Paediatrics & child_health-_april_2008_(_neonatology)

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Paediatrics & child_health-_april_2008_(_neonatology)

  1. 1. Paediatrics and Child HealthPaediatrics and Child Health is the continuously updated review of paediatrics and child health (formerly Current Paediatrics)Paediatrics and Child Health is an authoritative and comprehensive resource that provides all paediatricians and child health carespecialists with up-to-date reviews on all aspects of hospital/community paediatrics and neonatology, including investigations andtechnical procedures in a 4-year cycle of 48 issues. The emphasis of the journal is on the clear, concise presentation of information ofdirect clinical relevance to both hospital and community-based paediatricians. Contributors are chosen for their recognized knowl-edge of the subject. The journal is abstracted and indexed in Current Awareness in Biological Sciences. The layout of the journal,including the design and colour, enables fast assimilation of key information. For ease of reference, Paediatrics and Child Health isavailable in print and online formats.Editor-in-ChiefPatrick Cartlidge DM FRCP FRCPCHSenior Lecturer in Child Health and Honorary Consultant Neonatologist,Wales College of Medicine, Cardiff University, Cardiff, UKAssociate EditorsAllan Colver MA MD FRCPCH Richard Wilson MB FRCP FRCPCH DCHProfessor of Community Child Health, Sir James Spence Honorary Consultant Paediatrician, Kingston Hospital,Institute, Newcastle University, Newcastle, UK Kingston-upon-Thames, Surrey, UKHarish Vyas DM FRCP FRCPCHProfessor in PICU and Respiratory Medicine, Queen’s Alistair Thomson MA MD BChir FRCPCH FRCP DCH DRCOGMedical Centre, Nottingham University Hospital, UK Consultant Paediatrician, Leighton Hospital, Crewe, UKNicholas Mann MD FRCP FRCPCH DCH Colin Powell MBChB DCH MRCP FRACP FRCPCH MDConsultant Paediatrician, Department of Paediatrics, Consultant Paediatrician, University Hospital of Wales,Royal Berkshire Hospital, Reading, UK Cardiff, UKInternational Advisory BoardR Adelman (Phoenix, USA) A Bagga (New Delhi, India)Z Bhutta (Karachi, Pakistan) H Buller (Rotterdam, The Netherlands)MC Chiu (Kowloon, Hong Kong) M Hassan (Islamabad, Pakistan)P Malleson (Vancouver, Canada) A Martini (Genova, Italy)A Moosa (Saffat, Kuwait) C Morley (Carlton, Australia)BJC Perera (Colombo, Sri Lanka) J Pettifor (Johannesburg, South Africa)M Uchiyama (Niigata, Japan) M van de Bor (Nijmegen, The Netherlands)Paediatrics and Child Health has an eminent editorial board and a wide array of authors, all of whom are recognized experts in their field.Visit our website at: www.paediatricsandchildhealthjournal.co.uk for previous issues, subscription information and further details.
  2. 2. SympoSium: neonatologyTemperature control temperature tending to drift up and down with the ambient tem- perature. The aim in neonatal care is to provide a thermal envi-in the neonate ronment which keeps body temperature in the normal range, and which does not stress the infant to produce or lose large amounts of heat.andrew lyon The importance of keeping newborn babies warm has been known for centuries.1 In the 1950s William Silverman and others showed a clear link between temperature control and neonatal mortality. In a series of randomized controlled trials they showed that keeping babies warm in incubators resulted in an absolute reduction in mortality of 25%.2,3 In many of these studies a sig- nificant numbers of babies were under 1000 g birthweight andAbstract the improvement in survival was seen in all birthweight groups.the control of body temperature is a challenge to the newborn baby, No other single change in practice has had such a dramatic effectparticularly if immature or sick. Behavioural responses to environmental on mortality of the newborn baby.temperature changes are almost non-existent. the preterm baby has lim- The EPICure study of a cohort of babies under 26 weeks’ ges-ited ability to mobilize energy sources to combat high heat losses, par- tation, delivered in the UK in 1995, showed that low admissionticularly from evaporation. there is evidence that many preterm babies temperature was an independent risk factor for neonatal deathare still being allowed to get cold during stabilization and resuscitation. even after adjustment for other known risks.4 In this populationa low temperature at the time of admission to a neonatal unit is inde- study 30%, 43% and 58% of babies at gestations 25, 24 andpendently associated with an increased mortality in the preterm infant. 23 weeks, respectively, who were admitted to neonatal units,preventing evaporative heat losses at this time can abolish hypothermia had an admission temperature below 35 °C. The report of theon admission. Further studies are needed to determine the optimum CESDI 27/28 project showed that, in babies born at 27 and 28thermal management immediately after delivery. there are no studies weeks’ gestation, an admission temperature below 36 °C wasthat show any difference in outcome for preterm babies nursed in incu- found in 73% of those who died compared with 59% in thosebators compared to those under radiant heaters. High transepidermal who survived.5water loss (teWl) results in increased fluid and heat loss in the preterm The importance of early temperature as a predictor of out-baby. this can be managed by increasing environmental humidity al- come in preterm babies is shown by its inclusion in risk scoringthough this may be more difficult when babies are nursed under radiant systems such as the Clinical Risk Index for Babies (CRIB)6 andheaters. nursing the baby in high humidity reduces teWl but more work the Score for Neonatal Acute Physiology – perinatal extensionis needed to show if a reduction in water movement has an adverse ef- (SNAPPE-II).7fect on the rate of maturation of the skin. the way a baby interacts with Extended periods of cold stress can lead to harmful side effects,their environment is always changing and, whatever temperature and including delayed adaptation to extrauterine life, hypoglycaemia,humidity settings are first used, it is necessary to monitor continuously respiratory distress, hypoxia, metabolic acidosis, coagulationthe thermal balance. the continuous measurement and display of a cen- defects, acute renal failure, necrotizing enterocolitis, failure totral and a peripheral temperature gives an early indication of cold stress gain weight or weight loss and death.before there is any fall in the baby’s core temperature. Many factors are associated with an increased risk of hypo- thermia. These include prematurity, intrauterine growth restric-Keywords central–peripheral temperature difference; humidity; tion, central nervous system damage and congenital defects suchnewborn; preterm; temperature control; transepidermal water loss as abdominal wall defects where bowel is exposed to the air. Induced cooling may help protect the brain of the asphyxiated term newborn8 but prolonged exposure to cold in babies with no brain injury must be avoided. Overheating the baby with sus- pected asphyxial brain injury must also be prevented as hyper-Introduction thermia may increase the degree of damage.9Children and adults maintain a constant deep body tempera-ture over a wide range of ambient thermal conditions (homeo- Temperature control at deliverythermic). This is achieved by physiological and behaviouralresponses that control the rate at which heat is produced or The temperature of the fetus is between 0.5 and 1°C higher thanlost. The newborn infant is also homeothermic but control of that of the mother. At birth the infant is exposed to a colderbody temperature can only be achieved over a narrower range environment than in utero. Although some heat loss may beof ambient conditions. The preterm infant has even greater dif- important in stimulating onset of breathing and other adaptiveficulty in body temperature control, and the most immature mechanisms,10 it is important to avoid a continuing drop ininfants behave at times as if they are poikilothermic – their body body temperature. In the term baby this is achieved by drying, wrapping and placing under a radiant heater if resuscitation is needed.Andrew Lyon MA MB FRCP FRCPCH is Consultant Neonatologist at the The preterm baby often needs a period of stabilizationSimpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, or resuscitation and traditionally has been placed naked onLittle France, Edinburgh EH16 4SA, UK. a resuscitaire. Despite the use of direct radiant heat, studiespaeDiatRiCS anD CHilD HealtH 18:4 155 © 2007 elsevier ltd. all rights reserved.
  3. 3. SympoSium: neonatologysuch as EPICure and CESDI 27/28, have shown that many of gestation. A Cochrane review concludes that in this group con-these babies are cold by the time of admission to the neo- sideration should be given to their use in the delivery suite.18natal unit. In a study from the USA, of 5277 babies with a No study has yet been powered to show that these treatmentsbirthweight below 1500 g in the Neonatal Research Network, reduce neonatal mortality and long term outcome has not beenonly 10.8% had an admission temperature of 37 °C or above. evaluated. Further large, high quality randomized controlled tri-In nearly half the babies the first recorded temperature was als are still needed. Not least, we need to confirm that the mem-below 36 °C. Admission temperature was inversely related brane wrapped around the infant’s trunk does not damage theto mortality (28% increase per 1 °C) and late-onset sepsis. immature skin.There was an association of low temperature with the need forintubation at delivery, suggesting that radiant heat alone had Transportnot been sufficient to offset the heat losses during prolongedresuscitation.11 The transport of the newborn baby, particularly the preterm A baby exchanges heat with their environment by conduc- infant, presents many challenges. Transport is not only betweention, radiation, convection and evaporation. The preterm baby units but also within a hospital, e.g. from the delivery suite tois at high risk of net heat loss because of a high surface area to the neonatal unit or to and from the radiology department or thevolume ratio and increased transepidermal water loss, resulting operating room.in heat lost by evaporation. The normal surge in metabolic rate The most effective mode of transport within a hospital buildingwhich occurs after birth is much reduced, limiting the production will depend on the local configuration. Newly designed neonatalof heat from the mobilization of brown fat. The development units should be closely linked to the delivery suite to preventin the control of skin blood flow is also delayed in the imma- the need for transport over long distances along draughty corri-ture baby, reducing their ability to maintain heat by peripheral dors. A randomized controlled study comparing transfer from thevasoconstriction.12 delivery suite to the neonatal unit of babies under 28 weeks’ ges- Evaporation is the major mechanism of heat loss during resus- tation using a radiant warmer or a transport incubator showedcitation. The baby will lose 560 cal for every millilitre of water no difference in admission temperature in the two groups.19 Allevaporated from the skin (the heat of evaporation). Vohra et al babies in both groups had been managed with occlusive wrap-have shown that using polyethylene occlusive skin wrapping, ping in the delivery room.around the body up to the neck, during resuscitation of preterm Transfer between units is most commonly by road in anbabies under 28 weeks’ gestation significantly improves the ambulance. Although incubators are heated there is likely to becentral temperature on admission to the neonatal unit.13 This high radiative heat losses, especially in cold weather. This can beis due to a reduction in evaporative heat losses. In this random- reduced by covering the incubator and by using blankets aroundized study, comparing rectal temperature on admission of babies the baby. Evaporative heat losses can be reduced by using a plas-wrapped at birth with those managed without wrapping, body tic bag. There will be high evaporative heat losses from the respi-size was an important determinant of heat loss, the mean rectal ratory tract if ventilator gases are not heated and humidified.temperature increasing by 0.21°C with each 100 g increase in Heated gel mattresses, which warm patients through release ofbirthweight. latent heat of crystallization, can be used during transport. The The use of plastic bags, leaving just the head exposed, has baby gains heat by conduction. Safe use of this device is criticallyalso been found to be effective in reducing transepidermal dependent on gel temperature at the point of activation.20water and heat losses during resuscitation.14 It is important notto expose the skin once the baby is in the plastic bag – clini- Thermal care within the neonatal unitcal inspection and auscultation can be done through the bagand if vascular access is needed, a small hole can be cut in the The full-term newborn infant will maintain a normal temperatureplastic. if nursed fully dressed in a cot in a warm room. Recommenda- Whether a plastic bag or occlusive dressing is used, it is tions for optimum environmental conditions for nursing healthyimportant to remember that there is still significant heat losses infants in the newborn period have been published.21from the head which should be covered with a hat during resus- Skin-to-skin contact is an effective way of maintaining bodycitation and stabilization.15 temperature, even in the very preterm infants.22,23 Concern has been expressed about hyperthermia in some The preterm baby, even if well, may be unable to maintain anbabies, possibly secondary to the use of occlusive dressings or adequate temperature without some additional source of heat.plastic bags.16 Two babies in the study by Vohra et al13 had a There are a variety of ways of providing this, including incuba-rectal temperature above 37.5 °C. In a small study from Edin- tors, radiant heaters and heated mattresses. The heated gel- orburgh, 11 of 27 babies under 28 weeks’ gestation managed in water-filled mattress is very effective in helping maintain theplastic bags were found to have an admission temperature above temperature of the well preterm baby while allowing easy access37.5 °C. Of these, eight were above this temperature from birth, for parents and staff.possibly associated with a maternal pyrexia, while in the other Clothes act as a significant thermal barrier to heat loss. New-three the temperature increased (by no greater than 0.6 °C) after born infants needing intensive or high dependency care are oftenbeing placed in the bag.17 nursed naked to allow close observation and easy access for Preventing evaporative heat loss using occlusive dressings examination and treatment. This significantly affects tempera-or plastic bags has been shown to be effective in preventing ture control as the resistance to heat loss of a naked baby is threehypothermia after delivery, at least in babies under 29 weeks’ times less than that of a clothed, wrapped infant.24,25paeDiatRiCS anD CHilD HealtH 18:4 156 © 2007 elsevier ltd. all rights reserved.
  4. 4. SympoSium: neonatology Control of the thermal environment is important for all babies, resulting in increased evaporative heat losses. Increasing the airbut it is the unwell, immature babies who present the greatest temperature will compensate for the heat loss but incubators arechallenge. They are usually nursed either in an incubator or relatively slow to respond to such changes.on an open platform, under a radiant heater. The early clinical High humidity within the incubator can cause ‘rain out’ ontrials of Silverman and others showed that the use of incuba- the inside of the canopy. This is caused by water condensing ontors to keep babies warm improved outcome. There have never the cold walls and can be minimized by ensuring an adequatebeen any controlled studies that show that radiant heaters are as environmental temperature within the nursery (around 28 °C).effective clinically. Babies nursed with similar skin temperatureshave a higher basal metabolic rate when managed under radi- Radiant heatersant heaters compared with incubators.26 However, no study has TEWL is the major problem in babies nursed under radiantshown any significant difference in outcome for babies nursed heaters. A shield or plastic blanket can be used to cover theusing either of these devices, although Meyer et al27 reported a baby and create a humidified microenvironment. Warm humid-non-significant trend to better outcome in babies nursed under ified air can be passed under the shield or blanket but carea radiant heater. must be taken to control the temperature and to make sure it does not affect the skin servo probe attached to the baby. If the cover is removed the humidity falls rapidly and the baby startsTransepidermal water loss to lose large amounts of fluid. The radiant heater will compen-Silverman in the 1950s showed that babies are better able to sate for any fall in the baby’s temperature but fluid losses aremaintain their body temperature in a humid environment com- a concern.pared with a dry environment.28 In the 1970s it became possible to measure the evaporation Maintenance of skin integrityrate of water from the skin surface.29 Transepidermal water losses Damage to the fragile skin of the preterm baby occurs easily and(TEWL) are high in the immature baby. At 26 weeks’ gestation, results in a significant increases both in TEWL and the risk ofon day 1 of life, the baby can lose over 50 kcal/kg by evapora- infection. Maintaining skin integrity is very important and anytion, compared with less than 5 kcal/kg in the term infant.30 Data adhesives on the skin should be kept to a minimum.from Hammerlund et al30 suggest that the skin matures rapidlyafter birth and adult losses are reached around 10 d of age in all Skin coveringsbabies. After this time the major source of heat loss in all babies Transparent adhesive dressings on the skin reduce fluid loss butis from radiation. More recently others have shown that in the cause significant damage, making them impractical.very immature baby the maturation of the skin may take longer, Use of semipermeable non-adhesive dressings lowers TEWLand 30 weeks’ corrected age is a better estimate of the time taken and reduces the bacteria number in the covered skin.34 In a ran-to reach adult TEWL.31 In practical terms the amount of trans- domized controlled trial in infants less than 1000 g the skin cov-epidermal fluid losses after about 14 d are unlikely to remain a ered with a semipermeable membrane was in better condition,major problem. but there were no significant differences in fluid requirements or Evaporative water loss from the skin depends on the ambi- electrolyte status.35ent water vapour pressure, irrespective of how the baby is being Emollients are used to cover the skin and prevent fluid loss.nursed. The high rate of evaporation during care under a radiant They have been shown to be safe and do not cause burns whenheater is due to the low ambient water vapour pressure and not exposed to radiant heat or phototherapy. Their use reducesany direct effect of non-ionizing radiation on the skin.32 excessive drying, skin cracking and fissuring. However, the TEWL results in loss of both heat and fluid. Under a radi- effect of these products wears off after about 3 h, necessitatingant heater the temperature of the baby is maintained because repeated application.36 Treated infants had better skin scores andof radiant heat gain, but the large fluid losses can be a seri- there were no differences in bacterial skin counts, fungal countsous problem. Various interventions can help reduce evaporative or colonization patterns, or fluid requirements and electrolytefluid losses, mainly from the skin but also from the respiratory status.37tract. Ventilator humidityIncubators There can be high fluid and heat losses from the respiratory tractWithin an incubator it is relatively easy to raise the ambient of the ventilated baby. It is important to use adequate humidifi-water vapour pressure by introducing humidity within the can- cation in all ventilator circuits.opy. The use of a relative humidity of 80%, for the first 7–10 dof life, significantly reduces TEWL in even the most immature Phototherapyinfant.30 Modern designs use a sealed water system to produce The effect of phototherapy on TEWL is variable. No change wasthe humidity, minimizing the concerns about possible increased found in a group of thermally stable infants,38 yet others haveinfection risk in humidified incubators. reported an increase in TEWL despite skin temperature and rela- Opening the incubator portholes results in a rapid fall in tive humidity remaining unchanged.39 Rather than increase fluidhumidity although the air temperature within the canopy is intake just because phototherapy has been started, fluid balancemaintained. The handling of babies within incubators has been should be individually monitored and adjusted if necessary.shown to be associated with increased thermal stress33 and it Modern phototherapy units produce little heat but there isis likely that this is due to the fall in environmental humidity, still some increase in the temperature of the top of the incubatorpaeDiatRiCS anD CHilD HealtH 18:4 157 © 2007 elsevier ltd. all rights reserved.
  5. 5. SympoSium: neonatologycanopy. This will reduce radiative heat losses and the incubator probe between the scapulae and a non-conducting mattress.air temperature may have to be reduced to prevent a rise in the No tape is needed on the skin as the baby lies on the probe,baby’s temperature. holding it in place. If the probe is over an area of skin from which no heat can be lost by conduction, convection, radia-Transepidermal water loss and skin maturation tion or evaporation, then, with heat flow from the centre of theTransepidermal movement of water is essential for the acceler- body to the skin down a temperature gradient, this area of skinated maturation of the skin of the immature baby.40 It also helps will warm up to the same temperature as the body’s core. Thisin maintaining the epidermal barrier function.41 so-called zero heat flux temperature has been shown to be very Use of high ambient humidity in nursing preterm babies under close to the central temperature as measured by an oesophageal28 weeks’ gestation has been shown to reduce the rate of promo- probe.46tion of skin barrier development.42 The measurement of a single temperature tells us how well More work in the immature baby is needed to determine the the baby is maintaining that temperature, but nothing aboutoptimum level and duration of environmental humidity, as well how much energy is being used to achieve thermal balance. Theas the associated benefits and risks of use, and the effects of continuous measurement, and display, of a central (abdominal,humidification on clinically important outcomes.43 axilla or zero heat flux) and a peripheral (sole of the foot) tem- perature detects cold stress, with the peripheral temperature fall- ing before the central measurement changes.Temperature monitoring and its interpretation The preterm baby who appears to be comfortable in theirThe concept of the neutral thermal environment, in which a environment will have a central temperature, measured from ababy uses a minimum of energy to maintain thermal stability, skin probe, of 36.8–37.3 °C and a central–peripheral temperaturehas proven useful in determining the optimum environmental difference of 0.5–1 °C. An increasing central–peripheral tempera-temperature for nursing the newborn baby.44,45 The published ture difference, particularly above 2 °C, is usually due to colddata are now old and do not include any allowance for added stress, and occurs before any fall in central temperature.12humidity. This makes them less useful in the care of the very Hypovolaemic babies will vasoconstrict their peripheral circu-immature baby. lation in an attempt to maintain blood pressure. This results in an The way a baby interacts with their environment is always increase in the central–peripheral temperature difference but, inchanging and, whatever settings are first used, it is necessary such cases, there are usually other signs of hypovolaemia, suchto monitor continuously the thermal balance. Continuous mea- as rising heart rate and falling blood pressure.12surement of oxygen consumption, to allow calculation of energy A high central temperature, particularly if unstable, alongexpenditure, is not practical and, in normal day-to-day care, tem- with a wide central–peripheral gap is seen in septic babies.47perature monitoring is the only means of assessing the thermalstability of the baby. Conclusion There is no single deep body temperature as this will varydepending on the metabolic rate of a particular tissue. The brain Although we have known for a very long time the importance ofhas the highest temperature of any organ within the body. It is maintaining the temperature of the newborn, we are still facedhowever possible to find a central temperature that is representa- with new challenges in the care of the sick immature baby. Tem-tive of deep body temperature. Trends in this temperature reflect perature control during their period of adaptation to extrauterinechanges in the deep body temperatures of the body, at least with life is often poor and allowing these vulnerable babies to cool issufficient accuracy for day-to-day clinical care. associated with adverse outcome. Simple measures can prevent Traditionally, rectal temperature has been used as the mea- hypothermia following delivery. If cold at birth is associated withsure of deep body temperature. This is still used commonly in poor outcome there is no reason to believe that preventing ther-many countries but less so in UK. There is a significant risk of mal stress is any less important once the baby is in the neonataldamage to the mucosa of the rectum. Also, rectal temperature is unit. It is important that the risks and benefits associated withunreliable, being affected by the depth of insertion of the ther- various methods of controlling the infant’s temperature are fullymometer, whether the baby has just passed a stool and by the understood. ◆temperature of the blood returning from the lower limbs. It isdifficult to retain the probes in the same position, making this anunreliable site for continuous temperature monitoring. The temperature in the oesophagus, at the level of the heart,gives a measure of the temperature of the blood in the great RefeRenCeSveins returning from the body. This is possibly the best overall 1 Cone te. perspectives in neonatology. in: Sith gF, Vidyasagar D, eds.representation of the ‘deep body temperature’. Measurement of Historical Review and Recent advances in neonatal and perinataloesophageal temperature is, however, very invasive and not suit- medicine. mead Johnson nutritional Division, 1983, p. 9–33.able for clinical monitoring. 2 Silverman Wa, Fertig JW, Berger ap. the influence of the thermal The temperature of the skin over the liver or in the axilla environment upon survival of newly born preterm infants. Pediatricsreflects central temperature. Actual values will be lower than 1958; 22: 876–885.the deep body temperatures but, in the immature baby, these 3 Silverman Wa, agate FJ, Fertig JW. a sequential trial of thesites can be used to show the trend in central temperature. A nonthermal effect of atmospheric humidity on survival of humanmore accurate measurement can be obtained by placing the infants of low birth weight. Pediatrics 1963; 31: 710–724.paeDiatRiCS anD CHilD HealtH 18:4 158 © 2007 elsevier ltd. all rights reserved.
  6. 6. SympoSium: neonatology4 Costeloe K, Hennessy e, gibson at, marlow n, Wilkinson aR, for the 23 Bauer K, pyper a, Sperling p, uhrig C, Versmold H. effects of epiCure Study group. the epiCure study: outcomes to discharge gestational and postnatal age on body temperature, oxygen from hospital for infants born at the threshold of viability. Pediatrics consumption, and activity during early skin-to-skin contact between 2000; 196: 659–671. preterm infants of 25–30-week gestation and their mothers. Pediatr5 CeSDi project 27/28. available from: www.cemach.org.uk/ Res 1998; 44: 247–251. publications/p2728/mainreport.pdf 24 Hey en, Katz g, o’Connell B. the total thermal insulation of the6 parry g, tucker J, tarnow-mordi W, for the uK neonatal Staffing newborn baby. J Physiol 1970; 207: 683–689. Study Collaborative group. CRiB ii: an update of the clinical risk 25 Hey en. temperature regulation in sick infants. in: tinker J, Rapin m, index for babies score. 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Paediatr 1992; 81: 764–768.20 Carmichael a, mcCullough S, Kempley St. Critical dependence of 39 grunhagen DJ, de Boer mg, de Beaufort aJ, Walther FJ. acetate thermal mattress on gel activation temperature. Arch Dis transepidermal water loss during halogen spotlight phototherapy in Child Fetal Neonatal Ed 2007; 92: F44–45. preterm infants. Pediatr Res 2002; 51: 402–405.21 Hey en. the care of babies in incubators. in: gairdner D, Hull D, 40 Hanley K, Jiand y, elias pm, Feingold KR, Williams ml. acceleration eds. Recent advances in paediatrics, 4th edn. london: J & a of barrier ontogenesis in vitro through air exposure. Pediatr Res Churchill, 1971, p. 171–216. 1997; 41: 293–299.22 Whitelaw a, Heisterkamp g, Sleath K, acolet D, Richard m. Skin-to- 41 Denda m, Sato J, masuda y, et al. exposure to a dry environment skin contact for very low birthweight infants and their mothers. Arch enhances epidermal permeability barrier function. J Invest Dermatol Dis Child 1988; 63: 1377–1381. 1998; 111: 858–863.paeDiatRiCS anD CHilD HealtH 18:4 159 © 2007 elsevier ltd. all rights reserved.
  7. 7. SympoSium: neonatology42 Ågren J, Sjörs g, Sedin g. ambient humidity influences the rate of skin barrier maturation in extremely preterm infants. J Pediatr 2006; Practice points 148: 613–617.43 Sinclair l, Sinn J. Higher versus lower humidity for the prevention of • Hypothermia in the newborn infant is associated with adverse morbidity and mortality in preterm infants in incubators (protocol). outcome Cochrane Database Syst Rev 2007; issue 2. art. no.:CD006472. • Despite improvements in technology, the preterm baby is still doi:10.1002/14651858. at high risk of hypothermia immediately after delivery44 Hey en, Katz g. the optimum thermal environment for naked • prevention of evaporative heat losses eliminates hypothermia babies. Arch Dis Child 1970; 45: 328–334. at resuscitation45 Sauer pJJ, Dane HJ, Visser HKa. new standards for neutral thermal • High evaporative fluid losses must be prevented if the baby environment of healthy very low birthweight infants in week one of is nursed under a radiant heater life. Arch Dis Child 1984; 59: 18–22. • more studies are needed to determine the optimum46 Dollberg S, Xi y, Donnelly mm. a noninvasive alternative to rectal management after delivery and to show if reducing thermometry for continuous measurement of core temperature in transepidermal water loss has an effect on the rate of skin the piglet. Pediatr Res 1993; 34: 512–517. maturation47 messaritakis J, anagnostakis D, laskari H, Katerelos C. Rectal-skin • Continuous monitoring and display of a central and peripheral temperature difference in septicaemic newborn infants. Arch Dis temperature gives early warning of developing cold stress Child 1990; 65: 380–382.paeDiatRiCS anD CHilD HealtH 18:4 160 © 2007 elsevier ltd. all rights reserved.
  8. 8. SympoSium: neonatologyInvestigation and in terms of metabolic adaptation, and sought to compare nutri- tionally comparable time frames, e.g. suckling versus weaningmanagement of impaired periods. Whilst the processes of metabolic adaptation are well described in term and preterm human neonates, there are few,metabolic adaptation if any, clinical studies in human neonates of sufficient rigour to provide evidence for the circumstances in which brain injury maypresenting as neonatal occur, and thus it is not possible to provide evidence-based guide- lines for the prevention and management of clinically significanthypoglycaemia hypoglycaemia. Therefore, recommendations in this article, and in the referenced review articles by recognized experts, remain pragmatic and urge clinicians to individualize management forJ m Hawdon each baby, placing heavy emphasis on careful clinical evaluation rather than single numerical definitions of brain-injuring hypogly- caemia, and on detecting and treating underlying pathologies.1–6Abstractat birth, the newborn baby undergoes many adaptive changes to inde- Fetal metabolism, metabolic changes at birth andpendent extrauterine life. these include the changes of metabolic adap- ‘transitional hypoglycaemia’tation, which must be understood in order to identify and manage theconditions in which metabolic adaptation is delayed, impaired or fails, During intrauterine life, the fetus receives via the placenta a con-resulting in low levels of glucose and other metabolic fuels, which in turn stant supply of nutrients, initially for growth but in the third tri-affect neonatal neurological function and, if prolonged and severe, cause mester also for storage. Glucose crosses the healthy placenta at apotential adverse outcome. Babies identified as at risk of impaired met- rate of approximately 5 mg/kg/min. In addition to that requiredabolic adaptation must undergo clinical monitoring, including accurate for basal fetal metabolism, glucose is converted to glycogenblood glucose monitoring, tailored to their condition. Babies who present which is stored in the liver, cardiac muscle and central nervouswith abnormal clinical signs in association with a low blood glucose level system. In the third trimester excess glucose is converted to tri-must be investigated for underlying cause and treated promptly. preven- glycerides which are stored in adipose tissue.tion and treatment of clinically significant hypoglycaemia must be planned Insulin is an important fetal hormone to ensure glucose andto avoid compromising successful establishment of breast feeding. other substrates are utilized for growth and storage, but in nor- mal circumstances insulin is not required for fetal glucose con-Keywords alternative fuels; blood glucose; breast feeding; neonatal trol. The exception is for the infant of the mother with poorlymetabolic adaptation; operational thresholds; risk factors controlled diabetes, when transfer of glucose across the placenta is at a higher rate, driven by the maternal–fetal concentration gra- dient. This results in increased insulin secretion, excess growth, and increased storage of glycogen and adipose tissue (macroso-Introduction mia), along with increased risk of intracellular hypoxia.At birth, the newborn baby undergoes many adaptive changes to Conversely, in the fetus affected by severe placental insuffi-independent extrauterine life. These include the changes of met- ciency, transfer of glucose and other nutrients across the placentaabolic adaptation, essential to ensure energy provision to vital is at a lower rate, and the fetus is required to metabolize first itsorgans and then to sustain growth and further development. The own fuel stores and then structural proteins (e.g. in muscle) tochanges involved in metabolic adaptation must be understood in ensure energy delivery to the vital organs, assisted by the redis-order to identify and manage the conditions in which metabolic tribution of blood flow to these organs. Should placental functionadaptation is delayed, impaired or fails. The clinical outcome of deteriorate further, these adaptive responses fail. Fetal hypogly-these circumstances is usually referred to with the single short- caemia has been described in these circumstances.7,8hand diagnostic term ‘neonatal hypoglycaemia’. However, as When placental nutrition abruptly ceases at birth, the healthywill be illustrated in this article, it is not appropriate to ascribe a neonate is dependent upon endocrine changes to initiate meta-diagnostic label to neonatal hypoglycaemia, first because glucose bolic adaptation. Insulin levels fall steadily and the action of anyis not the only fuel in the neonate’s fuel economy and second, residual circulating insulin is overcome by the surge of the coun-because hypoglycaemia is the consequence of a number of vari- ter-regulatory hormones, glucagon and the catecholamines. Thisous underlying disorders and thus does not in itself warrant a change in the balance of glucoregulatory hormones induces thediagnostic label. activity of key enzymes for glycogenolysis (release of glucose There have been extensive studies of metabolic adaptation in from glycogen stores), gluconeogenesis (production of glucosehuman neonates and neonatal non-human mammals. The latter from precursors including glycerol and amino acids), lipolysisstudies have identified those mammals most similar to humans (release of free fatty acids and glycerol from adipose tissue stores) and beta-oxidation of fatty acids to produce ketone bodies.9,10 If fasting is prolonged, structural protein is broken down to releaseJ M Hawdon MA MBBS MRCP FRCPCH PhD is Consultant Neonatologist and gluconeogenic amino acids. Other than lipolysis and proteolysis,Honorary Senior Lecturer at UCL EGA Institute for Women’s Health, all of these processes take place in the liver. Glycogenolysis alsoElizabeth Garrett Anderson and Obstetric Hospital, University College takes place in cardiac muscle and the central nervous system,London Hospitals NHS Foundation Trust, Huntley Street, London, UK. providing immediate energy (in the form of glucose or lactate)paeDiatRiCS anD CHilD HealtH 18:4 161 © 2008 elsevier ltd. all rights reserved.
  9. 9. SympoSium: neonatologyat this crucial time.4,11 Clearly, during this catabolic phase of Impaired metabolic adaptationimmediate postnatal nutrition, prior to the establishment of suck-ling feeds, provision of energy for vital organ function is at the Risk factors for impaired metabolic adaptation vary and may beexpense of growth and fuel storage. related to any of the following: reduced body fuel stores; failure of The postnatal metabolic transition is characterized by low cir- the normal endocrine changes at birth; systemic illnesses whichculating blood glucose concentrations compared to those of older impede function of the liver, where the key metabolic processesinfants and children, often for a number of days.12 This is almost occur; or rarely inborn errors of metabolism (see Table 1).always of no pathological significance for a number of reasons, It is well recognized that significant hypoglycaemia will resultincluding differences in the function and metabolic requirements of in a reduced level of consciousness and/or fits. However, it isthe brain and, importantly, the production and utilization of alter- always important to be alert for, detect and treat an underlyingnative fuels, lactate and ketone bodies, which are in plentiful supply pathology which could be causing both the hypoglycaemia andin the neonate.3,4,12,13–20 An important finding from clinical studies the abnormal signs. Often, abnormal signs and hypoglycaemiaand of clinical relevance to those caring for mothers and babies is are co-morbidities, e.g. a primary neurological problem causesthat in all groups of infants studied to date, those who are breast both abnormal neurological signs and hypoglycaemia secondaryfed have higher circulating ketone body levels than those who are to poor feeding. For this reason, all possible underlying causesformula fed, even after correcting for blood glucose levels.10,21,22 for presentation with hypoglycaemia must be considered and There are circumstances, however, when hypoglycaemia is investigations planned accordingly. Investigations for inbornsevere and prolonged, and conditions when alternative fuel pro- errors of metabolism and endocrine disorders are most informa-duction is also impaired or fails. In these circumstances low blood tive if carried out when blood glucose levels are low.glucose levels do acquire clinical significance. The key metabolic There have been extensive efforts to use data from clinical stud-processes and the risk factors for impaired metabolic adaptation ies of the human neonate to determine the significance of neonatalare summarized in Table 1. hypoglycaemia in terms of neurophysiological, neurodevelopmental and neuroradiological sequelae. However, there are major difficul- ties in interpreting these clinical studies as, to date, these have been flawed by confounding factors, such as immaturity, placental insuf- ficiency and co-existing complications, by heterogeneity of subjects Metabolic changes at birth – key hormones and and by failure to take into account protective mechanisms.1,14,23 The metabolic processes and risk factors for impaired evidence from both animal and human studies suggests ‘pure’ hypo- metabolic adaptation glycaemic brain injury is rare, and for hypoglycaemic brain injury to Postnatal metabolic Risk factors occur there must be co-existing failure of metabolic adaptation such changes that alternative fuels are not available, There is no evidence that ‘transitional’ hypoglycaemia in the healthy neonate is associated Hormones with acute or long term sequelae and indeed, even for babies in the insulin falls neonatal hyperinsulinism – infant of at-risk groups, on many occasions protective factors will prevail. diabetic mother or idiopathic glucagon surge possibly blunted by iv glucose or Diagnosis of clinically significant hypoglycaemia formula feeds Catecholamine surge maternal beta-blocker medication ‘Neonatal hypoglycaemia’ is a commonly cited diagnosis, most (Cortisol – weak effect) (pituitary or adrenal insufficiency) often based on a single blood glucose level and using inaccurate Metabolic processes methods of measurement, and with disregard for the presence or glygogenolysis preterm, intrauterine growth absence of associated clinical signs. In the many published texts and restriction (iugR) – reduced stores local guidelines there is no consistency of approach. For this reason, perinatal hypoxia-ischaemia – stores a multinational group of experts attempted to examine critically the utilized evidence on which clinical recommendations should be made.1 Fol- Hyperinsulinism lowing detailed analysis, the authors considered it impossible to maternal beta-blocker medication define hypoglycaemia as a single blood glucose level and instead glycogen storage disorders suggested operational thresholds and therapeutic goals. They con- gluconeogenesis Hyperinsulinism cluded that low blood glucose levels accompanied by neurological maternal beta-blocker medication signs should be investigated and treated regardless of the blood glu- Hepatic dysfunction cose level. They also, pragmatically, concluded that a blood glucose Very rare inborn errors of metabolism level below 1.0 mmol/litre should be treated immediately. In babies lipolysis preterm, iugR – reduced stores who are at risk of impaired metabolic adaptation but who have no Hyperinsulinism clinical signs, it is recommended that interventions to raise blood maternal beta-blocker medication glucose level are considered if blood glucose levels are persistently Ketogenesis Defects of beta-oxidation of fatty below 2.0 mmol/litre. For sick and very low birthweight babies acids who are likely to have a requirement for intravenous glucose, there Hepatic dysfunction should be a ‘therapeutic goal’ to maintain blood glucose levels above 2.5 mmol/litre. Where there is known hyperinsulinism (aTable 1 very high-risk condition characterized by high intravenous glucosepaeDiatRiCS anD CHilD HealtH 18:4 162 © 2008 elsevier ltd. all rights reserved.
  10. 10. SympoSium: neonatologyrequirements to maintain normoglycaemia), an operational thresh- Only babies in at-risk groups, or babies who have abnormalold and therapeutic goal of 3.5 mmol/litre has been proposed.24 neurological signs should be subjected to blood glucose monitor- Finally, there must be careful consideration of the infant of the ing (Table 3).diabetic mother. In extreme and rare cases, there may be signifi- It is important not to commence blood glucose monitoring toocant, but transient, hyperinsulinism and in these cases the thera- soon after birth as to do so would fail to differentiate the babypeutic goal must be 3.5 mmol/litre. More commonly, babies whose with incipient hypoglycaemia from the baby undergoing the nor-mothers’ diabetes has been well controlled will have normal ‘tran- mal postnatal fall in blood glucose level. It is recommended, insitional hypoglycaemia’, or slightly delayed metabolic adaptation the otherwise healthy but at-risk baby, to wait until around 3 hwhile insulin levels fall postnatally. There must be careful and after birth to make the first blood glucose estimation.25,28 In prac-repeated clinical assessment, including blood glucose monitoring. tice, this is usually before the second feed, assuming best practiceFor infants of diabetic mothers who have no evidence of signifi- of offering a baby a breast (or if necessary formula feed) imme-cant hyperinsulinism and no abnormal clinical signs, there is no diately after birth. Clearly, if the baby is unwell or has abnormalevidence that the operational threshold for hyperinsulinism must clinical signs in the first 3 h, they will be treated according tobe applied. Indeed, to do so would result in separation of large clinical condition, which will include intravenous fluids, and thenumbers of healthy babies from their mothers with the conse- therapeutic goal described above would apply.quent impact upon breast feeding and resource allocation.25 Similarly, the temptation to measure blood glucose level The operational thresholds for various groups of babies are shortly (within 2 h) after intravenous glucose has been discon-summarized in Table 2. tinued must be avoided. In this circumstance, as at birth, blood The guidance relating to operational thresholds is predicated glucose levels fall and then subsequently rise in response to coun-upon the accurate measurement of blood glucose levels. It is now ter-regulation. It is this effective rise which must be assessed bywell known that the commonly used reagent strips are insufficiently blood glucose measurement at least 2 h after a change is madeaccurate to diagnose hypoglycaemia and monitor at-risk infants, (provided the baby remains clinically well).and there must be access to equipment which allows immediate Blood glucose levels rise after a feed and fall to a nadir beforeand accurate determination of blood glucose levels.1,4,26–28 the subsequent feed. As our concern is the lowest blood glucose level during the feed cycle and as this measurement may assist in determining best feed frequency, it is important that pre-feedBlood glucose monitoring blood glucose concentration is measured. There is no clinicalAn accurate method for blood glucose monitoring must be value in measuring a post-feed blood glucose level as this mayemployed, as described above. The sample should be free be falsely reassuring and this practice subjects babies to moreflowing venous or from a warm heel such that the blood flows frequent heel pricks or venesections than is necessary.freely without squeezing. Finally, consideration must be given to when to discontinue Blood of high haematocrit often yields low blood glucose lev- blood glucose monitoring. This will depend upon the baby’s clin-els because of dilution of glucose by red cell water. However, ical condition, feeding pattern and underlying disorder or riskthis is also clinically relevant because polycythaemia is itself a factors for impaired metabolic adaptation.high-risk situation. Therefore, in polycythaemic infants both thehaematocrit and blood glucose level must be monitored and both Prevention and management of clinically significantacted upon accordingly. hypoglycaemia In babies at risk of clinically significant hypoglycaemia, and who are well enough to tolerate enteral feeds, milk feeds are the Operational thresholds for blood glucose levels in the management of babies at risk of impaired metabolic adaptation1,24 At-risk babies for whom blood glucose monitoring is recommended Clinical condition Blood glucose level at which to consider intervention and abnormal neurological signs therapeutic goal Systemically unwell, e.g. suspected or proven infection, all at-risk babies <1.0 mmol/litre hypoxic–ischaemic encephalopathy preterm (< 37 weeks) abnormal neurological intervene regardless of blood intrauterine growth restriction (< 2nd centile and any baby with signs glucose level signs of wasting) Systematically unwell baby therapeutic goal of 2.5 mmol/litre infant of diabetic mother polycythaemia at-risk babies, no abnormal persistently <2.0 mmol/litre maternal beta-blocker medication neurological signs Suspected hyperinsulinism Hyperinsulinism 3.5 mmol/litre Suspected inborn error of metabolism or endocrine disorderTable 2 Table 3paeDiatRiCS anD CHilD HealtH 18:4 163 © 2008 elsevier ltd. all rights reserved.
  11. 11. SympoSium: neonatologymainstay of prevention. For babies who are able to feed orally,breast feeding should be first choice and there must be maximal Additional medication in specific conditions (ifsupport for the mother to do so. This is a key clinical priority for these are required there must also be referral to amidwives and paediatricians. specialist centre) If there are concerns regarding adequacy of breast feedingto prevent hypoglycaemia, the mother should be encouraged to Medication Indicationcommence expression of milk from very soon after birth. If thereis insufficient breast milk to prevent babies reaching the opera- glucagon intramuscular bolus dose of 200 μg/kgtional thresholds described above, there should be judicious use transient rise in blood glucose level, e.g.of formula milk, using only the smallest amount required to keep when difficulty re-siting intravenous infusionthe baby’s glucose in the required range. Formula milk in exces- Diazoxide Hyperinsulinismsive quantities has been demonstrated to suppress normal meta- Hydorcortisone pituitary or adrenal insufficiencybolic adaptation.21,22 In babies for whom early enteral feeds are not appropriate or Table 4not tolerated, or for whom enteral feeding does not prevent bloodglucose level falling below operational thresholds, intravenous is difficult to control by the measures described above and whoglucose infusion at rates around 4–5 mg/kg/min (58–72 ml/kg/d require these additional treatments should be cared for in a centreof 10% dextrose) are usually sufficient to prevent hypoglycae- which has expertise in metabolic and endocrinological conditions.mia. If blood glucose levels remain below therapeutic goals, therate of infusion may be steadily increased. Excess glucose infu- Summarysion over and above that required to maintain the therapeuticgoal will stimulate insulin and there is a risk of rebound hypo- Much controversy and confusion has surrounded neonatal hypo-glycaemia if high rate glucose infusions are too rapidly reduced. glycaemia, but this usually arises as a result of failure to under-Milk feeds, if tolerated, should be continued if intravenous glu- stand the processes of normal metabolic adaptation and the factcose is commenced. that hypoglycaemia is a presenting sign rather than a diagnosis If infused volume of glucose solution becomes excessive in in itself. Plans for investigation and management must be basedorder to maintain therapeutic goals or if fluid restriction must upon the most likely underlying cause of impaired metabolicbe applied, more concentrated glucose concentrations must be adaptation and take into account the clinical condition of theinfused through a central venous line. This is particularly rel- baby. This is counter to the current trend to propose rigid pro-evant to the hyperinsulinaemic baby in whom glucose infusion tocols and algorithms, and re-introduces the value of detailedrates in excess of 8–10 mg/kg/min are required to maintain ther- clinical evaluation and decision making. The mainstay of man-apeutic goals. There is a high risk of severe and brain-damaging agement is close clinical observation of vulnerable infants, andhypoglycaemia if treatment is delayed or fails to raise blood glu- energy provision tailored to their individual needs whilst avoid-cose levels, and management of these babies requires consulta- ing excessively invasive management (namely, unnecessary sep-tion with or referral to a specialist centre.24 aration of mother and baby, routine or excessive formula milk If there is presentation of hypoglycaemia with abnormal clinical supplementation or intravenous glucose administration) whichsigns or a very low blood glucose level (less than 1 mmol/litre), themselves inhibit protective metabolic responses and impedethis mandates urgent treatment with intravenous glucose. The rates successful establishment of breast feeding. ◆of glucose infusion described above are usually sufficient to bringthe blood glucose level rapidly to the therapeutic goal without abolus of glucose being necessary. In fact a bolus dose of glucosewill result in a peak blood glucose level and then an insulin surge, ReFeRenCeSmaking subsequent management problematical. This is minimized 1 Cornblath m, Hawdon Jm, Williams aF, et al. Controversies regardingby the use of a ‘mini-bolus’ should a bolus of glucose be required – definition of neonatal hypoglycemia: Suggested operational200 mg glucose/kg (2 ml/kg of 10% dextrose).28 Indications for thresholds. Pediatrics 2000; 105: 1141–1145.mini-bolus are infants presenting with fits or coma, or an ‘unre- 2 Cornblath m, ichord R. Hypoglycemia in the neonate. Semincordable’ or zero blood glucose level. A mini-bolus should always Perinatol 2000; 24: 136–149.be followed with glucose infusion, or an increased glucose infusion 3 Vannucci RC, Vannucci SJ. Hypoglycaemic brain injury. Seminrate if a baby already receiving intravenous glucose has required a Neonatol 2001; 6: 147–155.mini-bolus. 4 Rozance pJ, Hay WW. Hypoglycaemia in newborn infants: features The temptation to supplement enteral feeds with glucose associated with adverse outcomes. Biol Neonate 2006; 90: 74–86.polymers and energy supplements (e.g. Duocal) or to use oral 5 Hawdon Jm. Hypoglycaemia in newborn infants: defining theglucose gels or solutions (e.g. Hypostop) should be avoided as features associated with adverse outcomes – a challenging remit.this carries a risk of necrotizing enterocolitis, is likely to suppress Biol Neonate 2006; 90: 87–88.normal metabolic adaptation and will suppress the appetite of 6 Williams aF. neonatal hypoglycaemia: clinical and legal aspects.the baby for effective oral feeding. Semin Fetal Neonatal Med 2005; 10: 363–368. Finally, there are additional medications which may be employed 7 Soothill pW, nicolaides KH, Campbell S. prenatal asphyxia,in specific circumstances (Table 4). More detailed descriptions are hyperlacticaemia, hypoglycaemia and erythroblastosis in growthgiven elsewhere.24,27,28 Babies who have hypoglycaemia which retarded fetuses. BMJ 1987; 294: 1051–1053.paeDiatRiCS anD CHilD HealtH 18:4 164 © 2008 elsevier ltd. all rights reserved.
  12. 12. SympoSium: neonatology8 Hawdon Jm, Ward platt mp, mcphail S, Cameron H, Walkinshaw Sa. 22 de Rooy l, Hawdon Jm. nutritional factors that affect the postnatal prediction of impaired metabolic adaptation by antenatal Doppler metabolic adaptation of full-term small- and large-for gestational studies in small for gestational age fetuses. Arch Dis Child 1992; age infants. Pediatrics 2002; 109: e42. 67: 787–792. 23 Hawdon Jm. Hypoglycaemia and brain injury – when neonatal9 Deshpande S, Hawdon Jm, et al. adaptation to extrauterine life. in: metabolic adaptation fails. in: levene m, ed. Fetal and neonatal Rodeck C, Whittle m, eds. Fetal medicine: Basic Science and Clinical neurology and neurosurgery. edinburgh: Churchill livingstone, in practice. edinburgh: Churchill livingstone, 1999. press.10 Ward platt m, Deshpande S. metabolic adaptation at birth. Semin 24 Hussain K. Congenital hyperinsulinism. Semin Fetal Neonatal Med Fetal Neonatal Med 2005; 10: 341–350. 2005; 10: 369–376.11 eyre Ja, Stuart ag, Forsyth RJ, Heaviside D, Bartlett K. glucose 25 acolet D. Diabetes in pregnancy: Caring for the Baby after Birth. export from the brain in man: evidence for a role for astrocytic CemaCH, 2007; 2. glycogen as a reservoir of glucose for neural metabolism. Brain Res 26 Hussain K, Sharief n. the inaccuracy of venous and capillary blood 1994; 28: 349–352. glucose measurement using reagent strips in the newborn period12 Hawdon Jm, Ward platt mp, aynsley-green a. patterns of metabolic and the effect of haematocrit. Early Hum Dev 2000; 57: 111–121. adaptation for preterm and term infants in the first neonatal week. 27 Hawdon Jm. Disorders of blood glucose homeostasis in the neonate. Arch Dis Child 1992; 67: 357–365. in: Rennie Jm, ed. Roberton’s textbook of neonatology, 4th edn.13 Hawdon Jm, Ward platt mp, aynsley-green a. prevention and edinburgh: Churchill livingstone, 2005. management of neonatal hypoglycaemia. Arch Dis Child Fetal 28 Deshpande S, Ward platt mp. the investigation and management Neonatal Ed 1994; 70: F60–64. of neonatal hypoglycaemia. Semin Fetal Neonatal Med 2005; 10:14 Hawdon Jm. Hypoglycaemia and the neonatal brain. Eur J Paediatr 351–361. 1999; 158: S9–12.15 massieu l, Haces ml, montiel t, Hernández-Fonseca K. acetoacetate protects hippocampal neurons against glutamate-mediated neuronal damage during glycolysis inhibition. Neuroscience 2003; 120: 365–378.16 yamada Ka, Rensing n, thio ll. Ketogenic diet reduces hypoglycaemia-induced neuronal death in young rats. Neurosci Lett Practice points 2005; 385: 210–214.17 nehlig a. Brain uptake and metabolism of ketone bodies in animal • identify risk factors for impaired metabolic adaptation models. Prostaglandins Leukot Essent Fatty Acids 2004; 70: • Clinical monitoring, including accurate blood glucose 265–275. measurement, for at-risk babies18 Hernández mJ, Vannucci RC, Salcedo a, Brennan RW. Cerebral blood • Feed at-risk babies soon after birth and maintain thermal flow and metabolism during hypoglycemia in newborn dogs. homeostasis J Neurochem 1980; 35: 622–628. • take first blood glucose level at 3–4 h of age19 Vannucci RC, nardis ee, Vannucci SJ, Campbell pa. Cerebral • intervene in at-risk baby with no clinical signs if two carbohydrate and energy metabolism during hypoglycaemia in consecutive blood glucose measurements < 2.0 mmol/litre newborn dogs. Am J Physiol 1981; 256: H1659–H1666. • intervene in any baby with blood glucose measurement20 anwar m, Vannucci RC. autoradiographic determination of regional < 1.0 mmol/litre cerebral blood flow during hypoglycaemia in newborn dogs. Pediatr • intervene in any baby with abnormal clinical signs, regardless Res 1988; 24: 41–45. of blood glucose level21 Hawdon Jm, Williams aF, et al. Formula supplements given to • investigate for underlying cause of failure of metabolic healthy breastfed preterm babies inhibit postnatal metabolic adaptation adaptation: results of a randomised controlled trial. Arch Dis Child • maintain lactation and breast feeding 2000; 82: a30.paeDiatRiCS anD CHilD HealtH 18:4 165 © 2008 elsevier ltd. all rights reserved.
  13. 13. SympoSium: neonatologyResuscitation of the term Sometimes it is possible to predict babies who are likely to have respiratory depression at birth and to have appropriate per-and premature baby sonnel present at delivery. Guidelines for attendance at deliveries will vary with institution, but even when almost 40% of deliv- eries are attended there may still be a further 1.5% of babiesJonathan Wyllie who require unexpected resuscitation,5 a proportion that seems to remain whatever changes are made. The physiology of babies requiring help at birth has been summarized previously.1,6,7 It allows a logical approach to resus- citation (Figure 1) when evidence is lacking and may prompt further research.Abstract Resuscitation at birthalthough most newly born babies establish normal respiration andcirculation without help, up to 1−2% may require some resuscitation Preparationor stabilization. Babies who do not establish adequate regular normal At birth resuscitation is more likely in babies with intrapartumbreathing or who have a heart rate of less than 100 beats/min or other evidence of significant fetal compromise, those less than 35problems such as prematurity may require assistance. the differences in weeks’ gestation, those delivering vaginally by the breech andapproach to the resuscitation of such babies originate in the physiology in multiple births. Personnel trained in newborn resuscitationand pathophysiology of acute asphyxia at birth. However, management should be available at every delivery.1 Someone experienced inof airway and breathing remain the key features of resuscitation and tracheal intubation and advanced resuscitation should also bewhere cardiac depression has occurred, this is nearly always due to hy- easily available for normal low-risk deliveries in hospital and,poxia secondary to respiratory compromise. therefore, most babies will ideally, in attendance for deliveries with an increased likelihoodrespond within 2−3 min of effective aeration of the lungs and the need of needing resuscitation. In the latter cases the equipment andfor intubation, chest compressions or drugs is rare. the international environment can be prepared beforehand, including a discussionliaison Committee on Resuscitation (ilCoR) evaluated evidence in 2000 with the parents. Wash your hands, put on gloves and considerand 2005 in order to provide guidelines for resuscitation: they will do what help may be needed.so again for 2010. this evidence is limited in terms of both quantity andquality and controversies still exist. more research is needed to ensure Cord clampingthat our future actions are based upon evidence rather than history. this At birth it has long been known that delay in clamping the cordarticle will review the recommended approach to resuscitation as well as will lead to less anaemia in babies and reduce subsequent ironsome newer evidence. deficiency.8 However, few hospitals have practised this interven- tion due to worries about hypothermia and the need to resusci-Keywords guidelines; neonatal; newborn; premature; resuscitation tate or stabilize babies. In developed countries the advantages seemed to be outweighed by the potential disadvantages. A recent randomized controlled study of delayed clamping of the cord in premature babies found that the intervention group hadBackground less late-onset sepsis and fewer intraventricular haemorrhages.9In the UK, 669 601 babies were born alive in 2006 and most made This is a low-risk strategy, which needs further evaluation inthe transition to extrauterine life without problems. Those babies order to introduce it without increasing other risk factors in pre-who did not establish adequate regular normal breathing or who mature deliveries.had a heart rate of less than 100 beats/min may have requiredassistance.1 Factual evidence concerning the true requirement Assessment and temperature controlfor resuscitation at birth is sparse. Up to 10% of newborns may Assessment and temperature control for the newborn babyrequire some assistance to begin breathing with less than 1% should occur at all deliveries. The assessment indicates the needneeding extensive resuscitation.2 However, just because a baby for resuscitation. Babies may vary from 23 to 40+ weeks’ ges-received resuscitation does not necessarily mean that it was tation and in weight from 500 to 5000 g. They are born nakedrequired, and rates of intervention may be altered by educa- and wet and, if left, cannot cope with an environmental tem-tion3,4 or the personnel present at deliveries.5 In a UK tertiary perature of less than 32°C. However, if the term baby is imme-centre with a standard approach to resuscitation at birth, up to diately dried, put skin-to-skin with the mother and covered, the12% of all babies received some airway assistance with just over delivery room temperature can be as low as 25–28°C. Obviously,1% being intubated.3 In Sweden only 1% of babies over 2500 g the smaller the baby the greater the surface area to mass ratiorequired mask or endotracheal tube ventilation at birth, of which and the greater the risk of hypothermia. Compromised babiesmost responded to the former.4 are particularly vulnerable10 and hypothermia will lower oxygen tension,11 increase metabolic acidosis12 and inhibit surfactant production.13 An effective method of maintaining the temperature of prema-Jonathan Wyllie MBChB FRCPCH is Consultant Neonatologist at the James ture babies less than 28 weeks’ gestation is wrapping them withCook University Hospital, Marton Road, Middlesbrough TS4 3BW, UK. plastic before drying, and then placing them under a radiantpaeDiatRiCS anD CHilD HealtH 18:4 166 © 2008 elsevier ltd. all rights reserved.
  14. 14. SympoSium: neonatology Dry the baby Remove any wet towels and cover. Start the clock or note the time Assess colour, tone, breathing and heart rate Head in neutral position If not breathing If meconium present: Baby breathing well Do not suction the airway Open the airway Baby floppy and not breathing well Consider inspection and suction before inflation breaths If still not breathing If breathing: Inflation breaths Reassess heart rate and monitor baby Give 5 inflation breaths Use a well-fitting face mask Look for a response. connedted to a If heart rate is satisfactory but increasing: If no increase in heart rate, look for chest movement pressure-limited gas supply. Continue ventilation breaths at about 30 per Each breath 2–3 seconds minute until baby is breathing adequately duration at 30 cm H2O for a If no response term baby Re-check head position Apply Jaw thrust Repeat inflation breaths If heart rate is satisfactory but increasing: Look for a response. Continue ventilation breaths at about 30 per If no increase in heart rate, look for chest movement minute until baby is breathing adequately Get help from a second person If still no response to support the airway and/or inspect the oropharynx under direct vision and consider Try alternative airway opening manoeuvres suction and/or insert an Repeat inflation breaths oropharyngeal airway Look for a response. If no increase in heart rate, look for chest movement If the chest is not moving: When the chest is moving Recheck head position and repeat inflation breaths. If competent consider intubation If the chest is still not moving: Chest compressions If the heart rate is not detectable or slow (<60) The airway is the problem Comp/vent ratio 3:1 Start compressions Rate: 120 events per minute 3 compressions to each breath If heart rate is increasing: Ensure the chest moves Stop compressions. with each ventilation breath Reassess heart rate every 30 seconds Continue ventilation breaths at about 30 per Consider venous access and drugs minute until baby is breathing adequatelyFigure 1 newborn life support. (Courtesy of the Resuscitation Council, uK).heater.14 There is a small risk of hyperthermia so the temperature than the need to summon help early. APGAR scores are nevermust be monitored carefully. calculated to guide resuscitation. An assessment is made of the baby’s colour, tone, respira-tions and heart rate.1,2,7 The most important of these is heart rate Airwayand a stethoscope is more reliable than cord pulsation.15 How-ever, saturation monitors may offer a more reliable assessment If a baby is in primary apnoea, then, with an open airway, theof both heart rate and colour,16 but their interpretation requires first gasp will start to aerate the lungs and most babies will bea detailed knowledge of normal saturations at birth at differing able to ‘resuscitate’ themselves, as shown in physiological stud-gestations. A baby who is apnoeic and floppy in the absence of ies on animals. Neutral positioning of the baby’s head, chin lift,neurological disease is unconscious and likely to be in terminal jaw thrust, oropharyngeal airways and endotracheal intubationapnoea; however, this does not change the initial approach other may all be helpful in certain situations if performed correctly.17paeDiatRiCS anD CHilD HealtH 18:4 167 © 2008 elsevier ltd. all rights reserved.

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