A new report shows that monitoring and early intervention may help reduce adverse outcomes and malpractice claims.
Dr. Lockwood, Editor-in-Chief, is Dean of the Morsani College of Medicine and Senior Vice President of USF Health, University of South Florida, Tampa. He can be reached at DrLockwood@advanstar.com.
To get a sense of the magnitude of the medicolegal threat and economic drain posed by the plaintiff’s bar from cerebral palsy (CP) lawsuits, just google “cerebral palsy lawsuits.” You will be astonished by the misinformation and recklessness contained in many of the 350,000-plus sites that come up. Into this sea of misinformation sails the second edition of ACOG’s Neonatal Encephalopathy and Neurologic Outcome.1
ACOG’s Task Force on Neonatal Encephalopathy was commissioned by President Richard Waldman, MD, and chaired by Mary D’Alton, MD. At more than 230 pages, the report is not for the faint of heart, but it is crammed with the latest findings on the etiology, diagnosis, prevention, and treatment of neonatal encephalopathy (NNE) and CP.
I encourage all ob/gyns to read it carefully, and it is a must-read for department chairs, residency program directors, and those involved in hospital patient safety efforts.
First, definitions: NNE is defined as the clinical syndrome of “disturbed neurological function in the earliest days of life in an infant born at or beyond 35 weeks of gestation, manifested by a subnormal level of consciousness or seizures and often accompanied by difficulty with initiating and maintaining respiration and depression of tone and reflexes.”1
CP describes a cluster of disorders manifest by nonprogressive motor disabilities (spasticity, dyskinesis, and ataxia) that can occur to infants born at any gestational age. Not all cases of NNE result in CP and not all cases of CP are associated with prodromal NNE. The risk of CP increases with earlier gestational ages at delivery, with very preterm delivery (<32 weeks’ gestation) being the single-greatest risk factor. Hypoxic-ischemic encephalopathy (HIE) is but one of many causes of both NNE and CP. Neonatal encephalopathy complicates 2.7 to 3.3 per 1000 live births, CP 2 to 2.5/1000 live births, and HIE 1.3 to 1.7/1000 live births.1 The rates of CP among term infants have remained remarkably stable over time at 1.4 to 1.8 per 1000, despite a significantly increased cesarean delivery rate.1 The occurrence of CP without antecedent NNE excludes HIE as a cause.
Prior epidemiologic studies suggested that 69% of NNE cases were the result of factors occurring prior to the onset of labor, whereas only 29% were associated with intrapartum events and only 5% could be exclusively linked to intrapartum factors.2 Major risk factors for NNE include preterm and postterm birth, fetal growth restriction, preeclampsia, perinatal infections, chorioamnionitis, maternal thyroid disease, placental abnormalities, infertility treatment with resultant multiple gestations, and prematurity.
Our ability to determine timing and etiology of NNE/CP has vastly improved with the introduction of early (24 to 96 hours of birth) and sophisticated magnetic resonance imaging (MRI) technologies. While the focus of the first edition of ACOG’s Neonatal Encephalopathy and Neurologic Outcome monograph was on the apparent low prevalence of intrapartum hypoxic-ischemic events in the genesis of NNE/CP, recent MRI data suggest a far more common role for peripartum and intrapartum factors.
Advances in MRI include use of diffusion-weighted imaging, which measures random self-diffusion of water through neural tissue, and MR spectroscopy, in which the presence and relative abundance of specific molecular markers of neural injury (eg, lactate-to-N-acetylaspartate ratios) can be discerned over specific locations in the brain (eg, the thalamus). While early MRI assists in timing insults, repeat MRI at 10 days (7–21 days) can more precisely characterize the extent of lesions and provide crucial prognostic information.
These studies suggest that up to 80% of term NNE cases are in fact acute, although such studies cannot differentiate insults occurring in labor from those occurring within 24 hours or a few days of birth. Two primary patterns of acute neural injury have been observed that are associated with CP: 1) basal-ganglia-thalamus injury; and 2) watershed or borderline cortical white-matter injury. Animal studies suggest that the former pattern is associated with acute, near-total “asphyxia” and the latter with a less severe but more prolonged asphyxial process. If either of these 2 pathologic processes becomes extreme, a more global pattern of brain injury develops, resulting in death.
The impact of hypoxic-ischemic insults on the fetal and neonatal brain is dependent on not only the severity and duration of oxygen deprivation but also gestational age. Older fetuses have greater neural vulnerability, as well as concomitant fever and hypoglycemia, which greatly exacerbate hypoxic-ischemic injuries.
Different neural structures have different intrinsic metabolic rates, and thus, varying vulnerability to hypoxia. For example, the higher metabolic rates of the thalamus, basal ganglia, and other subcortical nuclei render these structures more vulnerable than the cerebral cortex. In addition, prior chronic hypoxia and nutrient deprivation due to uteroplacental vascular insufficiency exacerbate acute hypoxic-ischemic effects, accounting for the strong link between CP and fetal growth restriction.
A birth weight below the third percentile is associated with an odds ratio for NNE of 38.2 (95% CI: 9.4–154.8) and an odds ratio for CP of 6.4 (95% CI: 4.2–10.1).3 This finding helps to reconcile apparently disparate epidemiologic and MRI data, suggesting that antepartum factors greatly increase the potency of intrapartum factors that drive CP. This phenomenon also accounts for the link between postdate (>42 weeks) pregnancies and NNE, with an adjusted relative risk of 13.2.4
Genetic susceptibility factors such as polymorphisms for cytokine genes may also exacerbate or attenuate inflammation-associated neural damage, helping to explain why the same insult can have such different consequences in different fetuses and why low Apgar scores and umbilical artery pH values are such poor predictors of eventual outcome.
Moreover, most of the damage to neonatal brain cells accruing from in utero hypoxic-ischemic events actually occurs following reperfusion due to the detrimental effects of excitatory amino acids, reactive oxygen species, and inflammation, which collectively trigger apoptosis. This helps explain the remarkable therapeutic benefit of hypothermia when started within 8 hours of birth. Hypothermia therapy blunts all these secondary adverse effects and significantly reduces the risk of CP in at-risk neonates with a risk ratio of 0.64 (95% CI: 0.5–0.82).1
Finally, changes in circulation in response to hypoxic-ischemic events tend to maximize cerebral blood flow while reducing blood flow to the kidneys, the gastrointestinal tract, and striated muscle. The resistance of these organs to hypoxia helps explain why mul tiorgan failure is not a universal feature of NNE due to HIE.
The use of MRI can also better define non-hypoxic-ischemic causes of NNE. Malformations (eg, lissencephaly) and perinatal stroke are easily detected by such imaging. The latter occurs in about 1/3000 live births and often presents with seizures and focal deficits including hemiplegic but not quadriplegic CP. The etiologies of most strokes are unknown, although fetal thrombophilia, infection, and maternal cocaine use are major risk factors.
Fortunately, the recurrence risk for both fetal cerebral arterial and venous thrombi is low. Conversely, absence of discrete findings on early MRI in an infant with apparent NNE should suggest genetic causes (eg, chromosomal microdeletions and inborn errors of metabolism) and can trigger timely and potentially lifesaving interventions.
While it is still very difficult to confirm that a hypoxic-ischemic event was the cause of NNE, the following criteria are suggestive:
--Apgar score <5 at 10 minutes in association with an umbilical artery pH ≤7.0 and a base deficit of ≥12 mmol/L.
--Suggestive MR neuroimaging obtained within 24 to 96 hours of birth and read by a radiologist with expertise in pediatric neuroradiology, or suggestive MR spectroscopic findings. Repeat imaging at 10 days is more predictive of the full extent of the injury.
--Presence of multisystem organ failure (although, as noted, this is not an invariable correlate to HIE-induced NNE/CP).
--Suggestive intrapartum findings:
a Sentinel hypoxic-ischemic event occurring immediately before or during labor and delivery, including uterine rupture, severe abruption, umbilical cord prolapse, amniotic fluid embolism or other causes of maternal hemodynamic collapse, and fetal exsanguination (eg, associated with vasa previa, fetal-to-maternal hemorrhage, twin demise with monochorionic placentation).
b Suggestive fetal heart rate pattern (eg, conversion of a Category 1 to Category III tracing). The observation of a Category III tracing upon admission is strong evidence of pre-existent insult and NNE with or without the subsequent diagnosis of CP may occur despite appropriate management and expeditious delivery within 30 minutes.
--Spastic quadriplegic or dyskinetic CP.
The advent of improved neonatal MR neuroimaging and MR spectroscopy suggests that a significant number of infants with NNE and subsequent CP suffered causative intrapartum or peripartum events. Although the precise timing of such insults within 24 to 48 hours of delivery cannot be established from such contemporary imaging data, increased attention must be placed on optimizing intrapartum monitoring. Detection of HIE should prompt expeditious hypothermia therapy.
Moreover, because evidence is strong that a focused patient safety program can reduce the occurrence of such adverse obstetrical outcomes and reduce malpractice claims,5,6 every obstetric unit in the United States should adopt such a program.
1. The American College of Obstetricians and Gynecologists and the American Academy of Pediatrics. Neonatal Encephalopathy and Neurologic Outcome, second edition. American College of Obstetricians and Gynecologists (ACOG). Washington, DC, 2014.
2. Badawi N, Kurinczuk JJ, Keogh JM, et al. Intrapartum risk factors for newborn encephalopathy: the Western Australian case-control study. BMJ. 1998;317(7172):1554–1558.
3. Blair E, Stanley F. Intrauterine growth and spastic cerebral palsy. I. Association with birth weight for gestational age. Am J Obstet Gynecol. 1990;162(1):229–237.
4. Badawi N, Kurinczuk JJ, Keogh JM, et al. Antepartum risk factors for newborn encephalopathy: the Western Australian case-control study. BMJ. 1998;317(7172):1549–1553.
5. Pettker CM, Thung SF, Norwitz ER, et al. Impact of a comprehensive patient safety strategy on obstetric adverse events. Am J Obstet Gynecol. 2009;200(5):492.e1-8. doi:10.1016/j.ajog.2009.01.022.
6. Pettker CM, Thung SF, Lipkind HS, et al. A comprehensive obstetric patient safety program reduces liability claims and payments. Am J Obstet Gynecol. 2014;211(4):319–325. doi:10.1016/j.ajog.2014.04.038.