Recent research

World J Pediatr. Feb;5(1):18-22.

Prenatal diagnosis and treatment planning of congenital heart defects-possibilities and limits.

Nelle M, Raio L, Pavlovic M, Carrel T, Surbek D, Meyer-Wittkopf M (2009)
Contact: Division of Neonatology, University Hospital Berne, Berne, Switzerland,

BACKGROUND: Newborns with hypoplastic left heart syndrome (HLHS) or right heart syndrome or other malformations with a single ventricle physiology and associated hypoplasia of the great arteries continue to be a challenge in terms of survival. The vast majority of these forms of congenital heart defects relate to abnormal morphogenesis during early intrauterine development and can be diagnosed accurately by fetal echocardiography. Early knowledge of these conditions not only permits a better understanding of the progression of these malformations but encourages some researchers to explore new minimally invasive therapeutic options with a view to early pre- and postnatal cardiac palliation.
DATA SOURCES: PubMed database was searched with terms of "congenital heart defects", "fetal echocardiography" and "neonatal cardiac surgery".
RESULTS: At present, early prenatal detection has been applied for monitoring pregnancy to avoid intrauterine cardiac decompensation. In principle, the majority of congenital heart defects can be diagnosed by prenatal echocardiography and the detection rate is 85%-95% at tertiary perinatal centers. The majority, particularly of complex congenital lesions, show a steadily progressive course including subsequent secondary phenomena such as arrhythmias or myocardial insufficiency. So prenatal treatment of an abnormal fetus is an area of perinatal medicine that is undergoing a very dynamic development. Early postnatal treatment is established for some time, and prenatal intervention or palliation is at its best experimental stage in individual cases.
CONCLUSION: The upcoming expansion of fetal cardiac intervention to ameliorate critically progressive fetal lesions intensifies the need to address issues about the adequacy of technological assessment and patient selection as well as the morbidity of those who undergo these procedures.

Best Pract Res Clin Obstet Gynaecol. Feb;22(1):49-61.

In-utero intervention for severe congenital heart disease.

Gardiner HM (2008).
Contact: Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College, Queen Charlotte's and Chelsea Hospital, Du Cane Road, London, W12 ONN, UK.

The concept of fetal therapy is well established for many disorders diagnosed before birth but practical issues regarding its introduction into clinical practice are more difficult. Cardiac malformations are common, with major lesions affecting about 3.5 per thousand pregnancies; however, only a small proportion of these is likely to benefit from an intrauterine intervention. In addition, there are no good animal models of human cardiac disease and our knowledge of the underlying mechanisms is at best sketchy. This combination of factors has resulted in slow progress in developing effective therapies for the intrauterine management of cardiac disease. Recent research and clinical developments have included percutaneous valvuloplasty for severe aortic and pulmonary stenosis, perforation of the closed or restrictive inter-atrial septum and pacing for complete heart block. Progress in these endeavours has been variable but - overall - shows promise for treatment of the human fetus.

Ann Thorac Surg. 2008 May;85(5):1719-27.

Fetal stress response to fetal cardiac surgery.

Lam CT, Sharma S, Baker RS, Hilshorst J, Lombardi J, Clark KE, Eghtesady P (2008).
Contact: Division of Cardiothoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3032, USA.

BACKGROUND: A deleterious fetal stress response, although not fully elucidated, may account for poor outcomes after experimental fetal cardiac surgery. We set out to characterize this fetal stress response and its potential role in placental dysfunction.
METHODS: Fifteen ovine fetuses at gestational day 100 to 114 were placed on extracorporeal support for 30 minutes and were then followed 2 hours after cardiopulmonary bypass. Fetal plasma samples were analyzed for vasopressin, cortisol, and beta-endorphin levels, and correlated to fetal hemodynamics and placental gas exchange.
RESULTS: Unique temporal patterns of response were seen in release of the three stress hormones. Vasopressin demonstrated the most profound and early response followed by cortisol and beta-endorphin, the latter continuing to rise in the post-bypass period. A sharp rise in fetal mean arterial pressure and placental vascular resistance strongly correlated with rising vasopressin levels. Post-bypass deterioration of fetal gas exchange and hemodynamics correlated with the ensuing rise in cortisol and beta-endorphin. Rising fetal lactate levels correlated with elevations in all three stress hormones.
CONCLUSIONS: Fetal cardiopulmonary bypass leads to a profound, early rise in vasopressin concentrations that strongly correlates with placental dysfunction after fetal bypass. Vasopressin may play an important mechanistic role in pathogenesis of this placental dysfunction.

Early Hum Dev. Mar;84(3):149-53.

Controversies of fetal cardiac intervention

Pavlovic M, Acharya G, Huhta JC. (2008).
Contact: Department of Pediatrics, University of South Florida College of Medicine and All Children's Hospital, Children's Research Institute, St. Petersburg, FL, USA.

Remarkable advances in ultrasound imaging technology have made it possible to diagnose fetal cardiovascular lesions as early as 12-14 weeks of gestation and to assess their physiological relevance by echocardiography. Moreover, invasive techniques have been developed and refined to relieve significant congenital heart disease (CHD), such as critical aortic and pulmonary stenoses in the pediatric population including neonates. Recognition of the fact that certain CHDs can evolve in utero, and early intervention may improve the outcome by altering the natural history of such conditions has led to the evolution of a new fetal therapy, i.e. fetal cardiac intervention. Two entities, pulmonary valvar atresia and intact ventricular septum (PA/IVS) and hypoplastic left heart syndrome (HLHS), are associated with significant morbidity and mortality even with postnatal surgical therapy. These cases are believed to occur due to restricted blood flow, leading to impaired growth and function of the right or left ventricle. Therefore, several centers started the approach of antenatal intervention with the primary goal of improving the blood flow through the stenotic/atretic valve orifices to allow growth of cardiac structures. Even though centers with a reasonable number of cases seem to have improved the technique and the immediate outcome of fetal interventions, the field is challenged by ethical issues as the intervention puts both the mother and the fetus at risk. Moreover, the perceived benefits of prenatal treatment have to be weighed against steadily improving postnatal surgical and hybrid procedures, which have been shown to reduce morbidity and mortality for these complex heart defects. This review is an attempt to provide a balanced opinion and an update on fetal cardiac intervention.

Fetal Diagn Ther.;23(3):237-44.

Fetal cardiocentesis: a review of indications, risks, applications and technique.

Sarno AP Jr, Wilson RD (200).
Contact: Maternal-Fetal Medicine Section, Perinatal Center, St. Luke's Hospital and Health Network, Bethlehem, Pa 18015, USA.

Objectives: To review the indications, applications and technique of fetal cardiocentesis.
Methods: Review of published case reports and case series of fetal cardiocentesis utilizing the PubMed search engine of the National Library of Medicine.
Results: Case reports and case series demonstrate that fetal cardiocentesis may be an alternative method by which to facilitate prenatal diagnosis, intravascular therapy, multifetal and selective fetal reduction and in utero therapy of congenital heart disease. However, procedure-associated risk is higher than with cordocentesis and may limit use of this procedure.
Conclusions: Fetal cardiocentesis may be a reasonable option to obtain fetal intravascular access and facilitate therapeutic interventions when cordocentesis fails or is not feasible. However, expected benefit must clearly outweigh the procedure-associated risk.

World J Pediatr. Feb;4(1):5-7.

Fetal cardiac surgery--a big challenge in the 21st century.

Su ZK, Chen E (2008).

No abstract available.

Heart Rhythm. 2008 Sep;5(9):1347-9.

Managing the fetus with atrioventricular block.

Weber R, Golding F, Jaeggi E (2008)
Contact: Fetal Cardiac Program, Division of Cardiology, the Hospital for Sick Children, University of Toronto, Ontario, Canada

No abstract available.