Risk factors for perinatal arterial ischaemic stroke: a large case–control study

Abstract

Aim To identify maternal, obstetric, and neonatal risk factors related to perinatal arterial ischaemic stroke (PAIS) diagnosed within 28 days after birth and to understand the underlying pathophysiology. Method For case and control ascertainment, we used active surveillance in 345 paediatric hospitals and a population‐based perinatal database for quality assurance of hospital care. We analysed complete cases of PAIS using logistic regression. Multivariate analysis was guided by a directed acyclic graph. Results After exclusion of records with missing data, we analysed 134 individuals with PAIS and 576 comparison individuals. In univariate analysis, male sex, preterm birth (<37wks gestational age), small for gestational age (SGA), low umbilical artery pH (<7.1), low 5‐minute‐Apgar score (<7), multiple pregnancies, hypoxia, intubation/mask ventilation, nulliparity, Caesarean section, vaginal‐operative delivery, chorioamnionitis, and oligohydramnios were associated with an increased risk. Mutual adjustment yielded male sex (odds ratio [OR] 1.81; 95% confidence interval [CI] 1.20–2.73), multiple birth (OR 3.22; 95% CI 1.21–8.58), chorioamnionitis (OR 9.89; 95% CI 2.88–33.94), preterm birth (OR 1.86; 95% CI 1.01–3.43), and SGA (OR 3.05; 95% CI 1.76–5.28) as independent risk factors. Interpretation We confirmed the increased risk in males and the role of chorioamnionitis and SGA for PAIS, pointing to the importance of inflammatory processes and fetal–placental insufficiency. Multiple birth and preterm birth were additional risk factors. What this paper adds Chorioamnionitis and small for gestational age (SGA) precede perinatal arterial ischaemic stroke (PAIS). Chorioamnionitis and SGA are independent risk factors for PAIS. Inflammatory processes and fetal–placental insufficiency are the likely underlying mechanisms. Multiple birth and preterm birth are additional risk factors.

Perinatal inflammation and placental programming of neonatal stroke

“…By multiplying the risk of NAIS by 10, Sorg et al. reveal that chorioamnionitis far outweighs other identified determinants . Furthermore, perinatal inflammation was a constant independent risk factor in previous case–control studies of NAIS .…”

Clinical diversity of cerebral sinovenous thrombosis and arterial ischemic stroke in the neonate: a surveillance study.

“…However, some evidence supports our nding that newborns with CSVT often present later with unspeci c signs within the rst week of life [24]. In a recent paper we discussed risk factors for AIS and identi ed an important role for prenatal risk factors [25]. Perinatal asphyxia in AIS might as well be a consequence of AIS.…”

Benefits of hypothermia in neonatal arterial ischemic strokes: A preclinical study

“…Due to the efficient anastomosis of the circle of Willis in pups, our experimental design requires adding hypoxic stress to the ischemia‐induced by RCCA ligation to trigger a stroke. However, the triple‐hit (namely, bacterial (LPS) component exposure plus focal ischemia plus global hypoxia) used in our experimental design is relevant with the most prevalent causal pathway of human NAIS featured by the sequence of chorioamnionitis (Giraud et al, 2017; Martinez‐Biarge et al, 2013; Sorg et al, 2019), peripartum asphyxia identified in up to 26% of NAIS (Fluss et al, 2019; Martinez‐Biarge et al, 2013; Michoulas et al, 2011; Ramaswamy, Miller, Barkovich, Partridge, & Ferriero, 2004; Sorg et al, 2019), and arterial occlusion of the carotid tree (Fluss et al, 2016; Husson et al, 2016; Kirton et al, 2011; Suppiej et al, 2019).…”

“…Neonatal arterial ischemic strokes (NAIS) affects up to 1–2/6,000 newborns and results in lifelong sequelae, such as cerebral palsy and epilepsy, as well as cognitive and behavioral impairments (Dunbar & Kirton, 2018; Fluss, Dinomais, & Chabrier, 2019; Giraud, Guiraut, Chevin, Chabrier, & Sébire, 2017). Clinical studies show that perinatal infection/inflammation—often due to chorioamnionitis—is the main independent risk factor of NAIS (Giraud et al, 2017; Martinez‐Biarge, Diez‐Sebastian, Wusthoff, Mercuri, & Cowan, 2013; Sorg et al, 2019). To date, no controlled clinical trials have addressed the safety and efficacy of hypothermia (HT) in NAIS (Austin, Shanmugalingam, & Clarke, 2013; Harbert et al, 2011).…”