún tipo de tratamiento broncodilatador. Conclusión. En HDC, la HTP y la clínica respiratoria mejoran con el tiempo, siendo infrecuente la necesidad de tratamiento a partir del 6º mes. El LHR O/E predice la presencia y gravedad de HTP a corto y largo plazo

Introduction and objectives. The aim of this study is to identify respiratory clinic and pulmonary arterial hypertension (PAH) in congenital diaphragmatic hernia (CDH) and whether these could be predicted by prenatal measures. Material and methods. We studied fetal ultrasound: Observed/expected Lung to Head Ratio (O/E LHR) and classified patients according to their outcome (group 1: O/E LHR 55%) as well as the severity of PAH (group 0: non-PAH, group 1: mild, group 2: moderate, group 3: severe) in echocardiograms at birth, 1st, 6th, 12th and 24 months of life. We also evaluated gestational age, weight, bronchodilator treatment and number of hospital admissions. Results. 58 patients with CDH, 13 without prenatal diagnosis. 36 patients out of 45 had O/E LHR calculated at 22.4 ± 5.8 weeks. O/E LHR had significant association with the severity of PAH at birth and in the 1st, 6th, 12th and 24th months (p< 0.05). At 6 months, only 30.4% had PAH without any association with a higher risk of hospital admission [OR 1.07 (0.11-10.1)] and only three patients (5.1%) required bronchodilator treatment. Conclusion. In CDH, PAH and the respiratory clinic improve over time, being uncommon the need for treatment as of the 6th month. O/E LHR predicts the presence and severity of PAH in short and long term

[The role of fetal magnetic resonance imaging in the study of congenital diaphragmatic hernia]. / El papel de la resonancia magnética fetal en el estudio de la hernia diafragmática congénita.

INTRODUCTION AND OBJECTIVES: Different echographic and fetal magnetic resonance (MRI) measurements have been described in the diagnosis of associated malformations and the prognosis of congenital diaphragmatic hernia (CDH). We have reviewed our experience searching for useful isolated or combined parameters and how MRI can complement ultrasound. MATERIAL AND METHODS: We evaluated 29 fetuses with CDH. We examined ultrasonography: Lung to Head (LHR o/e) and in MRI: ipsilateral lung volume (IPV) and total expressed as percentage of observed / expected lung volume (VPT o/e) and percentage of herniated liver (PHH). We studied: survival, ECMO and associated malformations. RESULTS: LHR o/e was the measure that best predicted survival (p< 0.05). VPT o/e did not predict survival or the need of ECMO (p> 0.05). PHH ≥19% was related to the need of ECMO. IPV < 2 cc required ECMO more frequently (p< 0.018) and when it was 0 cc in all cases. No combination of MR measurements was superior to LHR o/e in prediction of survival. MRI complemented the ultrasound in 4 cases: diaphragmatic eventration diagnosed with HDC, right HDC with fluid in the sac that suggested thoracic cyst, differentiation between spleen and lung that measured together overestimated the LHR and/or suspicion of Cornelia de Lange due to facial malformations. CONCLUSIONS: Not a single or combined MRI measurement exceeds LHR o/e in survival prediction. MRI is related to prognosis and can be used to support ultrasound in making decisions. MRI occasionally provides complementary morphological information.

INTRODUCCION Y OBJETIVOS: Distintas medidas ecográficas y de resonancia magnética fetal (RM) han sido descritas en el diagnóstico de malformaciones asociadas y el pronóstico de la hernia diafragmática congénita (HDC). Hemos revisado nuestra experiencia buscando parámetros aislados o combinados útiles y cómo la RM puede complementar a la ecografía. MATERIAL Y METODOS: Evaluamos 29 fetos con HDC. Revisamos en ecografía: Lung to Head Ratio observado/esperado (LHR o/e) y en RM: volumen pulmonar ipsilateral (VPI) y total expresado como porcentaje del volumen pulmonar observado/esperado (VPT o/e) y porcentaje de hígado herniado (PHH). Estudiamos: supervivencia, oxigenación con membrana extracorpórea (ECMO) y malformaciones asociadas. RESULTADOS: El LHR o/e fue la medida que mejor predijo supervivencia (p< 0,05). El VPT o/e no predijo supervivencia ni la necesidad de ECMO (p> 0,05). El PHH ≥19% se relacionó con necesidad de ECMO. El VPI menor de 2 cc requirió ECMO más frecuentemente (p< 0,018) y cuando fue de 0 cc en todos los casos. Ninguna combinación de medidas de RM fue superior al LHR o/e en predicción de supervivencia. La RM complementó a la ecografía en 4 casos: eventración diafragmática diagnosticada como HDC, HDC derecha con líquido en el saco que sugería quiste torácico, diferenciación entre bazo y pulmón que medidos juntos sobreestimaba el LHR o/e y sospecha de síndrome de Cornelia de Lange por malformaciones faciales. CONCLUSIONES: Ninguna medida aislada o combinada de RM supera al LHR o/e en la predicción de supervivencia. La RM se relaciona con el pronóstico y puede usarse como apoyo de la ecografía en la toma de decisiones. La RM aporta ocasionalmente información morfológica complementaria.

El papel de la resonancia magnética fetal en el estudio de la hernia diafragmática congénita / The role of fetal magnetic resonance imaging in the study of congenital diaphragmatic hernia

Introducción y objetivos. Distintas medidas ecográficas y de resonancia magnética fetal (RM) han sido descritas en el diagnóstico de malformaciones asociadas y el pronóstico de la hernia diafragmática congénita (HDC). Hemos revisado nuestra experiencia buscando parámetros aislados o combinados útiles y cómo la RM puede complementar a la ecografía. Material y métodos. Evaluamos 29 fetos con HDC. Revisamos en ecografía: Lung to Head Ratio observado/esperado (LHR o/e) y en RM: volumen pulmonar ipsilateral (VPI) y total expresado como porcentaje del volumen pulmonar observado/esperado (VPT o/e) y porcentaje de hígado herniado (PHH). Estudiamos: supervivencia, oxigenación con membrana extracorpórea (ECMO) y malformaciones asociadas. Resultados. El LHR o/e fue la medida que mejor predijo supervivencia (p 0,05). El PHH ≥19% se relacionó con necesidad de ECMO. El VPI menor de 2 cc requirió ECMO más frecuentemente (p <0,018) y cuando fue de 0 cc en todos los casos. Ninguna combinación de medidas de RM fue superior al LHR o/e en predicción de supervivencia. La RM complementó a la ecografía en 4 casos: eventración diafragmática diagnosticada como HDC, HDC derecha con líquido en el saco que sugería quiste torácico, diferenciación entre bazo y pulmón que medidos juntos sobreestimaba el LHR o/e y sospecha de síndrome de Cornelia de Lange por malformaciones faciales. Conclusiones. Ninguna medida aislada o combinada de RM supera al LHR o/e en la predicción de supervivencia. La RM se relaciona con el pronóstico y puede usarse como apoyo de la ecografía en la toma de decisiones. La RM aporta ocasionalmente información morfológica complementaria (AU)

Introduction and objectives. Different echographic and fetal magnetic resonance (MRI) measurements have been described in the diagnosis of associated malformations and the prognosis of congenital diaphragmatic hernia (CDH). We have reviewed our experience searching for useful isolated or combined parameters and how MRI can complement ultrasound. Material and methods. We evaluated 29 fetuses with CDH. We examined ultrasonography: Lung to Head (LHR o/e) and in MRI: ipsilateral lung volume (IPV) and total expressed as percentage of observed / expected lung volume (VPT o/e) and percentage of herniated liver (PHH). We studied: survival, ECMO and associated malformations. Results. LHR o/e was the measure that best predicted survival (p 0.05). PHH ≥19% was related to the need of ECMO. IPV < 2 cc required ECMO more frequently (p < 0.018) and when it was 0 cc in all cases. No combination of MR measurements was superior to LHR o/e in prediction of survival. MRI complemented the ultrasound in 4 cases: diaphragmatic eventration diagnosed with HDC, right HDC with fluid in the sac that suggested thoracic cyst, differentiation between spleen and lung that measured together overestimated the LHR and/or suspicion of Cornelia de Lange due to facial malformations. Conclusions. Not a single or combined MRI measurement exceeds LHR o/e in survival prediction. MRI is related to prognosis and can be used to support ultrasound in making decisions. MRI occasionally provides complementary morphological information (AU)

[Mesenteric edema as a prenatal ultrasound sign of poor prognosis in gastroschisis]. / El edema mesentérico como signo ecográfico prenatal de mal pronóstico en gastrosquisis.

INTRODUCTION/AIM OF THE STUDY: Gastroschisis is a congenital malformation with an easy and early prenatal diagnosis, however, it has a variable post-natal outcome. Our aim was to determine if certain ultrasound markers or early delivery were related with a worse postnatal outcome. PATIENTS AND METHODS: Retrospective study of a cohort of patients with gastroschisis diagnosed between 2005-2014, with emphasis on prenatal ultrasounds, gestational age at delivery and post-natal outcome. Oligohydramnios, peel, mesenteric edema, fixed and dilated bowel with loss of peristalsis and small wall defect were considered ultrasonographic markers associated with poor prognosis. Outcome variables included: length-of-stay, complications, nutritional and respiratory factors. Non-parametric statistical analysis were used with p < 0,05 regarded as significant. RESULTS: Clinical charts of 30 patients with gastroschisis were reviewed (17M/13F). Gestational age at diagnosis was 20 (12-31) and at delivery 36 (31-39) weeks (33% of the patients over 36+3 weeks). A 73% of the patients presented at least one ultrasonographic marker factor during follow-up. Univariate analysis showed that mesenteric edema was associated with poor outcome variables: short-bowel syndrome (p= 0,000), PN-dependence (p= 0,007) and intestinal atresia (p= 0,02). The remaining risk factors analysed, including late delivery (> 36+3 weeks) were not associated with length-of-stay, ventilatory support, digestive autonomy, complications or mortality. CONCLUSIONS: Neither the presence of ultrasonographic markers classically associated with unfavorable outcomes, nor early delivery (< 36 weeks) resulted in worse postnatal outcome. Mesenteric edema was the only alarming ultrasound marker and that may suggest the need of closer follow-up.

INTRODUCCION: La gastrosquisis es una anomalía congénita de fácil diagnóstico prenatal y pronóstico postnatal variable. Nuestro objetivo es determinar si los signos ecográficos prenatales o el momento del parto se relacionan con peor pronóstico postnatal. PACIENTES Y METODOS: Se realiza un estudio retrospectivo de la cohorte de pacientes con gastrosquisis diagnosticados entre 2005-2014, registrando las ecografías prenatales, edad gestacional al parto y evolución postnatal. Se valoraron los hallazgos ecográficos prenatales: oligohidramnios, peel, edema mesentérico, asas fijas, aperistálticas y/o dilatadas y defecto pequeño de pared. Se consideraron variables resultado: la estancia hospitalaria, complicaciones, mortalidad y factores nutricionales y respiratorios. Se utilizaron pruebas no paramétricas, considerándose significativo un valor p < 0,05. RESULTADOS: Se analizaron 30 pacientes con gastrosquisis (17V/13M). La edad gestacional al diagnóstico fue de 20 (12-31) y al parto de 36 (31-39) semanas (33% mayores de 36+3 semanas). El 73% de los pacientes presentaron al menos un signo ecográfico de mal pronóstico. El análisis univariante asoció el edema mesentérico al síndrome de intestino corto (p= 0,000), falta de autonomía digestiva (p= 0,007) y mayor incidencia de atresia (p= 0,02). El resto de los factores, incluyendo la edad gestacional > 36+3 semanas, no tuvieron repercusión negativa en términos de estancia, asistencia respiratoria, autonomía digestiva, complicaciones o mortalidad. CONCLUSIONES: Ni la presencia de signos ecográficos considerados generalmente como desfavorables ni la tendencia a acercar el parto a la semana 36ª tienen repercusiones significativas en el curso postnatal. Únicamente el edema mesentérico parece un signo alarmante que sugiere la necesidad de aumentar la frecuencia de intervenciones (ecografías, pruebas de bienestar fetal).

El edema mesentérico como signo ecográfico prenatal de mal pronóstico en gastrosquisis / Mesenteric edema as a prenatal ultrasound sign of poor prognosis in gastroschisis

Introducción. La gastrosquisis es una anomalía congénita de fácil diagnóstico prenatal y pronóstico postnatal variable. Nuestro objetivo es determinar si los signos ecográficos prenatales o el momento del parto se relacionan con peor pronóstico postnatal. Pacientes y métodos. Se realiza un estudio retrospectivo de la cohorte de pacientes con gastrosquisis diagnosticados entre 2005-2014, registrando las ecografías prenatales, edad gestacional al parto y evolución postnatal. Se valoraron los hallazgos ecográficos prenatales: oligohidramnios, peel, edema mesentérico, asas fijas, aperistálticas y/o dilatadas y defecto pequeño de pared. Se consideraron variables resultado: la estancia hospitalaria, complicaciones, mortalidad y factores nutricionales y respiratorios. Se utilizaron pruebas no paramétricas, considerándose significativo un valor p< 0,05. Resultados. Se analizaron 30 pacientes con gastrosquisis (17V/13M). La edad gestacional al diagnóstico fue de 20 (12-31) y al parto de 36 (31-39) semanas (33% mayores de 36+3 semanas). El 73% de los pacientes presentaron al menos un signo ecográfico de mal pronóstico. El análisis univariante asoció el edema mesentérico al síndrome de intestino corto (p= 0,000), falta de autonomía digestiva (p= 0,007) y mayor incidencia de atresia (p= 0,02). El resto de los factores, incluyendo la edad gestacional > 36+3 semanas, no tuvieron repercusión negativa en términos de estancia, asistencia respiratoria, autonomía digestiva, complicaciones o mortalidad. Conclusiones. Ni la presencia de signos ecográficos considerados generalmente como desfavorables ni la tendencia a acercar el parto a la semana 36ª tienen repercusiones significativas en el curso postnatal. Únicamente el edema mesentérico parece un signo alarmante que sugiere la necesidad de aumentar la frecuencia de intervenciones (ecografías, pruebas de bienestar fetal) (AU)

Introduction/Aim of the study. Gastroschisis is a congenital malformation with an easy and early prenatal diagnosis, however, it has a variable post-natal outcome. Our aim was to determine if certain ultrasound markers or early delivery were related with a worse postnatal outcome. Patients and methods. Retrospective study of a cohort of patients with gastroschisis diagnosed between 2005-2014, with emphasis on prenatal ultrasounds, gestational age at delivery and post-natal outcome. Oligohydramnios, peel, mesenteric edema, fixed and dilated bowel with loss of peristalsis and small wall defect were considered ultrasonographic markers associated with poor prognosis. Outcome variables included: length-of-stay, complications, nutritional and respiratory factors. Non-parametric statistical analysis were used with p< 0,05 regarded as significant. Results. Clinical charts of 30 patients with gastroschisis were reviewed (17M/13F). Gestational age at diagnosis was 20 (12-31) and at delivery 36 (31-39) weeks (33% of the patients over 36+3 weeks). A 73% of the patients presented at least one ultrasonographic marker factor during follow-up. Univariate analysis showed that mesenteric edema was associated with poor outcome variables: short-bowel syndrome (p= 0,000), PN-dependence (p= 0,007) and intestinal atresia (p= 0,02). The remaining risk factors analysed, including late delivery (>36+3 weeks) were not associated with length-of-stay, ventilatory support, digestive autonomy, complications or mortality. Conclusions. Neither the presence of ultrasonographic markers classically associated with unfavorable outcomes, nor early delivery (<36 weeks) resulted in worse postnatal outcome. Mesenteric edema was the only alarming ultrasound marker and that may suggest the need of closer follow-up (AU)

[Intestinal complications in twin-to-twin transfusion syndrome (TTTS) treated by laser coagulation (LC)]. / Complicaciones intestinales en el síndrome de trasfusión feto fetal (STFF).

AIM OF THE STUDY: The hemodynamic imbalance due to placental vascular anastomoses in TTTS but also vascular changes generated after intrauterine treatment may lead to hypoxic-ischemic complications. Different intestinal complications in TTTS are reviewed in this paper. METHODS: Retrospective review of TTTS cases treated by laser coagulation (LC) from 2012-2015. Demographic data, fetal therapy, prenatal diagnosis (US, MRI) and perinatal outcome were recorded. We describe cases with intestinal complications and their postnatal management. Results are expressed by median and range. RESULTS: 29 monochorionic pregnancies with TTTS were treated (23 LC, 4 cord occlusions and 2 cord occlusions after LC). The diagnosis was made at 19 (16-26) weeks and 86% presented stage of Quintero ≥ II. In 70% of mothers survived at least one fetus with a median of 31 (24-37) weeks at birth. Four patients had intestinal complications (1 jejunal atresia, 2 ileal atresia, 1 perforated necrotizing enterocolitis), half of them had prenatal diagnosis. Postnatal resections of the affected segments and ostomies were performed. Intestinal transit was restored and there were no severe digestive sequelae after 21 (8-38) months of follow up. CONCLUSIONS: Different types of intestinal complications were associated with TTTS and LC. US and MRI enable prenatal diagnosis of these complications and this allows prompt decisions after birth.

INTRODUCCION: El desequilibrio hemodinámico secundario a la presencia de anastomosis vasculares placentarias en el STFF así como los cambios hemodinámicos generados durante y tras su tratamiento mediante fotocoagulación con láser (FC) puede dar lugar a complicaciones hipóxico-isquémicas en distintos sistemas. Revisamos nuestra experiencia en el tratamiento del STFF con FC y presentamos las complicaciones intestinales encontradas. MATERIAL Y METODOS: Estudio retrospectivo de casos tratados intraútero entre 2012 y 2015. Recogimos datos sociodemográficos, terapia fetal, pruebas diagnósticas prenatales (ecografía, RM) y resultados perinatales. Expresamos las medidas en medianas y rangos. RESULTADOS: Se procedió al tratamiento intraútero de 29 gestaciones monocoriales complicadas con STFF (23 FC, 4 oclusiones de cordón y 2 FC seguidas de oclusión). La edad gestacional en el procedimiento fue 19 (16-26) semanas y en el 86% de los casos se trataba de un estadio de Quintero ≥ II. El 70% de las madres tuvieron al menos 1 recién nacido vivo, con mediana de edad gestacional al parto de 31 (24-37) semanas. Presentaron problemas intestinales 4 pacientes (1 atresia yeyunal, 2 atresias ileales, 1 enterocolitis necrotizante con perforación), con sospecha prenatal diagnóstica en 2 de ellos. Postnatalmente se realizó resección del segmento afecto y ostomía. Actualmente se ha restablecido el tránsito intestinal en todos sin secuelas digestivas graves tras 21(8-38) meses de seguimiento. CONCLUSIONES: Hemos descrito distintos tipos de complicaciones intestinales asociadas al STFF y/o su tratamiento con FC. Es posible hacer el diagnóstico prenatal de dichas complicaciones mediante ecografía y RM. Su conocimiento pone al cirujano en alerta y es importante en la toma de decisiones postnatales.

Complicaciones intestinales en el síndrome de trasfusión feto fetal (STFF) / Intestinal complications in twin-to-twin transfusion syndrome (TTTS) treated by laser coagulation (LC)

Introducción: El desequilibrio hemodinámico secundario a la presencia de anastomosis vasculares placentarias en el STFF así como los cambios hemodinámicos generados durante y tras su tratamiento mediante fotocoagulación con láser (FC) puede dar lugar a complicaciones hipóxico-isquémicas en distintos sistemas. Revisamos nuestra experiencia en el tratamiento del STFF con FC y presentamos las complicaciones intestinales encontradas. Material y métodos: Estudio retrospectivo de casos tratados intraútero entre 2012 y 2015. Recogimos datos sociodemográficos, terapia fetal, pruebas diagnósticas prenatales (ecografía, RM) y resultados perinatales. Expresamos las medidas en medianas y rangos. Resultados: Se procedió al tratamiento intraútero de 29 gestaciones monocoriales complicadas con STFF (23 FC, 4 oclusiones de cordón y 2 FC seguidas de oclusión). La edad gestacional en el procedimiento fue 19 (16-26) semanas y en el 86% de los casos se trataba de un estadio de Quintero ≥ II. El 70% de las madres tuvieron al menos 1 recién nacido vivo, con mediana de edad gestacional al parto de 31 (24-37) semanas. Presentaron problemas intestinales 4 pacientes (1 atresia yeyunal, 2 atresias ileales, 1 enterocolitis necrotizante con perforación), con sospecha prenatal diagnóstica en 2 de ellos. Postnatalmente se realizó resección del segmento afecto y ostomía. Actualmente se ha restablecido el tránsito intestinal en todos sin secuelas digestivas graves tras 21(8-38) meses de seguimiento. Conclusiones: Hemos descrito distintos tipos de complicaciones intestinales asociadas al STFF y/o su tratamiento con FC. Es posible hacer el diagnóstico prenatal de dichas complicaciones mediante ecografía y RM. Su conocimiento pone al cirujano en alerta y es importante en la toma de decisiones postnatales

Aim of the study: The hemodynamic imbalance due to placental vascular anastomoses in TTTS but also vascular changes generated after intrauterine treatment may lead to hypoxic-ischemic complications. Different intestinal complications in TTTS are reviewed in this paper. Methods: Retrospective review of TTTS cases treated by laser coagulation (LC) from 2012-2015. Demographic data, fetal therapy, prenatal diagnosis (US, MRI) and perinatal outcome were recorded. We describe cases with intestinal complications and their postnatal management. Results are expressed by median and range. Results: 29 monochorionic pregnancies with TTTS were treated (23 LC, 4 cord occlusions and 2 cord occlusions after LC). The diagnosis was made at 19(16-26) weeks and 86% presented stage of Quintero ≥ II. In 70% of mothers survived at least one fetus with a median of 31 (24-37) weeks at birth. Four patients had intestinal complications (1 jejunal atresia, 2 ileal atresia, 1 perforated necrotizing enterocolitis), half of them had prenatal diagnosis. Postnatal resections of the affected segments and ostomies were performed. Intestinal transit was restored and there were no severe digestive sequelae after 21 (8-38) months of follow up. Conclusions: Different types of intestinal complications were associated with TTTS and LC. US and MRI enable prenatal diagnosis of these complications and this allows prompt decisions after birth

Vaginal progesterone as maintenance treatment after an episode of preterm labour (PROMISE) study: a multicentre, double-blind, randomised, placebo-controlled trial.

OBJECTIVE: To evaluate whether maintenance treatment with vaginal progesterone after an arrested preterm labour reduces the incidence of preterm delivery. DESIGN: Multicentre, randomised, double-blind, placebo-controlled trial. SETTING: Twelve tertiary care centres in Spain. POPULATION: A total of 265 women with singleton pregnancy, preterm labour successfully arrested with tocolytic treatment, and cervical length of <25 mm. METHODS: Randomisation was stratified by gestational age (from 24.0 to <31.0 weeks of gestation and from 31.0 to <34.0 weeks of gestation) and centre. Patients were randomly assigned, in a 1 : 1 ratio, to either daily vaginal capsules of 200 mg progesterone or placebo until delivery or 36.6 weeks of gestation, whichever occurred first. MAIN OUTCOME MEASURES: Primary outcome was delivery before 34.0 and 37.0 weeks of gestation. Secondary outcomes were discharge-to-delivery time, readmissions because of preterm labour, emergency service use, and neonatal morbidity and mortality. RESULTS: From June 2008 through June 2012, 1419 women were screened: 472 met the inclusion criteria and 265 were randomised. The final analysis included 258 women: 126 in the progesterone group and 132 in the placebo group. There were no significant differences between the progesterone and placebo groups in terms of delivery at <34 weeks of gestation [9/126 (7.1%) versus 10/132 (7.6%), P = 0.91] or <37 weeks of gestation [36/126 (28.6%) versus 29/132 (22.0%), P = 0.22]. There were no differences observed between groups when considering the two strata of gestational age at inclusion. CONCLUSIONS: A maintenance treatment of 200 mg of daily vaginal progesterone capsules in women discharged home after an episode of arrested preterm labour did not significantly reduce the rate of preterm delivery. TWEETABLE ABSTRACT: Maintenance progesterone in 258 women after arrested PTL showed no benefit.