(5) GUNNAR SEDIN 45-60 Upsala J Med Sci 111 (1): 45–60, 2006 Water and Heat – The Priority for the Newborn Infant Gunnar Sedin, Johan Ågren Department of Women’s and Children’s Health, Uppsala University Children’s, Hospital, Perinatal Research Laboratory, 751 85 Uppsala, SWEDEN ABSTRACT Free full-text copy of this article can be found at the web page of Upsala J Med Sci:http://www.ujms.se. Maintaining fluid and heat balance is of vital importance to the newborn infant. At birth, the infant is exposed to a cold and dry environment, and preterm neonates in particular, are then at risk of dehydration and hypothermia. These conditions may have serious consequences and significantly influence mortality and morbidity. Preterm neonates have a high rate of water and heat loss mainly as a consequence of their immature skin. The care environment influences the magnitude of water and heat exchange and needs to be individually tailored on the basis of the infant’s clinical sta- tus, maturity at birth and postnatal age. This paper reviews data obtained from series of studies on neonatal water and heat exchange using non-invasive measurements of insensible water loss and calculations of different modes of heat exchange. These stud- ies have influenced the way in which newborn infants are being nursed today. INTRODUCTION Long before the emergence of the field of perinatal medicine, humans kept their newborns warm by nursing them close to their own skin covered with clothing or blankets, just as animals in a litter huddle together to keep warm. At the time of Nils Rosén von Rosenstein (1706-1773), promotion of breastfeeding was in focus, and this included keeping both the breasts and the infant warm (1, 2). From the time of Rosén, the infant mortality decreased gradually in Sweden (3). More than 100 years later (1880), the first known couveuse or incubator to keep an infant warm was con- structed by Tarnier and used by his co-workers Pierre Budin and Alfred Auvard at The Paris Maternity Hospital. This couveuse was heated by letting a stream of air 45 Received 17 October 2005 Accepted 28 October 2005 pass over a number of containers of warm water and pass through a wet sponge, which might have served as a humidifier, but Pierre Budin never mentioned any- thing about humidification in his original text (4). During a long period of great improvements in health care in the 1900s (3), with a gradual decline in infant mortality, also in infants born preterm, new challenges concerning neonatal fluid balance and treatment of neonatal lung disorders appeared. Increased knowledge of newly recognised aspects of lung physiology (5, 6) formed the basis of improvements in assisted ventilation of the newborn infant, resulting in fewer severe complications. During 1971, the introduction of intermit- tent mandatory ventilation (7), continuous positive airway pressure (8) and high fre- quency positive pressure ventilation (9) contributed to better respiratory support for both the immature and mature newborn infant. To investigate differences in water exchange between the infant and the environ- ment, Hey and Katz (10) studied insensible water loss (IWL) both in fullterm infants and infants with a low birth weight, but their technique did not allow studies of the most preterm infants. In another investigation of insensible weight loss, Fanaroff et al (11) showed that this loss was very high in infants with a birth weight less than 1250 gram. There was no explanation, however, for the marked weight loss in the low birth weight infants. Studies published in 1956 by Bent Friis-Hansen (12) on body water compart- ments during growth showed that the newborn term infant has a water content of 77%. The relative total body water at birth is even higher in preterm infants than in term infants, being 82% at 32 weeks of gestation, 84% at 28 weeks and 86% at 24 weeks. This fact, together with the observation of the shiny, wet skin of a very preterm infant nursed in an incubator, gave us the idea to study the transepidermal water loss (TEWL) in infants of different degrees of maturity (13-15). A series of studies was undertaken to delineate the relation between TEWL and gestational age at birth, postnatal age and environmental conditions, and to clarify the importance of this water loss for neonatal water and heat balance. To achieve more accurate estimates of water and heat exchange, studies of respiratory water loss were also included in the project. These studies were made possible by the development of a novel technique. With the gradient method (13-15), transepidermal water loss (g/m2/h) could then be esti- mated by measuring the evaporation rate (ER g/m2/h) from the chest, an interscapu- lar skin area and a buttock. TEWL AT BIRTH AND AT DIFFERENT POSTNATAL AGES There is an exponential relationship between gestational age and TEWL at the first day after birth. Infants born at 25 weeks of gestation have TEWL values up to 15 times higher than those in term infants (16) (Fig. 1). The relationship between TEWL and gestational age at different postnatal ages during the first four weeks 46 after birth can be described with exponential equations (17, 18) (Fig. 2). In the most preterm infants TEWL gradually decreases and the difference in TEWL between the most preterm and the term appropriate for gestational age (AGA) infant dimin- 47 Figure 1. Transepidermal water loss (TEWL) in relation to gestational age (G.A.). AGA = appropriate for gestational age. w = completed weeks of gestation. (From ref 16) ishes with age, but four weeks after birth TEWL is still twice as high in the former as in the latter (18) (Fig. 2). Among small for gestational age infants, TEWL is again highest in the most preterm infants, but their water loss from the skin is lower than that in AGA infants (19). Evaporative water loss in relation to humidity There is an inverse linear relationship between evaporation rate (ER) from the skin surface and ambient humidity in both term and preterm infants at different postnatal ages. The evaporation rate is much higher at a low than at a high relative humidity (15, 16, 19) (Fig. 3). 48 Figure 2. Transepidermal water loss in relation to gestational age at birth at different postnatal ages in appropriate-for-gestational-age infants. (From ref 18) 49 Insensible water loss from the skin (IWL S ) IWL s in g/kg/day in infants can be calculated from TEWL, body surface area and weight (Fig. 4). Since TEWL is strongly related to postnatal age and since the ratio of body surface area to body weight is higher in the most preterm infants, it is obvi- ous that IWL s is considerably higher in preterm than in term infants. Accordingly, the environmental conditions (i.e. ambient humidity) have an even greater impact on the IWL S in the tiniest infants, particularly during the first week after birth (19). Figure 3. The relation between evaporation rate and ambient relative humidity in preterm newborn infants of different gestational age groups. (From ref 16) TEWL during activity and phototherapy There is a pronounced increase in TEWL when infants born at term increase their motor activity, but no sweating is observed. If infants are nursed in a warm environ- ment, the body temperature rises and TEWL increases markedly when they begin to sweat (20). In infants in thermal balance there is no indication that phototherapy increases the transepidermal water loss (21), respiratory loss or oxygen consump- tion (22). Previous observations of higher losses during phototherapy (23) might have been due to heat stress and not to the radiation from the phototherapy equip- ment (21, 22). TEWL and radiant heaters When very preterm infants are nursed first in an incubator at RH amb of 50%, the evaporation rate from the skin is significantly lower than when the same infants are nursed at a lower humidity under a radiant heater. Still, the evaporation rate is lower under the radiant heater than what can be expected from the environmental vapour pressure. As can be seen in Figure 5, the measured water loss is lower than the expected water loss at the vapour pressure in the environment (24). Thus there is no indication that radiant heat increases water loss from the skin under conditions with a low air velocity close to the infant. However, losses of water and heat from the 50 Figure 4. Insensible water loss from the skin (IWLs) in relation to postnatal age in infants born at a gestational age of 25-27 weeks. Data are given for three different ambient humidities. (From ref 28) skin surface can be increased if the normal gradient close to the skin surface is dis- turbed by movements of air in the nursery created by air condition systems and staff movements, for example. RESPIRATORY WATER LOSS A flow-through system for measurement of respiratory water loss (RWL), providing data on oxygen consumption and carbon dioxide production, was developed. The sys- tem uses a mass spectrometer, specially equipped with a water channel for analyses of gas concentrations (25). The studies showed that RWL in newborn term infants at rest is 4.9 mg/kg/min, i.e. about 50% of the total insensible water loss at an ambient air temperature of 32.5°C and an ambient humidity of 50% (26). RWL depends on the temperature and humidity of the inspired air and on the respiratory rate, tidal volume, dead space ventilation and the ability of the nose to dehumidify and cool expired air (25, 26). It was also found that there was an inverse relationship between RWL and ambient humidity, with higher losses at a low than at a high humidity (26) and that the insensible water loss from the respiratory tract (IWL R ) and the IWL S were of the same magnitude at an ambient humidity of 20 %, whereas IWL S was much lower than IWL R at a high ambient humidity. RWL increases with increasing activity in term infants. At rest both IWL S and IWLR 51 Figure 5. The calculated (open symbols) and measured (filled symbols) values for ER (g/m2/h) during care under a radiant heater, together with the corresponding regression lines for ER on PH 2 O at the air temperatures of the incubator and the radiant heater, in three infants (From ref 24) were 6 g/kg/day and IWLs increased very little, whereas IWL R could theoretically increase to 16 g/kg/day if the infant was able to have the highest level of activity for 24 hours. VO2 and VCO2 also increased during activity (27) (Fig. 6). WATER SUPPLY AND WATER BALANCE Nutrition and/or water supplementation should be provided soon after birth. In term infants, water balance can be adjusted by increasing or decreasing the daily pre- scribed supply. In preterm infants, especially in those who are extremely preterm, who have very high insensible water losses, sometimes leading to hyperosmolality, high levels of water loss have to be avoided. The supply of fluid depends on the insensible water loss and can be kept low in a humid environment. The local guide- lines for neonatal water balance are then: Day 1: 65 ml/kg Day 2: 75 ml/kg Day 3: 90 ml/kg Days 4-7: Increase gradually up to 150 ml/kg. The volume of all fluid given or collected should be noted. The basic prescription of fluid volumes may be changed if the serum osmolality 52 Figure 6. Respiratory water loss (RWL) at different levels of activity. Activity scale: 0 = asleep, no motor activity. 1 = asleep, minor motor activity. 2 = awake, quiet, no motor actitivy. 3 = awake, quiet, active. 4 = awake, crying, active. 5 = awake, furiously crying. (From ref 27) exceeds 300 mosm/l and when weight loss exceeds 10-15%. Even in very preterm infants nursed at a high ambient humidity, there is usually an increase in serum osmolality during the first 3 days after birth, accompanied by an increase in sodium concentration (28) (Fig. 7) and in such cases the body weight is carefully monitored so that it does not drop more than 15%. 53 Figure 7. (a) Mean serum osmolality (S-osm ±SD) and (b) mean serum sodium concentration (S-Na ±SD) in 11 infants born at a gestional age of 24 weeks, in relation to postnatal age. (From ref 28) WATER SUPPLY AND WATER BALANCE In preterm infants born at 24 and 25 weeks of gestation, TEWL during the first week after birth was slightly higher than that found previously in the group of infants born at 25-27 weeks (29). Importantly, in infants born at 24-25 weeks and nursed at a high ambient RH, TEWL at a postnatal age of 4 weeks was twice as high as had previously been reported for slightly more mature infants. These findings led to a speculation as to whether maintaining infants at a high humidity for a long time might influence the development of their skin barrier. Recently, we studied a cohort of very preterm infants born at a mean gestational age of 25 (range 23-27) weeks and nursed at a high humidi- ty (85%) during the first week after birth. At a postnatal age of one week the infants were randomized to continued care at either 75% or 50% RH for the following three weeks, but studied at the same humidity. Preliminary results from this study indicate that infants nursed at the lower level of humidity during the second, third, and fourth postnatal week have a lower TEWL than those exposed to the higher humidity. The results imply that the environmental humidity can significantly alter the process of postnatal skin barrier formation (30). These data need further assessment before publi- cation but may lead to changes in the way preterm infants are nursed at our institution. Mechanisms for transepidermal water transport The high loss of water from the skin surface reflects one aspect of immature organ function in preterm infants. The epidermis is not fully developed in these infants and its outermost layer, the stratum corneum, is thin and lacks the structure and composition needed to provide its barrier function properties. In addition, recent studies on perinatal rat skin have shown that aquaporins (AQP), a group of integral membrane proteins with high water permeability, are abundantly expressed in the immature skin (31, 32). In this experimental model, higher expression of AQP3 in the basal parts of the epider- mis was observed in immature than in more mature rat pups, and TEWL was much higher in the preterm pups. If these results are valid for the human preterm neonate, further studies on epidermal aquaporins might be of importance for human perinatal physiology, and interventions aimed at AQP inhibition might prove of clinical value. Heat and water balance in extremely preterm infants early after birth When extremely immature newborn infants are exposed to a cold, dry environment after birth, they are at risk of having a rapid drop in body temperature unless measures are taken to prevent heat loss (33, 34). Furthermore, the extremely preterm infants have only a limited capacity to produce heat. It is therefore of great importance to create a care environment that favours thermal balance in this situation (35). At birth the exchange of heat depends very much on the maturity of the infant, the environmental temperature and relative humidity and the postnatal age, as displayed in figures 8, 9, and 10. Different methods to maintain heat have been proposed such as the use of semipermeable membranes to lower the water and heat loss in infants nursed under a radiant heater (36-38). In a short time early after birth a semipermeable membrane, covering the infant, 54 55 Figure 8. Ambient temperature (Tamb) in relation to gestational age at ambient relative humidity of 20%, 40%, and 60%. (From ref 33, 34) Figure 9. Heat exchange through evaporation, radiation, and convection in relation to gestational age at relative ambient humidities of 20%, 40%, and 60%. (From ref 35) 56 Figure 10. Heat exchange between the infant and the environment in relation to postnatal age at relati- ve ambient humidity (RH) of 20%, 40%, and 60% in infants born at 25 to 27 weeks of gestation. (From ref 34, 35) can create a humid environment close to the infant’s skin and may lower the evapo- rative water and heat exchange during this period. An evaporative water loss from the skin will take place and contribute to a high humidity in the air between a mem- brane and the skin, which can lower evaporative heat loss temporarily (16). This type of care has not been evaluated concerning the fractional contribution of different modes of heat exchange. If the membrane is in direct contact with the skin, a compo- nent of heat conduction between the membrane and the skin may take place. All areas of the infant’s skin that are not covered by a membrane will be exposed to room air temperature, air movements, evaporation and the colder walls of the neona- tal intensive care unit. This will substantially alter the conditions for the heat exchange. Losses through convection can be considerably increased by air move- ments at low temperature in the vicinity of the very preterm infant (16, 34). These circumstances have further been discussed in a recent publication (39). Very preterm infants who are held skin-to-skin by the mother early after birth and are covered with a blanket, can often maintain a normal body temperature in the first week after life if the gestational age at birth is 28-30 weeks (40). It has also been shown that very preterm infants nursed on a heated water-filled mattress and covered with a blanket can maintain their body heat (41). Use of a cap on the infant’s head was proposed many years ago by Stothers (42) and may still be a way to save heat for the very preterm newborn infant. ACKNOWLEDGEMENTS These studies were supported by grants from the Swedish Research Council, HRH the Crown Princess Lovisa’s Fund for Scientific Research and the Åke Wiberg Foundation. REFERENCES 1. Rosén von Rosenstein N (1764) Underrättelser om barnsjukdomar och deras botemedel. Edition: The Swedish Academy of Science, Stockholm. 2. Rosén von Rosenstein N (1776) The diseases of children and their remedies. Edition: Cadell T, in the Strand, London. 3. The Swedish Board of Health and Welfare. National Statistics. Infant mortality rate 1751- 2004. 4. Budin P (1900) Edition: Le Nourrison, Paris: Dion. 5. Comroe JH, Forster RE, Dobois AB, Briscoe WA, Carlsen E (1955). The lung. Clinical physiolo- gy and pulmonary function tests. Edition: Year Book Medical Publishers. Chicago. 6. Peters RM (1969). The mechanical basis of respiration. An approach to respiratory pathophysiol- ogy. Edition: J & A Churchill Ltd, London. 7. Kirby RR, Robison EJ, Schulz J, DeLemos R (1971) A new pediatric volume ventilator. Anesth Analg 50:533-537. 8. Gregory GA, Kitterman JA, Phibbs RH, Tooley WH, Hamilton WK (1971) Treatment of IRDS with continuous positive airway pressure. New Engl J Med 284:1333-1340. 9. Jonzon A, Öberg PÅ, Sedin G, Sjöstrand U (1971) High-frequency positive-pressure ventilation by endotracheal insufflation. Acta Anaest Scand: Suppl 43. 10. Hey EN, Katz G (1969) Evaporative water loss in the newborn baby. J Physiol 200:605-619. 57 11. Fanaroff AA, Wald M, Gruber HS, Klaus MH (1972) Insensible water loss in low birth weight infants. Pediatrics 50: 236-245. 12. Friis-Hansen B (1956) Changes in body water compartments during growth. Acta Paed Scand: Suppl 110. 13. Nilsson G, Öberg PÅ, Sedin G (1975) Capteur servant à évoluer l'évaporation cutanée. A trans- ducer for measurement of evaporation from the skin. Proc. colloque international sur les capteur bio-medicaux. International conference on bio-medical transducers, 71-77 (Abstract). 14. Nilsson G (1977) Measurement of the water exchange through skin. Med Biol Eng Comput 15:209-218. 15. Hammarlund K, Nilsson G, Öberg PÅ, Sedin G (1977) Transepidermal water loss in newborn infants. I. Relation to ambient humidity and site of measurement and estimation of total transepi- dermal water loss. Acta Paediatr Scand 66:553-562. 16. Hammarlund K, Sedin G (1979) Transepidermal water loss in newborn infants. III. Relation to gestational age. Acta Paediatr Scand 68:795-801. 17. Hammarlund K, Sedin G Strömberg B (1982) Transepidermal water loss in newborn infants. VII. Relation to post-natal age in very pre-term and full-term appropriate for gestational age infants. Acta Paediatr Scand 71:369-374. 18. Hammarlund K, Sedin G, Strömberg B (1983) Transepidermal water loss in newborn infants. VIII. Relation to gestational age and post-natal age in appropriate and small for gestational age infants. Acta Paediatr Scand. 72:721-729. 19. Sedin G, Hammarlund K, Nilsson GE, Strömberg B, Öberg PÅ (1985) Measurements of transepidermal water loss in newborn infants. Clin Perinatol 12:79-99. 20. Hammarlund K, Nilsson G, Öberg PÅ, Sedin G (1979) Transepidermal water loss in newborn infants. II. Relation to activity and body temperature. Acta Paediatr Scand 68: 371-376. 21. Kjartansson S, Hammarlund K, Sedin G (1992) Insensible water loss from the skin during pho- totherapy in term and preterm infants. Acta Paediatr 81:764-768. 22. Kjartansson S, Hammarlund K, Riesenfeld T, Sedin G (1992) Respiratory water loss and oxygen consumption in newborn infants during phototherapy. Acta Paediatr 81:769-773. 23. Oh W, Karecki H (1972) Phototherapy and insensible water loss in the newborn infant. Am J Dis Child 124:230-232. 24. Kjartansson S, Arsan S, Hammarlund K, Sjörs G, Sedin G (1995) Water loss from the skin of term and preterm infants nursed under a radiant heater. Pediatr Res 37:233-238. 25. Hammarlund K, Riesenfeld T, Sedin G (1986) Measurement of respiratory water loss in newborn lambs. Acta Physiol Scand 127:61-65. 26. Riesenfeld T, Hammarlund K, Sedin G (1987) Respiratory water loss in fullterm infants on their first day after birth. Acta Paediatr Scand 76:647-653. 27. Riesenfeld T, Hammarlund K, Sedin G (1987) Respiratory water loss in relation to activity in fullterm infants on their first day after birth. Acta Pediatr Scand 76:889-893. 28. Sedin G (1996) Fluid management in the extremely preterm infant. In: Hansen TN, McIntosh N (eds), Current Topics In Neonatology, W B Saunders Company, London, pp 50-66. 29. Ågren J, Sjörs G, Sedin G (1998) Transepidermal water loss in infants born at 24 and 25 weeks of gestation. Acta Paediatr 87:1185-1190. 30. Ågren J, Sjörs G and Sedin G (2005) Ambient humidity influences skin maturation in extremely preterm infants. Pediatr Res 57:5 (Abstract). 31. Ågren J, Zelenin S, Håkansson M, Eklöf A-C, Aperia A, Nejsum L, Nielsen S,Sedin G (2003) Transepidermal water loss in developing rats: role of aquaporins in the immature skin. Pediatr Res 53:558-565. 32. Ågren J (2003) Water transport through perinatal skin. Barrier function and aquaporin water channels. Acta Universitatis Upsaliensis. Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1249. 48 pp. Uppsala, Sweden. 33. Hammarlund K, Sedin G (1982) Transepidermal water loss in newborn infants. VI. Heat exchange with the environment in relation to gestational age. Acta Paediatr Scand 71:191-196. 34. Sedin G (2004) Physics and Physiology of Human Neonatal Incubation. In: Polin R, Fox W (eds), Fetal and Neonatal Physiology. W B Saunders Company, Philadelphia, pp 570-582. 35. Hammarlund K, Strömberg B, Sedin G (1986) Heat loss from the skin of preterm and fullterm newborn infants during the first weeks after birth. Biol Neonat 50:1-10. 58 36. Bell EF, Weinstein MR, Oh W (1980) Heat balance in premature infants: comparative effects of convectively heated incubator and radiant warmer, with and without plastic heat shield. J Pediatr 96:460-465. 37. Baumgart S, Engle WD, Fox WW, Polin RA (1981) Effect of heat shielding on convective and evaporative heat losses and on radiant heat transfer in the premature infant. J Pediatr 99:948-956. 38. Baumgart S (1984) Reduction of oxygen consumption, insensible water loss, and radiant heat demand with use of a plastic blanket for low-birth-weight infants under radiant warmers. Pedi- atrics 74:1022-1028. 39. Sedin G (2004) To Avoid Heat Loss in Very Preterm Infants. Editorial on 2004308 Heat loss Prevention (HeLP) in the delivery room: A randomized controlled trial of polyethylene occlusive skin wrapping in very preterm infants. J Pediatr 145:720-722. 40. Bauer K, Pyper A, Sperling P, Uhrig C, Versmold H (1998) Effects of gestational and postnatal age on body temperature, oxygen consumption, and activity during early skin-to-skin contact between preterm infants of 25-30-week gestation and their mothers. Pediatr Res 44:247-251. 41. Sarman I, Bolin D, Holmer I, Tunell R (1992) Assessment of thermal conditions in neonatal care: use of a manikin of premature baby size. Am J Perinat 9:239-246. 42. Stothers JK (1981) Head insulation and heat loss in the newborn. Arch Dis Child 56:530-534. Corresponding author: Gunnar Sedin Department of Women’s and Children’s Health, Uppsala University Children’s Hospital, Perinatal Research Laboratory SE-751 85 Uppsala, Sweden Phone: 46-18-6115886, Fax +46-18-554079 gunnar.sedin@kbh.uu.se 59 60