J. clin. Path., 30, Suppl. (Roy. Coll. Path.), 11, 134-141

Hypoxia in the newborn infantE. 0. R. REYNOLDS

From the Department ofPaediatrics, University College Hospital and Medical School, London

Disorders of breathing are the commonest causes ofhypoxia and death in newborn infants (Chamberlainet al, 1975). The aim of this article is to describe thedisorders in which serious hypoxia is most oftenencountered, the ways in which it can be preventedor treated, and some of the consequences of hypoxia.

Normal cardio-pulmonary adaptation at birth

Many disorders of breathing in the newborn periodarise because of failure of normal cardio-pulmonaryadaptation. In order to understand the pathogenesisof these disorders it is necessary first to summarizethe changes that normally take place in the lungs andcirculation at birth.

In fetal life the respiratory centre is not, as wasonce thought, inactive. Breathing movements inutero, first suspected by Ahlfeld (1888), have beenclearly demonstrated in the fetal lamb and subse-quently in the human fetus (Boddy and Dawes,1975). At birth, the lungs replace the placenta as theorgan of gas exchange and the activity of therespiratory centre becomes closely adjusted to themetabolic needs of the body. The mechanismsresponsible have not been fully worked out but theyprobably depend on the interplay of a number ofdifferent stimuli which regularize and controlrespiratory neuronal discharge. For example, chillingof the skin at birth and stimulation of receptors nearthe larynx when liquid is cleared from the airwayhave both been shown to augment breathing(Johnson et al, 1973; Boddy and Dawes, 1975).Carotid chemoreceptor sensitivity to hypoxiaincreases greatly and there is some evidence for in-creased central chemoreceptor sensitivity as well(Purves and Biscoe, 1966).The fetal lung contains about 30 ml/kg of body

weight of liquid. This liquid is a secretion of lungtissue containing very little protein (25 mg/dl) andits composition differs both from that of an ultra-filtrate of plasma and from amniotic fluid (Adamsonet al, 1969; Olver et al, 1973). At birth the infantmakes forceful inspiratory efforts, sometimes -60cmH2O (Karlberg et al, 1962), in order to overcomethe resistance to the inspiration of air into the liquid-

filled lung. The inspiratory efforts not only suck airinto the alveoli, they also stretch the alveolarepithelium, which normally has an equivalent poreradius of only 0 5 nm, and is therefore extremelyimpermeable to solutes (Normand et al, 1971). Thepores are stretched to about 3-5 nm in radius (Eganet al, 1975) and the fetal alveolar liquid passesthrough them, down a protein osmotic pressuregradient, into the interstitial tissue of the lung. Fromthere it is absorbed, largely via lymphatics(Humphreys et al, 1967), into the circulation.Subsequently the pores in the alveolar epitheliumcontract back towards their fetal size. The secretionof lung liquid stops at birth for reasons that are notunderstood.Once breaths of air have been taken, reflex

mechanisms come into play which are responsiblefor rearranging the circulation from the fetal to theadult type. In fetal life, the pulmonary arterioles areconstricted and only 10 per cent of the cardiac out-put perfuses the lungs, the remainder shunting fromthe right to the left side of the circulation throughthe foramen ovale and ductus arteriosus (Dawes,1968). When air enters the lung the partial pressureof oxygen (PO2) rises sharply from the normal fetallevel of about 25 mmHg to above 60 mmHg. Thisincrease in P02 provides the major stimulus to thelarge pulmonary arteriolar vasodilatation thatoccurs at birth (Cook et al, 1963). Another importantfactor promoting vasodilatation is the developmentof surface-tension forces in the alveoli which exertradial traction on blood vessels (Cassin et al, 1964).As a result of pulmonary vasodilatation blood flowthrough the lungs increases and pressure in the leftatrium rises. At the same time, right atrial pressurefalls slightly, mainly because of cessation of theumbilical circulation. The foramen ovale closeswhen left atrial pressure rises above right atrialpressure. The ductus arteriosus constricts in responseto increasing P02 once breathing has started(Kovalcik, 1963). When the foramen ovale andductus arteriosus have both closed the whole of thecardiac output must pass through the lungs and fulloxygenation of the blood can occur.For several days, sometimes weeks, after birth the

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newborn infant remains extremely vulnerable toreopening of the fetal right-to-left shunts. If, due to apulmonary illness, atelectasis is present and the PG2of lung tissue falls, pulmonary vasoconstriction willinevitably follow, and the foramen ovale and ductusarteriosus are likely to reopen. Low pH, common inrespiratory illnesses, makes pulmonary vasocon-striction worse (Rudolph and Yuan, 1966). Theconsequences for the infant may be very serious,since venous blood bypasses the lungs and is directedinto the aorta. Reopening of fetal right-to-leftshunts is probably the single most important cause oflife-threatening hypoxia in the newborn period.Once anatomical closure of these structures hastaken place, usually by about two weeks of age, severehypoxia in association with respiratory illnessesbecomes very much less likely.

Failure of normal cardio-pulmonary adaptation atbirth

APNOEA AT BIRTH

By far the commonest causes of failure to breathe atbirth are intrapartum asphyxia and excessivematernal analgesia with opiates. Fetal asphyxiaevokes gasping but if the asphyxia is more pro-longed the central nervous system, including therespiratory centre, becomes depressed and theinfant does not respond to the normal stimuli thataugment breathing after birth. Opiates have a directinhibitory influence on the respiratory centre.The only sure way to resuscitate an infant who

shows no sign of breathing is by endotrachealintubation and positive pressure inflation of thelungs. Because the lungs are filled with liquid a highpressure, 25-30 cmH2O, is needed for the firstinflation. This pressure must be applied for aboutfive seconds so that the whole lung becomes evenlyinflated. Once the fetal lung liquid has been dis-placed from the alveoli the lungs can be inflated atlower pressures, about 10-15 cmH2O. Inflation of thelungs with a face mask or mouth-to-mouth breathingis not so effective as intubation because the necessarytranspulmonary pressure is more difficult to achieveand also because gastric distension occurs. Alkalitherapy is much less commonly used during resusci-tation than in the past. Once an infant is properlyoxygenated any metabolic acidosis due to anaerobicglycolysis will usually rapidly resolve, and there arepossible dangers associated with the overenthusias-tic use of hypertonic bicarbonate solution. Forexample, it might overload the circulation andincrease the risk of cerebral haemorrhage (Simmonset al, 1974). Nevertheless there is still a place for thecautious intravenous infusion of alkali if an infantremains cyanosed and slow to breathe following

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severe intrapartum asphyxia and in spite ofadequate inflation of the lungs with oxygen. Suchan infant may also benefit from external cardiacmassage.

Infants born apnoeic but with good tone and anormal heart rate can often be encouraged tobreathe by peripheral stimulation, and intubation isusually not needed. Warmth must always be providedduring resuscitation, to minimize oxygen con-sumption and prevent hypothermia. If the motherhas had excessive opiate analgesia and the infantdoes not breathe adequately, naloxone should begiven intravenously.

TRANSIENT TACHYPNOEA OF THE NEWBORN

(WET LUNG)Some infants who remain short of breath for a fewhours, or occasionally a day or two, after birth havechest radiographs showing oedema-like changes,with abnormal linear shadows fanning from the hila(Avery et al, 1966). The only adequate explanationfor this condition is that it is due to delayed removalof fetal lung liquid. Possibly the affected infants haveexcessive amounts of the liquid present in their lungsat birth or, if preterm, are unable to exert sufficienttranspulmonary pressure during breathing to clearthe liquid from their air spaces. Ususally oxygentherapy is the only specific treatment required toprevent hypoxia.

HYALINE MEMBRANE DISEASE (IDIOPATHICRESPIRATORY DISTRESS SYNDROME OF THE

NEWBORN)Hyaline membrane disease is probably still thecommonest cause of death in infants born in thiscountry (Chamberlain et al, 1975). It affects about 1per cent of all infants and the incidence increasessharply with decreasing gestation, so that at 27-31weeks 35-50 per cent of all infants are affected. Theillness probably does not occur at term.The cause of hyaline membrane disease is inade-

quate production of pulmonary surfactant by typeII alveolar pneumonocytes due mainly to immaturityof synthetic mechanisms (Avery and Mead, 1959;Gluck et al, 1972). Asphyxia around the time ofbirth may worsen the illness by damaging thesemechanisms (Reynolds et al, 1965; Gluck et al, 1972).Infants born by Caesarian section before the onset oflabour appear to have an increased incidence of theillness (Fedrick and Butler, 1972), possibly becausetheir lungs have not been exposed to the normalincrease in plasma cortisol level that occurs at theonset of labour. Whether the infants of diabeticmothers are more likely to develop hyaline membranedisease than other infants remains uncertain, mainlybecause infants of diabetic mothers seem often to be

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short of breath for reasons other than hyaline mem-brane disease.

In the absence of sufficient synthesis of pulmonarysurfactant the alveoli have an abnormal tendency tocollapse during expiration and are difficult to inflateduring inspiration. The infant therefore has to exert alarge inspiratory pressure with every breath. Thisinspiratory pressure causes the deep retractions ofthe chest wall which are the most characteristicphysical sign of the illness. Often a grunting noisecan be heard coming from the larynx. This grunt isdue to the partial closure of the glottis which retardsalveolar collapse during expiration. Pulmonaryvasoconstriction, with reversion to the fetal type ofcirculation, is particularly severe in infants withhyaline membrane disease, and is secondary to thecombined effects of atelectasis, hypoxia andrespiratory acidaemia. In addition to shuntingthrough reopened fetal channels, right-to-left shuntsare present through totally atelectatic areas of lungtissue (Murdock et al, 1970). As much as 80 per centof the cardiac output may be shunted from thevenous to the arterial circulation in the most seriouslyaffected infants (Strang and MacLeish, 1961). With-out adequate treatment profound hypoxia ensues,with the eventual development of metabolic acidae-mia, due to anaerobic glycosis, and death.The risk of the development of hyaline membrane

disease can be predicted in utero by measurement ofthe lecithin :sphingomyelin ratio in samples ofamniotic fluid (Gluck et al, 1971). If the ratio is above2, hyaline membrane disease is most unlikely. Thistest is valuable when a pre-term fetus is at high riskand a balanced judgment has to be reached whetherit is safer to deliver the baby or not.

Steroids are capable of stimulating surfactantproduction by the fetal lung (Avery, 1975). There has,therefore, been much interest in the possibility ofpreventing hyaline membrane disease by administer-ing steroids to the mother antenatally. Controlledtrials suggest that this treatment is effective, particu-larly if the infant is at 32 weeks of gestation or less,but the effect is rather small (Liggins and Howie,1972). If the mother is hypertensive steroids arecontraindicated. The exact role of steroid pro-phylaxis of hyaline membrane disease remainsuncertain, and more information is required.The treatment of established hyaline membrane

disease has become very much easier in recent yearsand mortality rates reported by major centres havefallen from 35 to 50 per cent 10 years ago to less than10 per cent (Reynolds, 1975) (fig 1). The main reasonfor this improvement has been the development ofeffective means for controlling oxygen therapy andpreventing hypoxia.

Instead of taking samples of arterial blood inter-

1. NIESATAL 50SURVYIVAL

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Fig 1 Neonatal survival rate for infants with 'severe'hyaline membrane disease admitted to the NeonatalUnit of University College Hospital in the years 1967-1975. 'Severe' means that the infants had an arterialoxygen tension (PaQ2) of less than 90 mmHg whilebreathing more than 60 per cent oxygen, as well as theusual clinical and radiological features of the illness.One hundred and ninety-four (61 per cent) of the infantsneeded mechanical ventilation.

mittently for blood gas analysis it is now possible toinsert a catheter with a miniaturized oxygen electrodebuilt into its tip into the aorta via the umbilicalartery (Conway et al, 1976). Aortic PaO2 is con-tinuously displayed and recorded (fig 2). The correctinspired oxygen concentration can therefore beselected with much greater precision than in the pastand a course can be steered between the dangers ofhypoxia (brain damage and death) on the one handand hyperoxia (retrolental fibroplasia and blindnessin preterm infants) on the other. A PaO2 of 65 mmHg is probably a reasonable level to aim for.The transcutaneous estimation of PaO2 has also

recently been shown to be feasible (Huch et al, 1974).If an oxygen electrode is applied to the skin andheated, capillary blood flow increases and trans-cutaneous oxygen tension (tcPO2) correlates wellwith PaO2 under most circumstances. In seriously illinfants with a poor skin blood flow tcPO2 under-estimates PaO2 and should not be relied upon. Thecontinuous recording ofPaO2 and tcPO2 is extremelyvaluable in all infants with significant respiratoryillness.

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1S minsFig 2 Continuous recording ofPaO2, from a 4-day-old, spontaneously breathing infant who was recovering fromhyaline membrane disease. She was born at 31 weeks of gestation and weighed 1867 g. She was active but not crying.The inspired oxygen concentration was 50 per cent throughout. PaO2 variedfrom 45 mmHg to more than 130 mmHgduring a 20-minute period.

Infants with hyaline membrane disease, whosePaO2 is falling in spite of an increasing inspiredoxygen concentration, can be treated with continuouspositive airway pressure (CPAP) (Gregory et al,1971). The aim is to raise the pressure in the infant'sairway so that lung collapse is, partly at least,prevented while spontaneous breathing continues.An adequate indication for initiating CPAP is a

PaO2 below 60 mmHg in an infant breathing morethan 60 per cent oxygen. PaO2 almost alwaysimproves when CPAP is started. Various methodshave been employed, including endotracheal tubes,head boxes, face masks, nasal prongs and negativepressure tanks. Possibly the face mask is the methodof choice for relatively mildly affected infants (Allenet al, 1975) and endotracheal tubes for worse affectedones (Gregory et al, 1971). Pressures of up to about6 cmH2O can be applied with the mask, and 10cmH2O with the endotracheal tube.

Infants who do not maintain a satisfactory PaO2(>35-50 mmHg) when being treated with CPAP or

who are tending to become apnoeic need mechanicalventilation. In the past the mortality rate of infantsventilated for hyaline membrane disease was highand many died from bronchopulmonary dysplasia

(see page 139). With improved ventilator techniquesthe outcome has greatly improved (Reynolds, 1974;1975), and bronchopulmonary dysplasia has becomea rarity.No infant born at a gestational age greater than

about 28 weeks should now die or be damaged as aresult of hypoxia due to hyaline membrane disease.

PERSISTENT FETAL CIRCULATION OFUNKNOWN AETIOLOGYIn most pulmonary illnesses hypoxia is due to acombination of interference with gas exchange in thelung with a variable degree of secondary right-to-leftshunting through reopened fetal channels. In a smallminority of hypoxic infants no pulmonary pathology(or congenital abnormality) can be demonstrated,yet the PaO2 remains low even though the infant isbreathing a high concentration of oxygen, indicatingright-to-left shunting of blood. Sometimes the pre-ductal PaO2 is much higher than the postductalPaO2, which implies that there is a much largershunt through the ductus arteriosus than throughthe foramen ovale. The condition has been calledpersistent fetal circulation, or persistent transitionalcirculation. The aetiology is unknown. Possibly some

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vasoactive substance is maintaining pulmonary vaso-constriction after birth. Spontaneous recovery takesplace within a few days if the infant is kept properlyoxygenated. Tolazoline, which dilates pulmonaryblood vessels more than systemic vessels, is ofteneffective in raising the PaO2 and can be given byconstant infusion if required.

RECURRENT APNOEA IN PRETERM INFANTSMost infants born at less than 32 weeks of gestationhave periodic breathing and short attacks of apnoeaeven if their lungs are normal and they are well in allother ways. Sometimes, prolonged apnoeic attacksoccur, particularly in the smallest infants, causingserious hypoxia. The reason for the irregularbreathing and apnoea is inadequate development ofvarious aspects of the control of breathing. Apnoeicattacks can be detected by using monitoring devicesset to sound after 10 to 15 sec of apnoea. Peripheralstimulation will almost always start the infantbreathing again.

Small preterm infants often have a PaO2 of about50 mmHg while breathing air. Increasing the inspiredoxygen concentration slightly, to 23-25 per cent,raises the PaO2 to about 70 to 80 mmHg and reducesthe incidence of apnoea. Increases in inspiredoxygen concentration should, however, never begiven without measurement of PaO2. The risk ofraising the PaO2 to a dangerously high level (> 100mmHg) is very great in infants with normal lungs,and it is these infants who are most at risk for retro-lental fibroplasia. The continuous measurement oftcPO2 may prove to be a valuable aid to therapy.

Other methods of treatment include CPAP and theuse of theophylline. Continuous positive airway pres-sure applied through a face mask (or some otherdevice) at a pressure of 3-4 cmH2O stimulatesstretch receptors in the lung or chest wall and is aneffective way of reducing the frequency of apnoea(Kattwinkel et al, 1975). Higher pressures must beavoided, because the lungs are normal and easilybecome overdistended, with the risk of pneumo-thorax or obstruction of the circulation.Theophylline is a respiratory stimulant which re-duces the incidence of apnoeic attacks (Shannon etal, 1975).

Infants whose breathing fails in spite of themethods described above can usually be mech-anically ventilated through a face mask (Allen et al,1975), thus avoiding the difficulties associated withprolonged intubation in very preterm infants.

Congenital malformations

By comparison with most other disorders causinghypoxia in newborn infants, congenital mal-

formations are rare. The commonest ones affectingthe lungs are diaphragmatic hernia and hypoplasticlungs. Many types of congenital heart disease alsocause hypoxia, because of right-to-left shunting ofblood, poor peripheral perfusion, or both. Commoncongenital heart lesions causing serious hypoxiainclude tricuspid atresia, transposition of the greatvessels, the hypoplastic left heart syndrome, totalanomalous pulmonary venous damage and severeforms of Fallot's tetralogy.

Acquired disorders

PNEUMOTHORAXSpontaneous pneumothoraces, probably due to thelarge inspiratory efforts made immediately afterdelivery, occur in about 1 per cent of all infants(Steele et al, 1971). Usually these pneumothoracesare small and resolve spontaneously. More seriouspneumothoraces occur as a complication of meco-nium aspiration. Drainage is often required, in orderto avoid dangerous hypoxia or obstruction of thecirculation. Pneumothorax is also a relatively com-mon hazard of the use of CPAP or mechanicalventilation, particularly for the treatment of hyalinemembrane disease, with an incidence of about 20 percent. Urgent treatment is usually required, but thelung almost always heals within a few days, as theunderlying illness resolves.

MECONIUM ASPIRATIONIntrapartum asphyxia causes gasping and evacuationof the bowel. Hence meconium can be aspirated intothe upper airways. Meconium aspiration is particu-larly commonly seen in postterm infants, and it isvery unusual in infants of less than 37 weeks ofgestation. Immediate pharyngeal, and if necessaryendotracheal, suction is required at birth, to preventthe meconium from being inhaled into the small air-ways. If large amounts of meconium are inhaleddeeply into the lung the infant becomes extremelyhypoxic, and is very difficult to treat. Mechanicalventilation is needed and tolazoline has been foundto be useful in improving oxygenation. In survivinginfants, full recovery takes place within a week.

HAEMORRHAGIC PULMONARY OEDEMA AND

MASSIVE PULMONARY HAEMORRHAGEThis condition is regarded as a major cause of deathin about 9 per cent of neonatal necropsies (Fedrickand Butler, 1971). It presents clinically as profoundcollapse, with blood-stained fluid pouring out of thetrachea. The fluid is usually a filtrate of plasma, witha small admixture of whole blood (Cole et al, 1973);in other words it is haemorrhagic pulmonaryoedema fluid, formed as a result of increased pul-

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monary capillary pressure. The likely reason for theincrease in pressure is that a severe asphyxial episode(of whatever aetiology) causes acute left heart failure,or centralization of the circulation. Any additionalfactors that tend to raise filtration pressure willincrease the risk of haemorrhagic pulmonaryoedema, for example hypoproteinaemia, as in severerhesus haemolytic disease. Disorders of haemostasisare often found and probably result from the under-lying asphyxial episode that caused the haemorrhagicoedema. A bleeding tendency encourages continuedhaemorrhage from ruptured capillaries. Treatmentby mechanical ventilation, if undertaken promptly, isoften successful, and the outlook for affected infantshas improved greatly in the past few years.By comparison with haemorrhagic pulmonary

oedema frank bleeding into the lung is rare andprobably occurs only in association with profoundhaemostatic failure or severe pneumonia.

HYDROPS FETALISHydrops fetalis is usually due to severe rhesus iso-immunization. Breathing is grossly impaired byoedema of the larynx, lungs and chest wall, togetherwith a reduction of thoracic volume due to thepresence of the enlarged liver and spleen and ascites.Unless treated by mechanical ventilation from birththe infants become very severely hypoxic. Many nowsurvive.

PNEUMONIAThe commonest organism causing severe pneu-monia in the immediate newborn period is the groupB f3-haemolytic streptococcus acquired before orduring delivery from the mother's genital tract.The clinical presentation and radiological appearancesometimes mimic hyaline membrane disease veryclosely (Ablow et al, 1976). Examination of gastricaspirate for organisms is helpful in making an imme-diate diagnosis. If any suspicion exists that an infantis infected with the group B streptococcus, or anyother organisms, such as E. coli, at birth, immediatetreatment with antibiotics, before the results of cul-tures are available, is mandatory. Once unequivocalclinical evidence of infection has developed, thechances of survivial are poor. A suitable combinationof antibiotics is penicillin and gentamicin.

CHRONIC LUNG DISEASEIn 1967, Northway et al gave the first clear descrip-tion of severe lung fibrosis following mechanicalventilation for hyaline membrane disease. They call-ed the condition 'bronchopulmonary dysplasia' andsuggested that it was caused by pulmonary oxygentoxicity. In the same year it was shown that the

development of bronchopulmonary dysplasia wasnot associated with persisting deficiency of pul-monary surfactant (Hawker et al, 1967). The mainlesions consist of severe disruption of terminal air-ways, with fibroblastic proliferation obstructing theirlumina and spreading out into the surroundingtissue. The presence of these lesions correlates withthe use of very high peak airway pressures (35-60cmH2O) for more than two days during mechanicalventilation, but not with the inspired oxygen con-centration (Taghizadeh and Reynolds, 1976). It hastherefore been concluded that the cause of theselesions is mechanical trauma to the lung. If ventilatortechniques are used that maintain alveolar inflationwithout the use of high peak airway pressuresbronchopulmonary dysplasia is very rarely seen(Reynolds, 1974; Reynolds and Taghizadeh, 1974).Convincing evidence that pulmonary oxygen toxicityplays any important part in pathogenesis is very hardtofind although it may have a minor role (Taghizadehand Reynolds, 1976). Surprisingly, the lungs ofinfants who survive appear to recover completely tonormal, although they may take months to do so(Stahlman et al, 1973).Another cause of chronic lung disease in newborn

infants is the 'Wilson-Mikity syndrome' (Wilson andMikity, 1960). This condition affects greatly preterminfants, who become somewhat hypoxic when theyare several days old and have a chest radiologicalappearance showing streaky shadows due to atelecta-sis or fibrosis interspersed with areas of compensa-tory or obstructive emphysema. Before 32 weeks ofgestation, infants are unable to protect the upper air-way, because they have no adequate cough reflex. Inaddition, the fine airways are narrow, poorly sup-ported with cartilage (Burnard et al, 1965), and easilybecome obstructed. Probably the Wilson-Mikitysyndrome is not a clinical entity but results from anydisorder that causes widespread uneven obstructionof airways in greatly preterm infants. For example,aspiration of feed, or retained pulmonary secretionsin infants ventilated through endotracheal tubes, canboth produce radiological appearance identical tothat originally described. After a protracted course,most affected infants recover.

Consequences of severe hypoxia

Lack of oxygen causes anaerobic glycolysis, with thedevelopment of a metabolic acidosis due to accumu-lation of lactic acid. The combination of hypoxia andacidosis impairs cardiac function (Downing et al,1965) and increases pulmonary vascular resistance(Rudolph and Yuan, 1966). In addition, severehypoxia causes interference with the production ofclotting factors from the liver and may also initiate

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disseminated intravascular coagulation. A tendencyto bleed is common in any severely hypoxic infant(Chessells and Wigglesworth, 1972).

There is a strong association between hypoxia andintraventricular haemorrhage-a very commoncause of death in preterm infants. The mechanism ofintraventricular haemorrhage is probably that anasphyxial episode produces an increase in intra-vascular pressure which ruptures vulnerable vesselsin the germinal matrix (Cole et al, 1974; Hambletonand Wigglesworth, 1976). Hypoxia is also a majorfactor in the pathogenesis of necrotizing entercolitis(Santulli et al, 1975). This illness often follows severeasphyxia at birth, or interference with blood flow toor from the gut by the use of umbilical arterial orvenous catheters (Bunton et al, 1977). The patho-logical results of hypoxia, including its effect on thebrain, are dealt with elsewhere in this symposium.

Conclusion

Hypoxia in newborn infants is becoming mucheasier to prevent, detect and treat. Nevertheless thesuccessful management of potentially hypoxicfetuses and newborn infants remains the majorchallenge to all physicians concerned with perinatalcare. What is at stake is not only that sick infantsshould survive, but equally or more importantly thatthe survivors should be normal children. Recentfollow-up studies show that this aim can, with fewexceptions, now be achieved (Stewart and Reynolds,1974; Davies and Stewart, 1975; Durbin et al,1976).

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