Abstract: Brainstem auditory evoked responses were recorded after acute asphyxia in 126 infants, ages birth through 18 months. Of these, 21 had markedly abnormal amplitude ratios, and all infants with abnormal amplitude ratios had severe neurologic handicaps. An abnormal amplitude ratio predicts long-term neurologic sequelae of acute asphyxia in infants. Normal amplitude ratios did not, however, ensure normal neurologic outcome; 10 infants with normal responses were severely handicapped.

Abstract: . Swanstrom, S. and Bratteby, L.-E. (Perinatal Research Unit of the Department of Paediatrics and the Unit of Paediatric Physiology of the Department of Clinical Physiology, University Hospital, Uppsala, Sweden). Metabolic effects of regional analgesia and of asphyxia in the newborn infant during the first two hours after birth. I. Arterial blood glucose concentration. Acta Paediatr Scand, 70: 791, 1981. Effects of obstetric regional analgesia and of asphyxia on the arterial blood glucose concentrations were inestigated in 83 newborn infants divided into a control group, an asphyxia group, a continuous epidural, and a paracervical + pudendal block group. Lidocaine was used in the analgesia groups. All infants except those of the asphyxia group had 1-minute Apgar scores ≥7. 1) In the asphyxiated infants high blood glucose values and strong correlations between blood glucose concentrations and different signs of asphyxia (Apgar score, base deficit and lactate) were found. 2) In infants whose mothers were given regional analgesia the results were: (a) high glucose values in 20 % of the infants and an association between increased glucose concentrations in these infants and signs of fetal distress, (b) low blood glucose values (< 1.67 mmol/1) in 27 % of the infants. It is recommended that the blood glucose is checked in the newborns after obstetric regional analgesia.

Abstract: The pathophysiology of respiration and hemodynamics during the agonal period of death by obstructive asphyxia was investigated. Experiments were carried out on ten dogs that were strangulated by ligature (seven cases) or asphyxiated by occlusion of the intubation tube (three cases). The following parameters were registered: Blood pressure in the arteria femoralis and arteria pulmonalis, electrocardiogram, endotracheal pressure, respiratory frequency, electroencephalogram. These were the most important findings: (a) An excessive and distinctly biphasic hypertonic reaction takes place after strangulation by ligature whereas occlusion of the intubation tube results in a slight increase of arterial blood pressure. (b) After occlusion of the tube more than after strangulation the endotracheal pressure becomes deeply negative during the inspiration trials. (c) After cessation of respiration a distinct pulmonary arterial hypertension develops in both forms of obstructive asphyxia. (d) The paralysis of the respiratory center takes place after about 4 min at the same time when the circulatory breakdown develops. The final cardiac failure occurs after about 9-10 min. The dysregulation of respiration and hemodynamics in the agony of obstructive asphyxia can be differentiated from other shock models. This results in special morphological alterations of the lung tissue which have been described elsewhere.

Abstract: Intracerebral hemorrhage in full-term infants is infrequent and has most often been associated with birth asphyxia or trauma.1.2This report describes a full-term newborn infant, born after an uncomplicated delivery, in whom a large intracerebral hemorrhage developed within the first 12 hours of life. The infant had the clinical and laboratory features of the hyperviscosity syndrome,3and an association with cerebral hemorrhage is postulated. Report of a Case.—The patient was a 2,880-g male born after 38 weeks of gestation to a 17-year-old gravida 1 woman following an uncomplicated pregnancy, labor, and delivery. Artificial rupture of membranes was performed four hours prior to spontaneous, controlled vaginal delivery. Total labor was 14 hours. Apgar scores were 8 and 9 at one and five minutes, respectively. The baby was noted to have minimal respiratory distress in the first hour after birth. In 24% oxygen, an arterial blood sample showed Po

Abstract: Why do the nerve cel ls of fetuses or newborns d i e or become destroyed äs a consequence of t h e f r exposure to oxygen d e f i c i e n c y states? The oldest and s t i l l most w i d e l y accepted In t e rp re t a t i on of the mechanlsms that u n d e r l l e both the loss of nervous System f u n c t l o n and the development of b r a l n I n j u r y w l t h oxygen depr iva t Ion i s a presumed de f i c i ency In energy a v a i l a b i l i t y to the ce l l s requ l red to support v i t a l c e l l u l a r processes ( 2 / 13). A s l m i l a r mechanism has been poslted to e x p l a l n the death of ce l l s In other parenchymal organs (3) . However/ recent s tudles from a number of laborator les have ralsed serlous doubts that a d e f l c i t of energy a v a i l a b i l i t y can account for the loss of nervous system f u n c t l o n w i t h oxygen d e f l c i e n c y (l , HO w h l l e other results obtained in our own laboratory have demonstrated a lack of cor re la t lön between the a v a i l a b i l i t y of h i g h energy phosphate d u r i n g exposure to a va r l e ty of oxygen d e f l c i e n c y states and the development of b r a l n pathology. Rather / our resul ts es tab l i sh a close corre la t ion between the t issue content of l ac t ic ac id at the end of exposure and whether or not b r a i n i n j u r y w i l l develöii (8/ 9/ IQ, 12). These results are now described. A reduced oxygen a v a i l a b i l i t y to an an ima l or to man causes redox changes in the b r a i n äs a consequence of an impa i r ed o x i d a t i o n of cytochrome oxidase the f i n a l l i n k in the electron transport cha in . An i m p a i r e d o x i d a t i o n of cytochrome oxidase/ in tu rn / leads to an i m p a i r e d o x i d a t i o n of a l l the var ious antecedent l i n k s in the electron transport cha in i n c l u d i n g n i c o t i n a m i d e aden ine d i n u c l e o t i d e / the water so lub l e ox ida t ion reduc t ion co-factor essent ial for many enzymatic t ransformat ions that take place in many m e t a b o l i c pathways important for c e l l u l a r bioenergetics. Thus/ the al tered redox state brought about by oxygen de f i c i ency reduces the a c t i v i t y of the electron transport cha in I t s e l f and increases both the absolute concentrat ion and the Proport ion of a v a i l a b l e n i c o t i n a m i d e adenine d i n u c l e o t i d e that is present in its reduced state. An i m p a i r e d electron transport is associated w i t h major reductions in ATP product ion and/ thus/ major d e f i c i t s in energy a v a i l a b i l i t y to the ce l l . The maln tenance of major port ions of a v a i l a b l e n i c o t i n a m i d e adenine d i n u c l e o t i d e and the electron transport c h a i n in a reduced state also leads to major impai rments i n c i t r i c ac id cycle f u n c t i o n because of a lack of hydrogen acceptors at the var ious dehydrogenase Steps äs orte progresses from i soc i t rä te / a-ketoglutarate/ succinate/ and malate . The maintenance of large amounts of n i c o t i n a m i d e adenine d i n u c l e o t i d e in the reduced state also i n h l b i t s the o x i d a t i v e decarboxyla t ion of pyruvate thereby I n t e r f e r l n g w i t h the fo rmat ion of acetyl-coenzyme A and f u r t h e r reducing c t t r l c . acid cycle func t i on . Ra ther / the presence of n i c o t i n a m i d e adenine d i n u c l e o t i d e p r i m ä r ! l y in the reduced state favors the reduct ion of p y r u v i c ac id to lact ic acid. As a consequence of a l l these a l t e r a t i ons i n b iochemica l f u n c t i o n / a l l a v a i l a b l e carbohydrate i n the t issue i n c l u d i n g that present äs free

Abstract: The total creatine phosphokinase (CPK) activity and the levels of activity of its MM, MB, and BB isoenzymes were measured in sera obtained within four hours after birth from 32 newborn infants. The total CPK level and activity of its MM, MB, and BB isoenzymes increased significantly with increasing acidosis. In addition, statistically significant correlations were found between the total CPK level in infants9 sera and their oneminute Apgar scores. The infants9 birth weight, gestational age, and mode of delivery did not correlate significantly with the serum total CPK activity. Infants who died within ten days after birth from causes related to asphyxia had significantly higher total CPK activity levels in their sera in comparison with the survivors. The data suggest that perinatal asphyxia with acidosis may result in the leakage of CPK and its isoenzymes from the damaged cells into the circulation and that a marked elevation of their values may indicate a poor prognosis for survival.

Abstract: Effects of obstetric regional analgesia and of asphyxia on the arterial blood gases and acid-base balance in the first two hours after birth were investigated in 85 newborn infants divided into a control group, an asphyxia group and a continuous epidural, an intermittent epidural and a paracervical + pudendal block group. Lidocaine was the drug used in the analgesia groups. In the asphyxia group the metabolic acidosis decreased and pH was normalized to the level of the control group between 10 and 30 min after birth. During this period in the asphyxia group PaO2 was higher than and PaCO2 similar to the corresponding control values. Compared with the control group, in the regional analgesia groups the metabolic acidosis tended to be less extensive and PaO2 higher, whereas PaCO2 was similar. A lower packed red cell volume in the asphyxia and in the regional analgesia groups, probably due to differences in placental transfusion, may have had influence on the results. Within the regional analgesia groups infants with hyperglycemia showed signs of an increased metabolic acidosis while infants with hypoglycemia had low base deficit and lactate values supporting the assumption that neonatal blood glucose concentration may reflect perinatal distress.

Abstract: Intracranial pressure (ICP) studies were carried out in 14 infants with severe birth asphyxia and brain damage. A markedly low cerebral perfusion pressure (CPP) was noted in infants who died and in 1 infant who survived with cerebral palsy. The long-term ICP tracing revealed negative waves and plateau waves in 2 infants. Cushing response was noted in 2 infants who had elevated ICP. The value and significance of evaluated CPP and of abnormal waveforms are discussed.

Abstract: To determine aetiological factors a seven year review of massive pulmonary haemorrhage (MPH) was performed at the Mercy Maternity Hospital, Melbourne and compared with 26,208 consecutive live births. Statistically significant correlations were found between MPH and prematurity, birth asphyxia, hyaline membrane disease, breech delivery, multiple births, fetal growth retardation, Caesarean delivery, and the presence of a patent ductus arteriosus. MPH was associated with a mortality of 92.6%. Three severely growth retarded infants with unexpected MPH are presented. These cases indicate that severe intrauterine hypoxia is a major factor predisposing to MPH. Clinicians should be alert for the possibility of MPH in severely growth retarded infants and with vigilance and anticipation a more favourable outcome may be possible.

Abstract: Birth Asphyxia. I. Measurement of Visual Evoked Potential (VEP) in the Healthy Fetus and Newborn Lamb

Abstract: . Swanstrom, S. and Bratteby, L.-E. (Perinatal Research Unit of the Department of Paediatrics and the Unit of Paediatric Physiology of the Department of Clinical Physiology, University Hospital, Uppsala, Sweden). Metabolic effects of regional analgesia and of asphyxia in the newborn infant during the first two hours after birth. II. Arterial plasma concentrations of glycerol, free fatty acids and beta-hydroxybutyrate. Acta Paediatr Scand, 70: 801, 1981.-Effects of obstetric regional analgesia and of asphyxia on the arterial blood concentrations of the lipid metabolites: glycerol, free fatty acids and beta-hydroxybutyrate were investigated in 85 newborn infants divided into a control group, an asphyxia group, a continuous epidural, an intermittent epidural and a paracervical + pudendal block group; lidocaine was the drug used in the analgesia groups. The postnatal changes in lipid metabolites followed three different patterns. After marked increases in glycerol and free fatty acids a steady level was reached after one hour in the control group and not before two hours in the regional analgesia groups. In the asphyxia group, however, a steady level was found already 10 min after birth. Between 30 and 120 min after birth the beta-hydroxybutyrate concentration increased in the control group, decreased in the asphyxia group and did not change in the three regional analgesia groups. The different patterns of lipid metabolites may indicate differences in sympathetic tone and/or in hormonal influences after birth.

Abstract: Thirty infants of low birth weight, 35 infants with perinatal asphyxia, and 16 infants of diabetic mothers were investigated for early neonatal hypocalcaemia. The infants were randomized into a group prophylactically given 1 alpha-hydroxy-vitamin D3, 0.05 or 0.10 micrograms/kg i.v. on the first 3 days of life, and an untreated control group. In infants of low birth weight and infants of diabetic mothers there were no differences in serum ion-Ca concentrations on days 2, 3, 5, and 7 between the treated and untreated groups. In infants with perinatal asphyxia, however, serum ion-Ca concentrations on days 5 and 7 were significantly higher in the treated than in the untreated group, while on days 2 and 3 the differences were not statistically significant. The hypocalcaemia in asphyctic infants was not correlated to bicarbonate treatment, but infants with severe signs of asphyxia had lower serum ion-Ca concentrations than infants with only mild or no signs. Hypocalcaemia in asphyctic infants might be explained by a decreased concentration of 1 alpha, 25-dihydroxy-vitamin D3 following reduced 1 alpha-hydroxylation in the kidney as a consequence of anoxia during perinatal asphyxia.

Abstract: Retrolental fibroplasia has now been reported to occur in over 190 infants in which oxygen administration was not a factor. Ashton injected glass ballotini into kitten retinal arteries and produced vasoproliferative changes “exactly as occur in retrolental fibroplasia.” (Brit.J.Ophthal. 49:225, 1965) He demonstrated that vasoproliferation is not due to O2 toxicity per se but is “merely a sequel of the obliteration of the vessels induced by oxygen.” Our hypothesis is that R.L.F. may develop in very low birth weight infants who have cerebral/retinal hypoperfusion/ischemia, at birth or in the neonatal period. These infants have impaired cerebral blood flow autoregulation, and a high incidence (40-80%) of intracranial bleeding. This hypothesis would explain the high incidence of non-O2 related R.L.F. in anencephalic infants and the rising incidence in very low birth weight infants <1000 grams with intracranial hemorrhage. We have observed two infants with severe R.L.F., whose clinical course (asphyxia, shock, intracranial bleeding) supports our hypothesis. In one infant cerebral hypoperfusion was documented. Imperfect TcPO2 and arterial blood gas monitoring did not reveal prolonged significant hyperoxemia. Our observations suggest that hyperoxemia is not the only cause of R.L.F., cerebral hypoperfusion and retinal ischemia may produce the same picture. Careful O2 monitoring alone will probably not eliminate R.L.F.

Abstract: Seventy-five infants ≤34 weeks gestation & birthweight ≥1000g had ultrasound brain studies to diagnose IVH and subependymal hemorrhages (SEH) on the first day of life (30′ to 23 hrs. after birth). They were grouped according to delivery (with & without labor). Diagnosis in the first 24 hours after birth & major IVH/SEH (IVH/SEH associated with ventricular enlargement) were considered. Infants born after labor had a higher incidence of major IVH/SEH even if those without RDS, PDA and asphyxia born with labor were compared with sick infants born without labor (2 Rh-hydrops, 14 RDS & PDA, 2 severe asphyxia). Labor seems important in the pathogenesis of large IVH/SEH in infants BW≥1000g.

Abstract: In rats a 25% D2O content of total body water was found to prolong survival time and the period of revivability in asphyxia by a better maintenance of cardiovascular function and gasp activity.

Abstract: Acute airway obstruction in the pharynx or larynx causing asphyxia is a proposed cause of SIDS and “near miss” SIDS. Documentation of these events in such cases is rare. We studied 2 infants at high risk for SIDS in whom absent respiratory efforts alternating with obstructed respiratory efforts (i.e., mixed apnea) produced episodes of asphyxia. Infant A (28wk gestation) had apnea and bradycardia spells through the first month of life. In polygraphic studies at 5days of age (heart rate, abdominal excursion, nasal and oral airflow, TcPO2), we identified 9 mixed apnea spells causing hypoxemia (TcPO2 as low as 29Torr) and bradycardia (as low as 33bpm). This infant died at home of SIDS (autopsy diagnosis) at 14wks of age. Infant B, a thriving 32wk gestation infant, had a family history of SIDS (half sibling) but no history of apnea or bradycardia until 4wks when he required resuscitation for sudden cardio-respiratory arrest (i.e., “near miss SIDS”). Spells of apnea, cyanosis and bradycardia recurred for 4wks in this otherwise healthy infant. We monitored 4 episodes of mixed apnea, each causing hypoxemia (TcPO2 as low as 36Torr) and bradycardia (as low as 70bpm). In infant B we found the site of obstruction to be above the larynx by using a pharyngeal catheter which detected transmission of thoracic pressure during obstructed breaths. Documentation of mixed apnea causing asphyxial spells in these at risk and subsequent SIDS infants supports the concept that mixed apnea with pharyngeal obstruction could be a cause of the fatal SIDS event. (NIH grant#HD 10993)

Abstract: In the human fetus the adrenergic system develops morphologically at an early stage. The development of adrenergic receptors occurs to a large extent before birth. The human fetus is capable of a large production of catecholamines, particularly during the last two months of fetal life. Normal labour and delivery elicits an increased release of catecholamines, a reaction that is markedly enhanced by asphyxia. beta-Receptor stimulants not only relax the uterine smooth muscle but also tend to modify the concentration of surfactant in lung fluid. beta-Receptor blocking agents, both non-selective and cardioselective, create a problem in clinical medicine since they provide an effective means of treating hypertension in pregnancy. Theoretical implications of such treatment present a risk to the fetus. Experimental evidence from the fetal sheep preparation indicate that beta-receptor blockade carriers an immediate risk to the severely asphyxiated fetus when the blockade is induced acutely. In this situation heart muscle contractility, heart rate and cardiac output fall abruptly while the capacity for anaerobic glycolysis is greatly diminished. Even though such acute animal experiments are far removed from clinical practice the results suggest that great caution should be exercised in the use of adrenergic blocking agents in obstetric practice.

Abstract: Naloxone, a specific opiate antagonist, greatly modifies the ventilatory response to asphyxia in the newborn rabbit (Chernick et al, Ped. Res. 14:357, 1980). Do endogenous opiates affect the neonatal adaptation to birth following fetal asphyxia? Pregnant does (day 30) were given naloxone (1 mg/kg I.V.) or saline (2.5 ml I.V.), and 5 minutes later placed in a chamber containing 7% CO2 in N2. The does expired at 3-4 min., the fetuses were delivered at 10 min., and kept warm by a heating lamp. A ‘blinded’ observer assessed the pups at 1,3,5,10,15 and 30 min. post delivery using a scoring technique for respiration, color, muscle tone, response to stimulation and general activity. Pups in the naloxone group (n=27) had significantly higher scores than those in the saline group (n=24) for the first 15 min. of life but by 30 min. the difference was not significant. Similar experiments were done in which pregnant does were given 7% CO2 in N2. At 10 min. I.P. fetal injection through the uterine wall of either saline or naloxone (0.5 mg/kg) was done and the fetus delivered. However, saline injected pups had high scores even at 1 min. and these scores remained high and not different from naloxone treated pups. Thus, endogenous opiates cause neonatal depression during the first 15 min. after birth following fetal asphyxia and this depression is reversed by naloxone and intraperitoneal injection per se. (Supported by M.R.C. Canada and the Children's Hospital of Winnipeg Research Foundation Inc.)

Abstract: Succinyldicholine-induced asphyxia in awake calves led to massive catecholamine release by the adrenal medulla. Hypertension and bradyarrhythmias resulted. Electroencephalograms recorded during periods of succinyldicholine-induced apnoea indicated that calves were probably conscious and under psychic stress for at least 4 min after the onset of apnoea. Electroencephalographic signs indicative of decreased consciousness became evident in one calf only after 4,8 min of apnoea but were absent in 3 calves subjected to maximum periods of apnoea of 4,1; 3,2 and 4,4 min. The latter 3 calves all recovered with no apparent neurological deficit after intravenous injection of plasma pseudocholinesterase.

Abstract: Fetal haemodynamic changes, together with changes in the fetal renin-angiotensin system and in circulating concentration of prostaglandin E, were studied in chronically prepared fetal sheep before, during and after asphyxia induced acutely by maternal aortic occlusion in last third of gestation. A total of thirty experiments were performed in seventeen animals. Severe fetal asphyxia (fall in PO2 greater than 30%) was associated with transient fall in heart rate and rise in blood pressure but not with changes in plasma concentrations of either prostaglandin E or renin substrate. Fetal plasma renin activity increased to 140% of control values during moderate asphyxia and to 400% during severe asphyxia. We conclude that the fetal renal angiotensin-renin system is activated by asphyxia.

Abstract: Umbilical cord complications play a leading role \ in the structure of perinatal morbidity and mortality. Thus, according to BRUCE et al. [2], who analyzed 8038 deliveries, various types of umbilical cord complications caused still-birth in 14.5%, asphyxia in 6.4% and postnatal deaths in 3.1 %. Almost the same results were obtained by other authors [8,10]. However, when the presence of umbilical cord pathology is diagnosed in time and the proper obstetrical tactics are chosen, the morbidity and mortality rate do not differ from average data [5, 8, 10]. Curriculum vitae

Abstract: The ability to accurately and non-invasively monitor blood pressure has focused attention on severe symptomatic hypertension (HBP) occurring in the neonatal period. In 1980, 19 of 880 admissions (2.2%) were identified as hypertensive (mean arterial pressure >70 mm. Hg. on 3 occasions). They included neonates with BW's from 0.63kg. to 4.6kg., GA 26-41 weeks, and multiple primary diagnoses, predominantly pulmonary disorders. Asphyxia occurred in only 4/19. Infants with HBP presented at a mean age of 11 days, range 1-52, and manifested congestive heart failure 8/19 and retinopathy 8/19. Renal findings included elevated BUN and creatinine 7/19, new appearance or increased severity of hematuria and proteinuria 6/19, elevated peripheral plasma renin 8/8, and varying abnormalities of IVP, abdominal ultrasound or renal scan 7/10. Strikingly, 14/19 (74%) of these infants had umbilical arterial catheters (UAC) all above the diaphragm. Onset of HBP occurred at a mean of 13 days after catheter placement, range 1-52. HBP was identified only following removal of the catheter in 6/14, mean 15 days, range 5-45. The response to a variety of antihypertensive agents has been satisfactory; no infant has required nephrectomy and only 7 needed therapy for >1 month. The possible association between HBP and high UAC neccessitates reevaluation of the optimal site for catheter placement and suggests that some HBP may be the result of thrombo-embolic complications of UAC. Other identifiable causes of HBP included asphyxia, renal anomalies and endocrine disorders.

Abstract: From January 1978 to December 1979 cortico-steroids to improve prenatal pulmonary maturity were administered to 174 patients. Patients with additional factors to accelerate pulmonary maturity or patients with additional factors to pre-dispose to pulmonary asphyxia during labor were not evaluated. 43 patients who delivered 47 children were studied. The cortico-steroid treatment and delay of delivery for over 48 hours improved the survival chances of the pre-mature infants. Following the administration of 4 times 2 mg beta-methasone-phosphate 26.7% of the infants had respiratory distress syndrome whereas no respiratory distress syndrome was found after 4 times 4 mg of beta-methasone-phosphate.