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State of the Art in Fetal Surgery: Past, Present and Future Perspectives

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Obstetrics & Gynecology".

Deadline for manuscript submissions: closed (29 July 2024) | Viewed by 7867

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Prof. Dr. Gabriele Tonni

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Department of Obstetrics & Gynecology, Istituto di Ricerca a Carattere Clinico-Scientifico, AUSL di Reggio Emilia, Italy
Interests: prenatal diagnosis; ultrasound; high-risk pregnancy; intrapartum fetal asphyxia; perinatal outcome
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Prof. Dr. Rodrigo Ruano

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Department of Obstetrics, Gynecology & Reproductive Sciences, Division of Maternal-Fetal Medicine, University of Miami Miller School of Medicine, Miami, FL, USA
Interests: congenital diaphragm hernia; fetal bladder obstruction; fetal spina bifida; twin-twin transfusion syndrome; fetal cystoscopy; prenatal imaging

Special Issue Information

Dear Colleagues,

It is with great pleasure that we are launching a Special Issue on “The State of the Art of Fetal Surgery: Past, Present and Future Perspectives”. The focus of this Special Issue is on compiling the ultimate scientific evidence on indications, complications, and outcomes of the main fetal surgeries for congenital conditions.

Fetal surgery is a complex intervention to treat a variety of life-threatening anomalies in babies before they are born. Recently, with the development of genetic diagnosis and imaging technology, we have a better understanding of fetal development, and the field of fetal surgery has evolved significantly.

Currently, the following conditions for fetal surgery can be accepted: twin–twin transfusion syndrome (TTTS); myelomeningocele/open spina bifida; severe, isolated, left congenital diaphragmatic hernia (CDH); neck masses occluding the upper airways; lower urinary tract obstruction (LUTO); and so on. However, the limited physical fetal access and technological aspects, and the problems linked to identifying ideal fetal candidates and optimal timing for antenatal intervention lead to risks such as premature, preterm rupture of membrane (pPROM) and preterm labor, iatrogenic rupture of the uterus after surgery, intrauterine fetal demise (IUFD), intra- and post-operative complications, and potential failure to treat birth defects. The technological advancements of three-dimensional ultrasound and fetal magnetic resonance imaging (MRI) play a central, clinical role in assisting in and planning the timing of surgical intervention. Futuristic imaging such as 3D physical models of congenital anomalies and the most recent the use of physician avatars using metaverse have further supported the modern antenatal diagnostic armamentarium towards generating an immersive reality. The use of digital reality may enhance the bonding of the parents-to-be with the type of fetal malformation and ameliorate the understanding of the genetic counseling and surgical planning. Furthermore, modern fetal surgeons have received new training tools that will be of paramount value in academic training settings and in preparing the procedures.

This Special Issue aims to collect original research papers and review articles which discuss the current state of the art, address existing knowledge gaps, and focus on the innovation of fetal surgery.

Prof. Dr. Gabriele Tonni
Prof. Dr. Rodrigo Ruano
Guest Editors

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Keywords

fetal surgery
early intervention
minimally invasive surgery
perinatal outcome
three-dimensional ultrasound
virtual reality

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Published Papers (8 papers)

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Research

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9 pages, 4468 KiB

Open AccessArticle

Treatment of Twin Anemia Polycythemia Sequence with Donor Transfusion and Partial Recipient Exchange Transfusion: Procedural Considerations and Outcomes

by Camille F. Shantz, Mara Rosner, Michelle L. Kush, Jena L. Miller and Ahmet A. Baschat

J. Clin. Med. 2024, 13(17), 5068; https://doi.org/10.3390/jcm13175068 - 27 Aug 2024

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Abstract

Background: Intrauterine transfusion (IUT) of the donor and partial exchange (pET) of the recipient is a temporizing treatment for pregnancies with Twin Anemia Polycythemia Sequence (TAPS). We aimed to provide a detailed description of the procedural approach and outcomes for sequential donor IUT and recipient pET in TAPS. Methods: Retrospective study of spontaneous TAPS referred to the Johns Hopkins Center for Fetal Therapy treated with donor IUT followed by recipient pET utilizing a double-syringe setup. Procedural characteristics and outcomes as well as the accuracy of existing transfusion formulas were analyzed and compared with the literature. Results: 5 of 78 patients with spontaneous TAPS underwent a total of 19 combined IUT/pET procedures (median first procedure to delivery interval 5.6 weeks [interquartile range IQR 1.9–6.0]). One pET was stopped due to fetal deceleration. The patients were delivered at 33.0 weeks [IQR 31.9–33.3] with two survivors and no neonatal transfusion requirements. The IUT volume was 48 mL [IQR 39–63 mL] and the pET volume was 32 mL [IQR 20–50], utilizing aliquots of 5–20 mL for the latter (p = 0.021). For the IUTs, the assumption of a fetal blood volume below 150 mL/kg underestimated the required transfusion volume. For the pETs, all formulas required adjustment of the dilution volume based on bedside testing (p < 0.05 for all). Conclusions: Donor transfusion followed by partial exchange in the recipient can prolong pregnancy in spontaneous TAPS and obviate the need for neonatal transfusion. A double-syringe setup facilitates efficient saline exchange. Because the accuracy of volume formulas is limited, bedside testing is recommended to achieve the target hemoglobin. Full article

(This article belongs to the Special Issue State of the Art in Fetal Surgery: Past, Present and Future Perspectives)

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9 pages, 235 KiB

Open AccessArticle

Gestational Diabetes in Women with Fetal Spina Bifida Repair—Influence of Perioperative Management

by Ladina Rüegg, Ladina Vonzun, Julia Zepf, Nele Strübing, Ueli Möhrlen, Luca Mazzone, Martin Meuli, Spina Bifida Study Group and Nicole Ochsenbein-Kölble

J. Clin. Med. 2024, 13(17), 5029; https://doi.org/10.3390/jcm13175029 - 25 Aug 2024

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Background/Objectives: Fetal spina bifida (fSB) is the most common neural tube defect, and intrauterine repair has become a valid treatment option for selected cases. If fSB repair is offered, the ideal time for surgery is from 24 to 26 gestational weeks (GWs). The preoperative steroids for lung maturation and preoperative tocolytics that are administered are known to increase the prevalence of gestational diabetes (GD), which normally occurs in about 10–15% of all pregnant women. This study assessed the prevalence, possible influencing factors, and consequences on the course of pregnancy regarding GD in this cohort. Methods: Between 2010 and 2022, 184 fSB cases were operated. Those patients operated on after 24 0/7 GWs received steroids before surgery. All the patients received tocolysis, and an oral glucose tolerance test was performed between 26 and 28 GWs at least 7 days after steroid administration. In 2020, we established an early postoperative mobilization protocol. The perioperative management procedures of those patients with and without GD were compared to each other, and also, the patients treated according to the early mobilization protocol were compared to the remaining cohort. Results: Nineteen percent were diagnosed with GD. Corticosteroids were administered in 92%. Neither the corticoid administration nor the interval between the administration and glucose tolerance test was different in patients with or without GD. Further, 99.5% received postoperative tocolytics for at least 48 h. The women with GD had significantly longer administration of tocolytics. The length of stay (LOS) was higher in those patients with GD. The gestational age (GA) at delivery was significantly lower in the cohort with GD. In the early mobilized group, we found a significantly higher GA at delivery (37.1 GWs vs. 36.2 GWs, p = 0.009) and shorter LOS (p < 0.001), and their GD rate was lower (10% vs. 20%), although not statistically significant. Conclusions: The GD incidence in the women after fSB repair was higher than in the usual pregnant population. Early mobilization, rapid tocolytics decrease, and shorter LOS could benefit the pregnancy course after fSB repair and may decrease the risk for GD in this already high-risk cohort without increasing the risk for preterm delivery. Full article

(This article belongs to the Special Issue State of the Art in Fetal Surgery: Past, Present and Future Perspectives)

14 pages, 262 KiB

Open AccessArticle

Intrauterine Transfusion for Rhesus Alloimmunization: A Historical Retrospective Cohort from A Single Reference Center in Brazil

by David Baptista da Silva Pares, Gilda Helena Arruda Sousa Pacheco, Guilherme Antonio Rago Lobo and Edward Araujo Júnior

J. Clin. Med. 2024, 13(5), 1362; https://doi.org/10.3390/jcm13051362 - 28 Feb 2024

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Objective: This study aimed to describe the historical experience of a single reference center in Brazil with intrauterine transfusion (IUT) for Rhesus (Rh) alloimmunization, evaluating the major complications and the perinatal outcomes of this procedure. Methods: This retrospective cohort study evaluated data from medical records of pregnant women between 20 and 34 weeks of gestation whose fetuses underwent IUT by cordocentesis between January 1991 and June 2021. The same experienced examiner performed all procedures. Univariate and multivariate logistic regression was used to assess the effect of fetal hydrops, duration of IUT, post-transfusion cord bleeding time, and bradycardia on death (fetal or neonatal). Results: We analyzed data from 388 IUTs in 169 fetuses of alloimmunized pregnant women with a mean age of 29.3 ± 5.1 years. Death and fetal hydrops were significantly associated at first IUT (p < 0.001). We had two cases of emergency cesarean section (mean of 0.51% per IUT) and three cases of premature rupture of the ovular membranes (mean of 0.77% per procedure). Thirty-six deaths were recorded, including 14 intrauterine and 22 neonatal. A higher percentage of neonatal deaths was observed in the group with post-transfusion cord bleeding time > 120 s (45.8%). The odds of neonatal death were 17.6 and 12.9 times higher in cases with hydrops and bradycardia than in cases without hydrops and bradycardia, respectively. The odds of death (fetal and neonatal) were 79.9 and 92.3 times higher in cases with hydrops and bradycardia than in cases without hydrops and bradycardia, respectively. Conclusions: The most common complications of IUT for Rh alloimmunization were post-transfusion cord bleeding, fetal bradycardia, premature rupture of ovular membranes, and emergency cesarean section. The IUT complication most associated with death (fetal and neonatal) was bradycardia, and the perinatal outcomes were worse in fetuses with hydrops. Full article

(This article belongs to the Special Issue State of the Art in Fetal Surgery: Past, Present and Future Perspectives)

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15 pages, 2491 KiB

Open AccessReview

Fetal Teratomas: Advances in Diagnosis and Management

by May Abiad, Nikan Zargarzadeh, Ali Javinani, Eyal Krispin and Alireza A. Shamshirsaz

J. Clin. Med. 2024, 13(20), 6245; https://doi.org/10.3390/jcm13206245 - 19 Oct 2024

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Abstract

Fetal teratomas, though rare, represent a significant proportion of tumors arising during fetal development. These tumors arise from pluripotent cells and can present in varying degrees of severity, ranging from incidental findings to life-threatening conditions. Prenatal imaging, via ultrasound and MRI, is necessary for diagnosis and risk assessment. The management of fetal teratomas, particularly those associated with complications like hydrops or airway obstruction, often requires a multidisciplinary approach. Interventions such as ex-utero intrapartum treatment (EXIT) procedures and minimally invasive alternatives have emerged as critical tools to improve neonatal outcomes in severe cases. Despite advances in fetal therapies, careful prenatal monitoring and individualized management remain essential, especially for tumors with high vascularity or those that risk compromising cardiac output. This review explores the diagnostic methods, management strategies, and outcomes associated with fetal teratomas, highlighting recent advancements that contribute to improving survival and reducing morbidity in affected neonates. Full article

(This article belongs to the Special Issue State of the Art in Fetal Surgery: Past, Present and Future Perspectives)

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10 pages, 593 KiB

Open AccessReview

Prenatal Surgery for Open Fetal Spina Bifida in Patients with Obesity: A Review of Current Evidence and Future Directions

by Giulia Bonanni, Nikan Zargarzadeh, Eyal Krispin, Weston T. Northam, Elisa Bevilacqua, Hiba J. Mustafa and Alireza A. Shamshirsaz

J. Clin. Med. 2024, 13(19), 5661; https://doi.org/10.3390/jcm13195661 - 24 Sep 2024

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Abstract

Background: Obesity rates have significantly increased globally, affecting up to 40% of women of childbearing age in the United States. While prenatal repair of open fetal spina bifida has shown improved outcomes, most fetal surgery centers exclude patients with a body mass index (BMI) ≥ 35 kg/m² based on criteria from the Management of Myelomeningocele Study (MOMS) trial. This exclusion raises concerns about healthcare equity and highlights a significant knowledge gap regarding the safety and efficacy of fetal spina bifida repair in patients with obesity. Objective: To review the current state of knowledge regarding open fetal surgery for fetal spina bifida in patients with obesity, focusing on safety, efficacy, and clinical considerations. Methods: A comprehensive literature search was conducted using the PubMed and EMBASE databases, covering articles from the inception of the databases to April 2024. Studies discussing fetal surgery for neural tube defects and documenting BMI measurements and their impact on surgical outcomes, published in peer-reviewed journals, and available in English were included. Quantitative data were extracted into an Excel sheet, and data synthesis was conducted using the R programming language (version 4.3.3). Results: Three retrospective studies examining outcomes of prenatal open spina bifida repair in a total of 43 patients with a BMI ≥ 35 kg/m² were identified. These studies did not report significant adverse maternal or fetal outcomes compared to patients with lower BMIs. Our pooled analysis revealed a perinatal mortality rate of 6.1% (95% CI: 1.76–18.92%), with 28.0% (95% CI: 14.0–48.2%) experiencing the premature rupture of membranes and 82.0% (95% CI: 29.2–98.0%) delivering preterm (<37 weeks). Membrane separation was reported in 10.3% of cases (95% CI: 3.3–27.7%), the mean gestational age at birth was 34.3 weeks (95% CI: 32.3–36.3), and the average birth weight was 2651.5 g (95% CI: 2473.7–2829.4). Additionally, 40.1% (95% CI: 23.1–60.0%) required a ventriculoperitoneal shunt. Conclusion: While current evidence suggests that fetal spina bifida repair may be feasible in patients with obesity, significant limitations in the existing body of research were identified. These include small sample sizes, retrospective designs, and a lack of long-term follow-up data. There is an urgent need for large-scale, prospective, multicenter studies to definitively establish the safety and efficacy of fetal spina bifida repair in patients with obesity. Such research is crucial for developing evidence-based guidelines, improving clinical outcomes, and addressing healthcare disparities in this growing patient population with obesity. Full article

(This article belongs to the Special Issue State of the Art in Fetal Surgery: Past, Present and Future Perspectives)

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15 pages, 1298 KiB

Open AccessReview

Placental Gene Therapy for Fetal Growth Restriction and Preeclampsia: Preclinical Studies and Prospects for Clinical Application

by Sanjukta Majumder, Kristen Lee Moriarty, Youngmok Lee and Timothy M. Crombleholme

J. Clin. Med. 2024, 13(18), 5647; https://doi.org/10.3390/jcm13185647 - 23 Sep 2024

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Abstract

In the last three decades, gene therapy has demonstrated significant progress. Over 700 active investigational new drug (IND) applications have been reported. Research on in utero gene therapy has advanced, but ethical and safety concerns persist. A novel approach under investigation is placental gene therapy, which holds promise for targeting diseases associated with placental dysfunction, such as fetal growth restriction (FGR) and preeclampsia. One of the underlying causes of placental insufficiency in these conditions is reduced placental growth factor-driven angiogenesis and endothelial cell dysfunction during fetal development. Studies have explored the overexpression of growth factor transgenes like IGF-1 to address FGR, yielding promising outcomes in animal models. Furthermore, intra-placental gene transfer, instead of systemic delivery of gene therapy vectors, has the potential to treat and cure these disorders. However, challenges and limitations akin to in utero gene therapy persist, including the risk of in utero infection, potential impairment of the mother’s future fertility, the risk of germline integration, and possible off-target effects of gene transfer in the fetus or the mother. Consequently, additional research and deliberation within the scientific and medical communities are warranted to fully comprehend the potential benefits and risks of placental gene therapy. Full article

(This article belongs to the Special Issue State of the Art in Fetal Surgery: Past, Present and Future Perspectives)

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13 pages, 4809 KiB

Open AccessReview

The Use of 3D Printing in Fetal Surgery for Surgical Planning: A Scoping Review

by Aaron J. Fils, Julia Kasmirski, Oluwateniayo Okpaise, John M. Reynolds, Gabriele Tonni, Heron Werner and Rodrigo Ruano

J. Clin. Med. 2024, 13(17), 4999; https://doi.org/10.3390/jcm13174999 - 23 Aug 2024

Viewed by 914

Abstract

Objectives: We sought to identify in which clinical scenarios 3D printed models are used to plan for fetal surgeries as well as the main purpose and the imaging method utilized for the models. In addition, we describe benefits and shortcomings of the models, as well as potential future improvements. Methods: In this scoping review, data were collected retrospectively from scientific databases (PubMed, Embase, Cochrane CENTRAL, CINAHL, Scopus, and the Web of Science platform) and screened by title, abstract, and full text against strict criteria. The inclusion criteria required the study be performed on a live fetus and involve 3D models used for fetal surgery. The models must have been designed from diagnostic imaging modalities such as CT, MRI, or ultrasound. The articles considered include clinical trials, review articles, cohort studies, case series, case reports, and conference abstracts. Results: Of the initial 742 articles collected, six met the inclusion criteria. Spina bifida and EXIT procedures were the most frequent use cases that inspired surgeons to print models for surgical planning. The ability to view patient-specific anatomy in a 3D handheld model was often touted as providing a great benefit to the surgical team’s ability to anticipate intraoperative challenges. Conclusions: Three-dimensional printing models have been applied to plan for fetal surgeries, more specifically, for EXIT procedures and fetoscopic surgical repair of spina bifida. The potential benefits of 3D printing in fetal surgery are enormous. Full article

(This article belongs to the Special Issue State of the Art in Fetal Surgery: Past, Present and Future Perspectives)

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7 pages, 208 KiB

Open AccessOpinion

Artificial Ex Utero Systems to Treat Severe Periviable Fetal Growth Restriction—A Possible Future Indication?

by Oluwateniayo O. Okpaise, Aaron J. Fils, Gabriele Tonni and Rodrigo Ruano

J. Clin. Med. 2024, 13(22), 6789; https://doi.org/10.3390/jcm13226789 - 11 Nov 2024

Viewed by 294

Abstract

Fetal growth restriction, or intrauterine growth restriction, is a common gestational condition characterized by reduced intrauterine growth. However, severe periviable fetal growth restriction is still associated with elevated perinatal mortality and morbidity. The current literature advises delivery once it is deemed that fetal compromise is evident. As uteroplacental insufficiency is the most common etiology of this condition, we hypothesize that the use of artificial ex utero systems to provide adequate nutrition and recreate the uterine environment may be a viable treatment option in this situation, even with the possibility of treating severe fetal growth restriction and prevent sequelae. There are promising experimental studies in sheep models investigating the artificial ex utero system for potential prenatal conditions, but future additional investigation is needed before translating to clinical trials in humans. Full article

(This article belongs to the Special Issue State of the Art in Fetal Surgery: Past, Present and Future Perspectives)

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