Termorregulacion Expo

Journal of Perinatology (2013) 33, 264–267 & 2013 Nature America, Inc. All rights reserved 0743-8346/13 www.nature.com/jp

ORIGINAL ARTICLE

Effect of delivery room temperature on the admission temperature of premature infants: a randomized controlled trial Y-S Jia1,2, Z-L Lin1, H Lv2, Y-M Li2, R Green3 and J Lin1,3 OBJECTIVE: To determine if increasing delivery room temperature to that recommended by the World Health Organization results in increased admission temperatures of preterm infants. STUDY DESIGN: Admission rectal temperatures of newborns p32 weeks gestation delivered in rooms with temperature set at 24 to 26 1C were compared with those of similar newborns delivered in rooms with temperature set at 20 to 23 1C. RESULT: Premature newborns delivered in rooms with mean temperature 25.1±0.6 1C (n ¼ 43), compared with those delivered in rooms with mean temperature 22.5±0.6 1C (n ¼ 48), had a lower incidence (34.9% vs 68.8%, Po0.01) of admission rectal temperature o36 1C and higher admission rectal temperatures (36.0±0.9 1C vs 35.5±0.8 1C, Po0.01). This difference persisted after adjustment for birth weight and 5 min Apgar score. CONCLUSION: Increasing delivery room temperatures to that recommended by the World Health Organization decreases cold stress in premature newborns. Journal of Perinatology (2013) 33, 264–267; doi:10.1038/jp.2012.100; published online 2 August 2012 Keywords: preterm infants; body temperature; hypothermia

INTRODUCTION Newborn infants, particularly those born prematurely, are vulnerable to cold stress. Their large surface area to body mass ratio, thin permeable skin, small amount of subcutaneous fat and limited metabolic response to cold may lead to rapid heat loss and a decrease in body temperature.1 Thus, premature infants are largely dependent upon an external heat source, and optimal thermal management of the preterm infant is very important.1,2 During resuscitation in the delivery room, heat loss often exceeds heat production in low birth weight preterm infants, more so in very low birth weight (VLBW) infants. A recent study from a large cohort of VLBW infants born in 15 academic medical centers in the United States demonstrates that 47% of the admission temperature were o36 1C.3 The EPIcure study, a large prospective observational study in the United Kingdom, evaluated outcomes of infants born at the threshold of viability (o26 weeks of gestation) and demonstrated that 40.4% of the extremely premature infants had admission temperatures o35 1C.4 Hypothermia is well known to have potentially serious metabolic consequences for VLBW infants, and hypothermic infants are significantly more likely to be acidemic and in more critical condition than are those with normal temperatures upon admission to the neonatal intensive care unit (NICU).4,5 The study by Silverman et al.6 in 1958 demonstrated that maintenance of body temperature through control of the thermal environment significantly reduced mortality in low birth weight infants and thermal management of the preterm infant became a cornerstone of neonatology.6,7 Efforts to minimize heat loss in newborn infants are important in the initial stabilization and resuscitation in the delivery room. As detailed in the Neonatal Resuscitation Program (NRP) of the American Academy of Pediatrics

and the American Heart Association, routine thermal care includes placing the infant under a radiant warmer, and immediately drying the infant; wet linens should be removed quickly.2 On the basis of the data obtained by Knobel et al.8 from a post hoc analysis, increasing the temperature of the delivery room, if possible, for an anticipated preterm delivery is also recommended in the NRP.2 Similarly, the World Health Organization (WHO) also advocates maintaining the temperature in the delivery room at 25 1C.9 This recommendation was supported by the data from a retrospective analysis of preterm infants p31 weeks gestation.10 However, with the assumption that an over head radiant warmer will maintain newborn temperature adequately, this recommendation is frequently ignored and delivery rooms and operating rooms in developed countries are usually maintained relatively cool (p23 1C) for the comfort of the laboring mother, staff and surgical personnel who must wear multiple layers of protective clothing. Furthermore, direct evidence from a large randomized control trial is still lacking as to whether increasing the delivery room temperature does decrease the incidence of hypothermia in premature infants upon admission to the NICU. An infant loses body heat by evaporation, convection, radiation and conduction. As soon as an infant is delivered, the transition from the warm intrauterine environment to the cool, drafty environment causes significant heat loss. We hypothesized that increasing the delivery room temperature would reduce heat loss during initial resuscitation and stabilization and therefore increase NICU admission temperature and decrease the incidence of hypothermia in newborns with gestational age p32 weeks. To test this hypothesis, we performed a prospective randomized controlled clinical trial comparing the NICU admission temperatures of premature infants delivered in warm rooms with the

1 Department of Neonatology, Yuying Children’s Hospital of Wenzhou Medical College, Wenzhou, China; 2Department of Nursing, The Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, China and 3Department of Pediatrics, Mount Sinai School of Medicine, New York, NY, USA. Correspondence: Dr Z Lin OR Dr J Lin, Department of Pediatrics, Mount Sinai School of Medicine, One Gustave L Levy Place, Box 1508, New York, NY 10029-6574, USA. E-mail: [email protected] or [email protected] Received 5 March 2012; revised 22 June 2012; accepted 5 July 2012; published online 2 August 2012

Delivery room temperature and hypothermia in premature infants Y-S Jia et al

265 temperature set at 24 to 26 1C with those delivered in regular rooms with the room temperature set at 20 to 23 1C. METHODS From 1 March 2010 to 28 February 2011, we conducted a prospective, randomized control trial in the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical College, a perinatal center located in eastern China with over 7000 annual deliveries. The 90 bed level III NICU also serves as the major referral center for the region of over 8 million people. The study protocol was approved by both the Institutional Ethics Committee of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical College and the Program for the Protection of Human Subjects of the Mount Sinai School of Medicine in New York.

Enrollment and randomization We set the room temperature at 24 to 26 1C in one of the delivery rooms and one of the obstetrical operating rooms as the warm rooms. We kept the room temperature at 20 to 23 1C in other operating rooms and other delivery rooms as the control rooms. We could not control or measure the humidity of the delivery rooms. All pregnant women who were expecting to deliver a preterm infant with gestational age p32 weeks were eligible to be enrolled into the study. After informed consent was obtained, the patient was assigned randomly to deliver in a regular delivery/operating room or in a warm delivery/operating room. The randomization was accomplished by opening a sealed preset envelope with either regular or warm room assignment. The randomization was over-ruled if a conflict for the delivery room assignment existed, in which case, the patient was not included into the study. This clinical trial was not blinded as the temperature difference between rooms was obvious to both laboring mother and staff. Preliminary data obtained for the trial demonstrated that babies born in a warm room had an average of 1.1±1.4 1C (mean±s.d.) higher admission temperature than those born in a regular room. We considered the difference of this magnitude to be clinically significant. In order to show this difference with an a of 0.05 (two tailed), and a 90% power, we needed 42 infants in each group.

Inclusion criteria Infants of the enrolled and randomized mothers who met all of the following criteria were included in the analysis: (a) born in the 2nd Affiliated Hospital/Yuying Children’s Hospital of Wenzhou Medical College and admitted alive into the NICU of Yuying Children’s Hospital, (b) maternal temperature o38 1C at delivery, (c) delivery at gestational age p32 weeks, (d) no major congenital anomalies and (e) the presence of a staff neonatologist for initial resuscitation and stabilization in the delivery room or operating room.

Data collection, analysis and statistics After delivery, all babies were resuscitated and stabilized in the delivery rooms equipped with a radiant warmer (Ningbo David Medical Device, Ningbo, China). The delivery room resuscitation was performed by our staff neonatologists according to the NRP guidelines. No changes were made to the routine delivery room management and resuscitation for this study. For each preterm delivery, in addition to recording all required information routinely done in the delivery rooms, the delivery room staff also recorded the actual room temperature from the wall glass thermometer specifically installed for this study. After initial delivery room management, babies were transported in a heated transport isolate (Atom Medical International, Japan) to the NICU. All babies admitted to the NICU were routinely cared for by the attending neonatologist. The research coordinator collected data for each enrolled infant by filling in a data collection sheet specifically designed for the study. The primary outcome measure was the rectal temperature which is routinely taken on admission to the NICU along with other vital signs within the first hour of life. The rectal temperature was measured with a standard mercury thermometer and recorded in the medical chart by our staff NICU nurses who were not aware of the group assignment. The admission vital signs, serum glucose level and the base deficit/excess from the first arterial blood gas were obtained from the medical record by the research coordinator. The five-item clinical risk index for babies (CRIB) II score was calculated from the birth weight, gestational age, sex, admission temperature and base excess as described by Parry et al.11 & 2013 Nature America, Inc.

Student’s t-test was used for comparison of the two groups for all normally distributed numerical data; the w2-test was used for categorical data. Simple linear regression was used to identify potential factors affecting admission temperature, and then a multivariable linear regression model was used to identify independent determinants of admission temperature. All numerical data are presented as mean and s.d. unless otherwise specific indicated. A P value o0.05 was considered statistically significant in all cases. All statistical analysis was performed by using PASW Statistics 18 (SPSS, IBM, Armonk, NY, USA).

RESULTS During the 1 year study period, we enrolled 96 mothers, 91 of whose newborns met the inclusion criteria and were included for data analysis. Of those 91 premature infants, 43 were born in warm rooms as the warm group; the other 48 infants were born in regular rooms as the control group. The range of the actual room temperature in the warm rooms was 24 to 26 1C with an average of 25.1±0.6 1C, which is significantly higher that that of the regular rooms in which the actual room temperature ranged from 20 to 23 1C with an average of 22.5±0.6 1C (Po0.001). The baseline clinical characteristics of the two groups were similar as shown in Table 1. The mean rectal temperature on admission to the NICU was significantly higher in the premature infants with gestational age p32 weeks who were born in warm rooms compared with the infants who were born in the regular rooms (Table 2). The increased delivery room temperature to an average of 25.1 1C from a regular 22.5 1C was associated with an increase of the mean admission rectal temperature by 0.5 1C and a decreased incidence of hypothermia (defined as rectal temperature o36.0 1C) from 68.8 to 34.9%. There were no differences between the two groups in the incidence of severe hypothermia (defined as rectal temperature o35.0 1C), base excess or the incidence of hypoglycemia (defined as the serum glucose o40 mg dl  1) on admission. To further determine if the delivery room temperature is a significant predictor of baby’s admission temperature adjusted for confounders, we performed a multiple linear regression analysis. First order regression of the admission temperature as a function of delivery room temperature and other potential factors is shown in Table 3. These results suggested using DR temperature, birth weight and Apgar scores as factors in a model predicting admission rectal temperature. Although there was not a significant difference in base excess between babies delivered in warm rooms and regular control rooms, the base excess was significantly correlated with the admission temperature. It was not used in the model, despite having the highest R value, because it is most likely the effect of the baby being cold rather than a cause for hypothermia. The 1 min Apgar score was not used in the model, because it did not have a significant effect when the 5 min Apgar score was included. As shown in Table 3, delivery room temperature, birth weight and 5 min Apgar score independently

Table 1.

Baseline clinical characteristics of the two groups

Gestational age (weeks) Multiple birth, n (%) Birth weight (kg) o1.00 kg, n (%) Apgar 1 min Apgar 5 min Gender, n (M/F)

Control group (n ¼ 48)

Warm group (n ¼ 43)

P

30.2±1.5

29.7±2.0

NS

6 (12.5) 1.32±0.27 5 (10.4) 7±2 8±1 26/22

7 (16.3) 1.33±0.30 5 (11.6) 7±2 8±1 25/18

NS NS NS NS NS NS

Abbreviation: NS, not significant.

Journal of Perinatology (2013), 264 – 267

Delivery room temperature and hypothermia in premature infants Y-S Jia et al

266 Table 2. The DR temperature and the primary and other outcomes of the two groups Control group (n ¼ 48)

Warm group (n ¼ 43)

P

22.5±0.6 20–23 35.5±0.8 33 (68.8) 6 (12.5)  4.3±4.3 16/48 (33.3)

25.1±0.6 24–26 36.0±0.9 15 (34.9) 3 (7.0)  3.9±3.9 10/40 (25.0)

o0.01

DR temperature ( 1C) Range ( 1C) Admission rectal T ( 1C) To36 1C, n (%) To35 1C, n (%) Base excess (mEq l  1) Base excesso  5.0, n/n (%) Serum glucose (mg dl  1) o40 mg dl  1, n (%) CRIB II score

o0.01 o0.01 NS NS NS

61.2±18.7

64.6±27.2

NS

6 (12.5) 6±2

4 (9.3) 6±3

NS NS

Abbreviations: CRIB, clinical risk index for babies; DR, delivery room; NS, not significant.

Table 3. Multiple linear regression analysis of factors related to the admission temperature of a premature infant and the correlation coefficient Variables DR temperature ( 1C) Birth weight (kg) Apgar 5 min Apgar 1 min Gestational age (weeks) Male gender Serum glucose (mg dl  1) Base excess (mEq l  1)

R*

P*

Coefficient (95% CI)**

P**

0.339 0.325 0.296 0.295 0.033

0.001 0.002 0.004 0.005 0.756

0.23 (0.11–0.35) 0.71 (0.10–1.32) 0.16 (0.04–0.29) Not included NS

o0.001 0.022 0.011 N/A N/A

0.002 0.030

0.985 0.780

NS NS

N/A N/A

0.389

o0.001

Not included

N/A

Abbreviations: CI, confidence of interval; DR, delivery room; N/A, not applicable; NS, not significant. *For univariate analysis. **For multivariable analysis.

contributes to the admission temperature of premature infants. The 0.23 coefficient of DR temperature in the multivariable model indicates a 0.23 1C increase in admission temperature for every degree increase in the delivery room temperature.

DISCUSSION Hypothermia on admission to neonatal units is a world-wide problem across all climates, particularly for small infants and those born prematurely.12 Minimizing the heat loss in preterm infants during the initial stabilization and resuscitation in the delivery room is critical for improved outcome in those babies. In the current study, we demonstrated that increasing the delivery room temperature, when a preterm delivery is anticipated, can significantly increase the admission temperature of premature infants. An increase in the room temperature to an average of 25.1 1C from a control room temperature of 22.5 1C is associated with a 0.5 1C higher mean NICU admission rectal temperature and a decrease in the incidence of hypothermia from 68.8 to 34.9% in premature infants with gestational age p32 weeks. Our study provides strong evidence that the environmental temperature of the delivery room has a direct impact on heat loss in premature infants and suggests that maintaining a modestly higher delivery room temperature will reduce the incidence of neonatal hypothermia. This prospective, randomized, controlled clinical Journal of Perinatology (2013), 264 – 267

trial provides direct evidence to support the recommendations by NRP and WHO for increasing the delivery room temperature for an anticipated preterm delivery. Major efforts have been devoted to preventing hypothermia of premature infants. In addition to the routine thermal care, techniques using barriers to prevent heat losses such as covering the infant in plastic wrapping or caps (food-grade, heat-resistant plastic) have been proven to be effective in the delivery room for preterm infants with gestational age o28 weeks.8,13–16 This technique has been recommended by NRP and the International Committee on Resuscitation for delivery of preterm infants with a gestational age o28 weeks.2,17 As only about 10% of our enrolled preterm deliveries had a gestational age o28 weeks or birth weight o1000 g, we did not use plastic wrap or caps in any of our enrolled infants during the trial period. Clearly, the 34.9% incidence of hypothermia in our warm group is still not acceptable for most of the neonatal units in developed countries. Implementing some of the evidence-based potentially better practices may further improve thermal care in the delivery room for very premature infants and reduce the incidence of hypothermia.18 Multiple factors contribute to the development of hypothermia of premature infants on NICU admission. Consistent with the literature,3 our results from multiple linear regression analysis indicate that in addition to the delivery room temperature, lower birth weight and lower 5 min Apgar score are independent variables associated with the admission hypothermia of premature infants. It is well established that the temperature control is vital for neonatal survival and that extent of reduced temperature on admission in premature infants is associated with both morbidity and mortality.3,6,19 By using multivariate analysis, Laptook et al.3 demonstrated that for every 1 1C decrease in admission temperature, the odds of late-onset sepsis are increased by 11%, and the odds of dying are increased by 28% in VLBW infants. Admission temperature is included as one of the five items (gestational age, birth weight, sex, admission temperature and base excess) in the CRIB II scoring system.11 The CRIB II score, which was developed as a valid and simple riskadjustment instrument for assessing the quality of care for individual NICUs, is better than either gestational age or birth weight alone in predicting death or major cerebral abnormality.11 However, despite the admission temperature being significantly higher in the warm group, none of the secondary outcomes, that is, base deficit, admission serum glucose level and CRIB II score, were different between the warm and control groups. There are several possible reasons for this including the fact that the current study was not powered to address these secondary outcomes and the possibility that the marginal improvement in admission temperature may be too small to have an effect on those parameters. Furthermore, the major clinical outcomes, such as death before discharge, intraventricular hemorrhage, late-onset neonatal sepsis, chronic lung disease and length of stay, were not part of the initial design because the NICU care of premature infants in China was not as advanced as that in the developed countries. Non-medical factors such as socio-economic issues still have a very important role in the care decision making and therefore the outcomes of VLBW infants in developing countries. In conclusion, ongoing improvements in outcome for the preterm baby will depend on an increasingly aggressive approach to all aspects of routine neonatal care, of which temperature control remains important.18,20 The current randomized controlled clinical trial shows that premature infants born in delivery rooms with room temperature set at 24 to 26 1C have less chance of being hypothermic on admission to the NICU than do those delivered in delivery rooms with room temperature set at 20 to 23 1C. This supports the WHO recommendation for delivery room temperature as part of a thermal care strategy for preterm delivery. It remains to be determined if this change can make a real difference in terms of the major clinical outcomes for premature infants. & 2013 Nature America, Inc.

Delivery room temperature and hypothermia in premature infants Y-S Jia et al

267 CONFLICT OF INTEREST The authors declare no conflict of interest.

ACKNOWLEDGEMENTS We would like to thank the staff of the Obstetrical and Neonatal Departments of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical College for their invaluable cooperation in this study and Dr Ian Holzman for advice and critical review of the manuscript.

Author contributions The results of this study were presented, in part, at the annual Pediatric Academic Society meeting in Boston, 28 April to 2 May 2012. This study was supported by a research grant from the Neonatal Resuscitation Program of American Academy of Pediatrics and a grant from Wenzhou City Bureau of Science and Technology, China (H20090074). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. All listed authors are fully involved in the preparation of this manuscript and have approved this final version.

REFERENCES 1 Lyon AJ, Pikaar ME, Badger P, McIntosh N. Temperature control in very low birthweight infants during first five days of life. Arch Dis Child 1997; 76: F47–F50. 2 American Academy of Pediatrics, American Heart Association. Resuscitation of babies born preterm. In Kattwinkel J (ed). Textbook of Neonatal Resuscitation. 6th edn. American Academy of Pediatrics: Elk Grove Village, IL, 2011. 3 Laptook AR, Salhab W, Bhaskar B. The Neonatal Research Network. Admission temperature of low birth weight infants: predictors and associated morbidities. Pediatr 2007; 119: e643–e649. 4 Costeloe K, Hennessy E, Gibson AT, Marlow N, Wilkinson AR. The EPICure study: outcomes to discharge from hospital for infants born at the threshold of viability. Pediatr 2000; 106: 659–671. 5 Loughead MK, Loughead JL, Reinhart MJ. Incidence and physiologic characteristics of hypothermia in the very low birth weight infant. Pediatr Nurs 1997; 23: 11–15. 6 Silverman WA, Fertig JW, Berger AP. The influence of the thermal environment upon survival of newly born preterm infants. Pediatr 1958; 22: 876–885.

& 2013 Nature America, Inc.

7 Narendran V, Hoath SB. Thermal management of the low birth weight infant: A cornerstone of neonatology. J Pediatr 1999; 134: 529–531. 8 Knobel RB, Wimmer JE, Holbert D. Heat loss prevention for preterm infants in the delivery room. J Perinatol 2005; 25: 304–308. 9 World Health Organization (WHO). Thermal control of the newborn: a practical guide. Maternal Health and Safe Motherhood Programme (WHO/FHE/MSM/93.2). WHO: Geneva, 1996. 10 Kent AL, Williams J. Increasing ambient operating theatre temperature and wrapping in polyethylene improves admission temperature in premature infants. J Pediatr Child Health 2008; 44: 325–331. 11 Parry G, Tucker J, Tarnow-Mordi W. for the UK neonatal staffing study collaborative group. CRIB II: an update of the clinical risk index for babies score. Lancet 2003; 361: 1789–1791. 12 McCall EM, Alderdice F, Halliday HL, Jenkins JG, Vohra S. Interventions to prevent hypothermia at birth in preterm and/or low birthweight infants. Cochrane Database Syst Rev 2010; 3: CD004210. 13 Vohra S, Frent G, Campbell V, Abbott M, Whyte R. Effect of polyethylene occlusive skin wrapping on heat loss in very low birth weight infants at delivery: a randomized trial. J Pediatr 1999; 134: 547–551. 14 Vohra S, Roberts RS, Zhang B, Janes M, Schmidt B. Heat loss prevention (HeLP) in delivery room: a randomized controlled trial of polyethylene occlusive skin wrapping in very premature infants. J Pediatr 2004; 145: 750–753. 15 Trevisanuto D, Doglioni N, Cavallin F, Parotto M, Micaglio M, Zanardo V. Heat loss prevention in very preterm infants in delivery rooms: a prospective, randomized, controlled trial of polyethylene caps. J Pediatr 2010; 156: 914–917. 16 Rohana J, Khairina W, Boo NY, Shareena I. Reducing hypothermia in preterm infants with polyethylene wrap. Pediatr Int 2011; 53: 468–474. 17 Perlman JM, Wyllie J, Kattwinkel J, Atkins DL, Chameides L, Goldsmith JP et al. International consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Part 11: neonatal resuscitation. Circulation 2010; 122: S516–S538. 18 Soll RF, Pfister RH. Evidence-based delivery room care of the very low birth weight infant. Neonatology 2011; 99: 349–354. 19 Silverman WA, Agate Jr FJ , Fertig JW. A sequential trial of the nonthermal effect of atmospheric humidity on survival of newborn infants of low birth weight. Pediatr 1963; 31: 719–724. 20 Lyon AJ, Freer Y. Goals and options in keeping preterm babies warm. Arch Dis Child Fetal Neonatal Ed 2011; 96: F71–F74.

Journal of Perinatology (2013), 264 – 267