Abstract: In an unselected series of 116 dyskinetic cerebral palsy cases, 35 hyperkinetic and 81 dystonic, 21% of the cases were considered to derive from the prenatal period, 67% from the perinatal, and 7% from the postnatal period, while 5% were untraceable. Isolated risk factors were found in 24% of the hyperkinetic and 24% of the dystonic cases and various combinations in 68% and 72%, respectively. Preterm appropriate-for-gestational-age cases with hyperbilirubinemia were found significantly more often among the hyperkinetics (47%) than among the dystonics (11%). Term appropriate-for-gestational-age cases with asphyxia were found significantly more often among the dystonics (30%) than among the hyperkinetics (9%). Term and preterm small-for-gestational-age cases with asphyxia and/or perinatal hypoxia were only found in the dystonic subgroup (14%). Both the hyperkinetic and the dystonic subgroups had significantly lower mean birth weights--2795 g and 2872 g, respectively--than that of the general population, 3500 g. The dystonic subgroup had birth weights significantly below the mean for gestational age. Both subgroups had birth weights significantly below the mean for the respectively birth length. This was particularly pronounced for the cases with birth asphyxia. All infants with birth weights less than or equal to -2.0 SD below the mean for birth length had had birth asphyxia, and the proportion decreased successively to 0% among those greater than +1.0 SD.

Abstract: A multivariate analysis of perinatal events occurring in infants with neonatal seizures who were enrolled in the National Collaborative Perinatal Project allowed prediction of outcome. This prediction of death or of mental retardation, cerebral palsy, or epilepsy was empirically confirmed 64% to 83% of the time. In an infant with neonatal seizures, a five-minute Apgar score of less than 7, the need for resuscitation after 5 minutes of age, the onset time of the seizures, and a seizure lasting more than 30 minutes are the best early predictors of which infants will die or will have significant neurologic sequelae. It is hypothesized that neonatal seizures may be a better indicator of the severity or duration of intrauterine asphyxia than the Apgar score. In the neonate with seizures, the use of the formula may allow identification of infants at high risk for adverse outcomes.

Abstract: A prospective study of 54 infants with birth weights of 1,000 gm or less was conducted over a period of two years. Of the 26 infants who survived, 24 weighed between 750 and 1,000 gm; two infants died after discharge and one was lost to follow-up, leaving 23 in whom serial observations were made over 18 months to 3 years of age. The incidence of neurologic deficit in these infants was 17% and of intellectual deficit, 13%. Of the four who were abnormal neurologically, two had spastic quadriparesis, one static encephalopathy, and one hydrocephalus secondary to intraventricular hemorrhage. The three with intellectual deficit had a developmental quotient less than 85. Of the perinatal factors examined, only birth asphyxia correlated significantly with both neonatal mortality and subsequent morbidity. Six (26%) of the surviving infants had mild, nonblinding retrolental fibroplasia; only one of them had a significant refractive error that required corrective lenses for vision. Sepsis was a significant contributor to neonatal mortality in ten of 28 infants who died, but was detected in only one survivor. Although the prognosis for the infant weighing 1,000 gm or less at delivery has improved significantly, there is promise for still further improvement by reducing perinatal asphyxia.

Abstract: The effect of applying brain-orientated neonatal intensive care for term infants with severe neonatal asphyxia was studied. Such treatment included protective phenobarbitone administration together with assisted ventilation and other measures to counteract postasphyxial cerebral oedema and any abrupt changes in blood pressure and oxygenation. The mortality rate and incidence of long-term sequelae were reduced appreciably, resulting in a 0-1 year mortality rate of 14% (previously 50%) and an incidence of neurodevelopmental handicap at 18 months of 17% (previously 50%). It is important in the management of infants with severe asphyxia at birth to avoid blood pressure fluctuations and to control neuronal epileptic activity by the use of barbiturates and early ventilator treatment.

Abstract: National mortality statistics for hyaline membrane disease (HMD) and the respiratory distress syndrome (RDS) and other major causalities were examined in this study for the years 1968 to 1978. A progressive reduction in total neonatal deaths began in 1971 such that only 56% as many newborn deaths occurred in 1978 as in 1968 (31,618 vs 66,456). In each of the 11 years surveyed, the majority of deaths occurred during the first four days of life, with more than half of the infants dying before 48 hours of age. HMD/RDS was the leading cause of death during nine of the 11 years analyzed, accounting for an average 19.5% of neonatal fatalities. Deaths associated with HMD/RDS increased for 1968 to 1971 plateaved and progressively decreased in the ensuing years between 1974 and 1978. Thus, the percent of all neonatal deaths attributable to HMD/RDS increased from 14.7% in 1968 to a maximum of 21.3% in 1974, before declining to 17.5% in 1978. The average contribution of other major causes of death to overall neonatal mortality were: perinatal asphyxia, 13.4%; immaturity, 13.4%; and complications of pregnancy, 11.1%. These data indicate that: (1) despite the declining incidence of fatal HMD/RDS the disorder accounted for an increasing percent of total deaths through the later part of the 11-year period; (2) prevention and/or improved management of asphyxia made the most significant (29%) contribution to reduced neonatal mortality; (3) less change occurred in fatal complications of pregnancy, implying a continuing need for improved maternal/fetal care. Comparing national mortality statistics with those of Wisconsin suggests that further reduction in HMD/RDS death rates should be possible and could have a marked influence on national neonatal mortality statistics.

Abstract: Neuropathologic findings and clinical features of three patients with congenital brain stem damage are reported. All of the infants were premature (32–36 weeks' gestation) and experienced respiratory difficulty in the immediate postnatal period. One infant was moribund at delivery, dying 3 h after birth. In two infants who survived for 12 and 16 days, detailed neurologic examinations demonstrated multiple cranial nerve palsies with absence of facial expression. Autopsies revealed similar changes in the brains of all three infants: bilateral symmetrical lesions were found predeminantly in the thalamus and brain stem. Histological features common to all three cases included prominent basophilic mineralized neurons, neuronal loss, astrocytosis, and axonal spheroids. Necrosis was observed in two cases. These changes are most compatible with one or more episodes of total asphyxia during fetal life. This study supports the hypothesis that, in some cases, Mobius' syndrome is the result of intrauterine asphyxia.

Abstract: In the present study, auditory brainstem responses (ABR) were recorded in 60 high-risk neonates in the intensive care unit selected by the following criteria: Birth-weight less than 2000 g, hyperbilirubinemia requiring phototherapy or exchange transfusion, idiopathic respiratory distress syndrome, artificial ventilation, asphyxia, sepsis or meningitis, intracranial haemorrhage, neurological symptoms and potential ototoxic medication (aminoglycoides, furosemide). The infants tested ranged in gestational age from 27-44 weeks. The ABR testing was performed in a sound-proof room using the Madsen (ERA-74) equipment. Four infants did not reveal responses to 70 dB HL ("nonresponders"), and the total of 10 neonates (16.6%) had abnormal ABR-tests, when the physiological changes related to gestational age and conceptional age (gestational age plus the age after birth) were taken into account. The 10 neonates with abnormal tests were reexamined after discharge, and in six there were no improvement of threshold sensitivity. three of the "nonresponders" were retested several times within the two years after birth (one died at age 18 months of pertussis), and none of them revealed ABR at stimulus intensity of 70 dB HL. They all attend an audiological training program started at age of six months as a consequence of the early diagnosis of impaired auditory function. It is our opinion that a routine ABR-evaluation should be performed on high risk neonates (criteria mentioned above) in the newborn intensive care unit. Retesting of infants with abnormal responses within three months, and several times within the next two years if abnormal responses persist, is important. Transient impairment of auditory functions is not uncommon in these infants. However, the children with persisting hearing impairment should be discovered early to attend an early audiological training program.

Abstract: The effect of the dopamine-receptor blocking agent prochlorperazine on the ventilatory response to hypercapnic hypoxia was studied in six healthy adults. Repeated episodes of transient hypoxia were induced at the mixed venous PCO2 level by a nonrebreathing technique in five males and one female before and after an intravenous bolus injection of prochlorperazine mesylate (12.5 mg = 10 mg base). The ventilatory response to CO2 was also studied before and after drug administration. Prochlorperazine produced a modest (15%) increase in resting ventilation (P less than 0.05) but a marked increase in the ventilatory response to asphyxia such that the group mean response was double the control value [2.0 +/- 0.7 vs. 4.2 +/- 1.5 l . min-1 . % arterial O2 saturation (%SaO2); P less than 0.001]. Two-thirds of this change in ventilatory response was due to an increase in frequency response to hypoxia (0.34 +/- 0.20 vs. 0.81 +/- 0.52 breaths . min-1 . %SaO2; P less than 0.001). The position of the ventilatory response line, as judged by the computed ventilation at 95% SaO2, was increased by prochlorperazine (22.2 +/- 9.6 vs. 35.9 +/- 10.9 l . min-1; P less than 0.01) due to an increase in both tidal volume (P less than 0.05) and frequency of breathing (P less than 0.0125). The ventilatory response to CO2 was unchanged by drug injection. In separate experiments prochlorperazine was shown to 1) increase the ventilatory response to steady-state eucapnic hypoxia (P less than 0.01) demonstrating that the drug effect was not dependent on either the presence of hypercapnia or rapidly changing states of arterial oxygenation; and 2) reverse the depressant effect of intravenously infused dopamine hydrochloride (5 micrograms . kg-1 . min-1) on the ventilatory response to transient asphyxia (P less than 0.01). We conclude that prochlorperazine augments hypoxic responsiveness in humans. The mechanism may be blockade of dopaminergic receptors that modulate carotid body discharge.

Abstract: The risk of neonatal respiratory disorders was calculated in an unselected, total population together with the relative contributions of some factors found associated with an increased risk. Postnatal asphyxia, expressed as a low one minute Apgar score, and low gestational age were substantially, independent risk factors. Caesarean section added, though less markedly, to the risk of the above disorders.

Abstract: The effect of asphyxia on theophylline clearance was studied in 30 newborns who were matched for gestational age, postnatal age, and the presence or absence of asphyxia. Asphyxiated newborns cleared theophylline at approximately half the rate of nonasphyxiated newborns. We found that, in order to achieve a steady-state plasma concentration of 8 mg/L of theophylline, asphyxiated neonates should receive 2.1 mg/kg/day, while nonasphyxiated neonates should receive 3.9 mg/kg/day.

Abstract: In this study, the effects of (1) asphyxia and (2) asphyxiation followed by resuscitation on brain levels of prostaglandins E2 and F2 alpha were evaluated in 2-day-old guinea pigs. Asphyxiation in a nitrogen atmosphere for either 3 min or 3 min 40 s did not alter brain PGF2 alpha levels but after 3 min 40 s of asphyxia, brain PGE2 levels were significantly elevated from control values. When asphyxiation was followed by resuscitation with 95% O2 and 5% CO2, brain PGF2 alpha levels rose significantly while PGE2 levels were not different from nonasphyxiated control values. Pretreatment of animals with indomethacin lowered brain levels of both prostaglandins below nonasphyxiated control levels and prevented any asphyxiation or resuscitation-induced rise in brain prostaglandin levels. Also, animals which were asphyxiated, resuscitated, and sacrificed 1 day after asphyxiation had brain prostaglandin levels which were not different from levels in nonasphyxiated control animals. These studies demonstrate a significant rise in brain PGF2 alpha levels following resuscitation from acute total asphyxia. We speculate that the resuscitation-induced rise in brain PGF2 alpha may contribute to restriction of cerebral blood flow in the postasphyxial period through its action as a vasoconstrictive agent.

Abstract: Sexual asphyxia, a solitary autoerotic activity practiced almost exclusively by males, is examined in this paper. The self‐induced asphyxia may be either chemical or mechanical, and its purpose it to heighten the sexual pleasure. The practice of sexual asphyxia can result in death; however, many such deaths may erroneously be viewed as suicides or homicides as a result of the lack of knowledge of the practice. Sixteen sexual asphyxiai deaths, reported in Dade County (Miami), Florida, are examined in detail. These data confirm that practitioners are overwhelmingly young, white, middle‐class, unmarried males. When the practice is fatal among older practitioners, the data show that some complicating factor, such as the use of alcohol or other drugs, may have contributed to the accident. The most frequent method of inducing the asphyxia was simple hanging by rope and in most cases there was no indication nor suspicion of suicidal intent

Abstract: In an unselected series of 116 dyskinetic cerebral palsy cases, 35 hyperkinetic and 81 dystonic, 21% of the cases were considered to derive from the prenatal period, 67% from the perinatal, and 7% from the postnatal period, while 5% were untraceable. Isolated risk factors were found in 24% of the hyperkinetic and 24% of the dystonic cases and various combinations in 68% and 72%, respectively. Preterm appropriate-for-gestational-age cases with hyperbilirubinemia were found significantly more often among the hyperkinetics (47%) than among the dystonics (11%). Term appropriate-for-gestational-age cases with asphyxia were found significantly more often among the dystonics (30%) than among the hyperkinetics (9%). Term and preterm small-for-gestational-age cases with asphyxia and/or perinatal hypoxia were only found in the dystonic subgroup (14%). Both the hyperkinetic and the dystonic subgroups had significantly lower mean birth weights--2795 g and 2872 g, respectively--than that of the general population, 3500 g. The dystonic subgroup had birth weights significantly below the mean for gestational age. Both subgroups had birth weights significantly below the mean for the respectively birth length. This was particularly pronounced for the cases with birth asphyxia. All infants with birth weights less than or equal to -2.0 SD below the mean for birth length had had birth asphyxia, and the proportion decreased successively to 0% among those greater than +1.0 SD.

Abstract: One hundred and seventy-eight infants with birth weights less than or equal to 1500 g born in 1973-1975 were followed for a period of 1-3 years, and the physical, neurological, and developmental outcome evaluated. Although there was a high incidence of maternal problems, these did not correlate with outcome. Asphyxia at birth followed by neonatal complications leading to ventilatory assistance was significantly correlated with poor outcome. Over 50% of infants less than 100 g birth weight required assisted ventilation, but the outcome in small ventilated infants was comparable to that of ventilated infants of 1001-1500 g birth weight. Infants with neurological abnormality showed a high incidence of associated abnormalities in growth, vision, hearing, and development. Spastic quadriplegia emerged as the most common neurological diagnosis. Despite the many perinatal problems, 82% of the group were normal neurologically and 66% developmentally. The overall outcome was generally favorable in these infants even for those requiring ventilation.

Abstract: . A retrospective study of case notes was undertaken at the Royal Children's Hospital Melbourne, over a five-year period 1974–1978 inclusive, to determine the need for long term anticonvulsant medication for infants who had convulsions in the neonatal period following birth asphyxia and/or trauma. Anticonvulsants were generally ceased before discharge from hospital. Of 38 infants available for follow up, 30 had no recurrence of convulsions by 12 months of age. Of the remaining 8 infants, one had a febrile convulsion, one infant remained on treatment because of a family history of convulsions and later convulsed with fever, one infant who convulsed at six weeks of age and five infants with major neurological sequelae who convulsed beyond the neonatal period, were recommenced on anticonvulsants. Twenty seven of the 38 infants were developmentally normal, and 11/30 had major neurological sequelae (five of these 11 had subsequent convulsions). If an infant ceases convulsing, and is behaving normally at discharge, long term anticonvulsants are not necessary.

Abstract: Study on 2500 consecutive deliveries revealed a perinatal mortality rate of 82.4/1000 births a stillbirth rate of 48/1000 births and a neonatal death rate of 36.1/1000 live births. Perinatal loss was found to be significantly higher in twin deliveries mothers with a poor obstetric history abnormal presentation and in cases where there is an extreme in maternal age or parity. Similarly perinatal mortality was found to increase with decreasing birth weight and gestational age. Asphyxia (32.5%) infections (11%) maternal diseases (8.7%) and congenital anomalies (8.7%) were found to be the major causes of perinatal deaths. Autopsy revealed anoxia (48%) and pulmonary lesions (28%) as the most common causes of death. (authors)

Abstract: Fourteen of 100 babies in an intensive care nursery showed abnormal BAEPs. An analysis of the clinical records identified nine risk factors. Neonatal asphyxia appeared to be associated with hearing loss only when repeated episodes of acidosis accompanied it. We conclude that the BAEPs can identify hard-of-hearing babies and estimate the type and amount of peripheral hearing loss. Prolonged perfusion of the cochlea with blood low in pH level may be the most common cause of hearing disorder in our group of nine risk factors.

Abstract: SUMMARY AND CONCLUSIONS We have presented evidence that the current strong climate of opinion against using sedatives, analgesics and general anaesthetics during labour and delivery is badly misguided and is based on an upside-down interpretation of the significance of ‘apnoea neonatorum’ as it occurs in heavily sedated or anaesthetized newborns. The brief delays the anaesthetized newborn exhibits in initiating breathing movements, rather than signalling a developing harm to the newborn brain, indicate its protected state. The evidencefrom the 1930s to the 1950s that suggests that these agents damage the fetal and newborn brain is flawed. On the contrary, substantial evidence supports the view that these agents protect the fetal and newborn brain and that they may be life-savingwhen used on proper obstetric indication, at proper dose levels, and with proper precautions. We have presented evidence that fetal asphyxia, in most instances, develops as a result of maternal anxiety leading to an increased sympathetic nervous system activity as depicted in Figure 5. The fear-produced increased sympathetic nervous system activity constricts the maternal uterine blood vesselsand diverts maternal blood flow away from the uterus and intervillous space. We have advocated that sedatives and analgesics should be administered to high-risk mothers, to anxious mothers, and to mothers whose fetuses are demonstrated to be asphyctic at dose levels sufficient to quiet or calm the mother. We believe that such sedation will reduce maternal sympathetic nervous system tonus, redistribute maternal blood-flow back to the uterus and intervillous space, and prevent or dramatically relieve fetal asphyxia. We believe this action will prove to be of prime importance and that these drugs should be used prophylactically at sedative dose levels in high-risk mothers early in labour and in low-risk mothers when fetal asphyxia has been identified by heart rate or other methods of monitoring. Wehave proposed that anaesthetizing the mother and fetus with pharmacological agents similar to the barbiturates will significantly extend both the maternal and the fetal brain tolerances to asphyxia and, through this mechanism, will protect the fetal brain from injury should fetal asphyxia continue and become more marked. Using a barbiturate-type general anaesthesia to protect the fetal brain from asphyxia should be viewed as a last resort therapeutic measure taken to guard the fetus against brain injury should the severity of fetal asphyxia advance sufficiently and if measures taken to prevent or reduce the fetal asphyxia have failed. Such a last-resort use of general anaesthesia administered to relieve fetal asphyxia and to protect the fetal brain should represent only the first step in preparing the mother for rapid caesarean section delivery. Table 5 summarizes our view of maternal anxiety and a typical pattern of physiological response as expressed in a small proportion of women who are predisposed. Table 5 also outlines proposed methods of treatment according to magnitude of response. Sedative and analgesic drugs should be used only under clearly defined obstetric circumstances to prevent fetal asphyxia from developing or if it has already developed to significantly reduce it. If fetal asphyxia develops and all measures to relieve it fail (including provision of psychological reassurance and use of sedatives and analgesics), general anaesthesia with barbiturates should be instituted as the first step in preparing the mother for surgical delivery.

Abstract: The purpose of this study was to investigate the effects of changes in renal function on gentamicin disposition following perinatal asphyxia. Gentamicin pharmacokinetics, renal function, mean arterial pressure (MAP) and five-minute Apgar scores were determined in 80 preterm infants admitted to two neonatal intensive care units over an 18 month period. A 2.5 mg/kg dose of gentamicin was infused intravascularly over 20 to 30 minutes in a retrograde fashion. The gentamicin half-life and clearance were prolonged in asphyxiated infants. For the asphyxiated infants gentamicin half-life increased and urine output decreased with a significant correlation (r = -0.66, p less than 0.05). Gentamicin clearance and urine output in the asphyxia group correlated with MAP (r = +0.67, p = 0.07). In non-asphyxia infants no such correlation was seen. This study does not distinguish between asphyxia-induced or gentamicin-induced nephrotoxicity following gentamicin therapy. We suggest that gentamicin concentrations be closely monitored in asphyxiated newborns who demonstrate compromised renal function.