Dallas 2015

TFQO: NameEVREV 1: Jonathan Wyllie COI #282EVREV 1: Jeff Perlman COI #262Taskforce: Newborn

Temperature Maintenance in the Delivery room NRP589

Dallas 2015COI Disclosure (specific to this systematic review)

EVREV Jonathan WyllieCommercial/industry• None

Potential intellectual conflicts• ERC, RC (UK) Newborn chair

EVREV Jeff PerlmanCommercial/industry• None

Potential intellectual conflicts• None

Dallas 20152010 CoSTR

Topic not reviewed in 2010.

Dallas 2015C2015 PICO

Population: Non-asphyxiated newborn babiesIntervention: Temperature maintained between 36.5-37.5 degrees centigrade from delivery to admission Comparison:Hypothermia or hyperthermiaOutcomes: Survival (9), Intraventricular Haemorrhage (7), Hypoglycaemia (6), Respiratory Distress (6) Sepsis (6)

Dallas 2015Inclusion/Exclusion& Articles Found

List Inclusions/ExclusionsIncluded human, comparative studies (prospective and retrospective), case series and reviews reporting outcomes for the temperature management of term and preterm neonates between birth and admission.Excluded animal studies and studies that did not specifically address the PICO question. Excluded unpublished studies, and studies only published in abstract form, unless accepted for publication.

2315 Articles initially identified79 Included in Evidence Profile tablesRefined to 67 included

3 RCTs but without any of these outcomes as primary outcomes 64 non-RCTs2248 excluded

Dallas 20152015 Proposed Treatment Recommendations

Draft Treatment Recommendations from SEERs

We recommend that the temperature of newly born infants be maintained above 36.5 degrees centigrade after birth through admission and temperature check. Hyperthermia should be avoided (Strong recommendation, Moderate quality of evidence). This should be a standard of care.

We suggest that the temperature on admission be recorded as a predictor of mortality and potential morbidity as well as a quality indicator.

Dallas 2015 Risk of Bias in studies

Dallas 2015 Risk of Bias in studies

Dallas 2015 Risk of Bias in studies

Jones 2011 Non-RCT 83 24-35 weeks No Low High High UnclearKalimba 2013 Non-RCT 382 <=900g No Low Low High Unclear

Kambarami 2003 Non-RCT 1,313 Admitted to NNU No Low Unclear High UnclearKent 2008 Non-RCT 156 <31 weeks No Low Low Unclear Low

Laptook 2007 Non-RCT 5,277 401-1499g No Low Low Low LowLazić-Mitrović 2010 Non-RCT 143 Term IUGR No Unclear High High Unclear

Lee 2008 Non-RCT 304 <1500g No Unclear Unclear Low Unclear

Lee2014

Non-RCT 12,528<1500g, <30 weeks No Low Unclear Unclear Low

Lenclen 2002 Non-RCT 120 <33 weeks No Low Unclear High UnclearLevene 1982 Non-RCT 146 <=34 weeks No Low Unclear High Unclear

Levi 1984 Non-RCT 71 <800g No Low Unclear High UnclearManani 2013 Non-RCT 289 <33 weeks No Low Unclear High Low

Manji2003

Non-RCT 1,633Admissions to NICU No High High High Unclear

Mathur

2005

Non-RCT 100 extramural hypothermic babies No High High High Unclear

Miller 2011 Non-RCT 8,782 VLBW No Low Low Low Unclear

Mullany2010

Non-RCT 23,240Newborns in Nepal No Unclear High Unclear High

Nayei 2006 Non-RCT 940 Newborn Babies No Low Low High UnclearNayeri 2005 Non-RCT 898 Newborn Babies No Low Low High Unclear

Obladen1985

Non-RCT 182Neonates who died No Low High High Unclear

Oglunesi2008

Non-RCT 150 Babies admitted in Nigeria No Low Unclear High Unclear

Pal 2000 Non-RCT 578 Newborn Babies No Low Unclear High UnclearRong 2012 Non-RCT <37 weeks No Low High Low UnclearRusso 2014 Non-RCT 361 <35 weeks No Low Low Unclear Low

Sasidharan2004

Non-RCT 604Newborns in India No Low Low Low Low

Shah2012

Non-RCT 1,502 admitted to NICU in Eritrea No Unclear Low Low High

Singh 2012 Non-RCT 154,669 Pregnant mothers No Low High High High

Sodemann2008

Non-RCT 2,926 Live births in Guinea-Bissau No Low Unclear Unclear Low

Stanley 1978 Non-RCT 692 <2000g No Low Unclear Unclear UnclearSzymonowicz 1984 Non-RCT 50 <1250g No Low Low High Unclear

Van 1986 Non-RCT 49 <34 weeks No Low Unclear High UnclearWykoff 2004 Non-RCT 65 Outborn `babies No Low Low Low LowZayeri 2005 Non-RCT 1,952 Inborn babies No Unclear Unclear High Unclear

Dallas 2015Evidence

Dallas 2015Evidence profile table(s)

Dallas 2015Evidence profile table(s)

Dallas 2015Proposed Consensus on Science statements

For the critical outcome of mortality, there is evidence from 35 observational studies, (Costeloe 2000, 2012, Laptook 2007, Miller 2011, Mullany 2010, Boo 2013, Garcia-Munoz 2014, de Almeida 2014) (Low quality of evidence but upgraded to moderate quality due effect size, dose effect, (Laptook 2007, Miller 2011, Mullany 2010, Boo 2013) and single direction of evidence) of increased risk of mortality associated with hypothermia at admission. We did not identify any evidence to address the critical outcome of “neurologically intact survival”.

There is evidence of a dose effect on mortality suggesting an increased risk of approximately 28 percent for each 1 degree below 36.5 degrees centigrade body temperature at admission (Laptook 2007) and effect size (Miller 2011, Mullany 2010, Boo 2013).

Dallas 2015Proposed Consensus on Science statements

1 small RCT (Meyer 2001) (moderate quality, downgraded for indirectness and imprecision) showed a reduction in adverse events, including death, intracranial haemorrhage, NEC and oxygen dependence with improved temperature management but two RCTs (Vohra 1999, 2004) (Very low quality as downgraded for indirectness and imprecision) did not show any significant improvement in mortality with significantly improved temperature control. 4 observational studies (Manani 2013, Billmoria 2013, Kent 2008, Lee 2008)(very low quality) did not find any improvement in mortality with improved admission temperatures but they were not powered to do so.

Dallas 2015Proposed Consensus on Science statements

There is evidence from nine observational studies (Costeloe 2000, Boo 2013, DeMauro 2013, Lee 201, Russo 2014 )(Low quality) showing an association between hypothermia and respiratory disease. 8 observational studies (Low Grade) have shown an improvement in respiratory outcomes following improved admission temperature maintenance. Two of these have shown a decrease in respiratory support with improved temperature maintenance). (DeMauro 2013, Russo 2014).

There are 7 observational studies (Low Grade) showing a significant association between hypothermia (< 36 OC) and hypoglycaemia (Anderson 1993, Lenclen 2002). Two of these (Grade Low), using historical controls, showed improved glycaemic control with improved normothermia (Lenclen 2002, A Abd-El 2012).

Dallas 2015Proposed Consensus on Science statements

9 observational studies (Grade Low to Mod) show hypothermia (< 36 OC) in preterm infants is associated with an increased likelihood of developing intraventricular hemorrhage (Boo 2013, Carroll 2010, Garcia-Munoz 2013, Miller 2011). 8 observational studies (Grade Low to Mod) found no association (Audeh 2011, Dincsoy 1990, Laptook 2007) . There is evidence from two observational studies (Low Grade) of an association between hypothermia on admission and late sepsis (Laptook 2007). One observational study (Low Grade) found no association after multivariate analysis Miller 2011. There was no published evidence addressing any effect of delivery room hypothermia upon survival to admission.There was no published evidence about newborn hyperthermia at admission.

Dallas 2015Draft Treatment Recommendations

We recommend that the temperature of newly born infants be maintained above 36.5 degrees centigrade after birth through admission and temperature check. Hyperthermia should be avoided (Strong recommendation, Moderate quality of evidence). This should be a standard of care. We suggest that the temperature on admission be recorded as a predictor of mortality and potential morbidity as well as a quality indicator. Values and preferences: In making these statements we place a higher value on the strong association of hypothermia with mortality, the apparent dose effect, the single direction of the evidence and the universal applicability over the lack of evidence for intervention changing mortality.

Dallas 2015Knowledge Gaps

Further studies are required to find if improved admission temperature improves mortality and other outcomes. Further studies are required to find if late inadvertent hypothermia is associated with the same risks and whether there are any long term morbidities associated with hypothermia at admission.

Dallas 2015Next Steps

This slide will be completed during Task Force Discussion (not EvRev) and should include:

Consideration of interim statementPerson responsibleDue date