Etiology and Ontogeny of Cerebral Palsy: Implications for Practice and Research
Mark I Evans1,2,3, David W Britt4, Lawrence D Devoe5
1Fetal Medicine Foundation of America, New York, NY, USA. evans@compregen.com.
Insights
Genetic factors cause at least one-third of cerebral palsy (CP) cases in term infants, challenging the focus on labor-related causes. New diagnostic techniques improve understanding and categorization of CP etiology.
Area of Science:
- Neurology
- Genetics
- Obstetrics
Background:
- Cerebral palsy (CP) is a group of neurologic disorders with diverse causes.
- Electronic fetal monitoring (EFM) use has increased interventions without significantly reducing CP incidence in term infants.
- Litigation over CP etiology highlights disputes about its causes, often favoring plaintiffs.
Purpose of the Study:
- To discuss previous attempts to understand CP etiologies and ontogenies.
- To explore how new diagnostic techniques improve CP case detection and understanding.
- To propose a spectrum for categorizing CP cases based on etiology and timing.
Main Methods:
- Review of previous studies on CP etiology.
- Analysis of recent advances in genetic testing, including whole exome sequencing.
- Development of a proposed categorization spectrum for CP cases.
Main Results:
- At least one-third of CP cases in term infants are genetic, not labor-related.
- Genetic testing reveals non-labor-related origins for a significant portion of CP cases.
- A new framework is proposed to categorize CP based on five etiological groups.
Conclusions:
- CP etiology is complex, with significant contributions from genetic and non-labor-related factors.
- Advances in genetic testing are crucial for accurate CP diagnosis and understanding.
- A refined categorization of CP cases is needed to guide prevention and management strategies.
Abstract:
Cerebral palsy (CP) has been recognized as a group of neurologic disorders with varying etiologies and ontogenies. While a percentage of CP cases arises during labor, the expanded use of electronic fetal monitoring (EFM) to include prevention of CP has resulted in decades of vastly increased interventions that have not significantly reduced the incidence of CP for infants born at term in the USA. Litigation alleging that poor obstetrical practice caused CP in most of these affected children has led to contentious arguments regarding the actual etiologies of this condition and often resulted in substantial monetary awards for plaintiffs. Recent advances in genetic testing using whole exome sequencing have revealed that at least one-third of CP cases in term infants are genetic in origin and therefore not labor-related. Here, we will present and discuss previous attempts to sort out contributing etiologies and ontogenies of CP, and how these newer diagnostic techniques are rapidly improving our ability to better detect and understand such cases. In light of these developments, we present our vision for an overarching spectrum for proper categorization of CP cases into that the following groups: (1) those begun at conception from genetic causes (nonpreventable); (2) those stemming from adverse antenatal/pre-labor events (possibly preventable with heightened antepartum assessment); (3) Those arising from intrapartum events (potentially preventable by earlier interventions); (4) Those occurring shortly after birth (possibly preventable with closer neonatal monitoring); (5) Those that appear later in the postnatal period from non-labor-related causes such as untreated infections or postnatal intracranial hemorrhages.
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