Hypoxic-Ischemic Encephalopathy in the Newborn

Fenichel, Gerald M.

doi:10.1001/archneur.1983.04050050029002

Cited by 131 publications

(56 citation statements)

References 57 publications

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“…24 " 27 At delivery those infants may be profoundly hypoxic and hypotensive. When Nelson and Ellenberg 23 reviewed the data of the Collaborative Perinatal Project of the National Institute of Neurologic and Communicative Disorders and Stroke of approximately 40,000 live births, an Apgar score of 3 or less at 5 minutes after birth was significantly correlated with adverse neurologic outcome. Forty-four percent of infants with such scores died within the first year, and 1 in 20 of the surviving infants developed major motor handicaps.…”

Section: Discussionmentioning

confidence: 99%

Beagle pup model of perinatal asphyxia: nimodipine studies.

Ment¹,

Stewart²,

Duncan³

et al. 1987

Stroke

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Calcium antagonists may be of significant benefit in the pharmacotberapy of cerebral ischemia, possibly by improving postischemic cerebral blood flow (CBF). This study evaluated the effects of the calcium antagonist nimodipine on CBF in a newborn beagle pup model of perinatal asphyxia lasting 5 minutes. Immediately after the asphyxia] episode, nimodipine (2 /ug/kg/min) or saline was infused for 10 minutes, following which [ u C]iodoantipyrine determinations of CBF were performed. In noninsulted pups, nimodipine caused both significant decreases in CBF to cortical and deep gray structures as well as a decrease in mean arterial blood pressure (MABP) (p < 0.05). In insulted pups, nimodipine similarly decreased MABP (p < 0.001) and CBF to cortical and deep gray matter regions. Nimodipine appeared to have no effect on arterial blood gases and EEG tracings in either insulted or noninsulted pups. Although nimodipine may be shown to improve neurologic outcome in asphyxiated newborn infants, the limits of this study do not show the mechanism to be that of improving CBF. 910 Hypoxic/ischemic insults are known to result in cerebral metabolic disturbances characterized by decreased concentrations of highenergy phosphate compounds and by increased cerebral lactate. Cerebral blood flow (CBF) falls, and secondary failure of the ion pump results in neuronal depolarization and calcium entry. This imbalance in intracellular calcium provokes the accumulation of free fatty acids, which in turn uncouples oxidative metabolism and produces additional neuronal permeability changes. "~1 4 In response to ischemic insult, calcium channel blockers have been reported to both act on vascular smooth muscle to increase CBF 1 " 315 and to block calcium influx at voltage-gated calcium channels to preserve neuronal integrity.16 " 18While much has been written about the efficacy of calcium antagonists in adult animal models of hypoxic/ischemic insult, little is known about the role of these agents in the response of the developing nervous system to such problems. 1920 Severe perinatal asphyxia, the classic hypoxic/ischemic insult of the newborn period, has been reported to occur in between 1 in 50 and 1 in 500 live births 21 Newborn beagle pups provide a good model for the study of the developing brain. Neuropathologic insults such as perinatal cerebral infarction and intraventricular hemorrhage may be produced by clinically relevant models and CBF may be determined. 3839The purpose of this study was to evaluate the effects of the calcium antagonist nimodipine on CBF in newbom beagle pups exposed to a clinically relevant model for perinatal asphyxia. To approximate clinical events, nimodipine was administered as an i.v. infusion after asphyxial insult. Materials and MethodsThe following studies were performed with the approval of the Yale University Committee on Animal Care.Newborn beagle pups (24-96 hours old) were lightly anesthetized with 20 mg/kg i.p. pentobarbital, tracheotomized after local 1% xylocaine infiltration, paralyzed with 1 mg/kg...

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Section: Discussionmentioning

confidence: 99%

Beagle pup model of perinatal asphyxia: nimodipine studies.

Ment¹,

Stewart²,

Duncan³

et al. 1987

Stroke

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“…In discriminant analysis, the positive predictive value of the combination of the 5-min Apgar score with umbilical arterial pH with respect to hypoxic-ischemic encephalopathy (16) was 80% and the negative value was 92%. The concentrations of AVP, EP, and HX were entered into the analysis separately, inasmuch as the number of infants with data on all three parameters was too small.…”

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confidence: 97%

Cord Plasma Vasopressin, Erythropoietin, and Hypoxanthine as Indices of Asphyxia at Birth

et al. 1988

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ABSTRACT. To assess the value of cord plasma arginine vasopressin (AVP), erythropoietin (EP), and hypoxanthine (HX) as indices of asphyxia, we studied 62 infants of mothers with preeclampsia, 34 acutely asphyxiated infants, with 5-min Apgar score 5 6 and/or umbilical arterial pH 57.05, and 38 control infants. Umbilical arterial AVP in the asphyxia group (geometric mean; 95% confidence interval: 180; 92-350 pg/ml) was higher than in the control group (23; 8-66, p = 0.002) and correlated with umbilical arterial pH ( r = -0.447, p = 0.028). AVP levels in the preeclampsia group did not differ from controls. Cord venous E P was higher in infants delivered by elective cesarean section from women with severe preeclampsia (115; 75-177 mU/ml, p < 0.001) than in control infants (23; 18-27); in the whole group EP correlated with pH (r = -0.493, p < 0.001). E P in the asphyxia group was similar (46; 35-65) to controls (40; 33-47) and did not correlate with pH. Cord arterial HX in the preeclampsia group was similar to controls (12.3; 9.5-16.0 pmol/liter), but elevated in the asphyxia group (23.7; 17.6-31.8, p = 0.001), in which HX correlated with pH ( r = 0.558, p = 0.008) and AVP ( r = 0.588, p = 0.005). E P did not correlate with AVP or HX in any group, nor did any of the variables correlate with the Apgar score. We conclude that cord plasma AVP and HX reflect acute asphyxia, whereas E P is elevated after more prolonged hypoxia. (Pediatr Res 24: 490-494,1988) Abbreviations AVP, arginine vasopressin EP, erythropoietin HX, hypoxanthine Fetal asphyxia and delivery trigger a rapid increase in the secretion of several "stress" hormones, e.g. catecholamines, glucocorticoids, ACTH, p-endorphin, and AVP, which in turn mediate the cardiovascular and metabolic adaptation to asphyxia (4-6). A more specific response to hypoxia is an increase in the synthesis of EP, followed by elevation of plasma levels (7,8). If tissue hypoxia becomes more severe, cellular ATP concentrations cannot be maintained, and increased concentrations of the purine nucleotide catabolic products, HX, xanthine, and uric acid, appear in body fluids (9).The aim of our study was to assess if three components of this physiological response, AVP, EP, and HX, could be useful as biochemic indices of the severity of asphyxia. Two different clinical conditions were studied: acute severe birth asphyxia and maternal preeclampsia, the latter as an example of a chronic but less severe compromise in fetal oxygen and nutrient supply.

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“…Cerebral, cardiac, renal, and lung dysfunction have been described in newborn infants with asphyxia (Shankaran et al 1991). The severity of the neurobehavioural disturbance in asphyxiated term newborn infants, characterized as hypoxic-ischaemic encephalopathy (HIE) (Fenichel 1983), is more predictive than Apgar scores of later neurodevelopmental outcome (Levene et al 1986). Several longitudinal studies have described the outcome of HIE in high-income countries (Robertson and Finer 1985, Hull and Dodd 1992, Peliowski and Finer 1992, Thornberg et al 1995.…”

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Outcome at 1 year of neonatal encephalopathy in Kathmandu, Nepal

Ellis¹,

Manandhar

Shrestha

et al. 1999

Develop Med Child Neuro

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To determine the outcome at 1 year of neonatal encephalopathy (NE) and to estimate the possible contribution of birth asphyxia to childhood disability in a lowincome South Asian country, a prospective cohort study was undertaken in the principal maternity hospital of Kathmandu, where over 50% of local women give birth. From a total population cohort of 21 609 live births, 131 term infants with NE (after exclusion of cases associated with neonatal sepsis, congenital malformations, or primary hypoglycaemia) and 208 term control infants were recruited. Of these, 102 (78%) infants with NE and 106 (51%) control infants were followed-up to 1 year of age. Outcome measures were death or neurodevelopmental impairment, graded as major, minor or none. Of the 131 term infants with NE, 83 were graded with moderate or severe NE according to conventional definition. By 1 year of age, 45 (44%) of the infants with NE had died, 18 (18%) had severe impairments, and two (2%) had minor impairments; four (4%) of the control subjects had died and two (2%) had minor impairments. Most deaths in subjects with NE occurred in the early neonatal period; NE carried no excess risk of death beyond the neonatal period. Of the 18 children with major impairment, 14 (78%) had spastic tetraplegic cerebral palsy and eight (44%) had multiple impairments. Compared with the control group the relative risk of death by 1 year was 5 (95% CI 1.4 to 15) for mild NE, 8 (95% CI 3 to 23) for moderate, and 26 (95% CI 10 to 67) for severe. Twenty-seven of 38 (71%) infants with moderate NE either died or survived with major impairment. An upper estimate for the prevalence of major neuroimpairment at 1 year attributable to birth asphyxia is 1 per 1000 live births in this population.

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Hypoxic-Ischemic Encephalopathy in the Newborn

Cited by 131 publications

References 57 publications

Beagle pup model of perinatal asphyxia: nimodipine studies.

Beagle pup model of perinatal asphyxia: nimodipine studies.

Cord Plasma Vasopressin, Erythropoietin, and Hypoxanthine as Indices of Asphyxia at Birth

Outcome at 1 year of neonatal encephalopathy in Kathmandu, Nepal

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