Neonatal Hemorrhagic Stroke: Prevalence and Outcomes

While neonatal hemorrhagic stroke (NHS) is fairly common, occurring in at least 1 out of every 6300 live births, many cases remain idiopathic, according to findings from a population-based study published in JAMA Pediatrics.¹

NHS has been plagued by low-powered studies and inconsistent terminology, both of which have contributed to the limited knowledge of prevalence and possible mechanisms.^2-6 This gap in clinical awareness is especially detrimental to outcomes, which are typically poor, and the development of preventive strategies.

In order to better understand the incidence, presentations, risk factors, and outcomes of NHS, a team of researchers led by Adam Kirton, MD, of Alberta Children’s Hospital in Calgary, Canada, conducted a nested case-control study in a large perinatal stroke cohort. In this study, NHS was defined as blood within the brain parenchyma as seen on imaging with or without intraventricular or subarachnoid hemorrhage.

Retrospective and prospective analyses revealed 86 cases (62% male) during the review period (1992 to 2010, 2007 to 2014): 51 cases of NHS, of which 32 were idiopathic; 30 with hemorrhagic transformation of primary ischemic injuries, of which 14 patients had neonatal cerebral sinovenous thrombosis, 11 had hypoxic ischemic encephalopathy, and 5 had neonatal arterial ischemic stroke; and 5 patients with presumed perinatal hemorrhagic stroke. Based on mean live births per year in Southern Alberta during the study period, the incidence for all forms of NHS was 1 in 6300 live births; for pure NHS, including presumed perinatal hemorrhagic stroke, the incidence was 1 in 9500 live births.

Most cases presented with seizures or encephalopathy within the first 28 days of life, with Apgar scores less than 5 at 1 minute in 36 cases and at 5 minutes in 12 cases. Most patients (88%) were admitted to the neonatal intensive care unit; however, monitoring history and data were not consistent given the time span of the study. Of note, neurosurgery was rare, with only 3 cases with documented surgical interventions. While the temporal lobe was the most common location of NHS (31%), a primary cause was only evident in 37% of cases of nonhemorrhagic transformation NHS. Idiopathic NHS was associated with younger maternal age (odds ratio [OR], 0.87; 95% CI, 0.78-0.94), primiparity (OR, 2.98; 95% CI, 1.18-7.50), prior spontaneous abortion (OR, 0.11; 95% CI, 0.02-0.53), difficult fetal transition (bradycardia [OR, 15.0; 95% CI, 2.19-101.9], low Apgar score [OR, 14.3; 95% CI, 2.77-73.5]), and small for gestational age (OR, 14.3; 95% CI, 1.62-126.1).

Follow-up data were available in 50 cases. Overall, outcomes were poor, though there was no recurrence of hemorrhagic stroke. Neurosurgical interventions including ventriculoperitoneal shunt insertion (n = 4), epilepsy surgery (n = 3), and arteriovenous malformation embolization (n = 1) occurred between 5 weeks and 7 years, and there were 3 deaths. Morbidities included a wide range of sensorimotor deficits, developmental delays, and epilepsy, with 78% of patients requiring physical, speech, and/or occupational therapy.

“Collectively, evidence suggests NHS pathophysiology involves rare events occurring in uniquely susceptible individuals rather than any controllable external factors, limiting opportunities for prevention,” the researchers concluded.

References

1. Cole L, Dewey D, Letourneau N, et al. Clinical characteristics, risk factors, and outcomes associated with neonatal hemorrhagic stroke: a population-based case-control study [published online January 17, 2017]. JAMA Pediatr. doi: 10.1001/jamapediatrics.2016.4151
2. Armstrong-Wells 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.
3. Saver JL, Warach S, Janis S, et al; National Institute of Neurological Disorders and Stroke (NINDS) Stroke Common Data Element Working Group. Standardizing the structure of stroke clinical and epidemiologic research data: the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Common Data Element (CDE) project. Stroke. 2012;43(4):967-973.
4. Looney CB, Smith JK, Merck LH, et al. Intracranial hemorrhage in asymptomatic neonates: prevalence on MR images and relationship to obstetric and neonatal risk factors. Radiology. 2007;242(2):535-541.
5. Bergman I, Bauer RE, Barmada MA, et al. Intracerebral hemorrhage in the full-term neonatal infant. Pediatrics. 1985;75(3):488-496.
6. Brouwer AJ, Groenendaal F, Koopman C, Nievelstein RJ, Han SK, de Vries LS. Intracranial hemorrhage in full-term newborns: a hospital-based cohort study. Neuroradiology. 2010;52(6):567-576.