ISUOG consensus statement on current understanding of the association of neurodevelopmental delay and congenital heart disease: impact on prenatal counseling.

Abstract

An association between congenital heart disease (CHD) and neurodevelopmental delay (NDD) has long been recognized, but remains poorly understood. It is almost certainly multifactorial1-8. A number of abnormal magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) or sonographic findings, specifically abnormal or delayed sulcation, reduced brain biometry and volumes and abnormal brain biochemistry, have been described in fetuses and neonates with some forms of CHD9-17. This suggests that genetic factors3 and the prenatal environment play an important role in the determination of postnatal neurodevelopmental function, in contrast to traditional concepts attributing adverse neurodevelopmental outcomes to postnatal events such as perinatal hypoxia and perisurgical damage. Furthermore, some large cohort trials have demonstrated an increased risk of NDD mainly – but not only – in children and young adults with univentricular circulation and, to a lesser extent, in those with transposition of the great arteries (TGA)14, 18-21. The increasing supportive evidence in this field has led to the publication of an official scientific statement by the American Heart Association22, in which the conclusions are that: ‘Children with CHD are at increased risk of developmental disorder or disabilities or developmental delay’ and, therefore, ‘…surveillance, screening evaluation and re-evaluation during childhood’ are recommended to diagnose and, if possible, treat the various aspects of these disabilities. Experience in the interpretation of any prenatal imaging modality is paramount in assessing its ability to detect real disease and, hence, its true clinical importance. This can be gained only in the setting of well-designed studies. Furthermore, the full extent of clinically important NDD cannot be determined during the first years of a child's life; thus, these studies also require adequate follow-up. The deficiencies in current published studies have raised genuine and widespread concerns that a discussion of possible adverse neurodevelopmental outcomes linked to CHD may lead couples to opt for termination of pregnancy in those cases of isolated CHD that are usually associated with low mortality and low long-term morbidity, such as TGA. However, the available evidence would suggest that it is neither possible nor ethical to ignore this risk during prenatal counseling14, 17, 23. A recent survey, conducted by an ISUOG (International Society of Ultrasound in Obstetrics and Gynecology) Task Force to gauge the attitudes and perceptions of health professionals from leading referral units for CHD worldwide found significant differences in the way in which prenatal counseling is conducted, particularly between North American and European centers24. D. Paladini*, Z. Alfirevic†, J. S. Carvalho‡§, A. Khalil‡, G. Malinger¶, J. M. Martinez**, J. Rychik††, Y. Ville‡‡ and H. Gardiner§§, on behalf of the ISUOG Clinical Standards Committee. *Fetal Medicine & Surgery Unit, Istituto G.Gaslini, Genoa, Italy; †Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK; ‡Fetal Medicine Unit, St George's Hospital and St George's University of London, London, UK; §Centre for Fetal Cardiology, Royal Brompton Hospital, London, UK; ¶OB-GYN Ultrasound Unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; **Fetal Medicine, Barcelona Center for Maternal Fetal and Neonatal Medicine, Hospital Clínic and Sant Joan de Déu, University of Barcelona, Barcelona, Spain; ††Fetal Heart Program, Children's Hospital of Philadelphia, Philadelphia, PA, USA; ‡‡Maternité, Hôpital Universitaire Necker-Enfants Malades, Université Paris Descartes, Assistance Publique-Hôpitaux de Paris, Paris, France; §§The Fetal Center, University of Texas Health Science Center at Houston, Houston, TX, USA