Fetal aortic valvuloplasty as the first step in a complex therapeutic strategy.

BACKGROUND: Fetal aortic valvuloplasty (FAV) is proposed to prevent hypoplastic left heart syndrome due to fetal critical aortic stenosis. OBJECTIVE: to report our experience on FAV as the first step in a complex therapeutic strategy. METHOD: Series of patients with FAV over an 18-year period. RESULTS: 27 FAVs were performed in 26 fetuses, with technical success in 82% (22/27) and periprocedural fetal demise in 22% (6/27), decreasing to 15% in the second half-cohort. Loss to follow-up was due to birth or postnatal therapy in other centers (5) and termination of pregnancy (1), A normal-sized LV at birth was observed in 46% (6/13), 4 neonates underwent aortic valvuloplasty and 2 cardiac surgeries, with 5/6 achieving biventricular circulation at 28 days, and 3 transplant-free survival at mid-term follow-up. The 7/13 born with a borderline LV underwent LV rehabilitation strategy, with survival at 28 days in 4/7 and at mid-term in 3: one with biventricular circulation, one with a ventricle-and-a-half repair, and one lost to follow-up. CONCLUSION: FAV was feasible in most cases, with no maternal complications, and biventricular circulation at 28 days in ∼40% of survivors. After FAV, a diverse range of postnatal cardiac interventions are performed, reflecting the challenging innovation in current cardiovascular therapy.

Monochorionic twin pregnancy from the perspective of the theory of complexity. / El embarazo gemelar monocorial desde la perspectiva de la teoría de la complejidad.

In practice, it is very common to associate monochorionic (MC) twin pregnancies with complex or complicated pregnancies, using both terms interchangeably. However, these are not synonyms; dynamism is the protagonist in complex systems, but not in complicated ones. In order to understand a MC pregnancy as a complex system, it is necessary to first look into its main characteristics. The placenta is one of the main sources of problems. Then, the MC pregnancy has to be analyzed from the perspective of complexity, identifying the system characteristics and its complications as emergent properties.

En la práctica, es muy frecuente asociar las gestaciones gemelares monocoriales (MC) con embarazos complejos o complicados, utilizando ambos términos en forma intercambiable. Sin embargo, no lo son; el dinamismo es protagonista en los sistemas complejos, pero no en los complicados. Para entender a la embarazada con una gestación MC como un sistema complejo, primero se desarrollarán las características principales de los embarazos MC; su placenta es una de las principales responsables de los problemas. Luego se analizará el embarazo MC desde la complejidad, identificando las características del sistema y sus complicaciones como propiedades emergentes.

Cervical-length as a screening for spontaneous preterm birth in uncomplicated twins: one vs. serial measurements.

OBJECTIVE: While cervical length (CL) provides an effective screening tool for spontaneous preterm birth in singletons, the performance in twins is still controversial. Our aim was twofold. First, to compare the performance of a single CL measurement at mid-gestation (∼20 weeks) versus serial measurements as a predictor of spontaneous preterm birth < 34 weeks in uncomplicated twin pregnancies. Second, to describe the performance of a single CL at ∼24, ∼28 and ∼32 weeks. MATERIAL AND METHODS: cohort study of twins followed at Hospital Italiano de Buenos Aires from 2013 to 2017. Inclusion criteria were dichorionic or monochorionic diamniotic twins with CL measurement between 18 and 33 + 6 weeks with available data of the delivery. Exclusion criteria included any of the following complications: iatrogenic preterm delivery <34 weeks, cerclage, fetal growth restriction, fetal death, structural anomalies, polyhydramnios, twin-twin transfusion syndrome, selective fetal growth restriction, twin anemia-polycythemia sequence, and twin reversed arterial perfusion sequence. Spontaneous preterm birth was defined as spontaneous delivery < 34 weeks. Two different cutoffs were used to classify CL as short (positive screening) or normal (negative screening): (a) a fixed cutoff of 25 mm at any gestational age (GA). The screening was considered positive if any CL measurement was <25 mm; and (b) a GA adjusted cutoff to a 10% false positive rate (FPR). The 10% FPR for each GA was calculated and the screening was considered positive if any of the CL measurements were below this 10% FPR cutoff. We report sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio and area under the ROC curve. RESULTS: Among 777 twins followed in our Unit, 381 met exclusion criteria and 18 were excluded due to incomplete follow-up. We included 378 patients, 284 (75%) dichorionic and 94 (25%) monochorionic. The performance of one CL at 20 weeks showed a sensitivity ≤ 20% with an area under the ROC curve of 0.58 (95% CI, 0.45-0.70), while the performance of serial measurements showed a sensitivity of 58.8% (95% CI, 40.7-75.4) with an area under the ROC curve of 0.70 (95% CI, 0.61-0.79) (p < .001). The analyses of the performance of a single CL at ∼24, ∼28 and ∼32 weeks showed similar AUC than the serial measurements and, for a FPR = 10%, the performance of one measurement at 24 and 32 weeks showed a sensitivity of 30% (95% CI, 14.7-49.4) and 31.6% (95% CI, (12.6-56.6), while the measurement at 28 weeks showed a sensitivity of 48.3% (95% CI, (29.4-67.5). CONCLUSION: Serial measurements showed a better performance than a single one in mid-gestation. Moreover, among single measurements the CL in mid-gestation showed the poorest performance, while the 28 weeks assessment detected half of the preterm deliveries. However, all the strategies showed modest performances.

Performance of the cervical shortening for prediction of spontaneous preterm birth in uncomplicated twins.

OBJECTIVE: There is a lack of consensus about the management of twins with significant cervical length (CL) shortening, especially if CL is above 25 mm. Therefore, it is important to define "abnormal" CL change over time, and to compare the performance of different strategies. The aim of this study was twofold, to describe the performance of the cervical shortening and that of an integrated strategy that includes both the cervical shortening and a fixed CL cutoff <25 mm in any measurement as predictor of spontaneous PTB (sPTB) < 34 weeks in uncomplicated twin pregnancies. MATERIAL AND METHODS: Retrospective cohort study of twins followed in our Twins Clinic at Hospital Italiano de Buenos Aires from 2013 to 2017. Inclusion criteria were dichorionic or monochorionic diamniotic twins with CL measurement between 18 and 33 + 6 weeks with available data of the delivery. Exclusion criteria included any of the following complications: iatrogenic preterm delivery <34 weeks, cerclage, fetal growth restriction, fetal death, structural anomalies, polyhydramnios, twin-twin transfusion syndrome, selective fetal growth restriction, twin anemia-polycythemia sequence, and twin reversed arterial perfusion sequence. Spontaneous preterm birth was defined as spontaneous delivery <34 weeks. Cervical shortening was analyzed in the following periods: 20-24 weeks, 20-28 weeks, 24-28 weeks, 24-32 weeks and 28-32 weeks. Cervical changes were analyzed as velocity of shortening over time (mm/week) and as the ratio of shortening over time (%/week). ROC curves for each period were constructed and two different cutoffs were used to classify changes of the CL as positive or negative screening: a) the shortening of CL associated to the highest value of the Youden Index and b) fixing a 10% false positive rate (FPR). For the second objective, we analyzed an integrated strategy considering a fixed cutoff of 25 mm at any GA and/or a significant shortening. The screening was considered positive if any CL measurement was <25 mm at any GA or there was a shortening of the CL ≥ the cutoff obtained for each period. We report sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio and area under the ROC curve. RESULTS: We included 378 patients and 1417 measurements, 284 (75%) dichorionic and 94 (25%) monochorionic. Between 20 and 28 weeks, with a change in CL cutoff = 1.6 mm/week or 4.1%/week the detection rate was 54.2% (32.8-74.4%) and the specificity 80.5% (75.1-85.1%) and 83.5% (78.5-87.8%) respectively. In the integrated strategy, the detection rate was 65.7% (47.8-80.9%) and the specificity 69 (63.7-74). All the ROC curves of the periods studied showed an AUC < 0.7. In the group of patients that delivered preterm the initial mean CL was shorter than in the term group, 39 (±12) mm vs. 43 (± 7.7) mm (p = .02) and the most important change in CL was at 20-24 weeks both in the velocity and in the ratio of shortening over time. Conversely, patients that delivered at term showed a higher change in CL in the third trimester. CONCLUSION: The performance of all the strategies analyzed as a predictor of sPTB <34 weeks was moderate. The period 20-28 weeks detected half of the patients at risk with a FPR around 10-20% and the integrated strategy increased the sensitivity up to a detection of two thirds of the patients at risk but with a FPR of ∼30%. Future analyses need to explore other strategies to improve the performance and to really identify the patients at higher risk.

Actualización del diagnóstico prenatal y cirugía fetal del mielomeningocele / Update on prenatal diagnosis and fetal surgery for myelomeningocele

A partir del estudio seminal Management of Myelomeningocele Study en el año 2011, el cual demostró que la reparación prenatal del defecto del mielomeningocele antes de la semana 26 mejoraba los resultados neurológicos, la cirugía fetal fue incorporada dentro de las opciones de estándar de cuidado. Así, el diagnóstico prenatal del mielomeningocele dentro de la ventana terapéutica se convirtió en un objetivo obligatorio y, por ello, se intensificó la investigación de estrategias de tamizaje, sobre todo, en el primer trimestre. Además, se desarrollaron distintas técnicas de cirugía fetal para mejorar los resultados neurológicos y disminuir los riesgos maternos. El objetivo de la siguiente revisión es actualizar los avances en tamizaje y diagnóstico prenatal en el primer y segundo trimestre, y en cirugía fetal abierta y fetoscópica del mielomeningocel

A seminal study titled Management of Myelomeningocele Study, from 2011, demonstrated that prenatal myelomeningocele defect repaired before 26 weeks of gestation improved neurological outcomes; based on this study, fetal surgery was introduced as a standard of care alternative. Thus, prenatal myelomeningocele diagnosis within the therapeutic window became a mandatory goal; therefore, research efforts on screening strategies were intensified, especially in the first trimester. In addition, different fetal surgery techniques were developed to improve neurological outcomes and reduce maternal risks. The objective of this review is to provide an update on the advances in prenatal screening and diagnosis during the first and second trimesters, and in open and fetoscopic fetal surgery for myelomeningocele

Update on prenatal diagnosis and fetal surgery for myelomeningocele. / Actualización del diagnóstico prenatal y cirugía fetal del mielomeningocele.

A seminal study titled Management of Myelomeningocele Study, from 2011, demonstrated that prenatal myelomeningocele defect repaired before 26 weeks of gestation improved neurological outcomes; based on this study, fetal surgery was introduced as a standard of care alternative. Thus, prenatal myelomeningocele diagnosis within the therapeutic window became a mandatory goal; therefore, research efforts on screening strategies were intensified, especially in the first trimester. In addition, different fetal surgery techniques were developed to improve neurological outcomes and reduce maternal risks. The objective of this review is to provide an update on the advances in prenatal screening and diagnosis during the first and second trimesters, and in open and fetoscopic fetal surgery for myelomeningocele.

A partir del estudio seminal Management of Myelomeningocele Study en el año 2011, el cual demostró que la reparación prenatal del defecto del mielomeningocele antes de la semana 26 mejoraba los resultados neurológicos, la cirugía fetal fue incorporada dentro de las opciones de estándar de cuidado. Así, el diagnóstico prenatal del mielomeningocele dentro de la ventana terapéutica se convirtió en un objetivo obligatorio y, por ello, se intensificó la investigación de estrategias de tamizaje, sobre todo, en el primer trimestre. Además, se desarrollaron distintas técnicas de cirugía fetal para mejorar los resultados neurológicos y disminuir los riesgos maternos. El objetivo de la siguiente revisión es actualizar los avances en tamizaje y diagnóstico prenatal en el primer y segundo trimestre, y en cirugía fetal abierta y fetoscópica del mielomeningocele.

Cardiopatías congénitas, diagnóstico y manejo prenatal / Congenital heart disease, prenatal diagnosis and management

Dentro de las malformaciones congénitas, las cardiopatías son las anomalías más frecuentes y se asocian a una elevada morbimortalidad perinatal y a largo plazo. El objetivo de esta actualización es revisar la tasa de detección prenatal, las características del tamizaje a lo largo del embarazo, tanto en el primero como en el segundo trimestre, las indicaciones de ecocardiografía avanzada, y establecer un algoritmo de manejo ante el diagnóstico prenatal de una cardiopatía congénita. Se discutirán los estudios invasivos y no invasivos que pueden realizarse y el seguimiento obstétrico. Finalmente, se revisarán las características principales de la terapia fetal en anomalías cardíacas, tanto intervencionismo cardíaco como el tratamiento intrauterino de las arritmias.

Among congenital malformations, heart defects are the most common type of anomaly, and these are associated with a high perinatal, long-term morbidity and mortality. The objective of this update was to review the rate of prenatal detection, screening characteristics throughout the pregnancy, in both the first and second trimesters, indications for advanced echocardiography, and to establish a management algorithm in case of prenatal diagnosis of a congenital heart disease. Potential invasive and non-invasive tests and obstetric follow-up will be discussed here. Finally, the main characteristics of fetal therapy in heart anomalies will be reviewed, both cardiac interventions and intrauterine treatment of arrhythmias.

Congenital heart disease, prenatal diagnosis and management. / Cardiopatías congénitas, diagnóstico y manejo prenatal.

Among congenital malformations, heart defects are the most common type of anomaly, and these are associated with a high perinatal, longterm morbidity and mortality. The objective of this update was to review the rate of prenatal detection, screening characteristics throughout the pregnancy, in both the first and second trimesters, indications for advanced echocardiography, and to establish a management algorithm in case of prenatal diagnosis of a congenital heart disease. Potential invasive and non-invasive tests and obstetric follow-up will be discussed here. Finally, the main characteristics of fetal therapy in heart anomalies will be reviewed, both cardiac interventions and intrauterine treatment of arrhythmias.

Dentro de las malformaciones congénitas, las cardiopatías son las anomalías más frecuentes y se asocian a una elevada morbimortalidad perinatal y a largo plazo. El objetivo de esta actualización es revisar la tasa de detección prenatal, las características del tamizaje a lo largo del embarazo, tanto en el primero como en el segundo trimestre, las indicaciones de ecocardiografía avanzada, y establecer un algoritmo de manejo ante el diagnóstico prenatal de una cardiopatía congénita. Se discutirán los estudios invasivos y no invasivos que pueden realizarse y el seguimiento obstétrico. Finalmente, se revisarán las características principales de la terapia fetal en anomalías cardíacas, tanto intervencionismo cardíaco como el tratamiento intrauterino de las arritmias.

Sonographic detection of open spina bifida in the first trimester: review of the literature.

In the beginnings, sonographic diagnosis of open spina bifida (OSB) relied on the meticulous scanning of the fetal vertebrae for abnormalities but many defects were missed. After the mid-1980s, however, with the description of the intracranial findings in the second trimester (the "lemon sign" and the "banana sign"), the prenatal diagnosis of OSB was enhanced. In the last 2 decades, there has been widespread uptake of routine ultrasound examination in the first trimester of pregnancy with the purpose of the measurement of fetal crown-rump length to determine gestational age, to screen for trisomy 21 and other aneuploidies, mainly with the nuchal translucency, and for diagnosis of many major abnormalities. Many papers were published focusing on early diagnosis of myelomeningocele (MMC), and the objective of this review is to summarize the different techniques described regarding prenatal diagnosis of OSB in the first trimester of pregnancy.

Discordance of cord insertions as a predictor of discordant fetal growth in monochorionic twins.

INTRODUCTION: The type of cord insertion within monochorionic twin pairs could be different. The purpose of study is to evaluate the association of different combinations of placental umbilical cord insertions with birth weight discordance in a large cohort of monochorionic twins. METHODS: All consecutive monochorionic placentas from either uncomplicated twin pregnancies or with fetal weight discordance examined and injected with color dye at our centers were included in this study (n = 374). Marginal or velamentous cord insertions were defined as abnormal. Placentas were categorized as concordant when the cord insertions of both fetuses were either normal-normal or abnormal-abnormal, and as discordant when they were normal-abnormal. Birth weight discordance was defined as a difference in birth weight of each twin ≥25%. The association of different cord insertion combinations with birth weight discordance was analyzed. RESULTS: The rate of discordant cord insertions was 55% (204/374) in monochorionic twins. A highly significant association between discordant cord insertions and discordant birth weight was observed (p < 0.01). The odds ratios (OR) for birth weight discordance in the discordant cord insertion group compared with the concordant group were 2.3 (95% CI: 1.2-4.4) for the normal-marginal and 5.9 (95% CI: 3.8-10.4) for the normal-velamentous cord insertion subgroup. Discordant cord insertions are associated with the occurrence of unequal placental sharing (OR 4.3, 95%CI 2.7-6.9). DISCUSSION: Discordance of cord insertions is associated with discordance of birth weight and may therefore be an important indicator of adverse outcome in monochorionic twins.

Stomach in Contact with the Bladder: A Sonographic Sign of Left Congenital Diaphragmatic Hernia.

The evaluation of the characteristics of the fetal stomach should be part of every routine prenatal ultrasound after 11 weeks. A position that has not been previously described in the literature is the stomach in contact with the bladder. We describe 6 cases with the ultrasonographic finding of the stomach in contact with the bladder, all of them in fetuses with left-sided congenital diaphragmatic hernia. Even though the reasons for this striking position of the stomach are not clear, our series highlights the fact that the visualization of the stomach in contact with the bladder may be a specific sonographic marker of congenital diaphragmatic hernia.

[Advances in fetal therapy]. / Avances en terapia fetal.

Fetal therapy may be needed in certain clinical settings with the primary indication to improve perinatal or long-term outcomes for the fetus or the newborn. It can be classified in pharmacotherapy or non-invasive, and invasive therapy. The first one involves the administration of drugs to the mother that cross the placenta and get to the fetus, a non-invasive approach. On the other hand, invasive therapy involves the use of needles, fetoscopic treatments or open fetal surgery. This review provides an update of non-invasive and invasive fetal therapy.

Avances en terapia fetal / [Advances in fetal therapy].

Fetal therapy may be needed in certain clinical settings with the primary indication to improve perinatal or long-term outcomes for the fetus or the newborn. It can be classified in pharmacotherapy or non-invasive, and invasive therapy. The first one involves the administration of drugs to the mother that cross the placenta and get to the fetus, a non-invasive approach. On the other hand, invasive therapy involves the use of needles, fetoscopic treatments or open fetal surgery. This review provides an update of non-invasive and invasive fetal therapy.

Foetal aortic valvuloplasty: experience of five cases.

OBJECTIVES: Foetal aortic valvuloplasty has been proposed as a strategy to improve left heart growth and function in foetuses with severe aortic stenosis at risk of progression to hypoplastic left heart syndrome. We report our experience with this intervention. METHODS AND RESULTS: Between 2005 and 2010, five foetuses with aortic stenosis and at risk of progression to hypoplastic left heart syndrome underwent ultrasound-guided percutaneous foetal aortic valvuloplasty. There were no associated maternal complications or foetal demise. In one case, the pregnancy was terminated a couple of weeks after the intervention, one foetus evolved to hypoplastic left heart syndrome, and three did not. CONCLUSIONS: Foetal aortic valvuloplasty seems to be a safe and feasible procedure. It has been reported that it has the potential to prevent progression to hypoplastic left heart syndrome in selected foetuses with severe aortic stenosis. Further investigation regarding physiological and clinical aspects of this disease both prenatally and postnatally will probably allow to improve therapeutic strategies and clinical outcome.

Avances en terapia fetal. / [Advances in fetal therapy].

Fetal therapy may be needed in certain clinical settings with the primary indication to improve perinatal or long-term outcomes for the fetus or the newborn. It can be classified in pharmacotherapy or non-invasive, and invasive therapy. The first one involves the administration of drugs to the mother that cross the placenta and get to the fetus, a non-invasive approach. On the other hand, invasive therapy involves the use of needles, fetoscopic treatments or open fetal surgery. This review provides an update of non-invasive and invasive fetal therapy.