Maintaining normal temperature immediately after birth in late preterm and term infants: NLS 5100

Conflict of Interest Declaration

The ILCOR Continuous Evidence Evaluation process is guided by a rigorous ILCOR Conflict of Interest policy. The following Task Force members and other authors were recused from the discussion as they declared a conflict of interest: None.

The following Task Force members and other authors declared an intellectual conflict of interest and this was acknowledged and managed by the Task Force Chairs and Conflict of Interest committees.

Authors Dawson and Kamlin have published studies on humidified gases used for resuscitation and were excluded from decisions about inclusion for these studies.

Author Trevisanuto has published one study on use of a woollen cap during skin-to-skin care and one oneffective temperature under a radiant warmer and was excluded from decisions about inclusion of bias assessment for these studies.

These authors acknowledged their potential intellectual conflicts of interest and participated in the Task Force discussion of the consensus on science and treatment recommendations.

CoSTR Citation

de Almeida MF, Dawson JA, Ramaswamy VV, Trevisanuto D, Nakwa FL, Kamlin COF, Hosono S, Rabi Y, Costa-Nobre DT, Davis PG, El-Naggar W, Fabres JG, Fawke J, Foglia EE, Guinsburg R, Isayama T, Kapadia VS, Kawakami MD, Kim HS, Lee HC, McKinlay CJD, Madar RJ, Perlman JM, Roehr CC, Rüdiger M, Schmölzer GM, Sugiura T, Weiner GM, Wyllie JP, Wyckoff MH, Liley HG on behalf of the International Liaison Committee on Resuscitation Neonatal Life Support Task Force. Maintaining normal temperature immediately after birth in late preterm and term infants.

[Internet] Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) Neonatal Life Support Task Force, [date]. Available from: http://ilcor.org

Methodological Preamble and Link to Published Systematic Review

Establishing the importance of maintaining normal temperature at birth, a systematic review conducted for ILCOR concluded that "For the critical outcome of mortality, there is evidence from 36 observational studies of increased risk of mortality associated with hypothermia at admission (low-quality evidence but upgraded to moderate-quality evidence due to effect size, dose-effect relationship, and single direction of evidence)". {Perlman 2015 S204} The same systematic review concluded that "There is evidence of a dose effect on mortality, suggesting an increased risk of at least 28% for each 1° below 36.5°C body temperature at admission and dose-dependent effect size". {Perlman 2015 S204} Although the size of effect in this estimate was influenced by inclusion of studies that enrolled very preterm infants, there was also evidence of adverse effects of hypothermia on survival in late preterm and term infants.

A systematic review estimated that hypothermia was common in infants born in hospitals (prevalence range, 32% to 85%) and homes (prevalence range, 11% to 92%), even in tropical environments. {Lunze 2013 24}

This current review was initiated following a priority list from the ILCOR NLS TF. The review was led by a group of TF members with the support of additional content experts.

The continuous evidence evaluation process for the production of Consensus on Science with Treatment Recommendations (CoSTR) started with a systematic review (Liley, 2021, Maintaining normal temperature immediately after birth in late preterm and term infants).

Systematic Review

Not yet available

PICOST

Population: In late preterm and term infants (≥34 weeks’ gestation, or equivalent birth weight), immediately after birth

Intervention: Increased room temperature ≥23.0°C, thermal mattress, plastic bag or wrap, hat, heating and humidification of gases used for resuscitation, radiant warmer (with or without servocontrol), early monitoring of temperature, warm bags of fluid, warmed swaddling/clothing, skin to skin care with a parent, or any combination of these interventions

Comparators: Drying, without any of the above interventions.

Outcomes:

Primary outcomes:

• Survival (critical)
• Rate of normothermia on admission to neonatal unit or postnatal ward (important)

Secondary outcomes:

• Rate of hypothermia and hyperthermia on admission to neonatal unit or postnatal ward (important)
• Response to resuscitation- e.g., need for assisted ventilation, highest FiO₂ (important)
• Important morbidity e.g., rates of admission to neonatal special or intensive care nursery, need for respiratory support (important)

Study Designs: Randomized controlled trials (RCTs) and non-randomized studies (non-randomized controlled trials, interrupted time series, controlled before-and-after studies, cohort studies) are eligible for inclusion. Unpublished studies (e.g., conference abstracts, trial protocols) are excluded. For this review, cohort studies will be considered to be those for which there was a defined strategy to ensure that the participants were either all of those who received an exposure of interest in a defined population (e.g. infants born at a particular hospital between specified dates), or they were sampled in a way that they can be considered representative of such a population.

Timeframe: All years and all languages were included as long as there was an English abstract; unpublished studies (e.g., conference abstracts, trial protocols) were excluded. Literature search was conducted on August 2, 2021.

PROSPERO Registration CRD42021270739

Consensus on Science

A search of MEDLINE (OVID interface), Embase (OVID interface), CINAHL, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, US, Australian/New Zealand and European clinical trials registries identified 4594 unique references. After review of titles and abstracts, 38 records were shortlisted for full text review, although a full text article was not available for one study. Thirty-five studies were identified (25 RCTs and 10 observational studies) which addressed the PICOST question. Of these, 20 of the RCTs and none of the observational studies provided data that could be extracted to evidence tables (for various comparisons between interventions) for the review. Among the 11 evidence tables developed, only 4 (designated comparisons 1 and 3-5 below) were considered to provide sufficient data to allow the development of Evidence to Decision tables that would inform the development of treatment recommendations.

Title and abstract screening, selection of articles from full text reports, risk of bias assessment and data extraction was performed by pairs of authors, with conflicts resolved by a third author or consensus of authors. These steps were performed in Covidence, except for data extraction. Analyses were performed in R. {R Core Team 2019 } Development of evidence tables, GRADE assessment of certainty of evidence {Guyatt 2011 383} and development of evidence to decision tables were performed in GRADEPro. Statistical heterogeneity was considered high if I² was greater than 50%, provided the large values were not due to difference between small and large magnitude of effects, and in this case random effects models were used for analysis. In most cases, the number of studies for each comparison was too low to investigate statistical heterogeneity using sensitivity analyses. Downgrading the evidence for imprecision was done if the 95% CI of the effect estimate crossed a clinical decision threshold. If the clinical decision threshold criteria was satisfied, the optimal information size (OIS) criterion for sample size and event rates for a 25% relative risk reduction was calculated. OIS was calculated as the sample size required for a single, adequately powered RCT (alpha 0.05, beta 0.80, control event rate equal to the pooled event rate in the control group for each comparison, effect size = relative risk 0.75 or 1 SD). Imprecision was considered present if the total number of participants included was less than optimal information size (OIS) for the outcome under consideration. {Guyatt 2011 }

In the interests of clarity and brevity, in the following paragraphs:

• · relative risk (RR), mean difference (MD) (and where relevant) absolute risk difference (ARD) and their 95% confidence intervals (CI) are presented in both text and tables if there was a statistically significant difference between intervention and comparison groups and for primary outcomes of the review.
• · Additional data, for comparisons where differences were not statistically significant are available in the tables for each comparison.

For assessment of risk of bias, Cochrane Risk of Bias 2 was used for randomized and pseudorandomized trials, {Sterne 2019 l4898} and ROBINS-I was used for observational studies. {Sterne 2016 i4919 }

Standard or routine hospital care for control groups appeared to have been variable in different studies. When this was uncertain or may have varied for different infants in the study, we used the term according to authors’ use. Few studies that were examining other interventions reported ambient temperatures.

Definitions used in the review

Comparison 1: Increased room temperature compared to no increased room temperature

The systematic review found a single cluster randomized trial involving 825 infants that examined operating room temperatures, not other birth locations (resulting in some indirectness with respect to the population the systematic review intended to address). The risk of bias for this study was considered very high because of the inevitable lack of blinding of study group allocation and of caregivers to the intervention.

The systematic review found one study enrolling 825 infants born by caesarean section at a single hospital. {Duryea 2016 505.e1}

In late preterm infants (≥ 34weeks gestation and term infants (or equivalent birth weight) born by caesarean section, an operating room temperature 23⁰C vs. an operating room temperature of 20⁰C:

• For the critical primary outcome survival to hospital discharge, there were no data.
• For the important primary outcome of normothermia on admission, there was possible clinical benefit; RR 1.26 95% CI 1.11 to 1.42, ARD 130 more per 1,000 (95% CI 55 more to 209 more) (very low certainty evidence, downgraded for very serious risk of bias and serious indirectness from one RCT enrolling 825 participants). {Duryea 2016 505.e1}

Among important secondary outcomes:

• For mean temperature on admission, there was possible clinical benefit (mean temperature 0.3ºC higher, 95% CI 0.23 to 0.37 higher) (very low certainty evidence, downgraded for very serious risk of bias and serious indirectness from one RCT enrolling 825 participants). {Duryea 2016 505.e1}
• For moderate hypothermia, there was possible clinical benefit (RR 0.26 95% CI 0.16 to 0.42, ARD 140 fewer per 1,000 (109 fewer to 158 fewer) (very low certainty evidence, downgraded for very serious risk of bias, and serious indirectness and imprecision from one RCT enrolling 825 participants). {Duryea 2016 505.e1}

The rationale for considering the beneficial effect moderate was that mean temperatures on admission were higher by 0.3ºC, a difference that was considered clinically significant.

Furthermore, for every 1000 infants exposed to an operating room temperature of 23ºC compared to a temperature of 20ºC

• From 55 more to 209 more were normothermic
• 109 fewer to 158 fewer were moderately hypothermic.

• For the important secondary outcome of hyperthermia , which was considered to be an adverse outcome in this and subsequent comparisons, clinical benefit or harm cannot be excluded (RR 4.13 95% CI 0.88 to 19.32) (very low certainty evidence, downgraded for very serious risk of bias, and serious indirectness and imprecision from one RCT enrolling 825 participants).

Comparison 2. Skin to skin care with a parent, vs no skin to skin care (routine hospital care as defined by study authors).

This systematic review found 10 randomised trials that addressed skin to skin care, when compared to no skin to skin care for late preterm and term infants. Findings were:

• For the critical primary outcome of survival to hospital discharge, clinical benefit or harm cannot be excluded (very low certainty evidence downgraded for very serious risk of bias and serious indirectness from one RCT enrolling 203 participants). {Ramani 2018 492}
• For the important primary outcome of normothermia on admission to a neonatal unit or postnatal ward, clinical benefit or harm cannot be excluded (RR 1.39, 95% CI 0.91 to 2.12) (very low certainty evidence, downgraded for very serious risk of bias, and serious inconsistency, indirectness and imprecision, from three RCTs enrolling 551 participants). {Ramani 2018 492, Safari 2018 32, Srivastava 2014 22}

For important secondary outcomes:

• Mean body temperature on admission was 0.32 ºC higher on admission (95% CI 0.10 – 0.54 ºC higher, I² = 95%) (very low certainty evidence, downgraded for very serious risk of bias and inconsistency and serious indirectness and imprecision from the pooled results of 8 RCTs enrolling 1048 infants). {Ramani 2018 492, Srivastava 2014 22, Safari 2018 32, Christensson 1992 488, Huang 2019 68, KoÇ 2017 1, Kollmann 2017 e0168783, Carfoot 2005 71}
• For hypoglycemia, there was possible clinical benefit (relative risk (RR) 0.16, 95% CI 0.05 – 0.53) (low certainty evidence, downgraded for very serious risk of bias and serious indirectness and imprecision from one RCT enrolling 326 infants). (KoÇ 2017 1)
• For admission to a neonatal special or intensive care unit, there was possible clinical benefit (RR 0.34, 95% CI 0.14 to 0.83, I²=0%) (very low certainty of evidence, downgraded for very serious risk of bias and serious indirectness and imprecision from three RCTs enrolling 512 participants) {Ramani 2018 492, Kollmann 2017 e0168783, Carfoot 2005 71}
• For severe hypothermia, the relative effect of skin to skin care was not calculable because there was a stated intention to report this outcome in only 1 RCT enrolling 203 infants, and there were no events in either group. {Ramani 2018 492}

The rationale for considering the overall effect moderate was that although no difference was found in primary or several secondary outcomes, mean temperatures on admission were higher by 0.32°C, a difference that was considered clinically significant. Furthermore, for every 100 infants exposed to skin to skin care compared to standard hospital care;

• from 15 fewer to 30 fewer were hypoglycemic

• • from 1 fewer to 6 fewer required admission to a neonatal intensive or special care unit.

• The review found no studies that reported whether skin to skin care, when compared to routine hospital care, altered rates of the important secondary outcome of hyperthermia or other adverse outcomes.

Comparison 3. Plastic bag or wrap compared to no plastic bag or wrap.

Note that for studies identified for this comparison, all studies used some other methods for maintaining normothermia in both study arms. This ‘other care’ included care under a radiant warmer or an incubator or a cot after drying and swaddling with a blanket with or without a head covering. Because of small numbers of studies, those that used drying prior to use of the plastic bag or wrap were combined with those that used no prior drying.

The systematic review found that for use of a plastic bag or wrap, (with or without prior drying) compared to no plastic bag or wrap (with drying):

• For the critical primary outcome of survival to hospital discharge, clinically significant benefit or harm cannot be excluded (very low certainty of evidence, downgraded for very serious risk of bias and inconsistency and serious indirectness and imprecision from 2 RCTs enrolling 305 participants). {Leadford 2013 e128, Shabeer 2018 1324}

• For the important primary outcome of normothermia on admission, there was possible clinical benefit RR; 1.50, 95% CI 1.20 to 1.89, ARD; 203 more per 1,000, 95% CI 81 more to 362 more) (very low certainty evidence, downgraded for very serious risk of bias and serious indirectness and imprecision from two RCTs enrolling 305 participants). {Leadford 2013 e128, Shabeer 2018 1324}

Among important secondary outcomes:

• For body temperature on admission, there was possible clinical benefit (MD; 0.2ºC 95% CI 0.2 to 0.38, I²=22%) (very low certainty evidence, downgraded for very serious risk of bias and serious indirectness from three RCTs enrolling 425 participants). {Cardona-Torres 2012 129, Leadford 2013 e128, Shabeer 2018 1324}
• For any hypothermia <36.5ºC, there was possible clinical benefit (RR; 0.57 95% CI 0.45 to 0.73, ARD; 204 fewer per 1,000 95% CI 261 fewer to 128 fewer) (very low certainty evidence, downgraded for very serious risk of bias and serious indirectness and imprecision from three RCTs enrolling 425 participants). {Cardona-Torres 2012 129, Leadford 2013 e128, Shabeer 2018 1324}
• For hypothermia <35ºC, there was possible clinical benefit (RR; 0.21 95% CI 0.05 to 0.91, ARD; 40 fewer per 1,000, 95% CI 48 fewer to 4 fewer) (very low certainty evidence, downgraded for serious risk of bias and serious indirectness and imprecision from two RCTs enrolling 400 participants). {Cardona-Torres 2012 129, Shabeer 2018 1324}

The rationale for considering the overall effect moderate was that although no difference was demonstrated for either primary or several secondary outcomes (or there were no data), mean temperatures on admission were higher by 0.29°C, a difference that was considered clinically significant.

Furthermore, for every 1000 infants exposed to a plastic bag or wrap (with our without prior drying) compared to no plastic bag or wrap;

• from 81 more to 362 more were normothermic
• from 128 fewer to 261 fewer had hypothermia <36.5ºC
• from 4 fewer to 48 fewer had hypothermia <35ºC

For the important secondary outcome of hyperthermia, clinical benefit or harm could not be excluded (very low certainty evidence from 3 RCTs enrolling 425 participants, downgraded for serious indirectness and very serious imprecision). {Cardona-Torres 2012 129, Johanson 1992 859, Shabeer 2018 1324}

Comparison 4. Plastic bag or wrap combined with skin to skin care with a parent, vs skin to skin care alone.

The systematic review found two RCTs comparing using a plastic bag or wrap, compared to no plastic bag or wrap for late preterm and term infants who are receiving skin to skin care. Findings were:

• For the critical primary outcome survival to hospital discharge, reported on by one RCT enrolling 271 participants, there was 100% survival in both groups. {Belsches 2013 e656}
• For the important primary outcome of normothermia on admission, there was possible benefit (relative risk (RR) 1.39 95% confidence intervals (CI) 1.08 to 1.79 I²=0%, ARD; 86 more per 1,000 95% CI 18 more to 174 more) (low certainty evidence, downgraded for serious indirectness and imprecision from 2 RCTs enrolling 692 participants). {Belsches 2013 e656, Travers 2021 55}

Among important secondary outcomes:

• For mean temperature on admission there was possible clinical benefit (mean temperature 0.2ºC higher, 95% CI 0.1 to 0.3ºC higher I²=0%) (low certainty evidence, downgraded for serious indirectness and imprecision from two RCTs enrolling 692 participants). {Belsches 2013 e656, Travers 2021 55}
• For hypoglycemia, the only study reporting this outcome did not provide a breakdown by study group, so no analysis was possible.
• For hypothermia <36.5ºC there was possible clinical benefit (RR 0.89 95% CIS 0.81 to 0.97, I² 30% ARD 85 fewer per 1,000 95% CI 148 fewer to 23 fewer) (low certainty evidence, downgraded for serious indirectness and imprecision from two RCTs enrolling 692 participants). {Belsches 2013 e656, Travers 2021 55}

• For moderate hypothermia, there was possible clinical benefit (RR 0.66 95% CI 0.54 to 0.81,I²=5%, ARD 148 fewer per 1,000 95% CI 200 fewer to 83 fewer) (low certainty evidence, downgraded for serious indirectness and imprecision from two RCTs enrolling 692 participants). {Belsches 2013 e656, Travers 2021 55}

The rationale for considering the effect moderate was that for every 1000 infants exposed to a plastic bag or wrap with skin to skin care, compared to skin to skin care alone

• From 18 more to 174 more were normothermic
• 23 fewer to 148 fewer were hypothermic <36.5ºC
• 83 fewer to 200 fewer were moderately hypothermic.

Mean temperatures on admission were higher by 0.2ºC, however, this difference that was considered to be of only marginal clinical significance because the mean temperatures remained in the cold-stressed range.

For the important secondary outcome of hyperthermia, clinical benefit or harm could not be excluded (very low certainty evidence, downgraded for serious indirectness and very serious imprecision from two RCTs enrolling 692 participants). {Belsches 2013 e656, Travers 2021 55}

Evidence to decision tables were not developed for the following comparisons, although studies were found, because of the lack of statistical and/or clinical significance, and because all provided very low certainty evidence.

Comparison 5. Thermal mattress vs. no thermal mattress

The systematic review found no studies that examined thermal mattresses. However, one RCT enrolling infants who were admitted to neonatal unit at a single hospital in a three arm study, compared the addition of either a plastic bag or a commercially available thermal nest (a combination of a warming pack comprised of phase changing material plus a swaddling device) to routine hospital care (which included room temperature ≥25°C, drying, swaddling in a towel, a cotton cap and a radiant warmer). {Shabeer 2018 1324}. Among the 199 infants in the study for whom the comparison between the thermal nest and standard hospital care applied, the only significant outcome difference (among 7 outcomes relevant to the review that were reported) was an increase in body temperature in the thermal nest group (MD 0.2°C, 95% CI 0.07 to 0.33°C). Various relative risks for other outcomes fell on both sides of the line of no effect. Thus this study was not considered sufficient to make a recommendation for practice, so an evidence to decision table was not constructed and further results are not presented. Evidence for all outcomes was very low certainty, downgraded for serious indirectness and imprecision.

Comparison 6. Plastic bag or wrap with drying compared to plastic bag or wrap without drying

The review found one RCT enrolling 60 participants that examined two secondary outcomes relevant to the review and found no significant differences. {Cardona-Torres 2012 129}

Comparison 7. Plastic bag or wrap without drying compared to a thermal mattress

The review found no studies that compared with a thermal mattress. However, one three-arm RCT enrolling 299 participants, in 200 participants compared a plastic bag or wrap to a thermal nest (see comparison 5). The study examined seven outcomes relevant to the review and found no significant differences. {Shabeer 2018 1324}

Comparison 8. Early skin to skin care compared to later skin to skin care.

The review found two RCTs enrolling 87 participants that together, examined four outcomes relevant to the review. {Crenshaw 2019 731, Walsh 2021 95} There were no significant differences for three of these outcomes. One study enrolling 47 participants found a difference in the rate of normothermia favouring early skin to skin group, but the very small sample size and the serious risk of bias, indirectness and imprecision led to a decision to not develop an Evidence to Decision table. {Walsh 2021 95}

Comparison 9. Continuously active warming blankets with skin to skin care compared to standard hospital care.

The review found one RCT enrolling 139 participants that examined one outcome relevant to the review and found no significant difference. {Stirparo 2013 186}

Comparison 10. Skin to skin care compared to a plastic bag or wrap.

The review found one RCT enrolling 197 participants that examined two outcomes relevant to the review and found no significant differences. {Johanson 1992 859}

Comparison 11. Woollen vs cotton cap

The review found one RCT enrolling 126 participants that examined two outcomes relevant to the review and found small differences in mean temperature and the rate of moderate hypothermia favouring the woollen cap group. {Lang 2004 843}

Subgroup analyses

There were insufficient data to conduct any of the prespecified subgroup analyses (by gestation groups, early vs later umbilical cord clamping, by low- vs high-resourced setting or by inborn vs outborn status) for any comparison.

For the following comparisons, or for any combination of these interventions, the systematic review found no RCTs:

• · Heating and humidification of gases used for resuscitation, vs. any other intervention or standard hospital care
• · The use of a radiant warmer, vs any other intervention or standard hospital care
• · Early monitoring of temperature vs no early monitoring of temperature
• · Warm bags of fluid compared to any other intervention or standard hospital care
• · Warmed swaddling/clothing vs any other intervention or standard hospital care

Observational studies and quality improvement studies

In addition to the RCTs or quasi-RCTs described above, the systematic review found 10 observational studies. {Agudelo 2020 105020, Albuquerque 2016 e2741, Aley-Raz 2020 476, Andrews 2018 e20171214, Datta 2017 e000183, Hill 1979 287, Nissen 2019 1, Patodia 2021 277, Shaw 2018 126, Sprecher 2021 270} Six of these studies used quality improvement (QI) methodology and examined multifaceted interventions. {Aley-Raz 2020 476, Andrews 2018 e20171214, Datta 2017 e000183, Patodia 2021 277, Shaw 2018 126, Sprecher 2021 270} These studies did not allow any definite conclusions to be drawn about the effectiveness of any component intervention. The overall risk of bias for all 10 studies was rated as serious or critical for all outcomes. Because of this and a high degree of heterogeneity in the interventions used, meta-analysis was not performed, and individual studies are difficult to interpret.

Of the QI studies that used methods such as “plan-do-study-act” cycles to reduce risk of hypothermia in newborn infants, all demonstrated improvements. {Aley-Raz 2020 476, Andrews 2018 e20171214, Datta 2017 e000183, Patodia 2021 277, Shaw 2018 126, Sprecher 2021 270} However, only one of the included studies described a sufficient ‘post-intervention’ phase to confirm sustainability of the interventions. {Patodia 2021 277}

Nevertheless, taken together, these studies suggest that hypothermia can be a common problem among late preterm and term infants in both low-income and high-income settings. They also suggest that multidisciplinary teams, working together to recognize local place, people, policy and procedure contributors to risk, and to test the effect of locally devised solutions, may be an effective way to reduce rates of hypothermia.

Treatment Recommendations

• In late preterm and term infants (≥34 weeks' gestation), we suggest the use of room temperatures of 23ºC compared to 20ºC at birth in order to maintain normal temperatures (weak recommendation, very low certainty evidence).
• In late preterm and term infants (≥34 weeks' gestation) at low risk of needing resuscitation, we suggest the use of skin to skin care immediately after birth rather than no skin to skin care to maintain normal temperature (weak recommendation, very low certainty evidence).
• The NLS Task Force considered that in late preterm and term infants ≥34 weeks' gestation, for routine use of a plastic bag or wrap vs no plastic bag or wrap, the balance of desirable and undesirable effects was uncertain and the certainty of evidence was very low. Furthermore, cultural values and maternal preferences in relation to this specific intervention and cost implications are not known, and therefore no treatment recommendation for routine use can be formulated. The NLS Task Force considered it important to promote skin to skin care. In some situations where skin to skin care is not possible, it is reasonable to consider the use of a plastic bag or wrap, among other measures to maintain normal temperature (weak recommendation, very low certainty evidence).
• The Task Force considered that in late preterm and term infants ≥34 weeks' gestation, for routine use of a plastic bag or wrap in addition to skin to skin care immediately after birth compared to skin to skin care alone, the balance of desirable and undesirable effects was uncertain. Furthermore, the cultural values and maternal preferences in relation to the use of plastic bags or wraps and the cost implications are not known, and therefore no treatment recommendation can be formulated.

Justification and Evidence to Decision Framework highlights

Overall Statements

• This topic was prioritized by the NLS Task Force because a systematic review conducted for ILCOR concluded that "For the critical outcome of mortality, there is evidence from 36 observational studies of increased risk of mortality associated with hypothermia at admission (low-quality evidence but upgraded to moderate-quality evidence due to effect size, dose-effect relationship, and single direction of evidence)". {Perlman 2015 S204} The same systematic review concluded that "There is evidence of a dose effect on mortality, suggesting an increased risk of at least 28% for each 1° below 36.5°C body temperature at admission and dose-dependent effect size". {Perlman 2015 S204} Although the size of effect in this estimate was influenced by inclusion of studies that enrolled very preterm infants, there was also evidence of adverse effects of hypothermia on survival in late preterm and term infants. Due to compilation of literature since the publication of the 2015 CoSTR, the Task Force was aware that new RCTs and observational studies had been published since the prior review.
• In making these recommendations, the NLS Task Force considered that the results of the review found evidence to support three treatment recommendations, without evidence of adverse effects.
• Although cost-effectiveness has not been accurately estimated, each of these interventions was thought likely to be of low to very low cost, which together with the balance of effects justifies their use despite what were moderate effects and low to very low certainty evidence. The suggested interventions were considered likely to be feasible.
• The interventions involving the use of skin to skin care is likely to improve equity, because of the low cost and because feasibility seems likely or has been demonstrated in low or middle income countries. Room temperatures may or may not be able to be easily and cost-effectively adjusted in various settings. Where a room temperature of 23^oC cannot be achieved, the importance of skin to skin care may be greater.

Detailed justification for raising room temperature:

• In the included study, raising operating room temperature to 23ºC appeared to be safe for most infants born by caesarean section, improved their body temperatures and reduced the risk of hypothermia, when compared to 20ºC. However, the certainty of evidence is very low.
• Although more infants became hyperthermic in the higher operating room group in the one included study (not statistically significant), hypothermia was avoided in many more. Maternal hypothermia was also reduced. The balance of effects is likely to favour operating room temperatures of 23ºC vs 20ºC.
• Because of the location and selection criteria for the one included study, the effects on infants other than those born by caesarean section are unknown. Although only operating room temperatures were studied, the NLS Task Force considered the effects were likely to apply to other birth locations.
• Although only a small increment in body temperature was noted, it was considered clinically significant, because maintaining normal temperature may take a combination of interventions, each making a small contribution. Raising delivery room temperatures to 23ºC to 25ºC has been recommended among a combination of interventions to maintain norm for preterm newborn infants <32 weeks’ gestation. {Perlman 2015 S204}
• Several included quality improvement studies confirmed feasibility, but the resources required, and effects on equity have not been assessed.

Detailed justification for skin to skin care

• Skin to skin care is simple, appears to be safe for most infants and improves their body temperatures, when compared to no skin to skin care. However, because of the selection criteria of included studies, there is insufficient evidence to make a recommendation for infants at high risk of needing resuscitation.
• Skin to skin care, when compared with standard hospital care, increased body temperatures on admission to a neonatal unit or postnatal ward, and reduced the risk of hypoglycaemia, and admission. No benefits were found for other outcomes of the review, but small samples, study selection criteria and the limited range of outcomes reported by several of the included studies may have limited the detection of benefits.
• No undesirable effects were identified. None of the included studies reported hyperthermia.
• Most of the evidence is very low certainty. Importantly, most studies excluded mothers who were not well, and infants who had needed or were at risk of needing resuscitation. Infants 34-36 weeks gestation were under-represented among the included studies.
• The balance of effects is likely to favour skin to skin care commenced within minutes after birth over other care, which in most studies consisted of drying and wrapping the infant, and placing the baby in a hospital cot. There are other well-described benefits of skin to skin care for the ongoing care of neonates.
• The task force noted the possibility of unmeasured risks of skin to skin care. These could include accidental newborn suffocation. However, the risks of uncommon or rare serious life-threatening events have not been compared in sufficient-sized studies to determine whether the rate is higher with skin to skin care or routine hospital care.
• Skin to skin care from immediately after birth is likely to be cost-effective, acceptable and feasible in high, middle and low income countries.

Detailed justification for use of plastic bags or wraps

• The systematic review found evidence to support the use of a plastic bag or wrap in the setting of standard hospital care to improve rates of normothermia and reduce risk of hypothermia in late preterm or term newborn infants (≥34 weeks' gestation, or equivalent birth weight) without evidence of adverse effects. Because of a low number of studies and enrolled infants, studies with and without prior drying were combined. The certainty of evidence was very low for all outcomes.
• Because of a low number of studies and enrolled infants, studies with and without prior drying were combined in the meta-analysis.
• The Task Force was concerned that there may be unmeasured adverse effects, such as adverse effects on establishment of a normal neonatal microbiome and on promotion of early breast feeding.
• There was also concern that the plastic bag or wrap might be regarded as a substitute to encouraging skin to skin care.
• The resources required are likely to be inexpensive, but costs may be large if the intervention is applied to all newborn infants. A clean, food-grade plastic bag or wrap is necessary, but costs may increase if purpose-designed sterile bags packaged for clinical use are used. Cost-effectiveness is unknown, but could be positive if improved rates of normothermia and avoidance of hypothermia results in avoidance of any admissions to a neonatal special or intensive care unit.
• Use of this low-cost fairly simple intervention may improve equity. The four studies suggesting benefit were conducted in middle- or low-income countries, suggesting feasibility in these settings. However, the overall effect on equity remains unknown. Equity could be adversely affected if use of plastic bags or wraps was diverted from more preterm infants for who potential to benefit is greater.

Detailed justification for no recommendation for plastic bag or wrap combined with skin to skin care

• The systematic review found evidence to support the use of a plastic bag or wrap as an adjunct to skin to skin care to improve rates of normothermia and reduce risk of any hypothermia or moderate hypothermia in late preterm or term newborn infants (≥34 weeks' gestation, or equivalent birth weight) without evidence of adverse effects. However, the overall balance of risks and benefits was considered to be uncertain.
• The certainty of the evidence was low or very low for all analysable outcomes.
• Despite the findings of the review, the Task Force remained uncertain about the balance of effects. There was concern plastic bags or wraps might impair the acceptability or safety of skin to skin care, and thereby cause harm.
• The resources required are likely to be inexpensive for individual babies, but costs may be a barrier if the intervention is applied to a high proportion of births. The cost-effectiveness is unknown, but could be positive if any admissions to a neonatal special or intensive care unit are prevented, or if confidence in and uptake of skin to skin care is improved.
• Use of this low-cost fairly simple intervention could improve equity. The two studies suggesting benefit were conducted in low-income countries, and suggested feasibility in these settings. However, the full range of effects on equity is unknown.

Knowledge Gaps

• The balance of risks and benefits for each evidence-based intervention when combined with other interventions is unknown or highly uncertain.
• There is a need for studies to examine the effectiveness of interventions for which no evidence was available or for which evidence was insufficient to make treatment recommendations. The Task Force considered that priorities among these included:
• Use of a thermal mattress, which may assume greater importance if a parent is unable to provide skin to skin care
• Caps made of various materials
• Use of heated, humidified gases for resuscitation, for those infants who receive assisted ventilation, particularly in the context of advanced resuscitation
• Early monitoring of temperature vs no early monitoring of temperature
• The role of low or moderately low-cost interventions such as prewarmed bags of IV fluid placed around the baby, or prewarmed swaddling and clothing.
• The effect of maternal hypothermia or hyperthermia on newborn infants’ temperatures.
• Since nearly all the included studies excluded infants who received or were at high risk of receiving resuscitation, more studies are needed to determine the best methods of maintaining normothermia in these infants.
• Standardising the timing and method of recording temperature for all infants would enhance the potential both for benchmarking and for meta-analysis of studies in future reviews.

Gaps in relation to room temperature:

• The balance of risks and benefits when combined with other measures to maintain normothermia (e.g. skin to skin care, plastic bag or wrap).
• The effect of other set temperatures (besides 20ºC or 23ºC) for operating room or birthing room temperatures.
• The effect of measures to control room temperatures in various settings on risk of airborne diseases.
• Whether the results found for operating room temperatures are applicable to other birthing locations.

Gaps in relation to skin to skin care

• The role of skin to skin care in maintaining normal temperature in babies requiring the resuscitation: (a) Can some resuscitation manoeuvres be performed during skin to skin care and (b) for infants who have required some resuscitation interventions, when can skin to skin care be safely commenced?
• The role of skin to skin care in maintaining normal temperature in the setting of delayed umbilical cord clamping.
• The balance of risks and benefits of skin to skin care in the setting of various ambient temperatures.

Gaps in relation to use of plastic bags or wraps

• The balance of risks and benefits of plastic bag or wrap in the setting of various ambient temperatures and maternal temperatures, and depending on the use of other concomitant measures to maintain normothermia in late preterm and term infants.
• Is there a role for adding a plastic bag or wrap as a serial or supplementary intervention, if other measures are insufficient?
• The role of plastic bags or wraps for out-of-facility births.
• The acceptability to parents and carers

Gaps in relation to use of a plastic bag or wrap with skin to skin care

• The balance of risks and benefits of plastic bag or wrap in combination with skin to skin care in the setting of various ambient temperatures, and depending on the use of other concomitant measures to maintain normothermia in late preterm and term infants.
• Is there a role for adding use of a plastic bag or wrap as a serial or supplementary intervention, if skin to skin care alone is insufficient to maintain normothermia, with the goal of sustaining skin to skin care?
• The acceptability to mothers and clinicians of addition of a plastic bag or wrap, in the setting of provision of skin to skin care.

Attachments

NLS 5100 Maintain Temp Et D Tables all for comparisons

References

Agudelo S, Diaz D, Maldonado MJ, Acuna E, Mainero D, Perez O, et al. Effect of skin-to-skin contact at birth on early neonatal hospitalization. Early Hum Dev. 2020;144:105020.

Albuquerque RS, Mariani CN, Bersusa AA, Dias VM, Silva MI. Newborns' temperature submitted to radiant heat and to the Top Maternal device at birth. Rev Lat Am Enfermagem. 2016;24:e2741.

Aley-Raz ES, Talmon G, Peniakov M, Hasanein J, Felszer-Fisch C, Weiner SA. Reducing neonatal hypothermia in premature infants in an israeli neonatal intensive care unit. Israel Medical Association Journal. 2020;22(9):476-480.

Andrews C, Whatley C, Smith M, Brayton EC, Simone S, Holmes AV. Quality-Improvement Effort to Reduce Hypothermia Among High-Risk Infants on a Mother-Infant Unit. Pediatrics. 2018;141(3):e20171214.

Belsches TC, Tilly AE, Miller TR, Kambeyanda RH, Leadford A, Manasyan A, et al. Randomized trial of plastic bags to prevent term neonatal hypothermia in a resource-poor setting. Pediatrics. 2013;132(3):e656-61.

Cardona-Torres LM, Amador-Licona N, Garcia-Campos ML, Guizar-Mendoza JM. Polyethylene wrap for thermoregulation in the preterm infant: a randomized trial. Indian Pediatrics. 2012;49:129‐132.

Carfoot S, Williamson P, Dickson R. A randomised controlled trial in the north of England examining the effects of skin-to-skin care on breast feeding. Midwifery. 2005;21(1):71-9.

Christensson K, Siles C, Moreno L, Belaustequi A, De La Fuente P, Lagercrantz H, et al. Temperature, metabolic adaptation and crying in healthy full-term newborns cared for skin-to-skin or in a cot. Acta Paediatrica. 1992;81(6-7):488-493.

Crenshaw JT, Adams ED, Gilder RE, DeButy K, Scheffer KL. Effects of Skin-to-Skin Care During Cesareans: A Quasiexperimental Feasibility/Pilot Study. Breastfeed Med. 2019;14(10):731-743.

Datta V, Saili A, Goel S, Sooden A, Singh M, Vaid S, et al. Reducing hypothermia in newborns admitted to a neonatal care unit in a large academic hospital in New Delhi, India. BMJ Open Qual. 2017;6(2):e000183.

Duryea EL, Nelson DB, Wyckoff MH, Grant EN, Tao W, Sadana N, et al. The impact of ambient operating room temperature on neonatal and maternal hypothermia and associated morbidities: a randomized controlled trial. Am J Obstet Gynecol. 2016;214(4):505.e1-505.e7.

Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):383-94.

Guyatt GH, Oxman AD, Kunz R, Brozek J, Alonso-Coello P, Rind D, et al. GRADE guidelines 6. Rating the quality of evidence--imprecision. J Clin Epidemiol. 2011;64(12):1283-93.

Hill ST, Shronk LK. The effect of early parent-infant contact on newborn body temperature. JOGN Nurs. 1979;8(5):287-90.

Huang X, Chen L, Zhang L. Effects of Paternal Skin-to-Skin Contact in Newborns and Fathers After Cesarean Delivery. J Perinat Neonatal Nurs. 2019;33(1):68-73.

Johanson RB, Spencer SA, Rolfe P, Jones P, Malla DS. Effect of post-delivery care on neonatal body temperature. Acta Paediatr. 1992;81(11):859-63.

KoÇ S, Kaya N. Effect of Kangaroo Care at Birth on Physiological Parameters of Healthy Newborns. Turkish Journal of Research & Development in Nursing. 2017;19(1):1-13.

Kollmann M, Aldrian L, Scheuchenegger A, Mautner E, Herzog SA, Urlesberger B, et al. Early skin-to-skin contact after cesarean section: A randomized clinical pilot study. PLoS One. 2017;12(2):e0168783.

Lang N, Bromiker R, Arad I. The effect of wool vs. cotton head covering and length of stay with the mother following delivery on infant temperature. Int J Nurs Stud. 2004;41(8):843-6.

Leadford AE, Warren JB, Manasyan A, Chomba E, Salas AA, Schelonka R, et al. Plastic bags for prevention of hypothermia in preterm and low birth weight infants. Pediatrics. 2013;132(1):e128-34.

Lunze K, Bloom DE, Jamison DT, Hamer DH. The global burden of neonatal hypothermia: systematic review of a major challenge for newborn survival. BMC Med. 2013;11:24.

Marín Gabriel MA, Llana Martín I, López Escobar A, Fernández Villalba E, Romero Blanco I, Touza Pol P. Randomized controlled trial of early skin-to-skin contact: effects on the mother and the newborn. Acta Paediatr. 2010;99(11):1630-4.

Nissen E, Svensson K, Mbalinda S, Brimdyr K, Waiswa P, Odongkara BM, et al. A low-cost intervention to promote immediate skin-to-skin contact and improve temperature regulation in Northern Uganda. African Journal of Midwifery & Women's Health. 2019;13(3):1-12.

Patodia J, Mittal J, Sharma V, Verma M, Rathi M, Kumar N, et al. Reducing admission hypothermia in newborns at a tertiary care NICU of northern India: A quality improvement study. J Neonatal Perinatal Med. 2021;14(2):277-286.

Perlman JM, Wyllie J, Kattwinkel J, Wyckoff MH, Aziz K, Guinsburg R, et al. Part 7: neonatal resuscitation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation. 2015;132(suppl 1)(16):S204‒S241.

R Core Team. R: A language and environment for statistical computing V3.5.2 Vienna Austria: R Core Team,; 2019 [Available from: https://www.r-project.org/.

Ramani M, Choe EA, Major M, Newton R, Mwenechanya M, Travers CP, et al. Kangaroo mother care for the prevention of neonatal hypothermia: a randomised controlled trial in term neonates. Arch Dis Child. 2018;103(5):492-497.

Safari K, Saeed AA, Hasan SS, Moghaddam-Banaem L. The effect of mother and newborn early skin-to-skin contact on initiation of breastfeeding, newborn temperature and duration of third stage of labor. Int Breastfeed J. 2018;13:32.

Shabeer MP, Abiramalatha T, Devakirubai D, Rebekah G, Thomas N. Standard care with plastic bag or portable thermal nest to prevent hypothermia at birth: a three-armed randomized controlled trial. J Perinatol. 2018;38(10):1324-1330.

Shaw SC, Devgan A, Anila S, Anushree N, Debnath H. Use of Plan-Do-Study-Act cycles to decrease incidence of neonatal hypothermia in the labor room. Med J Armed Forces India. 2018;74(2):126-132.

Sprecher A, Malin K, Finley D, Lembke P, Keller S, Grippe A, et al. Quality Improvement Approach to Reducing Admission Hypothermia Among Preterm and Term Infants. Hosp Pediatr. 2021;11(3):270-276.

Srivastava S, Gupta A, Bhatnagar A, Dutta S. Effect of very early skin to skin contact on success at breastfeeding and preventing early hypothermia in neonates. Indian J Public Health. 2014;58(1):22-6.

Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. Bmj. 2016;355:i4919.

Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. Bmj. 2019;366:l4898.

Stirparo S, Farcomeni A, Laudani A, Capogna G. Maintaining Neonatal Normothermia during WHO Rec-ommended Skin-to-Skin Contact in the Setting of Cesarean Section under Regional Anesthesia. Open Journal of Anesthesiology. 2013;3(3):186-188.

Travers CP, Ramani M, Gentle SJ, Schuyler A, Brown C, Dills MM, et al. Early Skin-to-Skin Care with a Polyethylene Bag for Neonatal Hypothermia: A Randomized Clinical Trial. J Pediatr. 2021;231:55-60.e1.

Walsh RS, Payne A, Cossler NJ, Thompson CL, Bhola M. Safety of immediate skin-to-skin contact after vaginal birth in vigorous late preterm neonates - A pilot study. J Neonatal Perinatal Med. 2021;14(1):95-100.

WHO. Thermal protection of the newborn: a practical guide. Maternal and Newborn Health/Safe Motherhood Unit [Internet]. 1997 8 February 2021:[2 p.]. Available from: https://apps.who.int/iris/bitstream/handle/10665/63986/WHO_RHT_MSM_97.2.pdf.