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.

Cognitive outcome at early school age in term-born children with perinatally acquired middle cerebral artery territory infarction.

BACKGROUND AND PURPOSE: To assess cognitive outcome at early school age in term-born children with middle cerebral arterial (MCA) territory infarction of perinatal onset and examine the correlation between cognitive abilities and the extent of lesions as seen on neonatal MRI, epilepsy, and hemiplegia. METHODS: Thirty-one children were seen as newborns with an acutely evolving MCA territory infarction documented on neonatal MRI scan. IQ was assessed (WIPPSI/WISC where appropriate) and they had a standardized neurological examination at early school age. Lesion(s) site was recorded from the neonatal images. RESULTS: Twenty-eight of 31 children were assessed (median age 5.75 range 5.33 to 10.33 years); 1 child died and 2 were abroad. IQ was within the normal range (mean 104, range 82 to 144) in 21 (78%); 1 child did not complete all tests but had a normal PIQ; 3 had a low and 3 an exceptionally low IQ. Verbal IQs were more varied and lower than performance IQs especially in children from multilingual backgrounds. There was no consistent association between cognitive impairment, side, or extent of the MCA lesion. Cognitive impairments were more frequent in children with seizures or hemiplegia. All 6 children with low IQ also had behavioral problems or unusual associated clinical or scan features. CONCLUSIONS: In our cohort a low IQ at early school age did not occur in children with the common presentation of neonatal unilateral MCA territory infarction. Cognitive impairment appeared more frequently when an MCA arterial territory infarction, even if relatively small, was associated with other risk factors.

Neurological status of low-risk Vietnamese newborns: a comparison with a British newborn cohort.

A shortened version of the Dubowitz newborn neurological examination, recently reassessed in rural Thailand, was applied to a group of 58 Vietnamese newborns. The aim was to establish the neurological status of newborns in this population for use in further studies and to compare with groups previously studied. Compared to the original British cohort, the Vietnamese newborns showed significantly lower scores in 10 of 25 items, including several related to truncal tone. Evidence was sought of thiamine and long-chain fatty acid deficiency as a possible cause for these findings, but no correlation was found between the neurological status and the maternal or infant blood levels of these nutritional indicators. The findings suggest that the neurological status of low-risk Vietnamese newborns appears to lie between that of British newborns and those ethnic minority Karen newborns in refugee camps on the Thai-Burmese border tested previously. Although no specific nutritional cause has been identified in the study, the findings may still reflect sub-optimal intake of some important nutrients.

The Dubowitz neurological examination of the full-term newborn.

In an ideal world, each neonate should have a comprehensive neurological examination but in practice this is often difficult. In this review we will describe what a routine neurological evaluation in the full-term neonate should consist of and how the Dubowitz examination is performed. The examination has been used for over 20 years and can be easily performed in a short time as the recording sheet provides simple instructions together with simple diagrams to make the recording and the scoring easier. We will also indicate how the examination can be used to identify infants with neurological abnormalities, describing clinical signs which can help to differentiate infants with peripheral neuromuscular disorders from those with central nervous system involvement. The correlation between clinical and imaging findings in infants with neonatal brain lesions will also be reported. Finally we will briefly describe how and when to apply an optimality scoring system in a research setting.

Neurological examination in healthy term infants aged 3-10 weeks.

OBJECTIVES: The neurodevelopmental progress of newborn term infants is checked routinely at around 6 weeks of postnatal age. The maturation of neurological signs in this age range however has not been systematically studied and normative data are not available. The aim of this study was to document any changes in posture, tone, reflexes, behaviour and movements in low-risk full-term infants between 3 and 10 weeks of postnatal age. STUDY DESIGN: We performed a structured neurological examination previously standardised in full-term newborns in the first 48 h after birth. In the current study, a total of 76 examinations were performed between 3 and 10 weeks of age in low-risk full-term infants. RESULTS: The results of the examinations were divided according to postnatal age. In most items, the scores changed with time, with a definite shift in their distribution occurring around 6 weeks. At this age, a reduction in flexor tone of the limbs was observed, together with an increase in active neck tone. Visual orientation in contrast had already improved by 3 weeks when all infants were able to follow a target in a full circle compared to newborns that are often only able to follow a target in an arc. CONCLUSIONS: Our results suggest that 6 weeks post-term birth is an important milestone for changes in neurological signs, particularly those related to muscle tone and posture, probably reflecting maturation of the nervous system. These findings provide important guidelines for the interpretation of the neurological examination performed at this age.

Prognostic value of the neurologic optimality score at 9 and 18 months in preterm infants born before 31 weeks' gestation.

OBJECTIVE: The Hammersmith Infant Neurological Examination was performed in a cohort of 74 preterm infants whose gestational age ranged between 24 and 30.5 weeks. The infants were examined between 9 and 18 months' chronologic age (6-15 months' corrected age) and scored with the optimality score system previously standardized in a cohort of low-risk term infants. The aim of the study was to establish the frequency distribution of the optimality scores in this cohort and to establish whether the scores can predict locomotor function at 2 years of age. RESULTS: The results showed that this standardized neurologic examination can be performed in preterm infants as early as 9 months' chronologic age to predict motor outcome at 2 years old. The scores showed no significant association with the degree of prematurity or the age of assessment. CONCLUSION: This examination should be particularly useful in very premature infants who are at high risk of severe neurologic and developmental disabilities and for whom the early prediction of motor function can be difficult.

A new approach for neurological evaluation of infants in resource-poor settings.

Research assessing the neurological development of infants in developing countries is scanty as no suitable standardised tests are available for field-use in constrained circumstances. We describe the development and application of two simple assessments. Firstly, we aimed to develop a test suitable for assessing acute neurological disturbances caused by such diverse effects as infections, drugs or toxins. This test (Shoklo Neurological Test) is aimed at infants between 9 and 36 months. The second test (Shoklo Developmental Test) is aimed not only to follow the evolution of the signs tested initially in the acute phase but also to evaluate later neurodevelopmental sequelae which might be caused by the same events. The latter test is suitable for infants aged from 3 to 12 months. Both tests can be performed easily in non-optimal conditions. The examinations were tested in a cohort of infants from a Karen refugee camp and administered in a rural setting by health workers, after appropriate training. In order to validate the tests we also applied them to a cohort of London infants. The Griffiths Developmental Scales were applied in the same infants and both the Shoklo Neurological and the Shoklo Developmental Tests showed good correlation with this standardised neurodevelopmental assessment.

Neonatal cerebral infarction and neuromotor outcome at school age.

OBJECTIVE: The aim of this study was to assess neuromotor function at school age in children who had cerebral infarction on neonatal magnetic resonance imaging (MRI). DESIGN: Twenty-two children with evidence of cerebral infarction on neonatal brain MRI (18 with arterial infarction and 4 with border-zone lesions) were assessed at school age with a structured neurologic examination and the Movement Assessment Battery for Children, a battery of tests designed to assess motor function. RESULTS: Of the 22 children, 6 (30%) had hemiplegia and a further 7 (30%) showed some neuromotor abnormality such as asymmetry on the neurologic examination (n = 4) or poor scores on the neuromotor test without any sign of asymmetry (n = 3). The remaining 9 children had a normal motor outcome. Hemiplegia was found only in children who had concomitant involvement of hemisphere, internal capsule, and basal ganglia on brain MRI. Children with involvement of the internal capsule, associated either with basal ganglia or hemispheric lesions, did not show hemiplegia but still had motor difficulties. CONCLUSIONS: Our results suggest that although hemiplegia occurs in a relatively small proportion of children with neonatal cerebral infarction, other signs of neuromotor impairment can be present, and these become more obvious at school age when a more specific assessment can be performed. These results also suggest that the involvement of the internal capsule on neonatal MRI can predict the presence of these abnormalities.

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.

Delayed visual maturation in Karen refugee infants.

Thirty-eight babies born to Karen mothers living in camps for displaced persons in north-western Thailand have delayed visual maturation (DVM type 1) that recovers within 6 months. Vitamin A concentrations were deficient in 16% of breast-milk samples from lactating mothers and vitamin B(1) concentrations were deficient in 60% of plasma samples. Infantile beriberi was common in this population. The levels of fatty acids in plasma and milk in Karen women were excellent at birth and in the postpartum period. The degree of deficiencies in these vitamins and the concentration of essential fatty acids in cord blood and maternal breast-milk did not correlate significantly with visual impairment in the infants. DVM might be caused by nutritional deficiency or toxic effects during critical periods of gestation that lead to delayed cortical myelination or structural defects which impinge on parietal cortex function.

Neurologic examination of preterm infants at term age: comparison with term infants.

OBJECTIVES: The aim was to establish the range of neurologic findings in preterm infants reaching term age, their relation to gestational age at birth, and the possible differences with healthy term newborns tested during the first days of life. STUDY DESIGN: The Dubowitz neonatal neurologic examination was performed at term age in 157 low-risk preterm infants born between 25 and 34 weeks' gestation who had cranial ultrasonograms that were normal or showed minor abnormalities. Infants were subdivided in 3 groups according to their gestational age at birth. RESULTS: Within the preterm cohort, the range of scores for the 3 gestational age subgroups was different from each other for 21 of the 34 items, although the median scores were different only in 10 of the 34 items. The range of scores and their median in preterm infants however was wider than that found in term infants. Preterm infants examined at term were also more hyperexcitable and tended to have less flexor tone in the limbs and less extensor tone in the neck in the sitting posture. CONCLUSIONS: The distribution of scores provides useful guidelines when a preterm infant is examined at term.