Abstract: To test the hypothesis that birth asphyxia has a role in the etiology of intraventricular hemorrhage (IVH), blood was collected from the umbilical artery (UA) at birth in 28 premature infants of 26 to 29 weeks gestation and analyzed for hydrogen ion concentration [H+], PCO2, standard bicarbonate level, and lactic acid level. The infants were followed up throughout their nursery stay until a diagnosis of IVH could be made or excluded, either by autopsy or clinical findings. Infants with IVH had lower Apgar scores. There were no differences in UA [H+] or bicarbonate or lactic acid levels. However, infants with IVH had a significantly higher UA PCO2. Although the difference appeared relatively small, the increase in PCO2 during labor may have been relatively large. It is concluded that hypercarbia, possibly by increasing cerebral blood flow, may be one important factor in the genesis of IVH.

Abstract: The newborn has a limited capacity to tolerate acute haemorrhage. Prompt diagnosis and therapy are essential for survival. Blood loss can occur in the newborn due to occult haemorrhage, prior to birth or during delivery, obstetric accidents, maternal haemorrhage, or secondary to recurrent blood sampling. Special precautions must be taken when events known to cause fetal haemorrhage have occurred during pregnancy. These include a maternal history of transfusion reaction in the absence of a transfusion, third trimester bleeding with placenta praevia, placenta abruptio and vasa praevia, emergency caesarean sections, twin pregnancies and amniocentesis. The clinical manifestations of post-haemorrhagic anaemia at birth depend on the extent and duration of blood loss. When acute massive blood loss has occurred, the infant is extremely pale and requires immediate transfusions or volume expanders. Although the haemoglobin may be normal initially, it rapidly falls within six to eight hours after birth. Other causes of extreme pallor in the newborn include asphyxia and anaemia secondary to haemolysis. Infants who have developed acute post-haemorrhagic anaemia are hypovolaemic, are neither jaundiced nor cyanotic, and respond to therapy with volume expanders. The clinical picture with chronic blood loss is usually mild and responds to conservative therapy with iron alone. Internal haemorrhage should be suspected when a 24 to 72 hour newborn rapidly deteriorates and has evidence for hypovolaemic shock without signs of external blood loss. The blood withdrawn for laboratory evaluation in the high risk newborn must be carefully monitored so that it can be replaced before the newborn becomes compromised.

Abstract: In forty-five children the hypoxanthine concentration in cerebrospinal fluid (CSF) was measured (fifty-two samples). In newborn infants (nineteen patients) the hypoxanthine levels were higher in patients with clinical conditions associated with hypoxia (idiopathic respiratory distress syndrome, asphyxia, apneic attacks) than in patients without clinical hypoxia (P less than 0.01). In hypoxic patients the hypoxanthine concentration varied between 5 and 28 mu mol/l. In children outside the neonatal period the hypoxanthine concentration in CSF varied considerably in different diseases. High levels were registered in meningitis prior to treatment, febrile convulsions and in lymphoblastic leukaemia, probably reflecting tissue hypoxia and an increased tissue catabolism.

Abstract: Summary: The aetiology of the sudden infant death syndrome: Current ideas on breathing and sleep and possible links to deranged thiamine Neurochemistry. The sudden infant death syndrome (SIDS) is now the commonest cause of death between one week and one year of age in most western countries. An asphyxia/ death, with unrecognised hypoxic episodes during sleep in the preceding weeks, has been postulated from autopsy evidence for both acute and chronic hypoxia; the evidence includes Po2 values, intra-thoracic distribution of petechiae, pulmonary arteriolar and right ventricular hypertrophy. Long-term monitoring of infants resuscitated from a “near miss” SIDS demonstrates sleep apnoea, sometimes associated with episodic collapse and obstruction of the upper airway. Physiological studies in healthy babies and animals highlight factors leading to vulnerability to asphyxia in different phases of sleep. In REM-sleep (rapid-eye-movement), inhibition of intercostal muscle activity leads to: inspiratory collapse of the rib-cage, impaired reflex compensation for airway obstruction, overall lung-deflation with reduction of O2-stores and rapid hypoxaemia during apnoea. In REM-sleep, breathing efforts are not augmented by hypercapnia and the defense against asphyxia depends on reflex responses to hypoxia. Sleep apnoea sometimes occurs in infants with a rare congenital defect of brain thiamine triphosphate. This draws attention to many similarities of modern SIDS and other infantile syndromes reported historically which involve deranged thiamine neurochemistry. Sudden unexpected deaths occur in apparently thriving infants of asymptomatic thiamine deficient mothers. Other similarities include: a peak incidence at 2–4 months of age; precipitation often by minor febrile episodes; seasonal and familial risk factors, with increased risk in twins; many common findings at autopsy. Although asymptomatic maternal thiamine deficiency is common in western communities ingesting high carbohydrate diets containing various thiamine antagonists, the effect on infant thiamine stores has received little attention. Future research is needed to evaluate SIDS incidence after identification and elimination of low thiamine states. Defective neural control of breathing during sleep should be evaluated in relation to thiamine-neurochemistry, particularly to the leaky blood-brain barrier, to glutamate and GAB A, to sympathetic denervation and to defective vagal reflexes of the lungs and larynx.

Abstract: The small vessel blood content (SVBC) of the ventricular walls of the heart of anesthetized closed chest rats was determined using 59FeCl3 to label the plasma siderophilin. SVBC was measured breathing air, 100% O2’, 5% CO2’ in 21% O2’ and during asphyxia. The average SVBC could be ranked: air 2’ 2 2’ values were not significantly above the ‘air’ values. Under control conditions, SVBC of the rat heart averaged 6.77 ± (SE) 0.23 ml blood/100 g tissue. Inhalation of 5% CO2 increased this to 8.68 ± 0.34, while asphyxia produced a maximal response to 14.40 ± 0.77. Comparison of SVBC were made between various regions of the ventricular walls. The only significant difference was that the right side of the septum had a lower SVBC than the left ventricular sub-epicardium under all conditions except CO2. These differences in SVBC are related to the number of open capillaries in the myocardium. Thus inhalation of CO2 decreases intercapillary distance while 100% O2 has no effect.

Abstract: The serum bilirubin concentration was studied in 114 full term and 199 preterm babies suffering from either perinatal asphyxia or idiopathic indirect hyperbilirubinaemia, in order to establish the effect of asphyxia on the serum bilirubin level. Infants with any other disease causing non-physiologic jaundice were excluded. It was found that perinatal asphyxia per se does not exaggerate hyperbilirubinaemia either in full term or in preterm babies. Weight loss correlated significantly with the peak bilirubin concentration in all groups of patients. This would suggest the possible role of feeding and hydration in the genesis of hyperbilirubinaemia.

Abstract: SIR,-During the past three months, six female members of a hospital staff of approximately 1600-three nurses, two domestics, and one administrator-have presented with a similar clinical picture. This consisted of the sharp onset of severe and persistent pain in the cervical region, which was rigidly held in the erect central position and resisted the least movement, active and passive, in any direction, the pain being greatly augmented by such attempts. With one exception resolution was complete within a few days and the impression gained was that this was spontaneous rather than attributable to the local application of heat and the collar supplied. One recurrence has taken place, of identical nature and duration. Systemic upset, pyrexia, other abnormal physical signs, and radiological changes were all absent. Although chest pains have not infrequently been reported among the staff during this period, no example suggestive of Bornholm disease has been encountered nor has inquiry in the medical wards yielded information of its presence or that of the stiff-neck syndrome among the patients. The clustering of the cases raises the possibility of an infective aetiology. It would be of interest to learn of experience of like nature.

Abstract: 20 full term infants had abnormal CT during the neonatal period. All had histories of peripartum asphyxia followed by seizures. Bleeding into the ventricles and/or adjoining brain tissue was present in 7 and was extensive in 5. Areas of decreased cortical density secondary to anoxia were present in the remaining 13. In 3, these changes were confined to one hemisphere with a pattern suggesting infarction of the middle cerebral artery. Severe edema obliterating the ventricles was present in 2 others. All patients have been followed for a minimum of 9 mo with a repeat CT done at 6-12 mo in 18. 12 of the 20 have severe neurological abnormalities: 2 hydrocephalus; 7 cerebral palsy; 3 microcephaly with retardation. All 18 follow-up CT show brain atrophy with localization and extent corresponding to the neonatal CT. The 5 children with extensive intracranial bleeding are severely defective; the other 2 have minimal dystonia and developmental delay. All 3 patients with unilateral changes are hemiplegic. The 2 patients with severe neonatal edema have central atrophy on follow-up CT and spastic quadriplegia with retardation. These results show that CT in the asphyxiated neonate is highly predictive of the type and severity of later neurologic deficits, especially in cases showing severe edema, major vessel infarction, or extensive intracranial hemorrhage.

Abstract: The body colour of immobilized carp was photoelectrically measured simultaneously with heart rate in order to examine one of the effects of asphyxia on autonomic functions of the cutaneous region. 1) Asphyxia induced marked body colour darkening and bradycardia. 2) Adequate increase in cardiac vagal activity was recorded during asphyxic bradycardia. 3) After atropine injection, body colour darkening, as in intact fish, was observed during asphyxia while heart rate was not changed. 4) After transection of anterior spinal cord, asphyxic stimulation did not induce body colour darkening. It is concluded that body colour darkening mediated by nervous pathways was observed during asphyxia simultaneously with the definite bradycardia. This response of body colour has provided the first indication for responses in cutaneous autonomic systems within the responses of the fish co-ordinated as a whole to asphyxia.

Abstract: Neonatal deaths make a major contribution to the infant mortality rate. In a large number of cases this is due to failure in establishing respiration at birth. Certain conditions have been found to be associated with asphyxia of the newborn so regularly that one should anticipate trouble and be prepared for an emergency whenever they occur. These conditions are the following: (1) Obstetric factors: (a) Prolapse of the cord or cord entanglements. (b) Abnormal uterine contractions. (c) Difficulty with the delivery of shoulders. (2) Maternal factors: (a) Maternal age over 35 years. (b) Grand multipara. (c) Prolonged labour. (d) Prolonged rupture of membranes. (e) Maternal diseases, e.g. diabetes, toxaemia, etc. (3) Foetal factors: (a) Meconium stained liquor. (b) Tachycardia (more than 160/min) or bradycardia (less than 100/min). (4) Effects of drugs given to mother.

Abstract: Results of brain studies in 38 premature infants with severe peri- and postnatal pathology (intracranial labor trauma, asphyxia, sepsis) are presented. Clinico-morphological data detected that profound prematurity and consequently a profound immaturity of the brain, complicated by hypoxic damages during labor and early developing septic infections, lead to an expressed retardation and irreversible degenerative changes, especially in the brain structures which develop later. From the neurological point of view the most serious in relation to the prognosis are those children who are in a state of a stable inhibition of the CNS.

Abstract: Vascular responses in the hindlimb muscles of anesthetized paralyzed cats during systemic asphyxia were studied. The cats were ventilated with 10% O2-10% CO2-80% N2 for 10-20 min periods, while blood flow to the skinned hindlimb was monitored (electromagnetic flowmeter). Mean arterial pressure rose and hindlimb flow typically fell during asphyxia, implying increased vascular resistance. After sympathetic denervation of the hindlimb, resistance increased in some groups of animals, and did not change in others during asphyxia. Functional adrenalectomy did not alter these response characteristics. Resistance also did not changes significantly if the control resistance was first increased to the predenervation level by electrically pacing the lumbar sympathetic chain. In contrast, pronounced vasodilatation occurred during asphyxia after blocking of the alpha receptors in the hindlimb (phenoxybenzamine) or after systemic catecholamine depletion (reserpine). We conclude that the vasoconstriction in innervated muscle during asphyxia was caused in part by increased discharge of sympathetic constrictor nerves to the muscle vasculature, with augmentation from a humoral alpha agonist of nonadrenal origin, possibly norepinephrine released from sympathetic nerves throughout the body.

Abstract: Inborn errors of metabolism which present in the newborn period may present with a clinical picture that is indistinguishable from that of neonatal asphyxia. Fortunately, most patients with metabolic disease go into coma after a period in which they are well enough to take feedings normally, usually for at least 12 hours. Among the tests useful in a neonatal patient who is completely unresponsive and on a respirator is the concentration of ammonia in the plasma. Infants who are not hyperammonemic should be studied for their degree of glycinemia. Patients with hyperglycinemia, and those with an anion gap, and some of the others should be studied by organic acid analysis.

Abstract: The present work summarises the effects of obstetric complications on the newborns. The neonate is adversely affected by toxaemia of pregnancy leading to a high incidence of low birth weight and preterm babies, high morbidity rate, increased incidence of asphyxia, sclerema and prematurity leading to high perinatal loss. Antepartum haemorrhage in the mother was associated with increased frequency of low birth weight, preterm babies, high morbidity rate and increased proneness to asphyxia and respiratory distress syndrome causing: high perinatal mortality. The neonates born of mothers having abnormal presentation, such as, breech, also had a greater predisposition to asphyxia and intracranial injury leading to high perinatal loss. Hydramnios in the mother gave rise to a high incidence of congenitally malformed, preterm babies associated with increased perinatal mortality.

Abstract: Blood volume and its components were estimated using 125iodinated human serum albumin in 194 newborn infants with 26 to 41 week gestations. Umbilical cords were ligated 15 seconds after vaginal delivery (n=141) and within 5 seconds after delivery by Caesarean section (n=53). The infants were divided into four groups according to the mode of delivery and presence of prenatal complications: group I: vaginal deliveries (n=96) and group II: Caesarean section (n=25) without preceding complications; group III: infants with intra-uterine asphyxia (n=56); group IV: infants with tight umbilical cord loops around neck (n=17). Subgroups were established with respect to gestational age and to one-minute Apgar scores. Significantly different blood volume (BV) and red cell mass (RCM) values between the subgroups were only found in group I with respect to different Apgar scores: Ia Apgar>5: BV 77.9±6.2; RCM 37.5±5.1 ml/kg; Ib Apgar<6: BV 70.0±4.4; RCM 29.6±2.9 ml/kg (P<0.005). Intra-partum asphyxia did not affect BV (71.3±4.8 ml/kg) and RCM (31.2±3.6 ml/kg) in group II. BV and RCM were significantly (P<0.005) lower than in group Ia. In group III, BV (90.4±7.0 ml/kg) and RCM (46.9±6.3 ml/kg) were significantly (P<0.005) higher than in group I, irrespective of the mode of delivery and Apgar scores. The infants of group IV had the lowest volumes (BV 67.5±5.7; RCM 27.4±2.7 ml/kg). Values obtained in premature and full-term infants were similar in the respective groups. These results indicate that infants with intra-partum asphyxia and with tight nuchal cords do not participate in placental transfusion or even lose some blood into the placenta. However, infants with intrauterine asphyxia (excepting those with tight nuchal cords) receive marked placental transfusion in utero.

Abstract: Summary: This investigation was undertaken to determine the nature of acute alterations in renal function following the production of hypoxemia, hypercarbia, and acidosis in newborn piglets 6–96 hr of age. After completion of the surgical procedure piglets were allowed to recover from the effects of anesthesia. When respiratory dead space was increased arterial oxygen tension decreased whereas arterial carbon dioxide tension and hydrogen ion concentration increased. There was little change in glomerular filtration rate. Total renal blood flow decreased and renal vascular resistance increased significantly (504 ± 78 mm Hg/liter/mm/m2 to 1422 ± 504). There was no change in distribution of intrarenal blood flow. Sodium excretion and urinary flow rate demonstrated significant parallel increases following the increase in dead space. Plasma renin concentration increased from 67 to 110 ng/ml. Speculation: Hypoxia, hypercarbia, and acidosis produced changes in renal function in newborn piglets. Therapeutic approaches to the newborn human with respiratory distress must consider the potential for modifications of renal function which may be detrimental to the infant.

Abstract: Experiments were performed on newborn piglets 6--96 hr of age. When the respiratory dead space was increased arterial pO2 decreased and pCO2 increased. During this time cardiac output was unchanged (Fig. 1), while heart rate, respiratory rate, and blood pressure increased (Figs. 2 and 3). After 90 min of asphyxia blood flow to the stomach and small and large intestines decreased. Changes in blood flow were associated with dilatation of segments of the small and large intestine with scattered areas of hemorrhage. Pathologic examination revealed scattered areas of mucosal necrosis (Fig. 6).

Abstract: Red cell mass (RCM) was estimated using 125I-labelled human serum albumin in 128 premature infants born after 26 to 36 weeks gestation. Infants of three different gestational periods (26--29, 30--32, and 33--36 weeks) with respiratory distress (RD) averaged lower one-minute Apgar scores and lower RCM than infants without RD (P less than 0.05). The incidence of RD was significantly (P less than 0.05) higher in infants with Apgar scores below 6 and in infants with RCM of less than 35 ml/kg than in the infants with greater values. The highest incidence of RD and the highest mortality rate were found in the infants with low Apgar scores and low RCM values. Prematures with similar Apgar scores showed a higher incidence of RD when RCM was low, and infants with similar RCM showed a higher incidence of RD when Apgar scores were low. Our results suggest that both birth asphyxia and deficiency of red cell mass interfere with postnatal cardio-respiratory adaptation. In high-risk premature infants, erythrocytes should be transfused when the venous haematocrit is below 0.459