In 2000, we first published a meta-analysis, or systematic review, of existing studies that evaluate the relationship between chorioamnionitis, or maternal intra-uterine infection, and cerebral palsy.1 We found that clinically diagnosed chorioamnionitis in the mother was associated with a 2-fold increased risk of cerebral palsy and a 3-fold increased risk of cystic periventricular white matter injury in preterm infants. In term infants, the 2 available studies suggested that clinical chorioamnionitis was associated with an even more elevated (5-fold) increased risk of cerebral palsy. We then studied risk factors for CP in a population of 230,000 term infants born at Kaiser Permanente in northern California.2 We found that chorioamnionitis was diagnosed in 14% of mothers of affected children, compared to 4% of unaffected children. Other risk factors for CP in our population were intrauterine growth restriction, black ethnicity and first-time delivery for the mother. We are currently extending this work by evaluating neonatal blood markers and genetic traits that increase the risk of cerebral palsy.
Perinatal arterial stroke is one of the most common causes of cerebral palsy among term infants. We found in term infants with congenital hemiparesis that perinatal arterial stroke is the most common underlying cause.3 In fact, if a term infant has moderate to severe right-sided weakness, the probability that the infant had a perinatal stroke was as high as 62% in our population, since perinatal strokes are more commonly located in the left brain.
We reported that perinatal stroke occurs in 1 per 5,000 term infants, and that large stroke size and injury to the deep structures of the brain increase the probability of CP following a perinatal stroke.4 We also identified several maternal complications that are independent risk factors for perinatal stroke, including a history of infertility, pre-eclampsia, and chorioamnionitis.5, 6 we are in the process of evaluating whether a genetic tendency for clot formation further increases the risk of stroke in the newborn.
Besides perinatal stroke, other types of perinatal brain injury can also lead to cerebral palsy in term infants. In newborns with a clot in the venous system of the brain, or sinovenous thrombosis, we found that multiple risk factors were usually present, often including a genetic clotting abnormality.7 We also found that in term infants with intraventricular hemorrhage, the most common underlying cause is sinovenous thrombosis, which is very different from preterm infants.8 Thus, term infants with intraventricular hemorrhage require special imaging studies to look for a clot in the venous system.
Neonatal encephalopathy, often referred to as birth asphyxia, is the strongest predictor of cerebral palsy in term infants. We reported that the incidence of birth asphyxia diagnoses is 4.5 per 1000 live births.9 The cause of neonatal encephalopathy is poorly understood in most cases. We found that black ethnicity, male gender and low socioeconomic status are all associated with increased risk of birth asphyxia, and we hope to extend this work by determining other prenatal and maternal risk factors for neonatal encephalopathy.
Finally, in a study of predictors of ambulation in CP, we published ambulation charts that can be used to evaluate the likelihood that a 2 year old child with CP will eventually walk over time.10
1 Wu YW, Colford JM. Chorioamnionitis as a risk factor for cerebral palsy: a meta-analysis. JAMA. 2000;284(11):1417-1424.
2 Wu YW, Escobar GJ, Grether JK, Croen LA, Greene JD, Newman TB. Chorioamnionitis and cerebral palsy in term and near-term infants. JAMA. Nov 26 2003;290(20):2677-2684
3 Wu YW, Lindan CE, Henning LH, Yoshida CK, Fullerton HJ, Ferriero DM, Barkovich AJ, Croen LA. Neuroimaging abnormalities in infants with congenital hemiparesis. Peds Neurol, in press.
4 Lee J, Croen LA, Lindan C, et al. Predictors of outcome in perinatal arterial stroke: A population-based study. Ann Neurol. Aug 2005;58(2):303-308
5 Lee J, Croen LA, Backstrand KH, et al. Maternal and infant characteristics associated with perinatal arterial stroke in the infant. Jama. Feb 9 2005;293(6):723-729.
6 Wu YW, March WM, Croen LA, Grether JK, Escobar GJ, Newman TB. Perinatal stroke in children with motor impairment: a population-based study. Pediatrics. Sep 2004;114(3):612-619.
7 Wu YW, Miller SP, Chin K, et al. Multiple risk factors in neonatal sinovenous thrombosis. Neurology. Aug 13 2002;59(3):438-440.
8 Wu YW, Hamrick SE, Miller SP, et al. Intraventricular hemorrhage in term neonates caused by sinovenous thrombosis. Ann Neurol. Jul 2003;54(1):123-126.
9 Wu YW, Backstrand KH, Zhao S, Fullerton HJ, Johnston SC. Declining diagnosis of birth asphyxia in California: 1991-2000. Pediatrics. Dec 2004;114(6):1584-1590.
10 Wu YW, Day SM, Strauss DJ, Shavelle RM. Prognosis for ambulation in cerebral palsy: a population-based study. Pediatrics. Nov 2004;114(5):1264-1271.