Fetal and Postnatal Effects of Hypoxia

Principal Investigator(s):

  • Richard A. Jonas, MD
  • Mary T. Donofrio, MD
  • Children’s National Medical Center


Project Abstract:

Background:
Brain injury and developmental delay are among the most important problems in babies who must undergo cardiac surgery for congenital heart disease (CHD). Congenital brain abnormalities and evidence of brain injury from decreased oxygen levels and abnormal blood flow in fetuses are thought to contribute to the neurologic abnormalities found in infants with CHD. The challenge for investigators is to determine how much impairment is related to limited potential from events in the womb versus acquired damage after birth. This knowledge is fundamental to the design of treatment strategies to best care for high-risk babies with CHD.

Objectives:
This research will determine if there are factors which put infants with complex CHD at increased risk for brain injury due to abnormalities in blood flow to the brain that occur in the womb as a result of CHD. This study will show whether brain abnormalities identified at birth by magnetic resonance imaging (MRI) are related to blood flow alterations in the womb, and whether brain abnormalities found at birth are worsened by low brain oxygen levels that occur before, during, and after heart surgery.

The specific aims of this study will be to show that abnormalities in blood flow in the brain assessed by ultrasound in fetuses with complex CHD are associated with abnormal brain findings on MRI obtained in the newborn period prior to surgery, and that sustained low oxygen levels in the brain measured in newborns using near infra-red spectroscopy (NIRS) monitoring before, during, and after repair of CHD, are associated with new or worsened findings on brain MRI obtained after surgery. A secondary aim will be to show that blood flow in the brain assessed by ultrasound in fetuses with complex CHD and preoperative brain abnormalities suggestive of delayed brain maturity will be associated with an increased frequency and/or severity of postoperative brain abnormalities shown to be associated with decreased brain oxygen levels.

We hypothesize that decreased resistance to blood flow in the major brain arteries in fetuses with complex CHD will be associated with preoperative abnormalities on MRI suggestive of brain injury or delayed maturity, and that low brain oxygen levels measured during surgery or in the postoperative period in newborns undergoing repair of complex CHD will be associated with new or worsened abnormalities on postoperative brain MRI. We also hypothesize that altered brain blood flow in fetuses will result in delayed brain maturity in newborns with complex CHD, and that the finding of delayed maturity will be associated with more frequent or worse brain injury that occurs as a result of low brain oxygen levels.

Methods:
The proposed study will identify fetuses diagnosed in the womb with CHD and will follow them through the remainder of the prenatal period, and postnatally prior to, during, and after surgical repair of their heart defects. While in the womb, fetuses will have brain blood flow assessment at 4 week intervals by ultrasound. Postnatally, they will have brain MRI using standard imaging in addition to new techniques called spectroscopy and diffusion tensor imaging prior to surgery and 3 to 4 weeks post-surgery. Brain oxygen levels will be recorded with NIRS before, during, and after surgery. Neurodevelopmental examination at 6, 15, and 21 months will be assessed as part of an ongoing follow-up study.

Impact:
This study may identify critical time points during the fetal, preoperative, intraoperative, and postoperative course that have the greatest impact on the neurodevelopmental outcome of high-risk infants with complex CHD. This study will provide useful information about the utility of specialized brain imaging with MRI, and brain oxygen monitoring with NIRS to identify newborns with CHD at risk for brain injury and poor neurodevelopmental outcome. If determined to beneficial, medical care strategies to improve brain oxygen levels can be designed with the ultimate goal being to improve long-term neurodevelopmental outcome for babies with CHD.