Protecting the newborn brain—the final frontier in obstetric and neonatal care
For newborns with encephalopathy, therapeutic hypothermia can improve brain function and long-term developmental outcomes. For ObGyns, being a part of joint care discussions is important as this therapy is used more frequently.
Dr. Barbieri is Editor in Chief, OBG Management; Chair, Obstetrics and Gynecology, Brigham and Women’s Hospital; and Kate Macy Ladd Professor of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, Massachusetts.
Dr. Barbieri reports no financial relationships relevant to this article.
During the past 40 years neonatologists have discovered new treatments to improve pulmonary and cardiovascular care of preterm newborns, resulting in a dramatic reduction in newborn mortality and childhood morbidity. Important advances include glucocorticoid administration to mothers at risk for preterm birth, surfactant and nitric oxide administration to the newborn, kangaroo (or skin-to-skin) care, continuous positive airway pressure, and high-frequency ventilation.1 In 1960, only 5% of 1,000-g newborns survived. In 2000, 95% of 1,000-g newborns survive.1
The successes in pulmonary and cardiovascular care have revealed a new frontier in neonatal care: the prevention of long-term neurologic disability by the early treatment of newborn encephalpathy with therapeutic hypothermia. This novel undertaking is an important one; approximately 1 in 300 newborns are diagnosed with encephalopathy.2
Until recently there were no proven treatments for newborns with encephalopathy. However, therapeutic hypothermia now has been proven to be an effective intervention for the treatment of moderate and severe encephalopathy,3,4 and its use is expanding to include mild cases.
This increased use can lead to more complex situations arising for obstetricians, for when a neonatologist decides to initiate therapeutic hypothermia of a newborn the parents may wonder if the obstetrician’s management of labor and delivery was suboptimal, contributing to their baby’s brain injury.
Therapeutic hypothermia: The basics First, we need to define therapeutic hypothermia. Both head hypothermia and whole-body hypothermia are effective techniques for the treatment of newborn encephalopathy.3,4 Most centers use whole-body (FIGURE) rather than head, hypothermia because it facilitates access to the head for placement of electroencephalogram (EEG) sensors.
Whole-body cooling wrap to induce therapeutic newborn hypothermia.
The key principles of therapeutic hypothermia include5,6:
Initiate hypothermia within 6 hours of birth.
Cool the newborn to a core temperature of 33.5° to 34.5°C (92.3° to 94.1°F). Some centers focus on achieving consistent core temperatures of 33.5°C (92.3°F).
Monitor core temperature every 5 to 15 minutes.
Cool the newborn for 72 hours.
Obtain head ultrasonography to detect intracranial hemorrhage.
Initiate continuous or intermittent EEG monitoring.
Treat seizures with phenobarbital, lorazepam, or phenytoin.
Obtain blood cultures, a complete blood count, blood gas concentrations, alactate coagulation profile, and liver function tests.
Sedate the newborn, if necessary.
Minimize oral feedings during the initial phase of hypothermia.
Obtain sequential magnetic resonance imaging (MRI) studies to assess brain structure and function.
For all newborns with suspected encephalopathy, the placenta should be sent to pathology for histologic study.7
The data on therapy effectivenessTwo recent meta-analyses independently reported that therapeutic hypothermia reduced the risk of newborn death and major neurodevelopmental disability.3,4 The Cochrane meta-analysis reported that the therapy reduced the risk of neuromotor delay, developmental delay, cerebral palsy, and abnormal MRI results (TABLE).4 The study authors also reported that therapeutic hypothermia reduced the risk of blindness and deafness, although these effects did not reach statistical significance.4 Therapeutic hypothermia did increase the risk of newborn sinus bradycardia and thrombocytopenia.3,4 Compared with usual care, the therapy increased the average survival rate with a normal neurologic outcome at 18 months from 23% to 40%.3 It should be noted that even with therapeutic hypothermia treatment, many newborns with moderate to severe encephalopathy have long-term neurologic disabilities.
Indications for therapeutic hypothermia are expandingIn the initial clinical trials of therapeutic hypothermia, newborns with moderate to severe encephalopathy were enrolled. Typical inclusion criteria were: gestational age ≥35 or 36 weeks, initiation of therapeutic hypothermia within 6 hours of birth, pH ≤7.0 or base deficit of ≥16 mEq/L, 10-minute Apgar score <5 or ongoing resuscitation for 10 minutes, and moderate to severe encephalopathy on clinical examination.3,4 Typical exclusion criteria were: intrauterine growth restriction with birth weight less than 1,750 g, severe congenital anomalies or severe genetic or metabolic syndromes, major intracranial hemorrhage, sepsis, or persistent coagulopathy.
Given the success of therapeutic hypothermia for moderate to severe newborn encephalopathy, many neonatologists are expanding the indications for treatment. In some centers current indications for initiation of hypothermia include the following:
gestational age ≥34 weeks
suspicion of encephalopathy or a seizure event
any obstetric sentinel event (including a bradycardia, umbilical cord prolapse, uterine rupture, placental abruption, Apgar score ≤5 at 10 minutes, pH ≤7.1 or base deficit of ≥10 mEq/L or Category III tracing, or fetal tachycardia with recurrent decelerations or fetal heart rate with minimal variability and recurrent decelerations).
Suspicion for encephalopathy might be triggered by any of a large number of newborn behaviors: lethargy, decreased activity, hypotonia, weak suck or incomplete Moro reflexes, constricted pupils, bradycardia, periodic breathing or apnea, hyperalertness, or irritability.8
Coordinate neonatology and obstetric communication with the familyGiven the expanding indications for therapeutic hypothermia, an increasing number of newborns will receive this treatment. This scenario makes enhanced communication vital. Consider this situation:
