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.

Laparoscopic Approach for Ectopic Pregnancy in a Rudimentary Horn: Stepwise Demonstration of Surgical Technique.

OBJECTIVE: To provide a comprehensive, step-by-step presentation of the laparoscopic resolution of ectopic pregnancy within a rudimentary uterine horn. DESIGN: A detailed demonstration of the laparoscopic technique presented through narrated video footage. SETTING: Pregnancy occurring in the rudimentary horn of a unicornuate uterus represents a rare form of ectopic pregnancy [1]. This condition is associated with a high risk of uterine rupture. Early detection is crucial for effective management and prevention of potential complications [2,3]. In this manuscript, we present a case study of a patient diagnosed with ectopic pregnancy in a rudimentary horn, who underwent successful laparoscopic resection. INTERVENTIONS: Ten main steps were identified and described in detail during the laparoscopic resection: Step 1: identification of the anatomy; Step 2: uterine mobilization; Step 3: Open retroperitoneum; Step 4: Coagulation and section of left round ligament; Step 5: Bladder dissection; Step 6: Identification of vessels; Step 7: Coagulation and section of left utero-ovarian vessels; Step 8: Coagulation and section of uterine vessels; Step 9: Section of uterine septum; Step 10: Specimen removed. CONCLUSION: This publication offers a detailed and instructive account of the laparoscopic resection of ectopic pregnancy within a rudimentary uterine horn. The stepwise approach demonstrated in the accompanying video contributes to a deeper understanding of this complex surgical technique. VIDEO ABSTRACT.

Experience of 300 cases of prenatal fetoscopic open spina bifida repair: report of the International Fetoscopic Neural Tube Defect Repair Consortium.

BACKGROUND: The multicenter randomized controlled trial Management of Myelomeningocele Study demonstrated that prenatal repair of open spina bifida by hysterotomy, compared with postnatal repair, decreases the need for ventriculoperitoneal shunting and increases the chances of independent ambulation. However, the hysterotomy approach is associated with risks that are inherent to the uterine incision. Fetal surgeons from around the world embarked on fetoscopic open spina bifida repair aiming to reduce maternal and fetal/neonatal risks while preserving the neurologic benefits of in utero surgery to the child. OBJECTIVE: This study aimed to report the main obstetrical, perinatal, and neurosurgical outcomes in the first 12 months of life of children undergoing prenatal fetoscopic repair of open spina bifida included in an international registry and to compare these with the results reported in the Management of Myelomeningocele Study and in a subsequent large cohort of patients who received an open fetal surgery repair. STUDY DESIGN: All known centers performing fetoscopic spina bifida repair were contacted and invited to participate in a Fetoscopic Myelomeningocele Repair Consortium and enroll their patients in a registry. Patient data entered into this fetoscopic registry were analyzed for this report. Fisher exact test was performed for comparison of categorical variables in the registry with both the Management of Myelomeningocele Study and a post-Management of Myelomeningocele Study cohort. Binary logistic regression analyses were used to assess the registry data for predictors of preterm birth at <30 weeks' gestation, preterm premature rupture of membranes, and need for postnatal cerebrospinal fluid diversion in the fetoscopic registry. RESULTS: There were 300 patients in the fetoscopic registry, 78 in the Management of Myelomeningocele Study, and 100 in the post-Management of Myelomeningocele Study cohort. The 3 data sets showed similar anatomic levels of the spinal lesion, mean gestational age at delivery, distribution of motor function compared with upper anatomic level of the lesion in the neonates, and perinatal death. In the Management of Myelomeningocele Study (26.16±1.6 weeks) and post-Management of Myelomeningocele Study cohort (23.3 [20.2-25.6] weeks), compared with the fetoscopic registry group (23.6±1.4 weeks), the gestational age at surgery was lower (comparing fetoscopic repair group with the Management of Myelomeningocele Study; P<.01). After open fetal surgery, all patients were delivered by cesarean delivery, whereas in the fetoscopic registry approximately one-third were delivered vaginally (P<.01). At cesarean delivery, areas of dehiscence or thinning in the scar were observed in 34% of cases in the Management of Myelomeningocele Study, in 49% in the post-Management of Myelomeningocele Study cohort, and in 0% in the fetoscopic registry (P<.01 for both comparisons). At 12 months of age, there was no significant difference in the number of patients requiring treatment for hydrocephalus between those in the fetoscopic registry and the Management of Myelomeningocele Study. CONCLUSION: Prenatal and postnatal outcomes up to 12 months of age after prenatal fetoscopic and open fetal surgery repair of open spina bifida are similar. Fetoscopic repair allows for having a vaginal delivery and eliminates the risk of uterine scar dehiscence, therefore protecting subsequent pregnancies of unnecessary maternal and fetal risks.

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.

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.

Laparoscopic surgery for treating adnexal masses during the first trimester of pregnancy.

OBJECTIVE: To evaluate the feasibility and safety of laparoscopic surgery for treating adnexal masses during the first trimester of pregnancy. STUDY DESIGN: An observational study of a prospective collection of data of all pregnant women who underwent laparoscopic surgery for adnexal masses during the first trimester of pregnancy between January 1999 and November 2012 at the Obstetrics and Gynecology Department of the Italian Hospital of Buenos Aires, Buenos Aires, Argentina was performed. RESULTS: A total of 13 women were included. The median (range) gestational age at the moment of surgical procedure was 7 weeks (range: 5-12 weeks). The main indication of surgery was cyst torsion in four cases (30.7%) and rupture of ovarian cysts in four cases (30.7%). Other indications included persistent ovarian cyst in three patients (23%) and heterotopic pregnancy in two cases (15.3%). Neither surgical complications nor spontaneous abortions occurred in any of the cases and the post-operative period was uneventful in all the cases. No cases of intrauterine growth retardation, preterm delivery, congenital defects, or neonatal complications were registered. CONCLUSION: The treatment of complicated adnexal masses by laparoscopic surgery during the first trimester of pregnancy appears to be a safe procedure both for the mother and for the foetus. Additional research on a larger number of cases is still needed to support these conclusions.

Feasibility and safety of prophylactic uterine artery catheterization and embolization in the management of placenta accreta.

PURPOSE: To evaluate the feasibility and safety of prophylactic uterine artery catheterization and embolization in the management of placenta accreta (PA). MATERIALS AND METHODS: Retrospective chart review was performed of 95 consecutive patients with prenatal suspicion of PA managed in a 10-year period with a strategy that included prophylactic bilateral uterine artery catheterization, delivery of the baby, uterine artery embolization if indicated, and subsequent surgery. Feasibility was defined as catheterization being possible to perform, technical success as embolization being possible when indicated and complete stasis of the vessels achieved, and clinical success as no maternal death or major blood loss. Median gestational age at delivery was 36 weeks (interquartile range, 24-39 wk). RESULTS: PA was confirmed in 79 patients (83%). Feasibility was 97% (92 of 95); in three cases (3%), acute early massive hemorrhage forced emergency delivery without catheterization. Embolization was performed in 83 of 92 patients (87%) to the extent of complete stasis; in the remaining nine, it was unnecessary because spontaneous placental detachment was visualized after fetal delivery (technical success rate, 100%). There were several complications, including bleeding requiring blood transfusion (49%) and bladder surgery (37%), but there were no major complications attributable to the endovascular procedures. There was one minor complication presumably related to embolization (transient paresthesia and decreased temperature of lower limb), with uneventful follow-up. Clinical success rate was 86%, with no maternal deaths, but 14% of patients received large-volume blood transfusion. CONCLUSIONS: Prophylactic uterine artery catheterization and embolization in the management of PA appeared to be feasible and safe in this consecutive series of patients.

Current controversies in prenatal diagnosis 2: prediction and prevention of adverse pregnancy outcomes requires a genomic rather than proteomic solution.

From both presentations, it is clear that understanding the APO associated with placental dysfunction represents one of the greatest challenges in the field of prenatal screening, diagnosis, and therapy. Their clinical impact on the health of the mother and child was well recognized by the debaters, and both have agreed that there is a paucity of knowledge in the etiophysiopathology of placental dysfunction and the associated clinical phenotypes. They also agreed that this marked limitation in our understanding is a significant problem when designing a research protocol, and both stressed the importance of proper study designs. When focusing on the specific topics of the debate, they showed different opinions about the role of genomics in the search for relevant answers. Leslie Myatt pointed out that the genome does not define the cellular phenotype, and although the proteome itself does not define phenotype, it is much closer to it than the genome. Conversely, Rossa Chiu suggested that genomic approaches offer a better chance of achieving the answers than by proteomics alone. Actually, she hypothesized that through genomic approaches, or rather through systems biology, that is, including genomics, epigenomics, transcriptomics, and proteomics, there would be a better chance of obtaining the best answers. She also raised the possibility of the potential use of cell-free fetal nucleic acids in maternal plasma, which in turn are mainly of placental origin. Finally, both debaters and the audience agreed that there was not an exclusive proteomic or genomic 'solution', but that we need a larger spectrum of research strategies to include both proteomics and genomics and other systems biology approaches, combined with detailed and standardized clinical, laboratory, and epidemiological criteria in appropriately designed studies in order to start filling the significant gaps in our knowledge about this highly complex area of placental mediated adverse pregnancy outcomes.

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.

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.

Impact of preconception thyrotrophin on obstetric outcomes in the fertile population.

INTRODUCTION: There is evidence that subclinical hypothyroidism is associated with infertility, miscarriage and obstetric complications. However, there is controversy regarding the optimal TSH value in women seeking pregnancy. Current guidelines recommend that hypothyroid women with levothyroxine replacement who are planning pregnancy should optimise the dose of levothyroxine to achieve thyrotrophin (TSH) levels <2.5 mU/l, since these requirements increase in pregnancy, thus reducing the risk of TSH elevation during the first trimester. In women with infertility, who undergo highly complex treatments and have positive thyroid autoimmunity, values of TSH <2.5 mU/l prior to fertility treatment are suggested. Although this is a different population, these «optimal¼ TSH levels were also extended to euthyroid women without evidence of infertility, who are seeking pregnancy. OBJECTIVES: Determine whether preconception TSH levels between 2.5 and 4.64 mIU/l are associated with adverse obstetric outcomes in euthyroid women. MATERIALS AND METHODS: Retrospective cohort study. We evaluated 3265 medical records of pregnant women aged 18-40 years, euthyroid (TSH 0.5-4.64 mU/ml), with TSH measurement at least one year before gestation. 1779 met inclusion criteria. The population was divided according to categories: TSH 0.5-2.4 mU/l (optimal) and TSH 2.5-4.6 mU/l (suboptimal). Information on maternal and fetal obstetric outcomes was collected from each group. RESULTS: We found no statistical difference in the occurrence of adverse obstetric events between the two groups. There was also no difference when adjusting for thyroid autoimmunity, age, body mass index, previous diabetes and previous arterial hypertension. CONCLUSION: Our results suggest that the reference range of TSH used in the general population could be used in women seeking pregnancy, even in the presence of thyroid autoimmunity. Treatment with levothyroxine should be considered only in patients with special situations.

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.

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.

Monoamniotic twin pregnancy discordant for lethal open cranial defect: management dilemmas.

OBJECTIVE: To report the sonographic findings, prenatal courses, and management options in four cases of monoamniotic twin pregnancy complicated by a discordant, lethal open cranial vault defect. METHODS: Cases were collected from two Latin American fetal medicine referral centers after the sonographic detection of a monoamniotic twin pregnancy in which one fetus was structurally normal and the other had a lethal open cranial vault defect. Three abnormal fetuses had acrania-anencephaly sequence and one had a large occipital encephalocele. The diagnosis was confirmed at referral, at which time umbilical cord entanglement was also diagnosed with color Doppler ultrasound in all cases. RESULTS: Two cases were managed with selective termination, one of which required referral to a fetal surgery center abroad because this option was illegal in Chile. The other case underwent radiofrequency ablation of the fetal intra-abdominal umbilical vessels after the corresponding ethics and legal committees approved the procedure. In both cases, the non-anomalous twin was born after 35 weeks and had no perinatal complications. Expectant management was performed in the other two cases, resulting in the death of the normal twin at 25 weeks. CONCLUSIONS: Monoamniotic twin pregnancy discordant for severe cranial vault defect is a serious condition with a high risk of fetal demise of the structurally normal fetus. Our experience, although limited, suggests that aggressive management with selective termination of the abnormal twin and transection of its umbilical cord in these cases may prevent the demise of the structurally normal co-twin.

Prenatal diagnosis of skeletal dysplasias: contribution of three-dimensional computed tomography.

OBJECTIVE: To describe the contribution of 3-dimensional computed tomography (3D-CT) in the prenatal diagnosis of skeletal dysplasias (SD) in a cohort of patients with inconclusive diagnosis by ultrasound (US). METHODS: Between May 2007 and February 2010, six pregnant women with suspected fetal SD on US examination but with no specific diagnosis were studied with 3D-CT. The images were evaluated by a multidisciplinary team who proposed a likely diagnosis. Further postnatal workup included clinical and radiological evaluation in all cases. Prenatal and postnatal diagnoses were compared. RESULTS: The use of 3D-CT provided a precise diagnosis confirmed postnatally in 5/6 patients. These included osteogenesis imperfecta type II (n = 2), osteogenesis imperfecta type III (n = 1), chondrodysplasia punctata (n = 1) and thanatophoric dysplasia type I (n = 1). A precise diagnosis could not be made in 1 case - either pre- or postnatally. CONCLUSION: Prenatal 3D-CT contributed to the diagnosis of the specific fetal SD in the majority of these cases. 3D-CT may have a complementary role to US where fetal SD is suspected, but no specific diagnosis can be made using US alone. Further studies on clinical performance and risk-benefit analysis are needed.

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.

[Non invasive prenatal diagnosis. Fetal nucleic acid analysis in maternal blood]. / Diagnóstico prenatal no invasivo. Acidos nucleicos de origen fetal en sangre materna.

Current prenatal diagnosis of monogeneic and chromosomal diseases, includes invasive procedures which carry a small but significant risk. For many years, analysis of fetal cells in maternal circulation has been studied, however it has failed its clinical use due to the scarcity of these cells and their persistance after delivery. For more than a decade, the presence of cell-free fetal DNA in maternal blood has been identified. These fetal DNA fragments would derive from the placenta and are not detected after delivery, making them a source of fetal material for carrying out diagnosis techniques using maternal blood. However, the vast majority of cell free DNA in maternal circulation is of maternal origin, with the fetal component contributing from 3% to 6% and rising towards term. Available methodologies do not allow separation of fetal from maternal cell free DNA, so current applications have been focused on the analysis of genes not present in the mother, such as Y chromosome sequences, or RHD gene in RhD-negative women, or paternal or de novo mutations. Also, the detection of cell-free fetal RNA in maternal blood offers the possibility of obtaining information regarding genetic expression profiles of embrionic tissues, and using genes expressed only at the feto-placental unit, controls for the presence of fetal material could be established, regardless of maternal genetic tissue. The present article describes the evidences regarding the passage of fetal nucleic acids to maternal circulation, its current prenatal diagnosis application and possible future perspectives.