Clinical trial NCT02996630: Assessing Neurodevelopment in Congenital Heart Disease.
Official title: Abnormal Neurodevelopment Detection in Congenital Heart Disease: Predictive Methods Based on Prenatal and Postnatal Factors.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Congenital Heart Disease
Keywords: LVOTO
Fallot
Great Arteries Transposition
Lead sponsor: Hospital Universitari Vall d'Hebron Research Institute
Sponsor class: OTHER
Collaborators: name: Hospital Sant Joan de Deu
name: Hospital Universitario La Paz
name: Hospital Universitario 12 de Octubre
name: Hospital General Universitario Gregorio Marañon
name: Fundacion Dexeus
First posted: 2016-12-19
Enrollment: 250
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns per year. Children with CHD are a known risk population for brain injury, with neurodevelopmental alterations shown over time in up to 50% of cases. No adequate description exists of the type of neurocognitive anomalies or risk factors associated with CHD, and consequently no prognostic markers that may allow identification of high-risk cases are available.

Detailed description: The main objectives of this study are: 1. to describe the neurodevelopmental outcome of patients with CHD at 24 months of age; 2. identify the subgroup with poorer outcome; and 3. evaluate the utility of fetal and postnatal diagnostic techniques for early detection of patients at risk for altered neurological outcomes.

Seven Spanish referral centers for CHD included in the research network on maternal and child health currently participating in this prospective multicentric case-control coordinated study. Fetuses with CHD (transposition of great arteries, tetralogy of Fallot, hypoplastic left heart syndrome and septal defects) will be studied from 24 weeks of gestation to 2 years of age. Diagnostic tests will be repeated throughout the study in all patients, from the fetal period to 24 months of age, and will include: fetal cerebral hemodynamic Doppler assessment, functional echocardiography, brain MRI, regional cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers analysis. Neurodevelopmental assessment will be made at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. From this data, statistical analysis will select the most useful as predictors of damage; to be then combined and create algorithms for predicting brain damage and poor neurodevelopment. Once description has been made, we will proceed to identify amongst our results, children with the poorest neurological outcome and remark possible common prenatal and early life markers in them as well as the CHD severity they present.

While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. Evidence available does not allow clinicians to assess on neurological prognosis although has opened up the possibility of finding prenatal markers of brain damage. Even though, no prospective studies have been performed until now. We present a multicentric prospective study able to recruit enough fetal CHD affected pregnancies to obtain neurological prognostic tools.

Eligibility criteria: Inclusion Criteria:

* Single pregnancies
* Major Congenital Heart Disease
* Informed Consent Signed

Exclusion Criteria:

* Major extra-cardiac malformations
* Parental Refusal to participate
* Maternal Chronic Disease
* Multiple Pregnancies

Primary outcomes:
measure: Bailey-III test punctuation
timeFrame: 45 minutes
Secondary outcomes:
measure: Biparietal diameter (mm)
timeFrame: one day
measure: Lateral sulcus depth
timeFrame: one day
measure: Cerebral insula
timeFrame: one day
measure: Brain biometries
timeFrame: one day
measure: Cerebral cingulata sulcus
timeFrame: one day
measure: Corpus callosum
timeFrame: one day
measure: Cerebellum
timeFrame: one day
measure: Umbilical doppler
timeFrame: one day
measure: Middle cerebral artery doppler
timeFrame: one day
measure: Angiogenic PLGF (placental growth factor)
timeFrame: Two days
measure: Angiogenic s-FLt (soluble fms-like tyrosine kinase)
timeFrame: Two days
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
Study officials:
affiliation: Hospital Universitari Vall d'Hebrón
name: Elisa Llurba, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002 Jun 19;39(12):1890-900. doi: 10.1016/s0735-1097(02)01886-7.
citation: Bellinger DC, Jonas RA, Rappaport LA, Wypij D, Wernovsky G, Kuban KC, Barnes PD, Holmes GL, Hickey PR, Strand RD, et al. Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. N Engl J Med. 1995 Mar 2;332(9):549-55. doi: 10.1056/NEJM199503023320901.
citation: Limperopoulos C, Majnemer A, Shevell MI, Rosenblatt B, Rohlicek C, Tchervenkov C. Neurodevelopmental status of newborns and infants with congenital heart defects before and after open heart surgery. J Pediatr. 2000 Nov;137(5):638-45. doi: 10.1067/mpd.2000.109152.
citation: Masoller N, Martinez JM, Gomez O, Bennasar M, Crispi F, Sanz-Cortes M, Egana-Ugrinovic G, Bartrons J, Puerto B, Gratacos E. Evidence of second-trimester changes in head biometry and brain perfusion in fetuses with congenital heart disease. Ultrasound Obstet Gynecol. 2014 Aug;44(2):182-7. doi: 10.1002/uog.13373. Epub 2014 Jul 8.
citation: Ruiz A, Cruz-Lemini M, Masoller N, Sanz-Cortes M, Ferrer Q, Ribera I, Martinez JM, Crispi F, Arevalo S, Gomez O, Perez-Hoyos S, Carreras E, Gratacos E, Llurba E. Longitudinal changes in fetal biometry and cerebroplacental hemodynamics in fetuses with congenital heart disease. Ultrasound Obstet Gynecol. 2017 Mar;49(3):379-386. doi: 10.1002/uog.15970.
citation: Ribera I, Ruiz A, Sanchez O, Eixarch E, Antolin E, Gomez-Montes E, Perez-Cruz M, Cruz-Lemini M, Sanz-Cortes M, Arevalo S, Ferrer Q, Vazquez E, Vega L, Dolader P, Montoliu A, Boix H, Simoes RV, Masoller N, Sanchez-de-Toledo J, Comas M, Bartha JM, Galindo A, Martinez JM, Gomez-Roig L, Crispi F, Gomez O, Carreras E, Cabero L, Gratacos E, Llurba E. Multicenter prospective clinical study to evaluate children short-term neurodevelopmental outcome in congenital heart disease (children NEURO-HEART): study protocol. BMC Pediatr. 2019 Sep 10;19(1):326. doi: 10.1186/s12887-019-1689-y.