Cerebral palsy in a term population: risk factors and neuroimaging findings.

CEREBRAL PALSY (CP) is a group of nonprogressive motor impairment syndromes caused by lesions of the brain arising early in development. (1) The etiology of CP remains unexplained in most cases, and the prevalence of CP, between 1.0 and 2.4 per 1000 live births, (2-7) has not diminished in recent decades despite advances in obstetric and neonatal care. (2-4,8,9) The risk of CP among term infants in the United States may, in fact, have increased between the years 1975 and 1991, from 1.7 to 2.0 per 1000 live births. (3) Based on these numbers, ~8000 children with CP are born annually in the United States. (10)

Because the diagnosis of CP does not specify a particular etiology or pathology, epidemiologic studies of CP have traditionally grouped children with CP into phenotypic subtypes based on the distribution of limb weakness and type of tone abnormality. (7) To devise rational and improved strategies for prevention, however, it is crucial that CP be recognized as a heterogeneous group of brain disorders with potentially different risk factors and causal pathways. With the increasing availability of head computed tomography (CT) and MRI, several types of brain injury underlying CP have been described, including brain malformations, hypoxic-ischemic brain injury, focal arterial infarction, and periventricular white matter injury. (6,11-14) Yet, most neuroimaging studies of CP have been hospital based and are, thus, susceptible to selection bias, and the evaluation of risk factors for CP has rarely taken into account the underlying types of brain injury present.

More than half of all children with CP are born at term, (5,6) but data regarding risk factors for CP in term infants are relatively sparse compared with the large number of studies performed in premature infants. Although populations in Europe, Scandinavia, and Australia maintain active CP registries, (4,6,8,15-18) few population-based studies of CP in term infants have been performed in the United States. These include the Collaborative Perinatal Project of the 1960s (19), a California study in the mid-1980s (20), and a study in the greater Atlanta area spanning birth years 1971-1991. (3) Given the paucity of recent data, we examined demographic and neuroimaging characteristics of infants with CP identified from a cohort of term and near-term infants born in northern California during the years 1991-2002, when head MRI and CT were widely available.

METHODS

We studied a cohort of all singleton live births [greater than or equal to] 36 weeks' gestation born between January 1, 1991, and December 31, 2002, in the Kaiser Permanente Medical Care Program (KPMCP). The KPMCP is a large managed care organization that provides care for >3 million residents of northern California. The members of KPMCP are demographically similar to the California population, except that the very poor and very wealthy are under represented. (21) KPMCP has 33 facilities, of which 12 have delivery rooms, and 6 have level III NICUs.

Case Identification

For all of the infants in the study cohort, we electronically searched KPMCP records for inpatient and outpatient physician diagnoses of CP (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] 343.0-343.9), (22) "paresis" (ICD-9-CM 342.1,342.8, 342.9, 344.0, 344.1, 344.30-344.32, and 344.5), "gait abnormality" (ICD-9-CM 781.2), or "cerebral degeneration" (ICD-9-CM 330) before April 1, 2005. A single child neurologist (Y. W.) then reviewed medical charts to confirm the diagnosis of CP. Because chart review revealed that 0 of the initial 141 infants with an isolated diagnosis of gait abnormality met study criteria for CP, we excluded the remaining 241 infants with an isolated diagnosis of gait abnormality without reviewing their charts. Infants with an isolated diagnosis of cerebral degeneration (N = 980) were also excluded without chart review, because a review of these patients' electronic records did not suggest CP.

We defined CP as a nonprogressive congenital motor dysfunction with examination findings of increased tone (spasticity, rigidity, and dystonia) or choreoathetosis. Hypotonic and ataxic CP were not included, because these entities are most likely etiologically distinct from spastic and dyskinetic CP. Children with a postnatal central nervous system insult occurring after 1 week of age or a neurologic condition not typically considered to be CP, such as a myopathy or neural tube defect, were also excluded a priori (see "Appendix" section for list of diagnoses). (23) Because the motor impairment seen in inherited disorders, such as Angelman's syndrome, has traditionally not been included in epidemiologic studies of CP, (24) we also excluded infants with a known genetic syndrome or chromosomal anomaly.

The degree of motor disability was determined as close to age 3 years as possible. We defined "mild" disability as minimal functional limitation; "moderate" disability as diminished use of the most affected limb; and "severe" disability as the lack of any functional use of the most affected limb. (5) When a young child with CP was found to be neurologically normal by 3 years of age, the CP was considered to have "resolved." (25) Infants in the study population who did not have an exclusion diagnosis and who did not receive a physician diagnosis of CP, paresis, gait abnormality, or cerebral degeneration constituted the control cohort.

Covariate Data

We electronically accessed the following information from the KPMCP patient data files: infant gender, race/ ethnicity (white, Hispanic, black, Asian, or other), maternal age at delivery, plurality (singleton or multiple gestation), birth weight, gestational age, time and date of birth, and whether the infant was admitted to the NICU. Infants delivered between 9 PM and 6:59 AM were considered to be born at night. (26) The months of June, July, and August were defined as summer, whereas December, January, and …