Quantification of Brain and Kidney Perfusion Before, During, and After Hypothermia Treatment in Neonates With Perinatal Asphyxia Using Contrast-enhanced Ultrasound

Perinatal asphyxia (PA) is the reduced supply of oxygen to vital organs during or immediately after birth. PA is one of the most common causes of neonatal mortality in full-term infants worldwide and of hypoxic-ischemic encephalopathy (HIE) with subsequent neurological deficits (spastic cerebral palsy). In addition to brain damage, perinatal asphyxia often leads to dysfunction of other organs. It is not uncommon for this to be accompanied by transient renal failure.

Hypothermia treatment is an established therapeutic measure for neuroprotection in clinical indications of HIE. This involves lowering the core body temperature of affected children to 33.5°C for 72 hours. The therapeutic effect is thought to be due to multifactorial mechanisms, including a reduction in endothelial dysfunction, reduced excretion of free radicals and attenuation of the inflammatory cascade.

In the guidelines for hypothermia treatment in neonatal asphyxia, regular ultrasound examinations are prescribed to clarify damage to the central nervous system (CNS) before, during and after hypothermia treatment.1 In infants, transfontal ultrasound makes it possible to visualize brain structures, vessels and their flow velocities.

The intravenous use of ultrasound contrast enhancers as an aid also opens up the possibility of recording the tissue perfusion of the CNS and kidneys, including the smallest vessels.8 This could provide significantly more information compared to conventional methods and expand our knowledge of the pathophysiology and individual status of tissue perfusion in patients.

For example, two studies at Erlangen University Hospital have successfully used contrast-enhanced ultrasound (CEUS) with the contrast agent known as SonoVue® to visualize postoperative perfusion of the brain after pediatric cardiac surgery.

In this clinical study, the new CEUS measurement and imaging technique will be used before, during and after hypothermia treatment in neonates with asphyxia. A contrast agent (SonoVue®) will be administered during the routine ultrasound examination and improved tissue visualization will be achieved. The aim is to gain new insights into brain and kidney perfusion as part of the treatment and to better assess the extent of organ damage in the individual patient through more specific vascular imaging. Improved visualization and assessment of the end-stream area will provide information on processes that promote the development of HIE and renal failure. Finally, the aim is to compare diagnostic and prognostic methods with the currently recommended measures. The CEUS is to be examined as a possible diagnostic imaging tool and possibly a supplement to existing diagnostic methods.

Inclusion criteria

• Fulfillment of the inclusion criteria for hypothermia treatment according to the AWMF guideline
• Severe acidosis (pH ≤7.0 or a base deficit ≥16 mmol/l) in umbilical cord blood or a blood sample from the first hour of life, and
• clinical signs of moderate or severe encephalopathy (severity grade 2 or 3 according to Sarnat & Sarnat), and
• postnatal age ≤6h, and
• gestational age ≥36 weeks' gestation
• Consent of the parents/legal guardians
• Time 1 (before the start of hypothermia treatment)

• Informing the parents/legal guardians present on site despite an emotionally stressful situation with high individual benefit for the patient
• If only one parent is present and able to provide information, their consent is sufficient - the second parent is informed repeatedly when they regain the ability to provide information
• Information adapted to the emergency situation, addressing the personal situation and comprehensible presentation of the plan
• Time 2 (during hypothermia treatment)

-->Offer of a further informative discussion/repeated explanation with the parents/legal representatives before the second measurement in order to answer any questions that may have arisen

• Suitable acoustic window
• Availability of the qualified examiner

Exclusion criteria

• Lack of consent of at least one parent
• Pre-existing brain malformations
• Absence of the competent examiner