Congenital Heart Disease in Children, Hypoxia, Neurodevelopmental Disorders, Complex Congenital Heart Disease
Conditions
Keywords
Congenital Heart Disease, Maternal Fetal, Neonatal Neurodevelopment
Brief summary
Determine 1) the impact of abnormal fetal cerebrovascular physiology with neurodevelopmental delay (ND) outcomes and 2) how this relationship is modified by patient and environmental factors such as chronic congenital heart disease (CCHD) lesion, maternal-fetal environment, and social determinants of heath (SDOH) in a diverse population using a multicenter design. Pregnant women will be approached during one of their fetal cardiology clinic visits.
Detailed description
Aim 1: Determine the association of baseline cerebrovascular resistance and reactivity and pre-operative neurobehavior in neonates with complex congenital heart disease (CCHD). Exposures: The baseline middle cerebral artery pulsatility index (MCA-PI) and change in MCA-PI. Analyses: Our principal analyses for Aim 1 will use separate linear regression models to relate the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) attention score to 1) the baseline MCA-PI while controlling for maternal age, infant sex, race/ethnicity, and SDOH measures (maternal education, socioeconomic status (SES), insurance status), and clinical site, and 2) the change in MCA-PI adjusted for baseline MCA-PI while controlling for the same set of covariates. If the NNNS attention score distribution is skewed, we will consider transformations so that model residual plots achieve approximate normality. The covariates in the above regression analyses exclude factors that may potentially lie on the causal pathway from the MCA-PI to the attention score to avoid risk of over adjustment. In secondary analyses, 2 regression analyses will be repeated after additional adjustment for the maternal-fetal environment indicator(s), CCHD category, and age at NNNS evaluation. As a secondary analysis, we will evaluate the interaction between baseline MCA-PI and change in MCA-PI. For this analysis, we will consider dichotomizing baseline MCA-PI to facilitate interpretation of the interaction effect. Aim 2: Determine the impact of patient and environmental factors on cerebrovascular resistance and reactivity Exposures: Patient factors including CCHD category, indicators of the maternal-fetal environment, and SDOH Analysis: The primary analysis for Aim 2 will investigate the joint relationship of the MCA-PI with SDOH measures and the maternal-fetal comorbidity indicator while accounting for the CCHD category (defined as Left sided obstructive lesion, Right sided obstructive lesion, Dextro-Transposition of the Great Arteries, and Other). We will apply multiple linear regression to relate the MCA-PI to the SDOH measures and a maternal-fetal comorbidity indicator for the presence of any of maternal hypertension, diabetes, pre-eclampsia, eclampsia, and abruption, prematurity, and small for gestational age. The CCHD category will also be a covariate in the regression model. Additional exploratory regression analyses will include pairwise interaction terms between the maternal-fetal comorbidity indicator(s) with the SDOH measures to assess if the association of the maternal-fetal environment indicator(s) with the MCA-PI varies across the different levels of the SDOH measures. We will perform a separate multiple regression with the change in the MCA-PI as the outcome and with the baseline MCA-PI as an additional covariate.
Interventions
PROCEDURESingle Arm
* Phase 1- Baseline: A fetal echocardiogram will be performed as part of routine standard clinical care. * Phase 2- MH: The participant will be placed on 8 litres of 100% FiO2 (inspired oxygen fraction) via a non-rebreather face mask for 10 minutes. After 10 minutes, additional images will be obtained. MH will be discontinued after additional imaging is complete. * Phase 3- Recovery: After at least 5 minutes of discontinuation of MH, additional images will be obtained to ensure any changes have returned back to baseline.
PROCEDURENeonatal Neurobehavioral Scale
Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) evaluation: All neonates with CHD expected to undergo neonatal cardiac intervention or surgery have pre-operative NNNS assessment as PCH as standard of care. The NNNS takes approximately 30 minutes to complete. It is administered by a licensed physical, speech, or occupational therapist who has completed training and additional certification. The NNNS therapist will be blinded to the results of the fetal echocardiogram and MCA-PI.
Sponsors
Primary Children's Hospital
National Heart, Lung, and Blood Institute (NHLBI)
University of Utah
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Interventional Research Design
Eligibility
Sex/Gender
FEMALE
Age
0 Years to 52 Years
Healthy volunteers
No
Inclusion criteria
* Pregnant women 18 years of age and over with a singleton fetus with known or suspected congenital heart disease anticipated to need intervention or surgery within 30 days of birth.
Exclusion criteria
* Known fetal chromosomal or genetic abnormalities * Multiple gestation pregnancy * Fetal extra-cardiac anomalies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pre-operative Neonatal Network Neurobehavioral Scale (NNNS) attention scores | <=30 days of life | The NeoNatal Neurobehavioral Scale (NNNS-II) examines the neurobehavioral organization, neurological reflexes, motor development - active and passive tone, and signs of stress and withdrawal of the at-risk and drug-exposed infant |
| Baseline MCA-PI and change in MCA-PI with Maternal Hyperoxia | <= 30 days of life | The fetal middle cerebral artery (MCA) pulsatility index (PI) |
Countries
United States
Contacts
Primary ContactWhitnee Hogan, MD
Backup ContactLisa M. Hansen, BA
Outcome results
None listed