Risk Factors for Neonatal Arterial Ischemic Stroke: The Importance of the Intrapartum Period.

OBJECTIVE: To investigate risk factors for neonatal arterial ischemic stroke (NAIS), and compare them with those present in term controls and infants with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: Antepartum and intrapartum data were collected at presentation from 79 infants with NAIS and compared with 239 controls and 405 infants with HIE. The relationships between risk factors and NAIS were explored using univariable and multivariable regression. RESULTS: Compared with controls, infants with NAIS more frequently had a family history of seizures/neurologic diseases, primiparous mothers, and male sex. Mothers of infants with NAIS experienced more intrapartum complications: prolonged rupture of membranes (21% vs 2%), fever (14% vs 3%), thick meconium (25% vs 7%), prolonged second stage (31% vs 13%), tight nuchal cord (15% vs 6%), and abnorm8al cardiotocography (67% vs 21%). Male sex (OR 2.8), family history of seizures (OR 6.5) or neurologic diseases (OR 4.9), and ≥1 (OR 5.8) and ≥2 (OR 21.8) intrapartum complications were independently associated with NAIS. Infants with NAIS and HIE experienced similar rates though different patterns of intrapartum complications. Maternal fever, prolonged rupture of membranes, prolonged second stage, tight nuchal cord, and failed ventouse delivery were more common in NAIS; thick meconium, sentinel events, and shoulder dystocia were more frequent in HIE. Abnormal cardiotocography occurred in 67% of NAIS and 77.5% of infants with HIE. One infant with NAIS and no infant with HIE was delivered by elective cesarean (10% of controls). CONCLUSIONS: NAIS is multifactorial in origin and shares risk factors in common with HIE. Intrapartum events may play a more significant role in the pathogenesis of NAIS than previously recognized.

The neurological assessment in young children treated with artesunate monotherapy or artesunate-mefloquine combination therapy for uncomplicated Plasmodium falciparum malaria.

BACKGROUND: Mefloquine and artesunate combination therapy is the recommended first-line treatment for uncomplicated malaria throughout much of south-east Asia. Concerns have been raised about the potential central nervous system (CNS) effects of both drug components and there are no detailed reports in very young children. METHODS: Children, aged between three months and five years, with acute uncomplicated Plasmodium falciparum malaria were randomized to either 7 days of artesunate monotherapy or the same schedule of artesunate plus mefloquine on day 7 and 8. Neurological testing targeting coordination and behaviour was carried out at day 0, 7, 9, 10, 14 and 28. Non-febrile healthy control children from the same population were tested on days 0, 7, 14 and 28. RESULTS: From December 1994 to July 1997, 91 children with uncomplicated P. falciparum, 45 treated with artesunate monotherapy, 46 treated with mefloquine and artesunate combination therapy and 36 non-febrile controls, underwent neurological testing. Malaria and fever had a significant negative impact on testing performance. By contrast, the anti-malarial treatments were not associated with worsening performances in the various components of the test. Artesunate and mefloquine do not appear to have a significant influence on coordination and behaviour. Children treated with mefloquine were significantly less likely to suffer recurrent malaria infection during follow-up compared to those treated with artesunate alone (P = 0.033). CONCLUSION: In keeping with the results of randomized controlled trials in adults, mefloquine was not associated with a decrease in specific items of neurological performance. Likewise, children treated with artesunate did not perform significantly differently to control children. This study does not exclude subtle or rare treatment CNS effects of artesunate or mefloquine. Treatment of acute uncomplicated malaria results in a significant improvement on items of neurological performance.

Origin and timing of brain lesions in term infants with neonatal encephalopathy.

BACKGROUND: The role of intrapartum asphyxia in neonatal encephalopathy and seizures in term infants is not clear, and antenatal factors are being implicated in the causal pathway for these disorders. However, there is no evidence that brain damage occurs before birth. We aimed to test the hypothesis that neonatal encephalopathy, early neonatal seizures, or both result from early antenatal insults. METHODS: We used brain MRI or post-mortem examination in 351 fullterm infants with neonatal encephalopathy, early seizures, or both to distinguish between lesions acquired antenatally and those that developed in the intrapartum and early post-partum period. We excluded infants with major congenital malformations or obvious chromosomal disorders. Infants were divided into two groups: those with neonatal encephalopathy (with or without seizures), and evidence of perinatal asphyxia (group 1); and those without other evidence of encephalopathy, but who presented with seizures within 3 days of birth (group 2). FINDINGS: Brain images showed evidence of an acute insult without established injury or atrophy in 197 (80%) of infants in group 1, MRI showed evidence of established injury in only 2 infants (<1%), although tiny foci of established white matter gliosis, in addition to acute injury, were seen in three of 21 on post-mortem examination. In group 2, acute focal damage was noted in 62 (69%) of infants. Two (3%) also had evidence of antenatal injury. INTERPRETATION: Although our results cannot exclude the possibility that antenatal or genetic factors might predispose some infants to perinatal brain injury, our data strongly suggest that events in the immediate perinatal period are most important in neonatal brain injury.