Dallas 2015 TFQO: EVREVs: de Almeida, Maria Fernanda COI# Trevisanuto, Daniele COI# Taskforce: Neonatal Warming Adjunts #599 Among preterm neonates who are under radiant warmers in the hospital delivery room (P), does increased room temperature, thermal mattress, or another intervention (I), compared with plastic wraps alone (C), reduce hypothermia (<36.0) on admission to NICU (O)?

Dallas 2015 COI Disclosure (specific to this systematic review) EVREV COI# De Almeida, Maria Fernanda Commercial/industry does not have any commercial/industry or potential intellectual conflicts Potential intellectual conflicts Coordinator of Brazilian NRP; Portuguese version of Textbook on Neonatal Resuscitation & DVD-ROOM – AAP & AHA 6 th edition EVREV COI# Trevisanuto, Daniele Commercial/industry Does not have any commercial/industry or potential intellectual conflicts Potential intellectual conflicts Co-author of two (one excluded) of the examined papers

Dallas CoSTR CONSENSUS on SCIENCE: “In the absence of polythene wrapping, use of exothermic mattresses maintained the temperature of newborn infants weighing <1500 g within the normal range (LOE2 123). A combination of exothermic mattresses and polythene wrapping during resuscitation is the most effective strategy to avoid hypothermia but may increase the risk of hyperthermia (LOE3 124). Delivery room temperatures of at least 26  C for newborns at <28 weeks’ gestation in combination with polythene wraps or bags maintained temperatures most effectively (LOE4 125; LOE3 126).” TREATMENT RECOMMENDATION: “Newborn infants of <28 weeks’ gestation should be completely covered in a polythene wrap or bag up to their necks without drying immediately after birth and then placed under a radiant heater and resuscitated or stabilized in a standard fashion. Infants should be kept wrapped until admission and temperature check. Hyperthermia should be avoided. Delivery room temperatures should be at least 26  C for infants of <28 weeks’ gestation.”

Dallas 2015 C2015 PICO Population: inborn preterm infants under radiant warmers in the hospital Intervention: warmer mattress, environmental room >=26 o C, heated and humidified gases; plastic cap; combination of interventions Comparison: plastic wrap Outcomes: (7 critical) hypothermia =38.0 o C

Dallas 2015 Inclusion/Exclusion & Articles Found Inclusions/Exclusions Inclusion Criteria: Randomized studies, studies with concurrent controls or with historical controls and meta-analysis. Exclusion Criteria: Review articles, animal studies and studies that did not specifically answer the question. Unpublished studies, and studies only published in abstract form, unless accepted for publication were also excluded. 14 finally evaluated 3 RCT 11 observational studies

Dallas Proposed Treatment Recommendations Among newly born preterm infants 38.0 o C) during application of all above interventions.

Dallas 2015 Risk of Bias in studies Study Total Patients Population Industry Funding Allocation: Generation Allocation: Concealment Blinding: Participants Blinding: Assessors Outcome: Complete Outcome: Selective Other Bias McCarthy 2013, e <31 wks GA NoLow High Low Mattress Doglioni 2014, <29 wks GA NoLow High Low Plastic cap Meyer 2014, [epub ahead of print] 203 <32 wks GA No Low High Low Heated gases Randomized Controled Trials

Dallas 2015 Risk of Bias in studies Observational Studies Study Total Patients Population Industry Funding Eligibility Criteria Exposure/ Outcome Confounding Follow up Billimoria 2013, BW<1000gNoLowHigh LowMattress Chawla 2011, 78043<32 wks GANoLow HighLowMattress Ibrahim 2010, <28 wks GANoLow HighLowMattress McCarthy 2011, <31 wks GANoHighLowHighLowMattress Singh 2010, 45145<30 wks GANoLow HighLowMattress Knobel 2005, 30440<29 wks GANoLow HighLow Room temperature te Pas 2010, e <32 wks GANoLow HighLowHeated gases DeMauro 2013, e BW<1250gNoLowHigh LowCombination Pinheiro 2014, e BW<1500gNoLowHigh LowCombination Russo 2014, e1259<35 wks GANoLowHigh LowCombination Lee 2014, e BW<1500g and/ or wks GA NoLowHigh LowCombination

Dallas 2015 Evidence profile table 1 Author(s): Trevisanuto, Daniele; de Almeida, Maria Fernanda Date: 13 Jan 2015 Question: Does WARMING MATTRESS + Plastic Wrap vs Plastic Wrap be used in preterm neonates under radiant warmers? Settings: hospital delivery room Bibliography: Billimoria, J Perinat Med 2013, 455; Chwala, J Perinatol 2011, 780; Ibrahim, Eur J Pediatr 2010, 795; McCarthy, Acta Paediatr 2011, 1534; McCarthy, Pediatrics 2013, e135; Singh, J Perinatol 2010, 45. QUALITY ASSESSMENTNO OF PATIENTSTSEFFECT Qual- ity Impor- tance No Stu dies Design Risk of bias Inconsis tency Indirect ness Im- precision Other MATTRESS+ wrap+ heater wrap+ heater Relative (95% CI) Absolute TEMPERATURE<36.0°C 1RTC serious 1 no serious very serious 2 none 2/37 (5.40%) 1/35 (2.85%) RR = 1.89 ( ) 30 more per 1000 [from 70 fewer to 120 more] ÅÅOO LOW CRITICAL 4 Observa- tional serious Seriousnone 81/350 (23.1%) 119/262 (45.4%) OR = 0.27 ( ) 210 fewer per 1000 [from 270 fewer to 140 fewer] ÅOOO VERY LOW CRITICAL TEMPERATURE>38.0°C 1 RTC serious 1 no serious very serious 2 none 8/37 (21.61%) 2/35 (5.71%) RR = 3.78 ( ) 160 more per 1000 [from 10 more to 310 more] ÅÅOO LOW IMPORTANT 4 Observa- tional serious none 13/254 (5.11%) 0/172 (0.00%) OR = 6.53 ( ) 40 more per 1000 [from 30 fewer to 100 more] ÅOOO VERY LOW IMPORTANT 1 Lack of blinding 2 Trial was stopped early; loss of study power for outcome Temperature<36.0°C

Dallas 2015 Evidence profile table 2 Author(s): Trevisanuto, Daniele; de Almeida, Maria Fernanda Date: 13 Jan 2015 Question: Does ENVIRONMENTAL TEMPERATURE >=26.0 O C + Plastic Wrap vs Plastic Wrap be used in preterm neonates under radiant warmers? Settings: hospital delivery room Bibliography: Knobel, J Perinatol 2005, 304. QUALITY ASSESSMENTNO OF PATIENTSTSEFFECT Qual- ity Impor- tance No Stu dies Design Risk of bias Inconsis tency Indirect ness Im- precision Other ROOM TEMP. >=26oC + wrap+ heater wrap+ heater Relative (95% CI) Absolute TEMPERATURE<36.0°C 1 Observa- tional serious noneNot available ÅOOO VERY LOW CRITICAL TEMPERATURE>38.0°C 1 Observa- tional serious none 1/10 (10.00%) 0/30 (0.00%) OR = 8.45 ( ) 100 more per 1000 [from 110 fewer to 310 more] ÅOOO VERY LOW IMPORTANT

Dallas 2015 Evidence profile table 3 Author(s): Trevisanuto, Daniele; de Almeida, Maria Fernanda Date: 13 Jan 2015 Question: Does HEATED UMIDIFIED GASES + Plastic Wrap vs Plastic Wrap be used in preterm neonates under radiant warmers? Settings: hospital delivery room Bibliography: Meyer, J Pediatr 2014 [epub ahead of print]; te Pas, Pediatrics 2010, e1427. QUALITY ASSESSMENTNO OF PATIENTSTSEFFECT Qual- ity Impor- tance No Stu dies Design Risk of bias Inconsis tency Indirect ness Im- precision Other HEATED GASES + wrap+ heater wrap+ heater Relative (95% CI) Absolute TEMPERATURE<36.0°C 1RCT serious 1 no serious very serious 2 none 10/100 (10.00%) 16/103 (15.53%) RR = 0.64 ( ) 60 fewer per 1000 [from 150 fewer to 40 more] ÅÅOO LOW CRITICAL 1 Observa- tional serious none 10/54 (18.51%) 31/58 (53.44%) OR = 0.20 ( ) 350 fewer per 1000 [from 510 fewer to 180 fewer] ÅOOO VERY LOW CRITICAL TEMPERATURE>38.0°C 1 Observa- tional serious none 0/54 (0.00%) 0/58 (0.00%) OR = not estimable ÅOOO VERY LOW IMPORTANT 1 Lack of blinding 2 Loss of study power for outcome Temperature<36.0°C

Dallas 2015 Evidence profile table 4 Author(s): Trevisanuto, Daniele; de Almeida, Maria Fernanda Date: 13 Jan 2015 Question: Does PLASTIC CAP + Plastic Wrap vs Plastic Wrap be used in preterm neonates under radiant warmers? Settings: hospital delivery room Bibliography: Doglioni, J Pediatr 2014, 261. QUALITY ASSESSMENTNO OF PATIENTSTSEFFECT Qual- ity Impor- tance No Stu dies Design Risk of bias Inconsis tency Indirect ness Im- precision Other PLASTIC CAP + wrap+ heater wrap+ heater Relative (95% CI) Absolute TEMPERATURE<36.0°C 1RCT serious 1 no serious very serious 2 none 6/50 (12.00%) 10/50 (20.00%) RR = 0.60 ( ) 80 fewer per 1000 [from 220 fewer to 60 more] ÅÅOO LOW CRITICAL TEMPERATURE>38.0°C 1RCT serious 1 no serious very serious 2 none 0/50 (0.00%) 1/50 (2.00%) RR = 0.33 ( ) 20 fewer per 1000 [from 70 fewer to 30 more] ÅÅOO LOW IMPORTANT 1 Lack of blinding 2 Loss of study power for outcome Temperature<36.0°C

Dallas 2015 Evidence profile table 5 Author(s): Trevisanuto, Daniele; de Almeida, Maria Fernanda Date: 13 Jan 2015 Question: Does COMBINATION OF INTERVENTIONS (environmental temperature o c, warm blankets, plastic body and head wrapping without drying, cap, thermal mattress) vs Plastic Wrap be used in preterm neonates under radiant warmers? Settings: hospital delivery room Bibliography: DeMauro, Pediatrics 2013, e1018; Lee, Pediatrics 2014, e1378; Pinheiro, Pediatrics 2014, e218; Russo, Pediatrics 2014, e1. QUALITY ASSESSMENTNO OF PATIENTSTSEFFECT Qual- ity Impor- tance No Stu dies Design Risk of bias Inconsis tency Indirect ness Im- precision Other COMBINA- TION+ wrap+ heater wrap+ heater Relative (95% CI) Absolute TEMPERATURE<36.0°C 4 Observa- tional serious none 361/4845 (7.45%) 736/4489 (16.39%) OR = 0.40 ( ) 90 fewer per 1000 [from 110 fewer to 80 fewer] ÅÅOO LOW CRITICAL TEMPERATURE>38.0°C 3 Observa- tional serious Seriousnone 91/4562 (1.99%) 78/4423 (1.76%) OR = 1.12 ( ) 0 more per 1000 [from 0 fewer to 10 more] ÅÅOO LOW IMPORTANT

Dallas 2015 Proposed Consensus on Science statements THERMAL MATTRESS + PLASTIC WRAP + RADIANT WARMER (I) Vs PLASTIC WRAP + RADIANT WARMER (C). For the critical outcome of “hypothermia (<36.0 o C) at NICU admission” we have identified low quality evidence (downgraded for serious risk of bias) from one RCT (McCarthy, 2013, e135) enrolling 72 preterm infants <32 weeks gestation showing no benefit (RR % CI ), and 4 observational studies (Billimoria, 2013, 455; Chawla, 2011, 780; Ibrahim, 2010, 795; Singh, 2010, 45) including 612 patients <32 weeks gestation showing benefit (OR % CI ). For the important outcome of “hyperthermia (>38.0 o C) at admission” we have identified low quality evidence (downgraded for serious risk of bias) from the same RCT and 4 observational studies (Billimoria, 2013, 455; Chawla, 2011, 780; McCarthy, 2011, 1534; Singh 2010, 45) including 426 patients showing no harm (RR % CI and OR % CI , respectively).

Dallas 2015 Proposed Consensus on Science statements ENVIRONMENTAL TEMPERATURE >=26°C + PLASTIC WRAP + RADIANT WARMER (I) Vs PLASTIC WRAP + RADIANT WARMER (C). For the critical outcome of “hypothermia (<36.0 o C) at NICU admission” we have not identified any study addressing this intervention alone. For the important outcome of “hyperthermia (>38.0 o C) at admission” we have identified low quality evidence (downgraded for serious risk of bias) from one observational study (Knobel, 2005, 304) including 40 patients <29 weeks gestation showing no harm (OR % CI ). HEATED AND HUMIDIFIED GASES + PLASTIC WRAP + RADIANT WARMER (I) Vs PLASTIC WRAP + RADIANT WARMER (C). For the critical outcome of “hypothermia (<36.0 o C) at NICU admission” we have identified low quality evidence (downgraded for serious risk of bias) from one RCT (Meyer, 2014, epub ahead of print) enrolling 203 patients <32 weeks gestation showing no benefit (RR % CI ), and one observational study (Te Pas, 2010, e1427) including 112 patients <33 weeks gestation showing benefit (OR % CI ). For the important outcome of “hyperthermia (>38.0 o C) at admission” we have identified low quality evidence (downgraded for serious risk of bias) from the same observational study showing no harm (OR not estimable).

Dallas 2015 Proposed Consensus on Science statements PLASTIC CAP + WRAP + RADIANT WARMER (I) Vs PLASTIC WRAP + RADIANT WARMER (C). For the critical outcome of “hypothermia (<36.0 o C) at NICU admission” we have identified low quality evidence (downgraded for serious risk of bias) from one RCT (Doglioni, 2014, 261) enrolling 100 patients <29 weeks gestation showing no benefit (RR % CI ). For the important outcome of “hyperthermia (>38.0 o C) at admission” we have identified low quality evidence (downgraded for serious risk of bias) from the same RCT showing no harm (RR % CI ). COMBINATION OF INTERVENTIONS (ENVIRONMENTAL TEMPERATURE 23-25°C + RADIANT WARMER + WRAP BODY AND HEAD IN PLASTIC WITHOUT DRYING + CAP + THERMAL MATTRESS) Vs RADIANT WARMER + PLASTIC WRAP. For the critical outcome of “hypothermia (<36.0 o C) at admission” we have identified low quality evidence (downgraded for serious risk of bias) from 4 observational studies (deMauro, 2013, e1018; Lee, 2014, e1378; Pinheiro, 2014, e218; Russo 2014, e1) enrolling 9334 patients <35 weeks gestation showing benefit (OR % CI ). For the important outcome of “hyperthermia (>38.0 o C) at admission” we have identified low quality evidence (downgraded for serious risk of bias) from 3 observational studies (deMauro, 2013, e1018; Lee, 2014, e1378; Pinheiro, 2014, e218) enrolling 8985 patients showing no harm (OR % CI ).

Dallas 2015 Draft Treatment Recommendations Among newly born preterm infants 38.0 o C) during application of all above interventions.

Dallas 2015 Knowledge Gaps Although a combination of interventions (increasing environmental temperature, warm blankets, thermal mattress, and cap) linked to quality improvement initiatives, are effective in reducing hypothermia (<36 o C) on NICU admission among newly born preterm infants <32 weeks gestation who are under radiant warmers and plastic wrap, the contribution of each intervention (increasing environmental temperature, thermal mattress, heated and humidified gases, and cap) remains to be established.

Dallas 2015 Next Steps This slide will be completed during Task Force Discussion (not EvRev) and should include: Consideration of interim statement Person responsible Due date