Original ArticleThe Role of Hypoxia-Ischemia in Term Newborns with Arterial Stroke
Introduction
Focal cerebral infarction in the distribution of a single (or multiple) major artery, also termed arterial stroke, is a distinctive pattern of perinatal brain injury of heterogeneous etiology that occurs predominately in term infants [1]. Although doubtlessly underrecognized during the newborn period, perinatal arterial stroke has been estimated to occur in approximately 1:2,500 to 1:5,000 term newborns [2] and accounts for 50-70% of hemiplegic cerebral palsy in this population [3]. The topography of perinatal arterial stroke identified by neuroimaging has demonstrated that 75% of lesions are unilateral, most commonly involving the distribution of the left middle cerebral artery [1].
Despite its frequent occurrence, the pathogenesis of perinatal arterial ischemic stroke remains poorly understood. Recognized causes include vascular maldevelopment, trauma, thrombosis from infection, coagulopathies, and emboli arising from cardiac sources, involuting placental and fetal vessels or traumatic catheter placement [1]. In a series of 250 newborns reported in the 1980s and 1990s, an underlying etiology could not be identified in 50%, and a specific underlying cause was identified in only approximately 15%. In the same series, 35% of strokes occurred in the context of perinatal asphyxia [1]. With more rigorous neuroimaging, focal/multifocal cerebral injury, especially focal arterial infarction (stroke), is increasingly recognized in term newborns with hypoxic-ischemic encephalopathy. In a prospective cohort study of 124 term newborns with neonatal encephalopathy related to hypoxia-ischemia, 6 had acute focal arterial stroke identified on neuroimaging [4]. The occurrence of stroke in this cohort was more frequent than in population-based data, which suggests that acute events during the intrapartum period are important in the pathogenesis of perinatal stroke and deserve to be examined more closely.
The objectives of this study were to compare the clinical risk factors or markers for hypoxic-ischemic insult in term newborns who had stroke alone or who had a combination of stroke and hypoxic-ischemic brain injury. Our hypothesis is that clinical risk factors for hypoxia-ischemia differ between term newborns with stroke alone compared to those who have a combination of stroke and additional nonfocal hypoxic-ischemic injury on neuroimaging.
Section snippets
Study Population
The study population comprised all term newborns (gestational age ≥36 weeks) admitted to a tertiary-level perinatal referral center between January 1995 and May 2007 in whom acute cerebral infarction in an arterial distribution was identified on neuroimaging (computed tomography [CT] and/or magnetic resonance imaging [MRI]) during the first week of life.
Review of neuroimaging was performed by a pediatric neuroradiologist (KP) who was blinded to the newborn’s medical history. Newborns were
Results
From January 1995 to May 2007, a total of 62 term newborns (36 boys) had acute focal or multifocal cerebral infarction in an arterial distribution on neuroimaging. Thirty-six (58%) had infarction alone (stroke group), and 26 (42%) had infarction as well as evidence of nonfocal hypoxic–ischemic brain injury on neuroimaging (stroke + hypoxia-ischemia group). The demographic data of these groups is compared in Table 1. There was no significant difference in the severity of neonatal encephalopathy
Discussion
Perinatal arterial stroke is not uncommon and often leads to significant long-term neurologic morbidity. We identified 62 term newborns with acute focal or multifocal arterial stroke during a 12-year study period. The location of infarction in our series is similar to previous reports, which demonstrated that most neonatal ischemic infarcts involve the anterior circulation with a predominance of unilateral left hemispheric lesions [1], which supports a thromboembolic etiology. Other possible
Conclusion
Few differences exist between term newborns who have stroke alone and those who have a combination of focal stroke and more extensive nonfocal hypoxic-ischemic injury in terms of clinical features and shared clinical risk factors or markers for hypoxia-ischemia. Thus hypoxic-ischemic insult may play a role in the genesis of arterial stroke in the term newborn even when it is not of sufficient magnitude to result in typical hypoxic-ischemic abnormalities on neuroimaging.
References (24)
- et al.
Neonatal arterial ischemic stroke: Obstetric issues
Semin Fetal Neonatal Med
(2009) Physiology of the fetal circulation
Semin Fetal Neonatal Med
(2005)Hemodynamics of the ductus venosus
Eur J Obstet Gynecol Reprod Biol
(1999)- et al.
Distribution of the circulation in the normal and asphyxiated fetal primate
Am J Obstet Gynecol
(1970) - et al.
The effect of reducing umbilical blood flow on fetal oxygenation
Am J Obstet Gynecol
(1983) - et al.
Simultaneous measurements of umbilical venous, fetal hepatic, and ductus venosus blood flow in growth-restricted human fetuses
Am J Obstet Gynecol
(2004) Neurology of the newborn
(2008)- et al.
Maternal and infant characteristics associated with perinatal arterial stroke in the infant
JAMA
(2005) - et al.
Perinatal stroke in term infants with neonatal encephalopathy
Neurology
(2004) - et al.
Seizure-associated brain injury in term newborns with perinatal asphyxia
Neurology
(2002)
Comparison of computer tomography and magnetic resonance imaging scans on the third day of life in term newborns with neonatal encephalopathy
Pediatrics
Perinatal stroke in children with motor impairment: A population-based study
Pediatrics
Cited by (25)
An exploratory study to identify neonatal arterial ischemic stroke: A single-center study
2022, Brain and DevelopmentCitation Excerpt :Many potential maternal (e.g., nulliparity, intrapartum fever, preeclampsia, oligohydramnios, gestational diabetes, prolonged second stage of labor, vacuum-assisted delivery, and emergency caesarean section, among others) and fetal/neonatal risk factors (e.g., male sex, small for gestational age, fetal heart rate abnormality, umbilical cord anomaly, meconium stain, 5 min Apgar score of <7, and resuscitation at birth, among others) have been reported [26,37–40]. Most of these risk factors are due to inadequate adaptation from intra- to extrauterine conditions, which overlap with the risks of HIE, as these conditions can occur simultaneously [41]. In the present study, maternal PVC was significantly more frequent in patients with NAIS than in those without.
Neonatal stroke: Clinical characteristics and neurodevelopmental outcomes
2022, Pediatrics and NeonatologyCitation Excerpt :In the current study, fetal distress and meconium-stained amniotic fluid were noted in more than 60% of infants and 37% of them had perinatal HIE. Few studies have reported HIE as a risk factor for neonatal stroke.28,29 We speculate that a generalized hypoxia-ischemia would lead to HIE whereas focal insults would result in stroke.
Limitations of Conventional Magnetic Resonance Imaging as a Predictor of Death or Disability Following Neonatal Hypoxic–Ischemic Encephalopathy in the Late Hypothermia Trial
2021, Journal of PediatricsCitation Excerpt :There is overlap in the presentation of infants with strokes and HIE; seizures are common in neonatal arterial ischemic stroke (NAIS), occur most frequently between 12 and 72 hours after birth, and may be accompanied by encephalopathy.31 A potential role for hypoxia–ischemia in the development of NAIS has been raised,32 and the coexistence of NAIS and HIE has been reported.33,34 All infants in the Late Hypothermia Trial with apparent NAIS met inclusion criteria of impaired placental gas exchange (some combination of a sentinel event, fetal acidemia, and need for resuscitation) accompanied by encephalopathy.
Perinatal Stroke
2019, Seminars in Pediatric NeurologyCitation Excerpt :These are nonspecific complications present in many cases of neonatal encephalopathy, other medical conditions, and normal children. There is also considerable overlap in the presentation and associations of NAIS with hypoxic-ischemic encephalopathy and the 2 may occur together.36 Another proposed mechanism of NAIS pathogenesis is direct vessel trauma.
Perinatal arterial ischemic stroke
2019, Handbook of Clinical NeurologyPerinatal stroke: mechanisms, management, and outcomes of early cerebrovascular brain injury
2018, The Lancet Child and Adolescent HealthCitation Excerpt :As a group, these risk factors do not satisfy established criteria for causation. Given the common co-occurrence of neonatal arterial ischaemic stroke with other forms of hypoxic-ischaemic encephalopathy,24 these associations might just be indicative of a fetus at risk of difficult transition, such as one connected to an abnormal placenta. There are six specific perinatal stroke diseases definable by clinical presentation and neuroimaging.