- Email: [email protected]
Applied physiology: the newborn skin
Current Paediatrics (2003) 13, 226 --230
c 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0957-5839(03)00008 -3
Applied physiology: the newborn skin Nicholas Rutter Professor of Paediatric Medicine, Academic Division of Child Health, Queen’s Medical Centre, Nottingham, UK
KEYWORDS epidermis; transepidermal water loss; percutaneous absorption; prematurity; adhesive; emollient
Summary The most important function of the skin is to provide a protective barrier between the body and the environment. It limits loss of body water, prevents absorption of noxious agents and protects against physical trauma.The epidermal barrier begins to develop in mid-gestation and is fully formed by about 32 weeks gestation. In the extremely preterm infant, it is poorly formed and functionally weak. Exposure to air after birth accelerates epidermal development. Transepidermal water loss is high in the immature infant, causing diff|culties in fluid balance and temperature control. The percutaneous absorption of topically applied agents may lead to accidental poisoning. Adhesive trauma strips the epidermis, predisposing to infection.These problems can be minimized by limiting the use of skin probes and adhesive tape, nursing the infant in a high ambient humidity and sparing use of aqueous chlorhexidine as an antiseptic.The routine use of emollients or skin coveringsis not recommended.
c 2003 Elsevier Science Ltd. All rights reserved.
INTRODUCTION PRACTICE POINTS *
*
*
* *
The epidermal barrier is well developed in the term infant but defective in the preterm infant A weak epidermal barrier leads to loss of water and heat, skin damage, infection and accidental percutaneous absorption Exposure to a gaseous environment accelerates barrier maturation Skin trauma should be kept to a minimum Increasing ambient humidity reduces loss of water and heat
The skin performs several diverse functions, the most important of which is to act as a barrier between the body and the external environment. This barrier prevents the loss of body contents, in particular body water, prevents the entry of noxious agents (including microorganisms) and acts as physical protection against trauma. It therefore allows the newborn baby to emerge from the aqueous environment of the amniotic fluid to survive in a gaseous terrestrial environment. Barrier function is a property of the epidermis, and this review will be dominated by its effectiveness in the newborn, although there will also be some discussion on the physiology of the underlying dermis.
RESEARCH DIRECTIONS There is a need to investigate: The mechanism underlying postnatal maturation of the epidermal barrier * Methods of protecting and enhancing a weak epidermal barrier
THE EPIDERMAL BARRIER
*
Correspondence to. NR.Tel.: +44 (0)115 924 9924 ext. 44041; Fax: +44 (0)115 970 9382; E-mail: [email protected]
The epidermis is generated from a basal layer of cells that migrate outwards towards the skin surface. The barrier lies entirely in the outermost layer, the stratum corneum, which is made up of stacks of flattened plates of overlapping cells f|lled with the f|brous protein keratin and containing no nuclei. Little water is able to pass directly through these cells -- most loss of water (transepidermal water loss, TEWL) takes place through the intercellular spaces. It is limited by the presence of a
APPLIED PHYSIOLOGY: THE NEWBORN SKIN
unique lipid mixture that f|lls the intercellular spaces of the stratum corneum like mortar between bricks, the lipid consisting of ceramides, cholesterol and free fatty acids. It is synthesized by cells in the layer immediately below the stratum corneum, the stratum granulosum, stored in the cytoplasm within lamellar bodies and discharged into the intercellular space above. Here, it spreads to form a thin, hydrophobic molecular bilayer that resists the passage of water. Skin barrier lipid in many ways shows similarities with pulmonary surfactant -- production by specialized cells (in this case, type 2 pneumocytes), storage in lamellar bodies, discharge by exocytosis (to the alveoli) and the formation of a thin layer over a large surface area. The production of both substances is stimulated by exposure to air. Maturation of epidermal lipid formation is hastened in animals by antenatal steroids, although this has not been demonstrated in the human. The nature of the lipid is, however, very different in that the stratum corneum contains virtually no phospholipid.
EPIDERMAL STRUCTURE IN THE NEWBORN The term infant has a mature epidermis with a welldeveloped stratum corneum,1 very similar to that of an adult. The epidermis develops in the second trimester from about 23 weeks gestation and is complete by about 32 weeks. Extremely preterm infants born at the limits of viability have a poorly developed epidermis (Fig. 1): it is only two or three cell layers thick, there is little or no def|ned stratum corneum, and the lipid content is low. It is clear from examination of the structure of the epidermis that there is no effective epidermal barrier at the moment when an extremely preterm infant moves from amniotic fluid to air.
POSTNATAL MATURATIONOF THE EPIDERMIS Exposure of the immature epidermis to air results in rapid structural maturation in the human (Fig. 2) and in the animal model.2,3 By 2 or 3 weeks of age, regardless of the degree of immaturity, the epidermis resembles that of a term infant.This accelerated development resembles the rapid healing of the adult epidermis that occurs after an injury such as adhesive stripping or burns.
BARRIER FUNCTIONOF THE EPIDERMIS Conservation of body water This is the most important function of the barrier.2,3 The barrier in the term infant is functionally, as well as
227
Figure 1 The effect of gestational age on epidermal development. Both photomicrographs are from abdominal skin at autopsy (magnif|cation 100). The upper picture is from an infant of 26 weeks gestation who died on the f|rst day of life. Note the thin epidermis with no stratum corneum formation. The lower photomicrograph is from a term infant who died in labour. The epidermis is several cell layers thick with a well-developed stratum corneum, similar to that of an adult. (Reproduced with permission from Rutter N. Percutaneous drug absorption. Clin Perinatol1987; 14: 911--930.)
structurally, mature. TEWL is low, lower even than in the adult. TEWL is low in mildly preterm infants, but with increasing immaturity it demonstrates an exponential rise (Fig. 3). Values of TEWL in infants at the limit of viability exceed 100 g/m2/h, as high as free evaporation from a water--air interface. Major problems of management result directly from this: *
*
High fluid loss.This results in weight loss, hypernatraemia, impaired renal function and occasionally hypovolaemia. High evaporative heat loss. The tiny immature infant is already at a disadvantage because surface area (and therefore heat loss by convection and radiation) is high in relation to mass (which determines heat generation). High evaporative heat loss results in hypothermia.
The functionally weak epidermal barrier is only temporary. In parallel with the rapid structural maturation, there is a marked functional maturation in the early postnatal period, and by 2--3 weeks of age, TEWL has fallen towards a term level. Thus, the management problems resulting from the high TEWL are themselves only
228
Figure 2 The effect of postnatal existence on epidermal development. The upper photomicrograph is the same as that shown in Fig.1, from an infant of 26 weeks gestation at 1 day old. The lower photomicrograph is from another infant of 26 weeks who died at the age of16 days.This shows a well-developed epidermis and the formation of a stratum corneum. (Reproduced with permission from Rutter N. Percutaneous drug absorption. Clin Perinatol1987; 14: 911--930.)
temporary. Given a little time, the extremely immature infant adjusts to survival in a gaseous environment.
Percutaneous absorption The mature epidermis of the term infant is a very effective barrier against the entry of chemicals into the body, but the immature epidermis of an infant of 25 weeks gestation is not.2-- 4 Low-molecular-weight, water- and lipid-soluble agents are readily absorbed percutaneously and may cause unexpected systemic effects. There are many reports of accidental poisoning in the newborn from the application of topical agents -- most involving preterm infants, particularly with the use of topical antiseptics. A degree of absorption is seen with all topical antiseptics in immature infants.
Gas diffusion Small amounts of oxygen and carbon dioxide diffuse through the skin along a vapour pressure gradient.3 The amount of oxygen that diffuses in and carbon dioxide that diffuses out is measurable but is insignif|cant in comparison with pulmonary gas exchange. Percutaneous gas exchange in the preterm infant exactly mirrors TEWL, being at its highest in the most immature infants in early postnatal life. It still remains small in relation to pulmonary gas exchange and serves little useful function.
CURRENT PAEDIATRICS
Figure 3 The effect of gestation on transepidermal water loss, which was measured from abdominal skin by evaporimetry. Infants were studiedin unhumidif|edincubatorsinthe f|rstfewdays of life.Reproduced with permission.3
Physical barrier to trauma The skin is an important barrier against a variety of forms of physical trauma.2 Two types of trauma are frequent in the newborn: adhesive stripping and needle penetration. The skin is a convenient site for the placing of monitoring probes (ECG electrodes, transcutaneous gas electrodes, temperature probes, etc.) and for securing intravenous and arterial lines using tape.The adhesive on the tape or electrode binds to the outermost layer of the stratum corneum, and when it is removed, it strips this off. If the epidermal barrier is weak and the adhesive is strong, one or two strippings are enough to remove the whole epidermis down to the basal layer. This leaves a raw area of skin, painful for the infant, which is made weaker still. In extreme cases, even the basal layer is damaged so that scarring can occur. The smallest, sickest infants are prone to this adhesive trauma. Their total area of skin is also much smaller, but the electrodes and tapes are not.
Barrier to micro-organisms Regardless of gestation, the skin is colonized by bacteria soon after birth. The organisms are usually non-pathogenic and do not give rise to systemic infection. One of
APPLIED PHYSIOLOGY: THE NEWBORN SKIN
229
the organisms, however, the coagulase-negative Staphylococcus (Staphylococcus epidermidis) may result in systemic infection in preterm infants, particularly the most immature ones with prolonged illness, frequent invasive procedures and the use of indwelling central lines. This is probably a reflection of their skin damage and their immature immune system rather than being the direct result of a weak epidermal barrier.
MANAGEMENTOF THE INFANT WITH A WEAK EPIDERMAL BARRIER First, do no harm Given time, the accelerated epidermal development will result in a fully effective barrier, so the problems associated with a weak barrier are only temporary. The f|rst aim must be to make sure that the skin is not damaged while this maturation takes place and that accidental poisoning from percutaneous absorption is avoided. Monitoring probes should be kept off the skin wherever possible, using indwelling lines and remote means to monitor heart rate, breathing and temperature. When probes do have to be placed on the skin, they should be kept as small as possible, and the adhesive should be as weak as it can be while still performing its function. It should allow the probe to be taken off and replaced without stripping the superf|cial layers of the epidermis. Two types of modern adhesive meet these requirements: pectins and hydrogels4.The same principles apply to adhesive tape used to f|x indwelling lines. Skin-piercing procedures should be kept to a minimum, although the more premature the infant, the greater the number of such procedures that occurs. Antiseptics should be used sparingly.They should be aqueous rather than alcohol based, aqueous chlorhexidine being the safest.
Manipulate the environment Modifying the environment helps to counteract the effects of a high TEWL on fluid balance and temperature control.4 This is usually achieved by nursing the infant in a closed incubator with water vapour added to the circulating air to increase the ambient relative humidity. TEWL is a physical process driven by the difference in water vapour pressure between the infant and the surrounding air.Unhumidif|ed room air warmed to 371C has a low relative humidity in the UK (25--35%) so TEWL is high if the epidermal barrier is weak (Fig 4). If the humidity is increased, the relative humidity can reach 90% or more; at this level, TEWL is very low regardless of the epidermal barrier. Nursing an immature infant (under 30 weeks and less than 1kg) in high humidity for the f|rst week or so of life greatly simplif|es fluid balance,
Figure 4 The effect of ambient relative humidity on transepidermal water loss (TEWL) in infants of varying maturity. As relative humidity falls, there is a linear decline in TEWL so that at 100% relative humidity there is noTEWL, even in the most immature infants. (Redrawn and modif|ed from the data of Hammarlund K, Sedin G. TEWL in newborn infants. III. Relation to gestational age. Acta Paediatr Scand1979; 68: 795--801.)
reduces hypernatraemia and allows the infant to be kept warm in an air temperature that does not exceed body temperature. There are, however, some practical and theoretical problems associated with use of added humidity. The condensation of water on the inner surface of the incubator canopy (rainout) is common because the canopy temperature is lower than the incubator air temperature.This makes it diff|cult to see the infant and looks unpleasant. It can be minimized by using a double-walled incubator (so that the temperature of the inner canopy and incubator air are similar), by having a high nursery air temperature and by keeping the incubator air temperature high.The latter is important when the infant’s body temperature is getting too high. The natural reaction is to turn the incubator air temperature down f|rst, keeping the humidity high, but this makes condensation more likely. It is better to turn the humidity down f|rst, keeping the incubator air temperature high. Another theoretical concern is an increased risk of infection if the incubator contents are continually moist. This is not borne out in practice, although to reduce the possibility, an external humidif|er should be used and ref|lled with sterile water. The use of humidity should be conf|ned to the early newborn period and stopped when it is no longer needed. Finally, water vapour is a gas, like oxygen. When the incubator portholes are opened, it escapes and the relative humidity falls. It then takes time to rise again when the portholes are closed. Hypothermia and hypernatraemia are thus particularly common when a newly born but extremely preterm infant is frequently handled within a humidif|ed incubator.
Manipulate the epidermal barrier Manipulation of the epidermal barrier5 can be achieved in two different ways.
230
By the use of emollients An emollient is a topical agent that moistens dry skin by reducing TEWL and thereby increasing skin water content. Most emollients used in medicine are ointments based on the hydrocarbon soft paraff|n (petrolatum, Vaseline). When soft paraff|n is applied to the skin of the newborn, it reduces TEWL by up to 50%, albeit only transiently. It also improves the outward appearance of the skin of preterm infants in the second week of life when the rapid formation of a stratum corneum gives the surface a dry, flaky or even cracked appearance. A controlled trial of the emollient Aquaphor (a mixture of soft paraff|n, mineral oil and lanolin) applied twice daily to the whole skin of 60 preterm infants showed no improvement in fluid balance or temperature control.6 There was, however, a dramatic reduction in the number of infants who developed nosocomial sepsis, mainly with Staph. epidermidis (3% in the treatment group and 27% in controls). A large-scale clinical trial conducted by the Vermont Oxford Network in the USA tried unsuccessfully to reproduce these f|ndings.7 Nearly 1200 preterm infants were randomized to receive twice-daily Aquaphor or nothing for 14 days. In this trial, nosocomial sepsis was signif|cantly more common in the treatment group (26% compared with 23% in controls), and there were no clinical benef|ts. The routine use of emollients cannot therefore be recommended, although they may be useful in the treatment of small areas of damaged skin in very preterm infants. By the use of skin coverings Skin coverings are widely used in surgery to dress wounds. Polyurethane semi-permeable dressings are inert and allow some TEWL, promoting healing more quickly than impermeable waterproof dressings. Such dressings (e.g. Tegaderm and Opsite) reduce TEWL and skin damage in the preterm newborn but are impractical as a major skin covering.They are, however, useful as skin dressings for skin that has been damaged by adhesives or by maceration. Maceration occurs in the neck, axillae and groins of very immature infants, sites where skin is in direct contact with skin and water is unable to evaporate.
THE DERMIS8 Sweating Sweat glands are fully formed by mid-trimester, but sweating in response to a thermal stimulus is weak in the term infant and absent in the preterm infant in the immediate newborn period. It steadily matures in early
CURRENT PAEDIATRICS
infancy. However, since keeping warm rather than keeping cool is the major problem for the newborn, there are no clinical consequences of this immaturity. An absence of sweating, seen in hypohidrotic ectodermal dysplasia, is important only beyond the immediate newborn period. Palmar--plantar sweating occurs in response to pain and arousal (emotional sweating) rather than thermal stress. It is detectable in term infants from birth but not in preterm infants.
Sensation The skin is an important organ of sensation because the dermis is rich in sensory nerve endings. Even the most immature infant has the ability to sense pain, producing behavioural, physiological and hormonal responses that demonstrate this. This is particularly relevant to neonatal intensive care, in which painful procedures that pierce the skin are very common.
Sebaceous glands Sebaceous glands are exocrine glands associated with hair follicles and produce the oily secretion sebum. The sebaceous glands are particularly active in the last trimester of pregnancy -- sebum being a major constituent of vernix caseosa, the white grease that covers the skin towards the end of pregnancy. It is possible that this waterproof covering allows the stratum corneum to mature while immersed in amniotic fluid.When the infant starts to produce pulmonary surfactant, some f|nds its way into the amniotic fluid, causing the vernix to become detached from the skin surface. At maturity, therefore, the amniotic fluid is made turbid by vernix, but the skin is exposed.
REFERENCES 1. Hoath S B, Narendran V. Development of the epidermal barrier. NeoReviews 2001; 2: 269--279. 2. Harpin V A, Rutter N. Barrier properties of the newborn infant’s skin. J Pediatr 1983; 102: 419--425. 3. Cartlidge P. The epidermal barrier. Semin Neonatol 2000; 5: 273-280. 4. Rutter N. Clinical consequences of an immature epidermal barrier. Semin Neonatol 2000; 5: 281--287. 5. Hoath S B, Narendran V. Adhesives and emollients. Semin Neonatol 2000; 5: 289--296. 6. Nopper A J, Horii K A, Sookdeo-Drost S et al. Topical ointment therapy benefits premature infants. J Pediatr 1996; 128: 660--669. 7. Edwards W H, Conner J M, Soll R F. The effect of prophylactic ointment therapy on nosocomial sepsis rates and skin integrity in infants of birth weight 501--1000 grams. Pediatrics 2003 (in press). 8. Rutter N. The dermis. Semin Neonatol 2000; 5: 297--302.
c 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0957-5839(03)00008 -3
Applied physiology: the newborn skin Nicholas Rutter Professor of Paediatric Medicine, Academic Division of Child Health, Queen’s Medical Centre, Nottingham, UK
KEYWORDS epidermis; transepidermal water loss; percutaneous absorption; prematurity; adhesive; emollient
Summary The most important function of the skin is to provide a protective barrier between the body and the environment. It limits loss of body water, prevents absorption of noxious agents and protects against physical trauma.The epidermal barrier begins to develop in mid-gestation and is fully formed by about 32 weeks gestation. In the extremely preterm infant, it is poorly formed and functionally weak. Exposure to air after birth accelerates epidermal development. Transepidermal water loss is high in the immature infant, causing diff|culties in fluid balance and temperature control. The percutaneous absorption of topically applied agents may lead to accidental poisoning. Adhesive trauma strips the epidermis, predisposing to infection.These problems can be minimized by limiting the use of skin probes and adhesive tape, nursing the infant in a high ambient humidity and sparing use of aqueous chlorhexidine as an antiseptic.The routine use of emollients or skin coveringsis not recommended.
c 2003 Elsevier Science Ltd. All rights reserved.
INTRODUCTION PRACTICE POINTS *
*
*
* *
The epidermal barrier is well developed in the term infant but defective in the preterm infant A weak epidermal barrier leads to loss of water and heat, skin damage, infection and accidental percutaneous absorption Exposure to a gaseous environment accelerates barrier maturation Skin trauma should be kept to a minimum Increasing ambient humidity reduces loss of water and heat
The skin performs several diverse functions, the most important of which is to act as a barrier between the body and the external environment. This barrier prevents the loss of body contents, in particular body water, prevents the entry of noxious agents (including microorganisms) and acts as physical protection against trauma. It therefore allows the newborn baby to emerge from the aqueous environment of the amniotic fluid to survive in a gaseous terrestrial environment. Barrier function is a property of the epidermis, and this review will be dominated by its effectiveness in the newborn, although there will also be some discussion on the physiology of the underlying dermis.
RESEARCH DIRECTIONS There is a need to investigate: The mechanism underlying postnatal maturation of the epidermal barrier * Methods of protecting and enhancing a weak epidermal barrier
THE EPIDERMAL BARRIER
*
Correspondence to. NR.Tel.: +44 (0)115 924 9924 ext. 44041; Fax: +44 (0)115 970 9382; E-mail: [email protected]
The epidermis is generated from a basal layer of cells that migrate outwards towards the skin surface. The barrier lies entirely in the outermost layer, the stratum corneum, which is made up of stacks of flattened plates of overlapping cells f|lled with the f|brous protein keratin and containing no nuclei. Little water is able to pass directly through these cells -- most loss of water (transepidermal water loss, TEWL) takes place through the intercellular spaces. It is limited by the presence of a
APPLIED PHYSIOLOGY: THE NEWBORN SKIN
unique lipid mixture that f|lls the intercellular spaces of the stratum corneum like mortar between bricks, the lipid consisting of ceramides, cholesterol and free fatty acids. It is synthesized by cells in the layer immediately below the stratum corneum, the stratum granulosum, stored in the cytoplasm within lamellar bodies and discharged into the intercellular space above. Here, it spreads to form a thin, hydrophobic molecular bilayer that resists the passage of water. Skin barrier lipid in many ways shows similarities with pulmonary surfactant -- production by specialized cells (in this case, type 2 pneumocytes), storage in lamellar bodies, discharge by exocytosis (to the alveoli) and the formation of a thin layer over a large surface area. The production of both substances is stimulated by exposure to air. Maturation of epidermal lipid formation is hastened in animals by antenatal steroids, although this has not been demonstrated in the human. The nature of the lipid is, however, very different in that the stratum corneum contains virtually no phospholipid.
EPIDERMAL STRUCTURE IN THE NEWBORN The term infant has a mature epidermis with a welldeveloped stratum corneum,1 very similar to that of an adult. The epidermis develops in the second trimester from about 23 weeks gestation and is complete by about 32 weeks. Extremely preterm infants born at the limits of viability have a poorly developed epidermis (Fig. 1): it is only two or three cell layers thick, there is little or no def|ned stratum corneum, and the lipid content is low. It is clear from examination of the structure of the epidermis that there is no effective epidermal barrier at the moment when an extremely preterm infant moves from amniotic fluid to air.
POSTNATAL MATURATIONOF THE EPIDERMIS Exposure of the immature epidermis to air results in rapid structural maturation in the human (Fig. 2) and in the animal model.2,3 By 2 or 3 weeks of age, regardless of the degree of immaturity, the epidermis resembles that of a term infant.This accelerated development resembles the rapid healing of the adult epidermis that occurs after an injury such as adhesive stripping or burns.
BARRIER FUNCTIONOF THE EPIDERMIS Conservation of body water This is the most important function of the barrier.2,3 The barrier in the term infant is functionally, as well as
227
Figure 1 The effect of gestational age on epidermal development. Both photomicrographs are from abdominal skin at autopsy (magnif|cation 100). The upper picture is from an infant of 26 weeks gestation who died on the f|rst day of life. Note the thin epidermis with no stratum corneum formation. The lower photomicrograph is from a term infant who died in labour. The epidermis is several cell layers thick with a well-developed stratum corneum, similar to that of an adult. (Reproduced with permission from Rutter N. Percutaneous drug absorption. Clin Perinatol1987; 14: 911--930.)
structurally, mature. TEWL is low, lower even than in the adult. TEWL is low in mildly preterm infants, but with increasing immaturity it demonstrates an exponential rise (Fig. 3). Values of TEWL in infants at the limit of viability exceed 100 g/m2/h, as high as free evaporation from a water--air interface. Major problems of management result directly from this: *
*
High fluid loss.This results in weight loss, hypernatraemia, impaired renal function and occasionally hypovolaemia. High evaporative heat loss. The tiny immature infant is already at a disadvantage because surface area (and therefore heat loss by convection and radiation) is high in relation to mass (which determines heat generation). High evaporative heat loss results in hypothermia.
The functionally weak epidermal barrier is only temporary. In parallel with the rapid structural maturation, there is a marked functional maturation in the early postnatal period, and by 2--3 weeks of age, TEWL has fallen towards a term level. Thus, the management problems resulting from the high TEWL are themselves only
228
Figure 2 The effect of postnatal existence on epidermal development. The upper photomicrograph is the same as that shown in Fig.1, from an infant of 26 weeks gestation at 1 day old. The lower photomicrograph is from another infant of 26 weeks who died at the age of16 days.This shows a well-developed epidermis and the formation of a stratum corneum. (Reproduced with permission from Rutter N. Percutaneous drug absorption. Clin Perinatol1987; 14: 911--930.)
temporary. Given a little time, the extremely immature infant adjusts to survival in a gaseous environment.
Percutaneous absorption The mature epidermis of the term infant is a very effective barrier against the entry of chemicals into the body, but the immature epidermis of an infant of 25 weeks gestation is not.2-- 4 Low-molecular-weight, water- and lipid-soluble agents are readily absorbed percutaneously and may cause unexpected systemic effects. There are many reports of accidental poisoning in the newborn from the application of topical agents -- most involving preterm infants, particularly with the use of topical antiseptics. A degree of absorption is seen with all topical antiseptics in immature infants.
Gas diffusion Small amounts of oxygen and carbon dioxide diffuse through the skin along a vapour pressure gradient.3 The amount of oxygen that diffuses in and carbon dioxide that diffuses out is measurable but is insignif|cant in comparison with pulmonary gas exchange. Percutaneous gas exchange in the preterm infant exactly mirrors TEWL, being at its highest in the most immature infants in early postnatal life. It still remains small in relation to pulmonary gas exchange and serves little useful function.
CURRENT PAEDIATRICS
Figure 3 The effect of gestation on transepidermal water loss, which was measured from abdominal skin by evaporimetry. Infants were studiedin unhumidif|edincubatorsinthe f|rstfewdays of life.Reproduced with permission.3
Physical barrier to trauma The skin is an important barrier against a variety of forms of physical trauma.2 Two types of trauma are frequent in the newborn: adhesive stripping and needle penetration. The skin is a convenient site for the placing of monitoring probes (ECG electrodes, transcutaneous gas electrodes, temperature probes, etc.) and for securing intravenous and arterial lines using tape.The adhesive on the tape or electrode binds to the outermost layer of the stratum corneum, and when it is removed, it strips this off. If the epidermal barrier is weak and the adhesive is strong, one or two strippings are enough to remove the whole epidermis down to the basal layer. This leaves a raw area of skin, painful for the infant, which is made weaker still. In extreme cases, even the basal layer is damaged so that scarring can occur. The smallest, sickest infants are prone to this adhesive trauma. Their total area of skin is also much smaller, but the electrodes and tapes are not.
Barrier to micro-organisms Regardless of gestation, the skin is colonized by bacteria soon after birth. The organisms are usually non-pathogenic and do not give rise to systemic infection. One of
APPLIED PHYSIOLOGY: THE NEWBORN SKIN
229
the organisms, however, the coagulase-negative Staphylococcus (Staphylococcus epidermidis) may result in systemic infection in preterm infants, particularly the most immature ones with prolonged illness, frequent invasive procedures and the use of indwelling central lines. This is probably a reflection of their skin damage and their immature immune system rather than being the direct result of a weak epidermal barrier.
MANAGEMENTOF THE INFANT WITH A WEAK EPIDERMAL BARRIER First, do no harm Given time, the accelerated epidermal development will result in a fully effective barrier, so the problems associated with a weak barrier are only temporary. The f|rst aim must be to make sure that the skin is not damaged while this maturation takes place and that accidental poisoning from percutaneous absorption is avoided. Monitoring probes should be kept off the skin wherever possible, using indwelling lines and remote means to monitor heart rate, breathing and temperature. When probes do have to be placed on the skin, they should be kept as small as possible, and the adhesive should be as weak as it can be while still performing its function. It should allow the probe to be taken off and replaced without stripping the superf|cial layers of the epidermis. Two types of modern adhesive meet these requirements: pectins and hydrogels4.The same principles apply to adhesive tape used to f|x indwelling lines. Skin-piercing procedures should be kept to a minimum, although the more premature the infant, the greater the number of such procedures that occurs. Antiseptics should be used sparingly.They should be aqueous rather than alcohol based, aqueous chlorhexidine being the safest.
Manipulate the environment Modifying the environment helps to counteract the effects of a high TEWL on fluid balance and temperature control.4 This is usually achieved by nursing the infant in a closed incubator with water vapour added to the circulating air to increase the ambient relative humidity. TEWL is a physical process driven by the difference in water vapour pressure between the infant and the surrounding air.Unhumidif|ed room air warmed to 371C has a low relative humidity in the UK (25--35%) so TEWL is high if the epidermal barrier is weak (Fig 4). If the humidity is increased, the relative humidity can reach 90% or more; at this level, TEWL is very low regardless of the epidermal barrier. Nursing an immature infant (under 30 weeks and less than 1kg) in high humidity for the f|rst week or so of life greatly simplif|es fluid balance,
Figure 4 The effect of ambient relative humidity on transepidermal water loss (TEWL) in infants of varying maturity. As relative humidity falls, there is a linear decline in TEWL so that at 100% relative humidity there is noTEWL, even in the most immature infants. (Redrawn and modif|ed from the data of Hammarlund K, Sedin G. TEWL in newborn infants. III. Relation to gestational age. Acta Paediatr Scand1979; 68: 795--801.)
reduces hypernatraemia and allows the infant to be kept warm in an air temperature that does not exceed body temperature. There are, however, some practical and theoretical problems associated with use of added humidity. The condensation of water on the inner surface of the incubator canopy (rainout) is common because the canopy temperature is lower than the incubator air temperature.This makes it diff|cult to see the infant and looks unpleasant. It can be minimized by using a double-walled incubator (so that the temperature of the inner canopy and incubator air are similar), by having a high nursery air temperature and by keeping the incubator air temperature high.The latter is important when the infant’s body temperature is getting too high. The natural reaction is to turn the incubator air temperature down f|rst, keeping the humidity high, but this makes condensation more likely. It is better to turn the humidity down f|rst, keeping the incubator air temperature high. Another theoretical concern is an increased risk of infection if the incubator contents are continually moist. This is not borne out in practice, although to reduce the possibility, an external humidif|er should be used and ref|lled with sterile water. The use of humidity should be conf|ned to the early newborn period and stopped when it is no longer needed. Finally, water vapour is a gas, like oxygen. When the incubator portholes are opened, it escapes and the relative humidity falls. It then takes time to rise again when the portholes are closed. Hypothermia and hypernatraemia are thus particularly common when a newly born but extremely preterm infant is frequently handled within a humidif|ed incubator.
Manipulate the epidermal barrier Manipulation of the epidermal barrier5 can be achieved in two different ways.
230
By the use of emollients An emollient is a topical agent that moistens dry skin by reducing TEWL and thereby increasing skin water content. Most emollients used in medicine are ointments based on the hydrocarbon soft paraff|n (petrolatum, Vaseline). When soft paraff|n is applied to the skin of the newborn, it reduces TEWL by up to 50%, albeit only transiently. It also improves the outward appearance of the skin of preterm infants in the second week of life when the rapid formation of a stratum corneum gives the surface a dry, flaky or even cracked appearance. A controlled trial of the emollient Aquaphor (a mixture of soft paraff|n, mineral oil and lanolin) applied twice daily to the whole skin of 60 preterm infants showed no improvement in fluid balance or temperature control.6 There was, however, a dramatic reduction in the number of infants who developed nosocomial sepsis, mainly with Staph. epidermidis (3% in the treatment group and 27% in controls). A large-scale clinical trial conducted by the Vermont Oxford Network in the USA tried unsuccessfully to reproduce these f|ndings.7 Nearly 1200 preterm infants were randomized to receive twice-daily Aquaphor or nothing for 14 days. In this trial, nosocomial sepsis was signif|cantly more common in the treatment group (26% compared with 23% in controls), and there were no clinical benef|ts. The routine use of emollients cannot therefore be recommended, although they may be useful in the treatment of small areas of damaged skin in very preterm infants. By the use of skin coverings Skin coverings are widely used in surgery to dress wounds. Polyurethane semi-permeable dressings are inert and allow some TEWL, promoting healing more quickly than impermeable waterproof dressings. Such dressings (e.g. Tegaderm and Opsite) reduce TEWL and skin damage in the preterm newborn but are impractical as a major skin covering.They are, however, useful as skin dressings for skin that has been damaged by adhesives or by maceration. Maceration occurs in the neck, axillae and groins of very immature infants, sites where skin is in direct contact with skin and water is unable to evaporate.
THE DERMIS8 Sweating Sweat glands are fully formed by mid-trimester, but sweating in response to a thermal stimulus is weak in the term infant and absent in the preterm infant in the immediate newborn period. It steadily matures in early
CURRENT PAEDIATRICS
infancy. However, since keeping warm rather than keeping cool is the major problem for the newborn, there are no clinical consequences of this immaturity. An absence of sweating, seen in hypohidrotic ectodermal dysplasia, is important only beyond the immediate newborn period. Palmar--plantar sweating occurs in response to pain and arousal (emotional sweating) rather than thermal stress. It is detectable in term infants from birth but not in preterm infants.
Sensation The skin is an important organ of sensation because the dermis is rich in sensory nerve endings. Even the most immature infant has the ability to sense pain, producing behavioural, physiological and hormonal responses that demonstrate this. This is particularly relevant to neonatal intensive care, in which painful procedures that pierce the skin are very common.
Sebaceous glands Sebaceous glands are exocrine glands associated with hair follicles and produce the oily secretion sebum. The sebaceous glands are particularly active in the last trimester of pregnancy -- sebum being a major constituent of vernix caseosa, the white grease that covers the skin towards the end of pregnancy. It is possible that this waterproof covering allows the stratum corneum to mature while immersed in amniotic fluid.When the infant starts to produce pulmonary surfactant, some f|nds its way into the amniotic fluid, causing the vernix to become detached from the skin surface. At maturity, therefore, the amniotic fluid is made turbid by vernix, but the skin is exposed.
REFERENCES 1. Hoath S B, Narendran V. Development of the epidermal barrier. NeoReviews 2001; 2: 269--279. 2. Harpin V A, Rutter N. Barrier properties of the newborn infant’s skin. J Pediatr 1983; 102: 419--425. 3. Cartlidge P. The epidermal barrier. Semin Neonatol 2000; 5: 273-280. 4. Rutter N. Clinical consequences of an immature epidermal barrier. Semin Neonatol 2000; 5: 281--287. 5. Hoath S B, Narendran V. Adhesives and emollients. Semin Neonatol 2000; 5: 289--296. 6. Nopper A J, Horii K A, Sookdeo-Drost S et al. Topical ointment therapy benefits premature infants. J Pediatr 1996; 128: 660--669. 7. Edwards W H, Conner J M, Soll R F. The effect of prophylactic ointment therapy on nosocomial sepsis rates and skin integrity in infants of birth weight 501--1000 grams. Pediatrics 2003 (in press). 8. Rutter N. The dermis. Semin Neonatol 2000; 5: 297--302.