Fetal Intervention at UPMC Magee-Womens: Innovative Multidisciplinary Care and Advanced Diagnostics for Complex, High Risk In Utero Procedures

For close to 20 years, the Center for Innovative Fetal Intervention (CIFI) at UPMC Magee-Womens Hospital has treated some of the rarest, most complex prenatal conditions amenable to in utero surgical intervention. At its core, the center is a multidisciplinary, highly collaborative program that treats fetuses with structural or functional anomalies of multiple organ systems. The CIFI was launched and continues to be led by Stephen P. Emery, MD, a maternal-fetal medicine doctor who specializes in advanced and innovative in utero surgical techniques and procedures. A defining characteristic of Dr. Emery’s program is that it resides within a women’s hospital and is directed by a maternal-fetal medicine specialist. This puts focus squarely on the safety of the mother and the health of the fetus.

The CIFI is an internationally recognized and respected fetal therapy center with the capabilities and expertise to treat the full spectrum of complex fetal conditions. For conditions for which treatment approaches are lacking or underdeveloped, the CIFI pioneers the development of new, innovative techniques.

"Our team is here to take care of patients from western Pennsylvania and beyond who are experiencing a pregnancy with a troubling or life-threatening diagnosis for which an in utero intervention may be the best or only option to save the developing fetus," says Dr. Emery. "We take this responsibility very seriously and have built a program and assembled the necessary multidisciplinary resources to ensure our patient can stay as close to home as possible for such complex care needs.”

Dr. Emery’s CIFI is part of the larger, multidisciplinary UPMC Magee Fetal Diagnosis and Treatment Centers (FDTC), which are run in partnership with UPMC Children’s Hospital of Pittsburgh and serve as the region’s referral center for high-risk maternal care and fetal therapy. Dr. Emery is also a member of the North American Fetal Therapy Network (NAFTNet), a multicenter, multidisciplinary collaboration of institutions in the United States and Canada that works to study, develop, and optimize fetal interventions for complex and life-threatening conditions. He currently serves as the vice-chair of the Executive Committee for the organization.

The FDTC employ an array of diagnostic, therapeutic, and surgical services to diagnose, monitor, and treat a wide range of conditions during pregnancy. Using high-resolution ultrasound, the FDTC can detect fetal anomalies earlier in pregnancy and with much greater accuracy. New minimally invasive techniques help to reduce the risk of surgical intervention by using small needles and cameras to enter the uterus, and in some cases the fetus itself, to correct an underlying or developing anomaly. The FDTC care for a wide range of conditions, including:

• twin-twin transfusion syndrome
• twin reversed arterial perfusion
• twin anemia-polycythemia sequence
• selective fetal growth restriction
• discordant anomalies
• fetal chest masses
• lower urinary tract obstruction
• placental chorangioma
• fetal anemia
• fetal myelomeningocele

Recent Advances in Fetal Intervention and Research at UPMC Magee-Womens

In Utero Spina Bifida Surgery

In early 2019, Dr. Emery, along with pediatric neurosurgeon Stephanie Greene, MD, and a multidisciplinary team of collaborators from UPMC Magee-Womens and UPMC Children’s performed western Pennsylvania’s first in utero surgery to close an open neural tube defect (spina bifida).

Two months after the in utero fetal procedure, the healthy baby girl was born and named Emery Greene in honor of the two lead surgeons who delivered her historic and pioneering care. Read more about this case on the UPMC Children’s website.

Developing a Minimally Invasive Treatment Approach for Giant Placental Chorangioma

In 2018, Dr. Emery and colleagues from the Departments of Radiology and Pathology at the University of Pittsburgh School of Medicine published a paper¹ in the American Journal of Perinatology Reports on their experiences developing a procedural approach and treating two cases of the rare disorder giant placental chorangioma.

Because of the rarity of the disorder and its complexity, very little is known about the natural history of the disease, nor have there been established protocols and procedural guidelines developed for how best to treat the condition. Leveraging their expertise in fetal intervention techniques and the multidisciplinary resources available at UPMC, Dr. Emery and team developed a new minimally invasive, extra-amniotic approach that entailed using micro-coil embolization placed percutaneously under ultrasound guidance to ablate the chorangioma.

With these initial experiences and procedural developments, Dr. Emery has consulted on several cases with colleagues around the United States to explain the approach.

The next steps for Dr. Emery and colleagues are to scientifically investigate the condition to learn more about the disease's natural history, collaborate with partners to elucidate optimal interventional approaches and strategies for managing the disorder, and determine optimal timing for intervention.

To accomplish this, Dr. Emery is developing a proposal for a multicenter research registry through NAFTNet to leverage the expertise and multidisciplinary nature of the organization to better examine the initial surgical approaches developed by his team. 

"We have developed what we think is a sound procedural intervention, but of course, from a scientific and ethical standpoint, the only way to validate safety and efficacy is through rigorous study. Moreover, for a disorder such as placental chorangioma, with its rarity, the only effective way to accomplish this is through a multicenter approach. NAFTNet can be the basis for this work. I am excited to move this registry forward in the future and continue exploring how best to intervene in these cases," says Dr. Emery.

Fetal Hydrocephalus and the Development of a Novel Shunt for AS

Fetal hydrocephalus carries a terrible neurologic prognosis. Those who survive into childhood are often devastated neurologically. In the 1980s, alongside the growth of ultrasound, ventriculoamniotic shunting was attempted as an intervention for cases of fetal hydrocephalus. However, it was quickly abandoned because of poor outcomes. The International Fetal Medicine and Surgery Society (IFMSS), of which Magee is currently a member, was the original body that put a moratorium on the use of the procedure. “Ultrasound technology at the time did not allow for the resolution needed for accurate diagnosis of which fetus could benefit and which could not. We simply did not have the technology in place to make it work, so the field abandoned the practice,” says Dr. Emery.

Today, the ability to diagnose with precision is vastly superior. Because of this, Dr. Emery, through NAFTNet and the University of Pittsburgh, is re-evaluating the use of in-utero shunting for fetal hydrocephalus — specifically aqueductal stenosis (AS), or obstruction of the aqueduct of Sylvius connecting the third and fourth ventricles in the fetal brain. Cerebral spinal fluid (CSF) continues to be produced but cannot circulate due to the stenosis, allowing pressure to continually build until brain injury occurs. Dr. Emery and NAFTNet colleagues will first determine their ability to make an accurate diagnosis of AS in real-time. If possible, the next step is to determine whether shunting will bypass the area of stenosis and drain the CSF from the ventricle into the amniotic cavity, thereby decreasing pressure and preventing brain injury.

These studies build off previous work by Dr. Emery and colleagues at Magee that examined the ability to accurately diagnose isolated aqueductal stenosis prenatally, as well as analysis of the original shunting procedures, performed several decades prior. The NAFTNet study is a much larger trial aimed at prospectively demonstrating the ability to accurately diagnose AS. Beyond these investigations, Dr. Emery has also been involved in designing and developing a new shunt device for use in the treatment of AS. Collaborating with bioengineers at the University of Pittsburgh Swanson School of Engineering, Dr. Emery and a group of colleagues have designed a shunt for use in AS that can achieve specific performance characteristics and uses materials already approved for other purposes by the U.S. Food and Drug Administration (FDA). This work continues in the pursuit of approval for the new device.

Combatting Congenital Diaphragmatic Hernia With a Common Vasodilator

In recent years, Dr. Emery has collaborated with UPMC Children’s laboratory of George K. Gittes, MD, who is the Benjamin R. Fisher Chair and Professor of Pediatric Surgery and Pediatrics and Director of the Richard King Mellon Foundation for Pediatric Research.

For a number of years, Dr. Gittes’ laboratory has been exploring the use of the vasodilator, Sildenafil, in a mouse model of congenital diaphragmatic hernia (CDH). Research published by his group in July 20202 has shown that by injecting Sildenafil into the gestational sacks of a mouse model of congenital diaphragmatic hernia, embryonic pulmonary blood flow could be improved and potentially be a therapeutic option for attenuating CDH in utero in human patients.

“CDH is a very tough diagnosis with about 40% mortality,” explains Dr. Emery. “Results from the recently completed fetoscopic endoluminal tracheal occlusion (FETO) randomized trial that came out in June in the New England Journal of Medicine3 were not as positive as everyone was hoping for in the use of tracheal occlusion to treat the disorder. This leaves us with an opportunity to try something new, and Dr. Gittes’ animal studies are setting the stage for future trials in human subjects."

As Dr. Emery explains, additional animal model studies are being conducted in the pursuit of FDA approval to launch phase 1 clinical trials. "The data from his lab is promising, and we may be ready for phase 1 studies in the next couple of years," says Dr. Emery.

References

1. Emery SP, Orons PD, Bonadio JF. Successful Management of Giant Placental Chorangioma by Microcoil Embolization. AJP Rep. 2018; 8(4): e230-e233.

2. Okolo F, Zhang GF, Rhodes J, Gittes GK, Potoka DA. Intra-Amniotic Sildenafil Treatment Promotes Lung Growth and Attenuates Vascular Remodeling in an Experimental Model of Congenital Diaphragmatic Hernia. Fetal Diagn Ther. 2020 Jul 14; 1-13. Online ahead of print.

3. Deprest JA, et al. Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia. 2021. N Eng J Med. 385: 107-118. 

Further Reading

Explore some of Dr. Emery’s other recent published research.

Patel A, Abou-Al-Shaar H, Chiang MC, Algattas HN, McDowell MM, Stone JG, Mitchell EB, Emery SP, Greene S. Neuroophthalmological Manifestations of Congenital Aqueductal Stenosis. J Neurosurg Pediatr. 2021 Jun; 25:1-6.

Seheult JN, Stram MN, Pearce T, Bub CB, Emery SP, Kutner J, Watanabe-Okochi N, Sperry JL, Takanashi M, Triulzi DJ, Yazer MH. The Risk to Future Pregnancies of Transfusing Rh(D)-Negative Females of Childbearing Potential With Rh(D)-Positive Red Blood Cells During Trauma Resuscitation Is Dependent on Their Age at Transfusion. Vox Sang. 2021 Aug; 116(7): 831-840. 

Bahtiyar MO, Baschat A, Deprest J, Emery S, Goodnight WH, Johnson A, McCullough L, Moldenhauer JS, Ryan G, Tsao K, Van Mieghem T, Wagner A, Zaretsky M. Fetal Interventions in the Setting of the Coronavirus Disease 2019 Pandemic: Statement From the North American Fetal Therapy Network. Am J Obstet Gynecol. 2020 Aug; 223(2): 281-284.

Emery SP, Lopa S, Waters JH. Impact of Intrauterine Transfusion on Fetal Coagulation Physiology by Thromboelastography. Prenat Diagn. 2020 Apr; 40(5): 585-589. 

Yazer MH, Delaney M, Doughty H, Dunbar NM, Al-Riyami AZ, Triulzi DJ, Watchko JF, Wood EM, Yahalom V, Emery SP. It Is Time to Reconsider the Risks of Transfusing Rhd Negative Females of Childbearing Potential With Rhd Positive Red Blood Cells in Bleeding Emergencies. Transfusion. 2019 Dec; 59(12): 3794-3799.

Emery SP, Narayanan S, Greene S. Fetal Aqueductal Stenosis: Prenatal Diagnosis and Intervention. Prenat Diagn. 2020 Jan; 40(1): 58-65.

Emery SP, Greene S, Murdoch G, Wiley CA. Histologic Appearance of Iatrogenic Obstructive Hydrocephalus in the Fetal Lamb Model. Fetal Diagn Ther. 2020; 47(1): 7-14.

Goodnight WH, Bahtiyar O, Bennett KA, Emery SP, Lillegard JB, Fisher A, Goldstein R, Jatres J, Lim FY, McCullough L, Moehrlen U, Moldenhauer JS, Moon-Grady AJ, Ruano R, Skupski DW, Thom E, Treadwell MC, Tsao K, Wagner AJ, Waqar LN, Zaretsky M; fMMC Consortium Sponsored by NAFTNet. Subsequent Pregnancy Outcomes After Open Maternal-Fetal Surgery for Myelomeningocele. Am J Obstet Gynecol. 2019 May; 220(5): 494.e1-494.e7.

Zaretsky MV, Tong S, Lagueux M, Lim FY, Khalek N, Emery SP, Davis S, Moon-Grady AJ, Drennan K, Treadwell MC, Petersen E, Santiago-Munoz P, Brown R; North American Fetal Therapy Network. North American Fetal Therapy Network: Timing of and Indications for Delivery Following Laser Ablation for Twin-Twin Transfusion Syndrome. Am J Obstet Gynecol MFM. 2019 Mar; 1(1): 74-81.