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Research & Clinical Trials

Research & Clinical Trials

Texas Children’s Fetal Center, together with our partner institution Baylor College of Medicine, is constantly seeking new and better treatments to improve outcomes for mothers and babies in pregnancies involving fetal abnormalities.

Through our strengths in research and our commitment to collaboration, we continue to gain new insight into these rare and complex conditions, translating that knowledge into improved diagnoses and treatments that are changing the lives of families around the world.

We are known for developing innovative fetal interventions that offer new hope even in the most challenging cases while improving the safety of fetal surgery for mother and baby.

Equally important, we are committed to continually gathering and publishing information on our patient volumes, procedures and outcomes, empowering families in their decision-making and ensuring ongoing breakthroughs in the treatment of fetal abnormities for future generations.


Clinical Trials


Grants


Publications

The physicians at Texas Children’s Fetal Center® regularly publish articles that contribute to the diagnosis and treatment of fetal anomalies. Below are some recent examples highlighting their contributions.

Abdominal Wall Defects

Diagnosis of pentalogy of cantrell in the fetus using magnetic resonance imaging and ultrasound.
McMahon CJ, Taylor MD, Cassady CI, Olutoye OO, Bezold LI. Pediatr Cardiol. 2007 May-Jun;28(3):172-5. Epub 2007 Mar 20.

Embryologic variants of pentalogy of Cantrell.
Kaul B, Sheikh F, Zamora IJ, Mehollin-Ray AR, Cassady CI, Ayres NA, Cass DL, Olutoye OO. J Surg Res. 2015 Apr 9. [Epub ahead of print]

Amniotic band syndrome

Perinatal outcome after fetoscopic release of amniotic bands: a single-center experience and review of the literature
Pouya Javadian, Alireza A Shamshirsaz, Sina Haeri, Rodrigo Ruano, Susan M Ramin, Darrell Cass, Oluyinka O Olutoye, Michael A Belfort Ultrasound Obstet Gynecol. 2013 Oct;42(4):449-55. doi: 10.1002/uog.12510

CHAOS

Fetal laryngoscopy to evaluate vocal folds in a fetus with congenital high airway obstruction syndrome (CHAOS).|

Ruano R, Cass DL, Rieger M, Javadian P, Shamshirsaz AA, Olutoye OO, Belfort MA.Ultrasound Obstet Gynecol. 2014 Jan;43(1):102-3.

Congenital Diaphragmatic Hernia (CDH)

Congenital diaphragmatic hernia (CDH) is a major birth defect involving a hole or opening in the diaphragm, the muscle that separates the organs in the abdomen (liver, intestines, etc.) from those in the chest (such as the lungs). This hole allows abdominal organs to move up into the chest, where they can compress one or both lungs and prevent lung growth, leading to breathing problems at birth. Reduced blood flow in the lungs leads to pulmonary hypertension, high blood pressure in the arteries of the lungs, causing the heart to work harder. Respiratory failure is the leading cause of morbidity and mortality in these infants.

Babies born with persistent pulmonary hypertension (PH) require extra oxygen support from an ECMO (extracorporeal membrane oxygen) machine. In this treatment, the baby’s blood is pumped outside of the body and through an artificial lung for oxygenation, then circulated back into the infant’s bloodstream.

With advances in prenatal interventions and postnatal care, survival rates for babies with CDH have increased. Select patients with severe CDH are increasingly being recommended for fetal endoscopic tracheal occlusion (FETO), a breakthrough surgery with the potential to dramatically improve lung growth before birth. In this minimally invasive procedure, a tiny balloon is inserted into the baby’s trachea in utero and inflated; the balloon is then removed a few weeks before delivery. This temporary blockage of the trachea causes fluid to accumulate in the fetal lungs, promoting their growth during pregnancy – and giving the child a head start by providing sufficient lung capacity at birth. FETO is associated with increased perinatal survival and reduces the need for ECMO.

A recent study led by Dr. Jimmy Espinoza, a maternal-fetal medicine expert at Texas Children’s Pavilion for Women, evaluated the impact of FETO on the resolution of pulmonary hypertension in fetuses with isolated severe CDH. A higher proportion (69%) of infants with severe CDH who underwent FETO had resolution of PH compared to infants with severe CDH in the non-FETO group (28%). They found in infants with severe CDH, FETO and ECMO are independently associated with increased resolution of PH by one year of life.

Congenital heart anomaly in newborns with congenital diaphragmatic hernia: a single-center experience.
Ruano R, Javadian P, Kailin JA, Maskatia SA, Shamshirsaz AA, Cass DL, Zamora IJ, Sangi-Haghpeykar H, Lee TC, Ayres NA, Mehollin-Ray A, Cassady CI, Fernandes C, Welty S, Belfort MA, Olutoye OO. Ultrasound Obstet Gynecol. 2015 Jun;45(6):683-8. Epub 2015 May 4.

Quantification of liver herniation in fetuses with isolated congenital diaphragmatic hernia using two-dimensional ultrasonography.
Britto IS, Olutoye OO, Cass DL, Zamora IJ, Lee TC, Cassady CI, Mehollin-Ray A, Welty S, Fernandes C, Belfort MA, Lee W, Ruano R. Ultrasound Obstet Gynecol. 2014 Nov 4. doi: 10.1002/uog.14718. PMID: 25366655

Persistent hypercarbia after resuscitation is associated with increased mortality in congenital diaphragmatic hernia patients.
Abbas PI, Cass DL, Olutoye OO, Zamora IJ, Akinkuotu AC, Sheikh F, Welty SE, Lee TC. J Pediatr Surg. 2015 May;50(5):739-43. 2015 Feb 20.

Pulmonary capillary hemangiomatosis in a neonate with congenital diaphragmatic hernia.
Akinkuotu AC, Sheikh F, Cass DL, Lee TC, Welty SE, Kearney DL, Olutoye OO. Pediatr Surg Int. 2015 May;31(5):501-4. Epub 2015 Feb 13.

Revisiting outcomes of right congenital diaphragmatic hernia.
Akinkuotu AC, Cruz SM, Cass DL, Cassady CI, Mehollin-Ray AR, Williams JL, Lee TC, Ruano R, Welty SE, Olutoye OO. J Surg Res. 2015 Apr 3.

Are all pulmonary hypoplasias the same? A comparison of pulmonary outcomes in neonates with congenital diaphragmatic hernia, omphalocele and congenital lung malformation.
Akinkuotu AC, Sheikh F, Cass DL, Zamora IJ, Lee TC, Cassady CI, Mehollin-Ray AR, Williams JL, Ruano R, Welty SE, Olutoye OO. J Pediatr Surg. 2015 Jan;50(1):55-9. Epub 2014 Dec 19.

Quantification of liver herniation in fetuses with isolated congenital diaphragmatic hernia using two-dimensional ultrasonography.
Britto IS, Olutoye OO, Cass DL, Zamora IJ, Lee TC, Cassady CI, Mehollin-Ray A, Welty S, Fernandes C, Belfort MA, Lee W, Ruano R. Ultrasound Obstet Gynecol. 2014 Nov 4.

Fetal lung volume and quantification of liver herniation by magnetic resonance imaging in isolated congenital diaphragmatic hernia.
Ruano R, Lazar DA, Cass DL, Zamora IJ, Lee TC, Cassady CI, Mehollin-Ray A, Welty S, Fernandes CJ, Haeri S, Belfort MA, Olutoye OO. Ultrasound Obstet Gynecol. 2014 Jun;43(6):662-9.

Prenatal MRI fetal lung volumes and percent liver herniation predict pulmonary morbidity in congenital diaphragmatic hernia (CDH).
Zamora IJ, Olutoye OO, Cass DL, Fallon SC, Lazar DA, Cassady CI, Mehollin-Ray AR, Welty SE, Ruano R, Belfort MA, Lee TC. J Pediatr Surg. 2014 May;49(5):688-93. Epub 2014 Feb 22.

Fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia: indications, outcomes, and future directions 

Ruano R, Ali RA, Patel P, Cass D, Olutoye O, Belfort MA. Obstet Gynecol Surv. 2014 Mar;69(3):147-58. doi: 10.1097/OGX.0000000000000045. Review.

Fetal cardiac tamponade in a case of right-side congenital diaphragmatic hernia.
Salmanian B, Shamshirsaz AA, Cass DL, Javadian P, Ruano R, Ayres NA, Mehollin-Ray A, Belfort MA. Obstet Gynecol. 2014 Feb;123(2 Pt 2 Suppl 2):447-50.

Repair of congenital diaphragmatic hernias on Extracorporeal Membrane Oxygenation (ECMO): does early repair improve patient survival?

Fallon SC, Cass DL, Olutoye OO, Zamora IJ, Lazar DA, Larimer EL, Welty SE, Moise AA, Demny AB, Lee TC. J Pediatr Surg. 2013 Jun;48(6):1172-6.

The presence of a hernia sac in congenital diaphragmatic hernia is associated with better fetal lung growth and outcomes.
Zamora IJ, Cass DL, Lee TC, Welty S, Cassady CI, Mehollin-Ray AR, Fallon SC, Ruano R, Belfort MA, Olutoye OO. J Pediatr Surg. 2013 Jun;48(6):1165-71.

Fetal MR imaging of congenital diaphragmatic hernia.
Mehollin-Ray AR, Cassady CI, Cass DL, Olutoye OO. Radiographics. 2012 Jul-Aug;32(4):1067-84.

Defining "liver-up": does the volume of liver herniation predict outcome for fetuses with isolated left-sided congenital diaphragmatic hernia?

Lazar DA, Ruano R, Cass DL, Moise KJ Jr, Johnson A, Lee TC, Cassady CI, Olutoye OO. J Pediatr Surg. 2012 Jun;47(6):1058-62.

Jugular vein hypoplasia can preclude extracorporeal membrane oxygenation cannulation in the neonate with congenital diaphragmatic hernia: potential identification of the neonate at risk by fetal magnetic resonance imaging.
Cassady CI, Mehollin-Ray AR, Olutoye OO, Cass DL. Fetal Diagn Ther. 2011;30(3):225-8. Epub 2011 Sep 28.

Impact of prenatal evaluation and protocol-based perinatal management on congenital diaphragmatic hernia outcomes.
Lazar DA, Cass DL, Rodriguez MA, Hassan SF, Cassady CI, Johnson YR, Johnson KE, Johnson A, Moise KJ, Belleza-Bascon B, Olutoye OO. J Pediatr Surg. 2011 May;46(5):808-13.

Fetal surgery for congenital diaphragmatic hernia: the North American experience.
Cass DL.Semin Perinatol. 2005 Apr;29(2):104-11. Review.

Longitudinal assessment of two-dimensional ultrasonographic lung measurements in fetuses with isolated left-sided congenital diaphragmatic hernia. 

Ruano R, Britto IS, Sangi-Haghpeykar H, Bussamra LC, da Silva MM, Belfot MA, Deter RL, Lee W, Tannuri U, Zugaib M. Ultrasound Obstet Gynecol  2015. 45:566-71. PMID: 24862641

Growth patterns of fetal lung volumes in healthy fetuses and fetuses with isolated left-sided congenital diaphragmatic hernia.  
Ruano R, Werneck IS, Sananes N, Sangi-Haghpeykar H, Lee W, Deter RL. Journal of Ultrasound in Medicine, in press.

Congenital Heart Disease

Prenatal Diagnosis, Birth Location, Surgical Center, and Neonatal Mortality in Infants with Hypoplastic Left Heart Syndrome.
Morris SA, Ethen MK, Penny DJ, Canfield MA, Minard CG, Fixler DE, Nembhard WN. Circulation. 2013 Oct 17. Falkensammer CB, Ayres NA, Altman CA, Ge S, Bezold LI, Eidem BW,  

Fetal cardiac malposition: incidence and outcome of associated cardiac and extracardiac malformations.
Kovalchin JP. Am J Perinatol. 2008 May;25(5):277-81. Epub 2008 Apr 9.

Characteristics and outcomes of fetuses with pericardial effusions.
Slesnick TC, Ayres NA, Altman CA, Bezold LI, Eidem BW, Fraley JK, Kung GC, McMahon CJ, Pignatelli RH, Kovalchin JP. Am J Cardiol. 2005 Aug 15;96(4):599-601.

American Society of Echocardiography guidelines and standards for performance of the fetal echocardiogram.
Rychik J, Ayres N, Cuneo B, Gotteiner N, Hornberger L, Spevak PJ, Van Der Veld M. J Am Soc Echocardiogr. 2004 Jul;17(7):803-10. No abstract available.

Images in cardiovascular medicine. Fetal diagnosis of right ventricular aneurysm associated with supraventricular tachycardia with left bundle-branch block aberrancy.
John JB, Bricker JT, Fenrich AL, Vick GW, El-Said HG, Ayres NA, Bezold LI. Circulation. 2002 Jul 2;106(1):141-2. No abstract available.

EXIT Procedures

Cervical lymphatic malformations (CLM) are rare, non-malignant masses that form in a baby’s neck or head during fetal development. If the neck mass is large or invasive, a fetus with CLM may face several complications, including obstruction of the airway or deviation of the trachea. In these cases, a surgical procedure known as ex-utero intrapartum treatment (EXIT) is used to deliver the baby to ensure the newborn can breathe adequately at birth. An EXIT procedure is similar to a cesarean section with some differences – the mother is under general anesthesia while a special device is used to open the uterus and deliver the baby’s upper body, enabling insertion of a breathing tube before the baby is separated from the oxygen-providing placenta.

A recent study led by Dr. Alireza Shamshirsaz, chief of Fetal Therapy and Surgery at Texas Children’s Hospital, reviewed 45 patients delivered by EXIT procedure at Texas Children’s between 2001 - 2018, with a focus on 10 cases delivered for CLM. The main findings of this study were:

  • Close monitoring for signs of polyhydramnios (excess amniotic fluid, caused by the fetus’ impaired ability to swallow) and structural neck involvement is important and may indicate the need for an EXIT delivery procedure.
  • Although preterm birth was higher among this group of patients compared to uncomplicated cesarean delivery, the babies had an overall low (10%) mortality rate.
  • The majority of the infants delivered via EXIT reached normal developmental milestones.
  • Delivery via the EXIT procedure was safe for the mother and did not result in any significant complications.
  • In this study, all infants delivered via EXIT experienced gastroesophageal dysfunction. A third of the patients required permanent tracheostomy, a surgical procedure to create an opening through the neck into the trachea (windpipe).
  • An experienced multidisciplinary team of highly trained physicians and surgical staff is crucial for effective management of obstructed fetal airway in CLM and to ensure successful outcomes for the babies and mothers.

These results provide important additional information for parents to consider regarding the safety of the EXIT procedure for mother and child versus the difficulties these children may experience later in life.

Tracheoesophageal displacement index and predictors of airway obstruction for fetuses with neck masses.
Lazar DA, Cassady CI, Olutoye OO, Moise KJ Jr, Johnson A, Lee TC, Cass DL. J Pediatr Surg. 2012 Jan;47(1):46-50.

Case scenario: anesthesia for maternal-fetal surgery: the Ex Utero Intrapartum Therapy (EXIT) procedure

Garcia PJ, Olutoye OO, Ivey RT, Olutoye OA. . Anesthesiology. 2011 Jun;114(6):1446-52. No abstract available.

Ex-utero intrapartum treatment procedure for giant neck masses--fetal and maternal outcomes.
Lazar DA, Olutoye OO, Moise KJ Jr, Ivey RT, Johnson A, Ayres N, Olutoye OA, Rodriguez MA, Cass DL. J Pediatr Surg. 2011 May;46(5):817-22.

Extra-corporeal Membrane Oxygenation (ECMO)

Outcomes comparing dual-lumen to multisite venovenous ECMO in the pediatric population: the Extracorporeal Life Support Registry experience.
Zamora IJ, Shekerdemian L, Fallon SC, Olutoye OO, Cass DL, Rycus PL, Burgman C, Lee TC. J Pediatr Surg. 2014 Oct;49(10):1452-7. Epub 2014 Sep 8.

Initial experience with single-vessel cannulation for venovenous extracorporeal membrane oxygenation in pediatric respiratory failure.
Fallon SC, Shekerdemian LS, Olutoye OO, Cass DL, Zamora IJ, Nguyen T, Kim ES, Larimer EL, Lee TC. Pediatr Crit Care Med. 2013 May;14(4):366-73.

The use of ECMO for persistent pulmonary hypertension of the newborn: a decade of experience.
Lazar DA, Cass DL, Olutoye OO, Welty SE, Fernandes CJ, Rycus PT, Lee TC. J Surg Res. 2012 Oct;177(2):263-7. Epub 2012 Aug 10.

The use of ECMO for persistent pulmonary hypertension of the newborn: a decade of experience.
Lazar DA, Cass DL, Olutoye OO, Welty SE, Fernandes CJ, Rycus PT, Lee TC. J Surg Res. 2012 Aug 10. [Epub ahead of print]

Extracorporeal membrane oxygenation support of a severe metabolic crisis in a child with methylmalonic acidemia.
Stark RJ, Naik-Mathuria BJ, Lam FW, Olutoye OO, Sutton VR, Shekerdemian LS. ASAIO J. 2012 Jul;58(4):438-9

Outcomes of neonates requiring extracorporeal membrane oxygenation for irreversible pulmonary dysplasia: the Extracorporeal Life Support Registry experience.
Lazar DA, Olutoye OO, Cass DL, Fernandes CJ, Welty SE, Johnson KE, Rycus PT, Lee TC. Pediatr Crit Care Med. 2012 Mar;13(2):188-90.

Venovenous cannulation for extracorporeal membrane oxygenation using a bicaval dual-lumen catheter in neonates.
Lazar DA, Cass DL, Olutoye OO, Kim ES, Welty SE, Fernandes CJ, Lee TC. J Pediatr Surg. 2012 Feb;47(2):430-4.

Jugular vein hypoplasia can preclude extracorporeal membrane oxygenation cannulation in the neonate with congenital diaphragmatic hernia: potential identification of the neonate at risk by fetal magnetic resonance imaging.
Cassady CI, Mehollin-Ray AR, Olutoye OO, Cass DL. Fetal Diagn Ther. 2011;30(3):225-8. Epub 2011 Sep 28.

Fetal Diagnosis

Comparing characteristics and outcomes in infants with prenatal and postnatal diagnosis of esophageal atresia.
Fallon SC, Ethun CG, Olutoye OO, Brandt ML, Lee TC, Welty SE, Ruano R, Cass DL. J Surg Res. 2014 Jul;190(1):242-5. Epub 2014 Mar 27.

Fetal MRI improves diagnostic accuracy in patients referred to a fetal center for suspected esophageal atresia.
Ethun CG, Fallon SC, Cassady CI, Mehollin-Ray AR, Olutoye OO, Zamora IJ, Lee TC, Welty SE, Cass DL. J Pediatr Surg. 2014 May;49(5):712-5. Epub 2014 Feb 22.

The use of combined ultrasound and magnetic resonance imaging in the detection of fetal anomalies.
Santos XM, Papanna R, Johnson A, Cass DL, Olutoye OO, Moise KJ, Jr, Belleza-Bascon B, Cassady CI. Prenat Diagn. 2010 May;30(5):402-7.

Prenatal Diagnosis of Renal Vein Thrombosis: A Case Report and Literature Review.
Moaddab A, Shamshirsaz AA, Ruano R, Salmanian B, Lee W, et al. Fetal diagnosis and therapy. 2015; PubMed [journal]    

Evaluation of the prenatally diagnosed mass.
Lee TC, Olutoye OO. Semin Fetal Neonatal Med. 2012 Aug;17(4):185-91. Epub 2012 Mar 15. 

Impact of prenatal diagnosis and therapy on neonatal surgery.
Cass DL. Semin Fetal Neonatal Med. 2011 Jun;16(3):130-8. Epub 2011 May 6. Review.

Prenatal diagnosis of CLOVES syndrome confirmed by detection of a mosaic PIK3CA mutation in cultured amniocytes
Emrick LT, Murphy L, Shamshirsaz AA, Ruano R, Cassady CI, Liu L, Chang F, Sutton VR, Li M, Van den Veyver IB. Am J Med Genet A. 2014 Oct;164A(10):2633-7. doi: 10.1002/ajmg.a.36672. Epub 2014 Jul 14.

Fetal Doppler

ISUOG Practice Guidelines: use of Doppler ultrasonography in obstetrics
Bhide A, Acharya G, Bilardo CM, Brezinka C, Cafici D, Hernandez-Andrade E, Kalache K, Kingdom J, Kiserud T, Lee W, Lees C, Leung KY, Malinger G, Mari G, Prefumo F, Sepulveda W and Trudinger B. Ultrasound Obstet Gynecol 2013; 41: 233-239.

Fetal Echocardiography

Collaborative study of 4-dimensional fetal echocardiography in the first trimester of pregnancy.
Espinoza J, Lee W, Viñals F, Martinez JM, Bennasar M, Rizzo G, Belfort M. J Ultrasound Med. 2014;33:1079-84.  PMID: 24866615

Diagnosis and treatment of fetal cardiac disease. A scientific statement from the American Heart Association.
Donofrio MT, Moon-Grady AJ, Hornberger LK, Copel J, Sklansky MS, Abuhamad A, Cuneo BF, Huhta JC, Jonas RA, Krishnan A, Lacey DO, Lee W, Michelfelder EC, Rempel GR, Silverman NH, Spray TL, Strassburger JF, Tworetzky W, Rychik J. Circulation 2014; 129:  2183-242.    

AIUM practice guideline for the performance of fetal echocardiography.
Task Force Chair. American Institute of Ultrasound in Medicine. J Ultrasound Med 2013; 32: 1067 – 1082.  

ISUOG Practice Guidelines (updated): sonographic screening  examination of the fetal heart

Carvalho JS, Allan LD, Chaoui R, Copel JA, DeVore GR, Hecher K, Lee W, Munoz H, Paladini D, Tutschek B, Yagel S. Ultrasound Obstet Gynecol 2013; 41: 348-59.

Re: Nuchal translucency and major congenital heart defects in  fetuses with normal karyotype: a meta-analysis.
Lee W.  Referee commentary. A. Sotiriadis, S. Papatheodorou, M.  Eleftheriades, and G Makrydimas.  Ultrasound Obstet Gynecol  2013; 42: 373.

The fetal cardiovascular response to increased placental vascular impedance to flow determined with 4-dimensional ultrasound using spatiotemporal image  correlation and virtual organ computer-aided analysis.
Hamill N, Romero R, Hassan S, Lee W, Myers SA, Mittal P, Kusanovic JP, Balasubramaniam M, Chaiworapongsa T, Vaisbuch E, Espinoza J, Gotsch F, Goncalves LF, Mazaki-Tovi S, Erez O, Hernandez-Andrade E, Yeo L. Am J Obstet Gynecol 2013; 208:153.e1-13.

Fetal Gastrointestinal Problems

Advances in fetal and neonatal surgery for gastrointestinal anomalies and disease.
Cass DL, Wesson DE.Clin Perinatol. 2002 Mar;29(1):1-21. Review.

Fetal Growth

Fetal growth cessation in late pregnancy: its impact on predicted size parameters used to classify small for gestational age neonates.
Deter RL, Lee W, Sangi-Haghpeykar H, Tarca AL, Yeo L, Romero R. J Matern Fetal Neonatal Med 2015; 28: 745-54. Jun 17: 1-11. PMID: 24936858

A modified prenatal growth assessment score for the evaluation of fetal growth in the third trimester using single and composite biometric parameters.
Deter RL, Lee W, Sangi-Haghpeykar H, Tarca AL, Yeo L, Romero R. J Matern Fetal Neonatal Med. 2015; 28: 745-54. PMID: 24993892

Reference ranges for 2-dimensional sonographic lung measurements in healthy fetuses: a longitudinal study.
Britto IS, Araujo Júnior E, Sangi-Haghpeykar H, Bussamra LC, Deter RL, Belfort MA, Lee W, Ruano R. J Ultrasound Med. 2014; 33: 1917-23.  PMID: 25336478

Customized growth curves for the identification of large-for-gestational age neonates delivered to pre-eclamptic women.
Espinoza J, Lee W, Martin SR, Belfort MA. Ultrasound Obstet Gynecol. 2014; 43:165-9. 

Individualized fetal growth assessment: critical evaluation of key concepts in the specification of third trimester size trajectories.
Deter RL, Lee W, Sangi-Haghpeykar H, Tarca AL, Yeo L, Romero R.  J Matern Fetal Neonatal Med. 2014; 27: 543-51.   

Prospective validation of fetal weight estimation using fractional limb volume.
Lee W, Deter R, Sangi-Haghpeykar H, Yeo L, Romero R. Ultrasound Obstet Gynecol 2013; 41: 198-203.  

Personalized third trimester fetal growth evaluation: comparisons of individualized growth assessment, percentile line, and conditional probability measurements.
Deter RL, Lee W, Sangi-Haghpeykar H, Tarca AL, Li J, Yeo L, Romero R.  J Matern Fetal Neonatal Med. 2015 Sep 25:1-9. [Epub ahead of print] PMID: 25491881

Does the use of automated fetal biometry improve clinical workflow efficiency?
Espinoza J, Good S, Russell E, Lee W.  J Ultrasound Med 2013; 32:847-50.

Fetal Neurosonography

Magnetic resonance diffusion-weighted imaging: reproducibility of regional apparent diffusion coefficients for the normal fetal brain
Boyer AC, Gonçalves LF, Lee W, Shetty A, Holman A, Yeo L, Romero R. Ultrasound Obstet Gynecol 2013; 41:190-7.

Spatial mapping of translational diffusion coefficients using diffusion tensor imaging: a mathematical description.
Shetty AN, Chiang S, Maletic-Savatic M, Kasprian G, Vannucci M, Lee W. Concepts Magn Reson Part A Bridg Educ Res 2014; 43: 1-27.     

Fetal Wound Healing, Fetal Response to Fetal Surgery

Age-dependent recruitment of neutrophils by fetal endothelial cells: implications in scarless wound healing.
Naik-Mathuria B, Gay AN, Zhu X, Yu L, Cass DL, Olutoye OO. J Pediatr Surg. 2007 Jan;42(1):166-71.  

Neutrophil recruitment by fetal porcine endothelial cells: implications in scarless fetal wound healing.
Olutoye OO, Zhu X, Cass DL, Smith CW. Pediatr Res. 2005 Dec;58(6):1290-4.  

Giant Neck Masses

Prenatally diagnosed neck masses: long-term outcomes and quality of life.
Sheikh F, Akinkuotu A, Olutoye OO, Pimpalwar S, Cassady CI, Fernandes CJ, Ruano R, Lee TC, Cass DL. J Pediatr Surg. 2015 Jul;50(7):1210-3. Epub 2015 Mar 21.

EXIT procedure for fetal neck masses.
Olutoye OO, Olutoye OA. Curr Opin Pediatr. 2012 Jun;24(3):386-93.

Tracheoesophageal displacement index and predictors of airway obstruction for fetuses with neck masses.
Lazar DA, Cassady CI, Olutoye OO, Moise KJ Jr, Johnson A, Lee TC, Cass DL. J Pediatr Surg. 2012 Jan;47(1):46-50.

Ex-utero intrapartum treatment procedure for giant neck masses--fetal and maternal outcomes.
Lazar DA, Olutoye OO, Moise KJ Jr, Ivey RT, Johnson A, Ayres N, Olutoye OA, Rodriguez MA, Cass DL. J Pediatr Surg. 2011  May;46(5):817-22.

Hypoplastic Left Heart Syndrome

Hypoplastic left heart syndrome (HLHS) is a severe and complex congenital heart defect in which the left side of the heart is underdeveloped, leaving it too small to support blood flow to the rest of the body. HLHS is fatal without surgical intervention and is responsible for 25% to 40% of all neonatal cardiac deaths.

In these patients, absence of communication (an opening) between the upper chambers of the heart (atria) results in severe obstruction of pulmonary venous blood flow, frequently causing vascular injury.

Surviving babies suffer high (50%) neonatal mortality from profound lack of oxygen since oxygenated blood cannot exit the left atrium. Current postnatal interventions are suboptimal due to the progressive hypoxemia/acidosis (oxygenation deprivation) that occurs until a hole can be created in the wall between the top chambers of the heart, known as the atrial septum, and a left-to-right shunt is created enabling proper blood flow.

Making a perforation in the atrial septum in-utero can improve postnatal heart function and potentially lower mortality. However, the ultrasound-guided needle procedure is technically difficult. It requires a high degree of precision and is highly affected by the position of the baby, the penetration of ultrasound (visualization), and miniscule movements of the fetus and/or needle. A small left atrium and thick septum in these babies complicate the procedure and make it increasingly difficult to perforate the wall without damaging the left atrium or other nearby structures.

Typically, the outcomes for these in-utero atrial septal repair procedures for babies with HLHS are poor – the babies may present with severely low oxygen and pulmonary swelling.

Recently, our fetal and pediatric heart experts, led by Dr. Michael Belfort, obstetrician/gynecologist-in-chief at Texas Children’s Pavilion for Women, devised an innovative thulium laser-assisted procedure to place an atrial septal stent. By using laser energy to vaporize a hole in the septum, the intervention avoided the need for force or disturbance to the baby or any of the intrathoracic structures, which can impair visualization and delay or prevent successful intervention. Moreover, they found combining 4-D and 2-D ultrasonography can help surgeons ascertain the proper placement of the interatrial stent.

Indications for Fetal Surgery and Treatment

Mainstem bronchial atresia: a lethal anomaly amenable to fetal surgical treatment.
Zamora IJ, Sheikh F, Olutoye OO, Cassady CI, Lee TC, Ruano R, Cass DL. J Pediatr Surg. 2014 May;49(5):706-11. Epub 2014 Feb 22. Review.

Defining hydrops and indications for open fetal surgery for fetuses with lung masses and vascular tumors.
Cass DL, Olutoye OO, Ayres NA, Moise KJ Jr, Altman CA, Johnson A, Cassady CI, Lazar DA, Lee TC, Lantin MR.  J Pediatr Surg. 2012 Jan;47(1):40-5.

Impact of prenatal diagnosis and therapy on neonatal surgery.
Cass DL. Semin Fetal Neonatal Med. 2011 Jun;16(3):130-8. Epub 2011 May 6. Review. [PubMed - indexed for MEDLINE]

Lower Urinary Tract Obstruction (LUTO)

Fetal Lower Urinary Tract Obstruction - A proposal of Standardized Multidisciplinary Prenatal Management based on Disease Severity
Rodrigo Ruano, Nicolas Sananes, Clark Wilson, Jason Au, Chester J. Koh, Patricio Gargollo, Alireza A. Shamshirsaz, Jimmy Espinoza, Adnan Safdar, Amirhossein Moaddab, Nicolas Meyer, Darrell L. Cass, Oluyinka O. Olutoye, Olutoyin A. Olutoye, Stephen Welty, David R. Roth, Michael C. Braun, Michael A. Belfort; Ultrasound Obstet Gynecol. 2015 Dec 22. doi: 10.1002/uog.15844. [Epub ahead of print]

Defining and predicting ‘intrauterine fetal renal failure’ in congenital lower urinary tract obstruction
Rodrigo Ruano, Adnan Safdar, Jason Au, Chester J. Koh, Patricio Gargollo, Alireza A. Shamshirsaz, Jimmy Espinoza, Darrell L. Cass, Oluyinka O. Olutoye, Olutoyin A. Olutoye, Stephen Welty, David R. Roth, Michael A. Belfort, Michael C. Braun; Pediatr Nephrol. 2016 Apr;31(4):605-12. doi: 10.1007/s00467-015-3246-8. Epub 2015 Nov 2.

Prenatal Diagnosis and Perinatal Outcomes of Congenital Megalourethra: A Multicenter Cohort Study and Systematic Review of the Literature
Amirhossein Moaddab, Nicolas Sananes, Simone Hernandez-Ruano, Ingrid Schwach Werneck Britto, Yair Blumenfeld, François Stoll, Romain Favre, Rodrigo Ruanol; J Ultrasound Med. 2015 Nov;34(11):2057-64. doi: 10.7863/ultra.14.12064. Epub 2015 Oct 7.

Fetal intervention for severe lower urinary tract obstruction: a multicenter case-control study comparing fetal cystoscopy with vesicoamniotic shunting.
Ruano R, Sananes N, Sangi-Haghpeykar H, Hernandez-Ruano S, Moog R, Becmeur F, Zaloszyc A, Giron AM, Morin B, Favre R. Ultrasound Obstet Gynecol. 2015 Apr;45(4):452-8. Epub 2015 Mar 2.  

Outcomes of fetuses with lower urinary tract obstruction treated with vesicoamniotic shunt: a single-institution experience.
Ethun CG, Zamora IJ, Roth DR, Kale A, Cisek L, Belfort MA, Haeri S, Ruano R,Welty SE, Cassady CI, Olutoye OO, Cass DL. J Pediatr Surg. 2013 May;48(5):956-62.

Lung Lesions/CCAM

Are all pulmonary hypoplasias the same? A comparison of pulmonary outcomes in neonates with congenital diaphragmatic hernia, omphalocele and congenital lung malformation.
Akinkuotu AC, Sheikh F, Cass DL, Zamora IJ, Lee TC, Cassady CI, Mehollin-Ray AR, Williams JL, Ruano R, Welty SE, Olutoye OO. J Pediatr Surg. 2015 Jan;50(1):55-9. Epub 2014 Dec 19

Fetal MRI lung volumes are predictive of perinatal outcomes in fetuses with congenital lung masses.
Zamora IJ, Sheikh F, Cassady CI, Olutoye OO, Mehollin-Ray AR, Ruano R, Lee TC, Welty SE, Belfort MA, Ethun CG, Kim ME, Cass DL. J Pediatr Surg. 2014 Jun;49(6):853-8; discussion 858.    

EXIT-to-resection for fetuses with large lung masses and persistent mediastinal compression near birth.
Cass DL, Olutoye OO, Cassady CI, Zamora IJ, Ivey RT, Ayres NA, Olutoye OA, Lee TC. J Pediatr Surg. 2013 Jan;48(1):138-44.    

Defining hydrops and indications for open fetal surgery for fetuses with lung masses and vascular tumors.
Cass DL, Olutoye OO, Ayres NA, Moise KJ Jr, Altman CA, Johnson A, Cassady CI, Lazar DA, Lee TC, Lantin MR.  J Pediatr Surg. 2012 Jan;47(1):40-5.  

Fetal lung interstitial tumor: a cause of late gestation fetal hydrops.
Lazar DA, Cass DL, Dishop MK, Adam K, Olutoye OA, Ayres NA, Cassady CI, Olutoye OO. J Pediatr Surg. 2011 Jun;46(6):1263-6.  

Prenatal diagnosis and outcome of fetal lung masses.
Cass DL, Olutoye OO, Cassady CI, Moise KJ, Johnson A, Papanna R, Lazar DA, Ayres NA, Belleza-Bascon B.  J Pediatr Surg. 2011 Feb;46(2):292-8.  

Prenatal presentation and outcome of children with pleuropulmonary blastoma.
Miniati DN, Chintagumpala M, Langston C, Dishop MK, Olutoye OO, Nuchtern JG, Cass DL. J Pediatr Surg. 2006 Jan;41(1):66-71.  

Elevated platelet-derived growth factor-B in congenital cystic adenomatoid malformations requiring fetal resection.

Liechty KW, Crombleholme TM, Quinn TM, Cass DL, Flake AW, Adzick NS. J Pediatr Surg. 1999 May;34(5):805-9; discussion 809-10. J Pediatr Surg. 2015 Jan;50(1):55-9. Epub 2014 Dec 19

Increased cell proliferation and decreased apoptosis characterize congenital cystic adenomatoid malformation of the lung.
Cass DL, Quinn TM, Yang EY, Liechty KW, Crombleholme TM, Flake AW, Adzick NS.J Pediatr Surg. 1998 Jul;33(7):1043-6; discussion 1047.

Cystic lung lesions with systemic arterial blood supply: a hybrid of congenital cystic adenomatoid malformation and bronchopulmonary sequestration.
Cass DL, Crombleholme TM, Howell LJ, Stafford PW, Ruchelli ED, Adzick NS. J Pediatr Surg. 1997 Jul;32(7):986-90.

Maternal Outcomes following Fetal Surgery

Maternal morbidity and reproductive outcomes related to fetal surgery.
Zamora IJ, Ethun CG, Evans LM, Olutoye OO, Ivey RT, Haeri S, Belfort MA, Lee TC, Cass DL.J Pediatr Surg. 2013 May;48(5):951-5.

Multiple Gestations

Clinical significance of amniotic fluid sludge in twin pregnancies with a short cervical length.
Boyer A, Cameron L, Munoz-Maldonado Y, Bronsteen R, Comstock CH, Lee W, Goncalves LF. Am J Obstet Gynecol. 2014;211:506.e1-9. PMID: 24881831

Does Early Second-Trimester Sonography Predict Adverse Perinatal Outcomes in Monochorionic Diamniotic Twin Pregnancies?
M Baraa Allaf, Winston A Campbell, Anthony M Vintzileos, Sina Haeri, Pouya Javadian, Amir A Shamshirsaz, Paul Ogburn, Reinaldo Figueroa, Joseph Wax, Glenn Markenson, [...], Rodrigo Ruano, Haleh Sangi-Haghpeykar, Bahram Salmanian, Marjorie Meyer, Jeffery Johnson, Ali Ozhand, Sarah Davis, Adam Borgida, Michael A Belfort, Alireza A Shamshirsaz; J Ultrasound Med. 2014 Sep;33(9):1573-8. doi: 10.7863/ultra.33.9.1573.

Neural Tube defects (NTD) or Spina bifida

Spina bifida is a type of birth defect that occurs when the spine and spinal cord form improperly, resulting in severe to mild motor and cognitive disabilities. Also known as a neural tube defect, spina bifida can be diagnosed during pregnancy or after birth.

Optimal Delivery Mode for NTD Patients

Despite significant advances in the prevention, diagnosis and treatment of neural tube defects in recent decades, there remains controversy regarding the optimal mode of delivery for babies with neural tube defects who have not undergone prenatal repair. Several reports from the 1970s and 1980s suggested vaginal delivery could negatively impact neurological function in these babies. However, a recent systematic review and meta-analysis conducted by our experts, and led by Dr. Ahmed Nassr, did not find this to be true, suggesting vaginal birth could be a safe option for such babies.

Safety of Fetoscopic and Open MMC Surgeries

Prenatal repair of myelomeningocele (MMC), one of the most common and severe forms of spina bifida, is shown to improve motor function and is increasingly being used to treat babies diagnosed in utero with spina bifida. Hysterotomy, or open fetal surgery to repair the defect using an incision in the uterus, is associated with some complications, leading to the development of minimally invasive fetoscopic surgical approaches in recent years to improve neurological outcomes while reducing fetal and maternal morbidity.

Our experts are recognized leaders in the area of neural tube defects and are actively engaged in developing new and better treatment options for patients.

A major concern regarding the new fetoscopic approaches is the effect of carbon dioxide (CO2), which is used to inflate the uterus, on fetal development and the risk of fetal acidosis. In a recent study, a team of Texas Children’s Fetal Center experts, led by Magdalena Sanz Cortes, fetal surgeon at Texas Children’s Pavilion for Women, performed the first-ever detailed assessment of the effects of fetoscopic and open MMC repair on fetal and postnatal growth and found no significant differences. Additionally, they did not observe any adverse effects due to CO2 exposure, supporting the safety of the fetoscopic procedure.

In a separate retrospective study, a team of physicians led by Dr. Sanz Cortes compared open and fetoscopic neural tube defect repair procedures for any alterations in placental and/or amniotic membranes. They did not find any signs of inflammation or cell death in placental/amniotic membranes or observe any negative outcomes in patients who underwent the surgeries.

A recent study of 34 patients who underwent second trimester fetoscopic neural tube defect repair at Texas Children’s Pavilion for Women showed that despite fetoscopic repair these babies can be delivered at advanced gestational ages.

Hydrocephalus and Neural Tube Defects

Babies with neural tube defects often experience a condition called hydrocephalus, where excess cerebrospinal fluid leaks into the brain’s ventricles (cavities). Significant hydrocephalus is associated with brainstem compression, a leading cause of death in infants with neural tube defects.

A common surgical way to treat hydrocephalus is to place a shunt (small drainage tube) in the brain to relieve the pressure caused by excess fluid accumulation. This intervention, known as ventriculoperitoneal (VP) shunting, requires lifelong monitoring and the majority of patients (75%) require additional shunt procedures over time. Most babies (82%) with neural tube defects who undergo postnatal repair require VP shunting in the first year after birth, whereas a significantly smaller number (40%) of those who undergo repair before birth need VP shunting.

Recently, Dr. Sanz Cortes led a retrospective study to find reliable clinical predictors of infants likely to need hydrocephalus treatment (HT) after prenatal repair of myelomeningocele, to help establish realistic expectations and appropriately plan for postnatal care needs.

They found that a detailed in‐utero MRI assessment of the lowest part of the brain for any downward movements, conducted six weeks after prenatal repair, is a reliably good predictor for whether these infants will develop hydrocephalus and need postnatal hydrocephalus treatment. This metric provided a more accurate estimate than prenatal ultrasound or MRI ventricular assessment alone.

The predictors developed in this study will benefit families and healthcare providers by aiding in prenatal counseling and delivery planning, including selection of a medical center best suited to optimize outcomes for these babies – namely a tertiary medical center with cutting-edge fetal imaging technology and specialized postoperative neurosurgical care.

Fetoscopic Repair of Meningomyelocele.
Belfort MA, Whitehead WE, Shamshirsaz AA, Ruano R, Cass DL, Olutoya OO. Obstet Gynecol. 2015 Apr 28. [Epub ahead of print]

Communication about maternal-fetal surgery for myelomeningocele and congenital diaphragmatic hernia: preliminary findings with implications for informed consent and shared decision-making.
Blumenthal-Barby JS, Krieger H, Wei A, Kim D, Olutoye OO, Cass DL. J Perinat Med. 2015 Apr 14. pii: /j/jpme.ahead-of-print/jpm-2015-0039/jpm-2015-0039.xml. [Epub ahead of print]

Sacrococcygeal Teratoma (SCT)

Tumor volume to fetal weight ratio as an early prognostic classification for fetal sacrococcygeal teratoma.
Rodriguez MA, Cass DL, Lazar DA, Cassady CI, Moise KJ, Johnson A, Mushin OP, Hassan SF, Belleza-Bascon B, Olutoye OO. J Pediatr Surg. 2011 Jun;46(6):1182-5.

Twin-Twin Transfusion Syndrome

Comparison between laparoscopically assisted and standard fetoscopic  laser ablation in patients with anterior and posterior placentation in twin-twin transfusion syndrome: a single center study

Shamshirsaz AA, Javadian P, Ruano R, Haeri S, Sangi-Haghpeykar H, Lee TC, Molohon J, Cass DL, Salmanian B, Mollett L, Moaddab A, Espinosa J, Olutoye OO, Belfort MA.. Prenat Diagn. 2015 Apr;35(4):376-81. Epub 2015 Mar 1.  

Fetoscopic laser ablation of placental anastomoses in twin-twin transfusion syndrome using 'Solomon technique'

Ruano R, Rodo C, Peiro JL, Shamshirsaz AA, Haeri S, Nomura ML, Salustiano EM, de Andrade KK, Sangi-Haghpeykar H, Carreras E, Belfort MA.. Ultrasound Obstet Gynecol. 2013 Oct;42(4):434-9. Epub 2013 Sep 2.

Vasa previa

Vasa previa: clinical presentations, outcomes, and implications for management
Bronsteen R, Whitten A, Balasubramanian M, Lee W, Lorenz R, Redman M, Goncalves L,  Seubert D, Bauer S, Comstock C..  Obstet Gynecol  2013; 122: 352-7.

Fetoscopic laser ablation of vasa previa for a fetus with a giant cervical lymphatic malformation.
Hosseinzadeh P, Shamshirsaz AA, Cass DL, Espinoza J, Lee W, Salmanian B, Ruano R, Belfort MA. Ultrasound Obstet Gynecol. 2015 Jan 22.  


For more information or to schedule an appointment,

call Texas Children’s Fetal Center at 832-822-2229 or 1-877-FetalRx (338-2579) toll-free.

Our phones are answered 24/7. Immediate appointments are often available.