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A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy
Published on: November 3, 2016
Does the risk of cerebral palsy increase or decrease with increasing gestational age?
K S Joseph1, Alexander C Allen, Samawal Lutfi
1Perinatal Epidemiology Research Unit, Departments of Obstetrics & Gynecology and of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada. kjoseph@dal.ca
Insights
The risk of cerebral palsy (CP) increases with gestational age when considering fetuses at risk, not just live births. This new perspective reframes understanding and prevention of CP.
Area of Science:
- Epidemiology
- Perinatal Medicine
- Developmental Neuroscience
Background:
- Cerebral palsy (CP) is traditionally linked to live birth gestational age.
- Prenatal factors like malformations, vascular insults, and maternal infection suggest CP originates before birth.
- Viewing CP as a fetal condition offers new epidemiological insights.
Purpose of the Study:
- To explore the epidemiologic implications of viewing cerebral palsy (CP) as a fetal condition.
- To re-evaluate gestational age-specific CP rates using a "fetuses-at-risk" model.
- To compare conventional and alternative epidemiological formulations for CP.
Main Methods:
- Utilized published data from Shiga Prefecture, Japan, and North-East England.
- Calculated conventional gestational age-specific CP rates per live birth.
- Calculated alternative "fetuses-at-risk" CP rates per fetus at risk for a given gestation.
Main Results:
- Conventional rates showed decreasing CP risk with increasing gestational age.
- The "fetuses-at-risk" approach revealed increasing CP risk with longer gestational duration.
- Rates shifted from 63.9/1,000 live births (<28 weeks) to 0.9/1,000 (≥37 weeks) conventionally.
- Rates shifted from 0.08/1,000 fetuses (<28 weeks) to 0.9/1,000 (≥37 weeks) using the alternative model.
Conclusions:
- The "fetuses-at-risk" model is the appropriate epidemiological approach for causal analysis of CP.
- This formulation demonstrates that CP risk escalates with increased gestational duration.
- This perspective may redirect research toward understanding and preventing CP more effectively.
Abstract:
BACKGROUND: It is generally accepted that the risk of cerebral palsy decreases with increasing gestational age of live born infants. However, recent studies have shown that cerebral palsy often has prenatal antecedents including congenital malformations, vascular insults and maternal infection. Cerebral palsy is therefore better viewed as occurring among fetuses, rather than among infants. We explored the epidemiologic implications of this change in perspective. METHODS: We used recently published data from Shiga Prefecture, Japan and from North-East England to examine the pattern of gestational age-specific rates of cerebral palsy under these alternative perspectives. We first calculated gestational age-specific rates of cerebral palsy as per convention, by dividing the number of cases of cerebral palsy identified among live births within any gestational age category by the number of live births in that gestational age category. Under the alternative formulation, we calculated gestational age-specific rates of cerebral palsy by dividing the number of cases of cerebral palsy identified among live births within any gestational age category by the number of fetuses who were at risk of being born at that gestation and being afflicted with cerebral palsy. RESULTS: Under the conventional formulation, cerebral palsy rates decreased with increasing gestational age from 63.9 per 1,000 live births at <28 weeks gestation to 0.9 per 1,000 live births at 37 or more weeks gestation. When fetuses were viewed as potential candidates for cerebral palsy, cerebral palsy rates increased with increasing gestational age from 0.08 per 1,000 fetuses at risk at <28 weeks gestation to 0.9 per 1,000 fetuses at risk at 37 or more weeks gestation. CONCLUSIONS: The fetuses-at-risk approach is the appropriate epidemiologic formulation for calculating the gestational age-specific rate of cerebral palsy from a causal perspective. It shows that the risk of cerebral palsy increases as gestational duration increases. This compelling view of cerebral palsy risk may help refocus research aimed at understanding and preventing cerebral palsy.
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