Prevalence and Predictors of Perinatal Hemorrhagic Stroke

Abstract

Source: Armstrong-Well J, Johnston SC, Wu YW, et al. Prevalence and predictors of perinatal hemorrhagic stroke: results from the Kaiser Pediatric Stroke Study. Pediatrics.2009;123(3):823–828; doi:10.1542/peds.2008–0874To determine the prevalence and predictors of perinatal hemorrhagic stroke (PHS), investigators from the University of California at San Francisco and Kaiser Permanente Medical Program in Oakland, CA performed a case-control study nested within a cohort of infants born from 1993 to 2003 in the Northern California Kaiser Permanente Medical Care Program. Cases of symptomatic perinatal hemorrhagic stroke and arterial ischemic stroke in neonates older than 28 weeks’ gestational age through 28 days of life were retrospectively identified through electronic searches of databases and confirmed by medical chart review. Cases of pure intraventricular hemorrhage were excluded. Three controls for each case were randomly selected from the cohort, matched by year and medical facility of birth.Among 323,532 live births, 20 cases of PHS were identified (19 intracerebral hemorrhage and one subarachnoid hemorrhage). Three case infants (15%) were premature (31 weeks gestation), and five (25%) were postmature; three case infants (15%) had birth weights <2500 g and three had birth weights of >4000 g. The prevalence of PHS was 6.2 in 100,000 live births, or 1 in 16,000 live births. In comparison, 93 cases of perinatal arterial ischemic stroke were identified, a prevalence of 29 in 100,000 or 1 in 3,500 live births.Cases of PHS presented with encephalopathy (100%) and seizures (65%). The etiology was idiopathic in 15 (75%), thrombocytopenia in 4 (20%), and cavernous malformation in 1 (5%). Neuroimaging abnormalities were unifocal in 14 of 19 (74%) and unilateral in 15 (83%). Lesions were more likely to be left-sided (56%) than right-sided (28%) or bilateral (16%), and more likely to be parietal (47%) and frontal (37%) than temporal (16%) in location.Univariate predictors of PHS included fetal distress, emergent cesarean delivery, prematurity, and postmaturity but not birth weight or difficult vaginal delivery. Fetal distress and postmaturity continued to be independent predictors of PHS in a multivariate model. The authors conclude that fetal distress and postmaturity (although not large birth weight) are independent predictors of perinatal hemorrhagic stroke.Dr. Millichap has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Published reports have classified and defined the prevalence and risk factors for perinatal arterial ischemic stroke,1,2 but PHS has not been studied as frequently.3 The risk associated with postmaturity in the Kaiser Permanente study is not explained by macrosomia or obstetrical trauma. No maternal health factors predicted PHS.In contrast, previously reported risk factors for perinatal arterial ischemic stroke include chorioamnionitis, prolonged rupture of membranes, preeclampsia, placental thrombi, intrauterine growth retardation, prothrombotic and hematological factors, congenital heart disease with cerebral thromboembolism, infection, and inflammation.4In the current study, PHS most commonly presented with encephalopathy or seizures. In comparison, congenital hemiplegia and epilepsy are the most common neurologic deficits resulting from perinatal arterial ischemic stroke.4 Preterm children with a history of perinatal cerebral hemorrhage and severe brain injury have delays in cognitive function and require educational intervention at 12 years of age.5In a retrospective study of 85 infants and children (age range 7 days to 17 years) with nontraumatic intracranial hemorrhage and stroke at Children’s Hospital Columbus, OH,6 location of hemorrhage was subarachnoid in 10 (12%), intraparenchymal in 61 (72%), and subdural in 14 (16%). Risk factors included intracranial vascular anomalies in 24 (28%; arteriovenous malformation [AVM] in 11), congenital heart disease in 14 (16%), and brain tumor in 13 (15%). Infection was associated in five (6%) cases, and coagulation deficiencies in four (5%). Mortality was 34%. Of 48 survivors with follow-up information, 26 (54%) had no deficits, and 22 (46%) had mild deficits.Another study of 251 patients with childhood stroke (aged 1 month through 16 years) admitted to Beijing Children’s Hospital, China, from 1996 to 2006 found that arterial ischemic stroke accounted for the majority of cases (62.5%) and hemorrhagic stroke for 37.5%.7 Vitamin K deficiency was a major etiology of hemorrhagic stroke in China, diagnosed in 72 (76.6%) of 94 cases, most occurring in breastfed infants who had received no vitamin K after birth. Cerebral vascular abnormality was present in seven (7%) cases, and AVM in six. Infection played a role in 10%, including viral encephalitis, varicella zoster, mycoplasma, and Epstein-Barr virus infections. Etiological factors associated with childhood hemorrhagic stroke in China differ from those reported in Western countries, where AVM is the most frequent cause.In contrast to childhood stroke, the mechanisms underlying PHS remain an enigma, but the association with fetal distress suggests that prenatal factors may be paramount.