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Birth Asphyxia
Introduction
Perinatal asphyxia occurs when blood flow or gas exchange to or from the fetus is disrupted immediately before, during, or after birth. This condition can lead to severe systemic and neurological complications due to reduced oxygen and blood supply to vital organs, including the brain, heart, liver, and muscles. When placental (prenatal) or pulmonary (postnatal) gas exchange is compromised, partial (hypoxia) or complete (anoxia) oxygen deprivation occurs, causing progressive hypoxemia and hypercapnia. If severe, this oxygen deficit triggers anaerobic metabolism and lactic acidosis. Neonatal hypoxic-ischemic encephalopathy (HIE) specifically refers to the neurological damage resulting from perinatal asphyxia and ischemia.[1][2]
A neonatal hypoxic event can present with:
- Metabolic acidosis
- Base deficit
- Low Apgar scores
- Presence of multiple organ-system failure
- Clinical evidence of encephalopathy, including hypotonia, abnormal oculomotor or pupillary movements, weak or absent suck, apnea, hyperpnea, or clinical seizures
- Neurologic findings that cannot be attributed to other causes such as inborn errors of metabolism, genetic disorders, congenital neurologic disorders, or medication effects
- Characteristic findings on magnetic resonance imaging (MRI).
Etiology
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Etiology
Perinatal asphyxia can occur due to any condition that affects the flow of blood or oxygen to the fetus. Etiologies include problems with maternal circulation or oxygenation, factors with the placenta, or issues intrinsic to the fetus. Some common causes include maternal hemodynamic compromise (amniotic fluid embolus, sepsis, shock), uterine conditions (uterine rupture), placenta and umbilical cord considerations (placental abruption, umbilical cord knot or compression), and infection. The asphyxia can occur immediately before the birth or can occur immediately following birth in a compromised patient requiring resuscitation.[3][4][5] Most cases of perinatal asphyxia occur intrapartum, although 20% occur antepartum, and still other cases occur in the early postnatal period. A careful obstetrical and peripartum history is essential to determine the etiology. However, only a minority of neonates with HIE will have a documented sentinel event.[6]
Epidemiology
The incidence of term perinatal asphyxia is 2 per 1000 births in high-resource countries. The rate is 10 times higher in countries with limited maternal and neonatal care access.[7] Of those infants affected, 15% to 20% die in the neonatal period, and up to 25% of survivors are left with permanent neurologic deficits.[8] In preterm infants, the cause of perinatal asphyxia is often unclear, and its incidence can be particularly high, especially in low-resource settings.[9][10][11]
Pathophysiology
Brain injury in HIE is a process that occurs via sequential stages. First, an immediate primary neuronal injury occurs due to the interruption of the oxygen and glucose supply to the brain. Depending on the acuteness of the injury, the brain may be able to redirect blood flow to protect its most vital parts, such as the brainstem and the cerebellum, which would result in injuries to the watershed areas. The basal ganglia may be affected more if the injury is more acute.[6]
The initial decrease in adenosine triphosphate (ATP) causes a failure in the ATP-dependent sodium-potassium pump. Sodium enters the cell, followed by water, causing cell swelling, widespread depolarization, and cell death. Cell death and lysis cause the release of glutamate, an excitatory amino acid, which causes an increase in intracellular calcium via N-methyl-D-aspartate channels, causing further cell death.[6] Following the immediate injury, there is a latent period of about 6 hours during which reperfusion occurs, and some cells recover; the inflammatory processes begin. Late secondary neuronal injury occurs over the next 24 to 48 hours as reperfusion results in blood flow to and from damaged areas, spreading toxic neurotransmitters and widening the area of the brain affected.
History and Physical
Perinatal asphyxia can result in systemic effects, including neurologic insult, respiratory distress and pulmonary hypertension, and liver, myocardial, and renal dysfunction. Depending on the severity and timing of the hypoxic insult, a neonate with HIE due to perinatal asphyxia may demonstrate various neurologic findings. The Sarnat staging for encephalopathy can be a helpful classification scale. In Sarnat stage I, the least severe stage, there is a generalized increased sympathetic tone, and the neonate may be hyperalert with prolonged periods of wakefulness, mydriasis, and increased deep tendon reflexes. In Sarnat stage II, the neonate may be lethargic or obtunded, with decreased tone, strong distal flexion, and generalized increased parasympathetic tone with miosis, bradycardia, and increased secretions. Seizures are common in Sarnat stage II. Sarnat stage III, the most severe, is characterized by a profoundly decreased level of consciousness, flaccid tone, decreased deep tendon reflexes, and very abnormal electroencephalogram (EEG) results. Clinical seizures are less common in Sarnat stage III due to the profound injury in the brain preventing the propagation of clinical seizures. Sarnat staging may not be as accurate in extremely preterm neonates whose neurological systems are less well-developed. In addition, preterm infants may present differently, with fewer patients showing clinical signs of seizures but more patients with white matter injury and intraventricular hemorrhage.[12]
Evaluation
An arterial blood gas screen is useful in distinguishing respiratory and metabolic acidosis and determining the degree of hypoxemia. Serum transaminase levels and coagulation factors can determine liver damage. Troponin and creatine kinase MB isoenzyme can be useful in determining myocardial insult, and creatinine and blood urea nitrogen can ascertain the extent of renal dysfunction. Physiologically stressed infants rapidly deplete glucose stores and can develop profound hypoglycemia. Frequent blood glucose checks during the critical period of resuscitation are recommended.[13][14][15]
Constant monitoring for the development of seizures or other neurological dysfunctions is also vital. If seizures are suspected, an EEG or video EEG should be obtained. MRI is frequently performed 5 to 10 days after the insult, depending on the stability of the neonate. The areas of injury vary, depending on the severity or level of the insult, but a majority of neonates with even mild HIE show evidence of brain injury.[16]
Treatment / Management
No specific management exists for preterm infants or term infants with mild injury. Therapeutic hypothermia is the treatment for moderate to severe neonatal HIE in infants over 35 weeks gestation.[17] Following the immediate primary neuronal injury, during which there is an interruption of oxygen and glucose to the brain, there is a latent period of up to 6 hours before a secondary phase of injury occurs as the injured areas are reperfused and damaged cells lyse, releasing toxic neurotransmitters. The goal of therapeutic hypothermia is to intervene during the latent period and minimize damage from the secondary neuronal injury.[18][19][20][21][22] See StatPearls' companion resource, "Neonatal Therapeutic Hyperthermia," for more information on the diagnostic criteria for initiating therapeutic hypothermia in term and near-term infants.[17] For infants not undergoing therapeutic hypothermia (such as preterm infants), normothermia should be maintained, and supportive care should be initiated.(A1)
The treatment of respiratory distress, pulmonary hypertension, coagulopathy, and myocardial dysfunction is supportive. Infants with respiratory distress and pulmonary hypertension may require intubation, surfactant, oxygen, and inhaled nitric oxide. Coagulopathy is treated with the prudent use of blood products to maintain oxygen-carrying capacity and coagulation. Myocardial dysfunction may result in a need for vasopressors. Renal dysfunction may result in oliguria or anuria; therefore, caution should be exercised when using crystalloid fluid and blood products.
Whether the clinician is maintaining normothermia in infants who have not met the criteria for therapeutic cooling or treating infants with therapeutic hypothermia, close monitoring of these other crucial functions is vital. For example, many infants with birth asphyxia will compensate for their metabolic acidosis by decreasing their carbon dioxide levels, which can further cause a decrease in oxygenation.[23] Moreover, during resuscitation, hyperoxia should also be avoided as it can increase free radical production, further causing damage to the brain and other organs.[24] In addition, given that the brain is the major consumer of glucose for the neonate, maintaining euglycemia is critical.[25] Blood pressure should also be maintained to avoid hyper- and hypotension and ensure an adequate and consistent supply of oxygen to the brain.
Differential Diagnosis
When evaluating an infant for birth asphyxia, it is essential to consider other conditions that may present with similar clinical signs. Key differential diagnoses that should be assessed to ensure accurate diagnosis and appropriate management include:
- Brain tumors
- Developmental defects
- Methylmalonic acidemia
- Propionic acidemia
- Sepsis
- Neuromuscular disorders, including neonatal myopathy
Pertinent Studies and Ongoing Trials
While therapeutic hypothermia has been proven effective for term infants with moderate-to-severe HIE, its safety and efficacy in preterm populations remain under investigation. Ongoing research is exploring the potential benefits of therapeutic hypothermia for preterm infants born between 33 and 35 weeks gestation, as well as for those with mild HIE. Studies aim to determine whether cooling therapy can reduce neurological damage and improve outcomes in these vulnerable groups and establish optimal protocols for its use. These studies' findings could expand therapeutic hypothermia's application to a broader neonatal population.
Staging
The modified Sarnat examination determines the initial stage of encephalopathy and eligibility for therapeutic hypothermia in babies over 35 weeks (see Table. Modified Sarnat Examination). Generally, an infant must show abnormalities in at least 3 categories to be considered to have encephalopathy. If there is a tie within the various categories, the level of consciousness can be used as the 'tiebreaker.' Of note, this exam is not validated for significantly preterm babies.
Table. Modified Sarnat Examination
| Category | Mild encephalopathy | Moderate encephalopathy | Severe encephalopathy |
| Level of consciousness | Excessive alertness | Lethargic | Stupor or coma |
| Activity | Normal or mildly decreased | Decreased | None |
| Tone | Increased | Decreased | Flaccid |
| Posture | Normal or mild distal flexion | Distal flexion, complete extension | Decerebrate |
| Primitive reflexes |
Normal suck Possible hyperactive Moro |
Weak suck or incomplete Moro | Absent suck or Moro |
| Autonomic system |
Normal |
Constricted pupils, or Bradycardia, or Periodic breathing |
Pupils deviated, dilated, or not reactive to light, or Variable heart rate, or Apnea |
Prognosis
Birth asphyxia is associated with high morbidity and mortality. Long-term complications can range from mild to life-threatening. The condition is reported to have a mortality of over 30%, with the majority of deaths occurring within the first few days after birth. Those infants who survive are often left with mild-to-severe neurological deficits, and they also may end up dying from aspiration or systemic infections. Long-term survivors have been found to have disabling cerebral palsy, inadequate mental development or low psychomotor scores, seizures, blindness, and severe hearing impairment.[3][26]
There are very few studies that accurately measure the degree of dysfunction in preterm babies with birth asphyxia. The long-term prognosis of these infants has been difficult to assess. Still, the injury patterns seem to differ compared to term or near-term babies.[12][27] MRI performed soon after birth can predict neurodevelopmental disability or death in infants with more severe injury but is less predictive in those with mild or moderate injury patterns.[28] While various systems have been developed, the mainstay remains the clinical exam and continued evaluation of the infants as they grow.[29][30][31]
Complications
Birth asphyxia can lead to a wide range of serious complications, affecting multiple organ systems. The brain is particularly vulnerable, often resulting in HIE, which can cause long-term neurological impairments such as cerebral palsy, developmental delays, and cognitive deficits. In severe cases, birth asphyxia may also lead to seizures, poor muscle tone, feeding difficulties, and death. Systemic complications include multi-organ dysfunction, such as renal failure, liver damage, and cardiovascular instability. Additionally, respiratory complications like persistent pulmonary hypertension and metabolic disturbances such as lactic acidosis are common. These complications can significantly impact both short- and long-term outcomes for affected infants.
Consultations
Newborns affected by birth asphyxia often require consultations with a multidisciplinary team to ensure comprehensive care. A neonatologist is essential for immediate resuscitation and ongoing management, while a pediatric neurologist may be needed to assess and monitor potential brain injury, such as HIE. Cardiologists and nephrologists may be consulted to manage heart and kidney complications, respectively, while a pulmonologist can address respiratory issues. In cases of multi-organ involvement, a pediatric intensivist might be necessary, or alternatively, a pediatric palliative care specialist. Outpatient developmental pediatricians and physical and occupational therapists are often involved early to help with developmental support and rehabilitation planning.
Enhancing Healthcare Team Outcomes
Birth asphyxia is not an uncommon event, and because of its high morbidity and mortality, the condition is best managed by a well-coordinated interprofessional team approach to ensure patient-centered care, improved outcomes, patient safety, and enhanced team performance. Neonatologists are responsible for diagnosing and implementing critical interventions like neonatal resuscitation and therapeutic hypothermia. They also develop care plans in collaboration with other specialists. Advanced practitioners and nurses play crucial roles in monitoring the infant’s condition, administering treatments, and providing bedside care, ensuring that protocols are followed precisely to minimize further injury. Pharmacists are integral to ensuring safe medication administration, particularly during neonatal resuscitation and post-asphyxia management. They provide dosing guidance for medications like anticonvulsants.
Skills in neonatal resuscitation, therapeutic hypothermia application, and multi-organ system monitoring are essential for all clinicians. Strategies involve timely intervention within the first 6 hours of life, ensuring adherence to evidence-based protocols and guidelines. Ethical responsibilities include maintaining the infant’s best interest by providing life-saving treatments while communicating transparently with the family about the prognosis, risks, and potential long-term outcomes. Ethical dilemmas can arise regarding the extent of interventions in cases with poor prognosis, where the team must consider quality of life and family wishes.
Interprofessional communication is key to seamless care coordination. Team members must regularly update one another on the infant’s evolving status, share observations, and align treatment plans to avoid errors. Care coordination also involves ensuring appropriate consultations with specialists, scheduling diagnostic imaging, and preparing for possible long-term care needs. By working collaboratively, the interprofessional healthcare team can ensure that every aspect of care is addressed, optimizing patient outcomes, enhancing team performance, and safeguarding patient safety through clear communication and strategic care planning.
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