1. Temperature Control in the Neonate Pearl S. Park, D.O. PGY-2 August 30, 2007

2. Introduction Hypothermia associated w/ increased morbidity/mortality in newborns of all birth weights/ages Hypothermia associated w/ increased morbidity/mortality in newborns of all birth weights/ages Now considered independent risk factor for mortality in preterm Now considered independent risk factor for mortality in preterm Western philosophy of conventional care – premature baby should be Western philosophy of conventional care – premature baby should be Placed under radiant warmer Placed under radiant warmer Uncovered for full visualization and to allow radiant heat to reach body Uncovered for full visualization and to allow radiant heat to reach body More attn now focused on thermal care immediately after birth and during resuscitation More attn now focused on thermal care immediately after birth and during resuscitation

3. Premature Susceptibility to Heat Loss High surface area to volume ratio High surface area to volume ratio Thin non-keratinized skin Thin non-keratinized skin Lack of insulating subQ fat Lack of insulating subQ fat Lack of thermogenic brown adipose tissue (BAT) Lack of thermogenic brown adipose tissue (BAT) Inability to shiver Inability to shiver Poor vasomotor response Poor vasomotor response

4. Thermoregulation Metabolic rate of fetus per tissue wt. higher than adult Metabolic rate of fetus per tissue wt. higher than adult Heat also transferred from mother to fetus via placenta/uterus Heat also transferred from mother to fetus via placenta/uterus Fetal temp consistently 0.3-0.5 deg C higher than mother’s (always in parallel) Fetal temp consistently 0.3-0.5 deg C higher than mother’s (always in parallel) Even when mother’s temp elevates (eg fever) Even when mother’s temp elevates (eg fever) Despite BAT in utero, fetus cannot produce extra heat Despite BAT in utero, fetus cannot produce extra heat Exposed to adenosine and prostaglandin E2  inhibitors of non-shivering thermogenesis (NST) Exposed to adenosine and prostaglandin E2  inhibitors of non-shivering thermogenesis (NST) Metabolic adaptation for physiologically hypoxic fetus since NST requires oxygenation Metabolic adaptation for physiologically hypoxic fetus since NST requires oxygenation Inhibition of NST allows accumulation of BAT Inhibition of NST allows accumulation of BAT

5. Thermoregulation Heat gain/loss controlled by hypothalamus and limbic system Heat gain/loss controlled by hypothalamus and limbic system Thermoregulatory system immature in newborns (esp premature newborn) Thermoregulatory system immature in newborns (esp premature newborn) In term infant, response to cold stress relies on oxidation of brown fat (NST) In term infant, response to cold stress relies on oxidation of brown fat (NST) Development begins 20th wk until shortly after birth (comprises 1% body wt at that time) Development begins 20th wk until shortly after birth (comprises 1% body wt at that time) High concentration stored TG’s High concentration stored TG’s Rich capillary network densely innervated by sympathetic nerve endings Rich capillary network densely innervated by sympathetic nerve endings Temperature sensors on posterior hypothalamus stimulate pituitary to produce thyroxine (T4) and adrenals to produce norepinephrine Temperature sensors on posterior hypothalamus stimulate pituitary to produce thyroxine (T4) and adrenals to produce norepinephrine Lipolysis stimulated  energy produced in form of heat in mitochondria instead of phosphate bonds by uncoupling protein-1 (aka thermogenin) Lipolysis stimulated  energy produced in form of heat in mitochondria instead of phosphate bonds by uncoupling protein-1 (aka thermogenin)

6. Risk Factors All neonates in 1st 8-12hrs of life All neonates in 1st 8-12hrs of life Prematurity Prematurity SGA SGA CNS problems CNS problems Prolonged resuscitation efforts Prolonged resuscitation efforts Sepsis Sepsis

7. Adverse Consequences of Hypothermia High O2 consumption  hypoxia, bradycardia High O2 consumption  hypoxia, bradycardia High glucose usage  hypoglycemia / decreased glycogen stores High glucose usage  hypoglycemia / decreased glycogen stores High energy expenditure  reduced growth rate, lethargy, hypotonia, poor suck/cry High energy expenditure  reduced growth rate, lethargy, hypotonia, poor suck/cry Low surfactant production  RDS Low surfactant production  RDS Vasoconstriction  poor perfusion  metabolic acidosis Vasoconstriction  poor perfusion  metabolic acidosis Delayed transition from fetal to newborn circulation Delayed transition from fetal to newborn circulation Thermal shock  DIC  death Thermal shock  DIC  death

8. Modes of Heat Loss Conduction - direct heat transfer from skin to object (eg mattress) Conduction - direct heat transfer from skin to object (eg mattress) Convection - heat loss through air flow Convection - heat loss through air flow Also depends on air temp Also depends on air temp Radiation - direct transfer by electromagnetic radiation in infrared spectrum Radiation - direct transfer by electromagnetic radiation in infrared spectrum Heat gained by radiation from external radiant energy source Heat gained by radiation from external radiant energy source Heat lost by radiation to cooler walls of incubator Heat lost by radiation to cooler walls of incubator Evaporation - heat loss when water evaporates from skin and respiratory tract Evaporation - heat loss when water evaporates from skin and respiratory tract Depends on maximum relative humidity of surroundings  less humidity = more evaporation Depends on maximum relative humidity of surroundings  less humidity = more evaporation

9. Heat Loss at Birth Hammarlund et al, 1980 Hammarlund et al, 1980 Evaporative H20 loss Evaporative H20 loss 81-125 gm/m 2 /h when unwiped in ambient temp ~25.8deg C and 42% humidity 81-125 gm/m 2 /h when unwiped in ambient temp ~25.8deg C and 42% humidity Heat loss through Heat loss through Evaporation: 60-80 W/m 2 Evaporation: 60-80 W/m 2 Radiation: 50 W/m 2 Radiation: 50 W/m 2 Convection: 25 W/m 2 Convection: 25 W/m 2 Conduction: negligible Conduction: negligible Total heat loss = 135-155 W/m 2 Total heat loss = 135-155 W/m 2 All babies that were >3250g - body temp decreased 0.9deg C in 15min All babies that were >3250g - body temp decreased 0.9deg C in 15min

10. Heat Loss at Birth Hammarlund et al, 1979 Hammarlund et al, 1979 Naked infants <28wks need ambient temp ~40deg C to maintain nl temp in 20% humidity Naked infants <28wks need ambient temp ~40deg C to maintain nl temp in 20% humidity Increasing humidity to 60% halved losses Increasing humidity to 60% halved losses

11. Attempt to Overcome Losses Radiant heaters insufficient to warm preterm baby Radiant heaters insufficient to warm preterm baby Esp during resuscitation Esp during resuscitation 750g baby w/ surface area of ~ 0.06m 2 requires at least 9.3W to compensate for losses at birth 750g baby w/ surface area of ~ 0.06m 2 requires at least 9.3W to compensate for losses at birth At mattress lvl, max of 9W absorbed by baby if radiant heat absorbed by, at least, 50% of mattress At mattress lvl, max of 9W absorbed by baby if radiant heat absorbed by, at least, 50% of mattress

12. Thermoneutral Environment Temp and environmental conditions at which metabolic rate and O2 consumption are lowest Temp and environmental conditions at which metabolic rate and O2 consumption are lowest Silverman et al Silverman et al Maintaining constant abdominal skin temp b/w 36.2-36.5 deg C optimal Maintaining constant abdominal skin temp b/w 36.2-36.5 deg C optimal WHO classification of hypothermia WHO classification of hypothermia Mild: 36-36.4deg C Mild: 36-36.4deg C Mod: 32-35.9deg C Mod: 32-35.9deg C Severe: <32deg C Severe: <32deg C

13. Kangaroo Mother Care (KMC) Introduced in 1983 by Rey and Martinez in Colombia Introduced in 1983 by Rey and Martinez in Colombia LBW infants nursed naked (wearing only cloth diaper) between mothers’ breasts LBW infants nursed naked (wearing only cloth diaper) between mothers’ breasts Data from other countries show infants nursed by KMC have Data from other countries show infants nursed by KMC have Fewer apneic episodes Fewer apneic episodes Similar or better blood oxygenation Similar or better blood oxygenation Lower infxn rtes Lower infxn rtes Are alert longer and cry less Are alert longer and cry less Are breastfed longer and have better bonding Are breastfed longer and have better bonding Improved survival in low-resource settings Improved survival in low-resource settings

14. KMC Bergman et al, 2004 Bergman et al, 2004 Randomized controlled trial comparing KMC to pre-warmed servo-controlled closed incubator after birth Randomized controlled trial comparing KMC to pre-warmed servo-controlled closed incubator after birth 20 infants b/w 1200-2199g using KMC vs 14 controls 20 infants b/w 1200-2199g using KMC vs 14 controls Excluded if C-sec, mother too ill to look after self/infant, known HIV, BW outside 1200-2199g, 5min Apgar <6, congenital malformations Excluded if C-sec, mother too ill to look after self/infant, known HIV, BW outside 1200-2199g, 5min Apgar <6, congenital malformations 1/20 subjects vs 8/14 controls had initial temps < 35.5deg C (P = 0.006) 1/20 subjects vs 8/14 controls had initial temps < 35.5deg C (P = 0.006) 1/20 subjects vs 3/14 controls had bl glucoses < 2.6 mmol/L (though 40mg/dL = 2.2mmol/L) 1/20 subjects vs 3/14 controls had bl glucoses < 2.6 mmol/L (though 40mg/dL = 2.2mmol/L) Stability of cardio-respiratory system in preterm infants (SCRIP) score was 2.88 points higher w/in 1st 6hrs in KMC group (95% CI 0.3-5.46) Stability of cardio-respiratory system in preterm infants (SCRIP) score was 2.88 points higher w/in 1st 6hrs in KMC group (95% CI 0.3-5.46)

15. SCRIP Score SCRIP210 HRRegular Decel to 80-100 Rte 200 bpm RRRegular Apnea <10s or periodic breathing Apnea >10s or tachypnea >80 O 2 sat >89%80-89%<80%

16. Barriers to Heat Loss Cochrane database review Cochrane database review 4 studies compared barriers to heat loss vs. no barriers 4 studies compared barriers to heat loss vs. no barriers 2 comparison subgroups 2 comparison subgroups Plastic wrap/bag vs routine care Plastic wrap/bag vs routine care Stockinet cap vs routine care Stockinet cap vs routine care Plastic wrap/bag vs routine care Plastic wrap/bag vs routine care 3 studies involving 200 infants all <36wks 3 studies involving 200 infants all <36wks All placed under radiant warmer, wrapped to shoulders while still wet, heads dried and resuscitated according to guidelines All placed under radiant warmer, wrapped to shoulders while still wet, heads dried and resuscitated according to guidelines GA <28wks: wrap group had temps 0.76deg C higher than controls (95% CI 0.49-1.03) GA <28wks: wrap group had temps 0.76deg C higher than controls (95% CI 0.49-1.03) GA 28-31wks: no statistical difference GA 28-31wks: no statistical difference

17. Barriers to Heat Loss Plastic wrap/bag vs routine care (cont) Plastic wrap/bag vs routine care (cont) 1hr after admission for GA <28wks, no statistical difference (though direction was in favor of intervention) 1hr after admission for GA <28wks, no statistical difference (though direction was in favor of intervention) Plastic wrap significantly reduced risk of hypothermia (core temp <36.5deg C) on admission to NICU Plastic wrap significantly reduced risk of hypothermia (core temp <36.5deg C) on admission to NICU RR 0.63 (95% CI 0.42-0.93) RR 0.63 (95% CI 0.42-0.93) NNT found to be 4 (95% CI 3-17) - so 4 infants would need to be wrapped in plastic to prevent 1 from becoming hypothermic NNT found to be 4 (95% CI 3-17) - so 4 infants would need to be wrapped in plastic to prevent 1 from becoming hypothermic No significant differences found in duration of O 2 therapy, major brain injury, duration of hospitalization, or death No significant differences found in duration of O 2 therapy, major brain injury, duration of hospitalization, or death

19. Barriers to Heat Loss Stockinet cap vs routine care Stockinet cap vs routine care 1 study involving 40 AGA infants w/ GA’s 32-36wks 1 study involving 40 AGA infants w/ GA’s 32-36wks Exclusion critera: 5min Apgar 37.8deg C during labor Exclusion critera: 5min Apgar 37.8deg C during labor Cap group had caps placed ASAP after drying under radiant warmer and infants <2500g were transported in incubator Cap group had caps placed ASAP after drying under radiant warmer and infants <2500g were transported in incubator BW <2000g: Cap group had core temps 0.7deg C higher than control (95% CI -0.01-1.41) - borderline statistical difference BW <2000g: Cap group had core temps 0.7deg C higher than control (95% CI -0.01-1.41) - borderline statistical difference BW >/= 2000g: no sig dif BW >/= 2000g: no sig dif No sig dif in preventing hypothermia No sig dif in preventing hypothermia

20. External Heat Sources Cochrane database review Cochrane database review 2 studies compared external heat sources to routine care 2 studies compared external heat sources to routine care 2 comparison subgroups 2 comparison subgroups Skin-to-skin vs routine care (already mentioned) Skin-to-skin vs routine care (already mentioned) Transwarmer mattress vs routine care Transwarmer mattress vs routine care

21. External Heat Sources Brennan et al, 1996 Brennan et al, 1996 24 infants w/ BW </= 1500g 24 infants w/ BW </= 1500g Transport Mattress (TM) - made of sodium acetate - activated to ~40deg C when delivery imminent Transport Mattress (TM) - made of sodium acetate - activated to ~40deg C when delivery imminent Infant placed upon blankets covering mattress, dried, then placed on TM directly Infant placed upon blankets covering mattress, dried, then placed on TM directly Control group = same intervention but w/o TM Control group = same intervention but w/o TM Both groups resuscitated according to guidelines then transferred to NICU on radiant warmer surface Both groups resuscitated according to guidelines then transferred to NICU on radiant warmer surface

22. External Heat Sources Brennan et al, cont Brennan et al, cont Increase of 1.6deg C in TM group (95% CI 0.83- 2.37) Increase of 1.6deg C in TM group (95% CI 0.83- 2.37) Evidence suggests that TM significantly reduces risk of hypothermia w/ RR 0.3 (95% CI 0.11- 0.83) Evidence suggests that TM significantly reduces risk of hypothermia w/ RR 0.3 (95% CI 0.11- 0.83) NNT = 2 (95% CI 1-4) NNT = 2 (95% CI 1-4) No adverse occurrences reported in this study, though other studies have had infants sustain 3rd deg burns No adverse occurrences reported in this study, though other studies have had infants sustain 3rd deg burns

23. In Conclusion Plastic barriers effective in reducing heat loss in newborns <28wks Plastic barriers effective in reducing heat loss in newborns <28wks No evidence yet to suggest plastic barriers decrease duration of O 2 therapy, hospitalization, or incidence of major brain injury/death No evidence yet to suggest plastic barriers decrease duration of O 2 therapy, hospitalization, or incidence of major brain injury/death Stockinet caps effective in reducing hypothermia in newborns /= 2000g Stockinet caps effective in reducing hypothermia in newborns /= 2000g KMC shown to be effective in stable newborns down to 1200g in reducing risk of hypothermia KMC shown to be effective in stable newborns down to 1200g in reducing risk of hypothermia TM decreases incidence of hypothermia </= 1500g TM decreases incidence of hypothermia </= 1500g In the end, the smaller the baby, the more likely any intervention will be of benefit In the end, the smaller the baby, the more likely any intervention will be of benefit

24. Areas of Further Study Need more studies w/ larger population bases Need more studies w/ larger population bases Short- and long-term outcomes need to be studied further (especially w/ neurdevelopmental F/U) Short- and long-term outcomes need to be studied further (especially w/ neurdevelopmental F/U) Secondary outcomes that need further study: Secondary outcomes that need further study: HypoglycemiaRDS Intubation/ve- ntilation Length of stay Metabolic acidosis ARFGrowth Adverse events

25. Neonatal Energy Triangle

26. References Laroia, N. “Double wall versus single wall incubator for reducing heat loss in very low birth weight infants in incubators.” Cochrane Database of Systematic Reviews. Vol (3) 2007. Laroia, N. “Double wall versus single wall incubator for reducing heat loss in very low birth weight infants in incubators.” Cochrane Database of Systematic Reviews. Vol (3) 2007. Fienady, V. “Radiant warmers versus incubators for regulating body temperature in newborn infants” Cochrane Database of Systematic Reviews. Vol (3) 2007. Fienady, V. “Radiant warmers versus incubators for regulating body temperature in newborn infants” Cochrane Database of Systematic Reviews. Vol (3) 2007. Asakura, H. “Fetal and Neonatal Thermoregulation.” Journal of Nippon Medical School. Vol. 71 (2004), No. 6. Asakura, H. “Fetal and Neonatal Thermoregulation.” Journal of Nippon Medical School. Vol. 71 (2004), No. 6. Ibe, O.E. “A comparison of kangaroo mother care and conventional incubator care for thermal regulation of infants <200 g in Nigeria using continuous ambulatory temperature monitoring.” Annals of Tropical Paediatrics (2004) 24, 245-251. Ibe, O.E. “A comparison of kangaroo mother care and conventional incubator care for thermal regulation of infants <200 g in Nigeria using continuous ambulatory temperature monitoring.” Annals of Tropical Paediatrics (2004) 24, 245-251. Bergman, N.J. “Randomized controlled trial of skin-to-skin contract from birth versus conventional incubator for physiological stabilization in 1200- to 2199-gram newborns.” Acta Paediatrica (2004) 93: 779-785. Bergman, N.J. “Randomized controlled trial of skin-to-skin contract from birth versus conventional incubator for physiological stabilization in 1200- to 2199-gram newborns.” Acta Paediatrica (2004) 93: 779-785. McCall, E.M. “Interventions to prevent hypothermia at birth in preterm and/or low birthweight babies.” Cochrane Database of Systematic Reviews. Vol (3), 2007. McCall, E.M. “Interventions to prevent hypothermia at birth in preterm and/or low birthweight babies.” Cochrane Database of Systematic Reviews. Vol (3), 2007. Watkinson, M.A. “Temperature Control of Premature Infants in the Delivery Room.” Clin Perinaol 33 (2006) 43-53. Watkinson, M.A. “Temperature Control of Premature Infants in the Delivery Room.” Clin Perinaol 33 (2006) 43-53. “Knobel, R.B. “Heat Loss Prevention for Preterm Infants in the Delivery Room.” J Perinaol 25 (2005) 304-308. “Knobel, R.B. “Heat Loss Prevention for Preterm Infants in the Delivery Room.” J Perinaol 25 (2005) 304-308. The neonatal energy triangle Part 2: Thermoregulatory and respiratory adaptation.” Paediatric Nursing. Sept. Vol 18 no 7. The neonatal energy triangle Part 2: Thermoregulatory and respiratory adaptation.” Paediatric Nursing. Sept. Vol 18 no 7.

27. Thank You!!