MANUSCRIPT CITATION:

Abiramalatha T, Ramaswamy VV, Bandyopadhyay T, Pullattayil AK, Thanigainathan S, Trevisanuto D, Roehr CC. Delivery Room Interventions for Hypothermia in Preterm Neonates: A Systematic Review and Network Meta-analysis. JAMA Pediatr. 2021 May 24:e210775. doi: 10.1001/jamapediatrics.2021.0775. Epub ahead of print. PMID: 34028513.

REVIEWED BY: 

Islam Nour
Associate Professor of Pediatrics,
Department of Pediatrics/Neonatology, Mansoura University Children’s Hospital, Mansoura, Egypt.

Nehad Nasef
Professor of Pediatrics,
Department of Pediatrics/Neonatology, Mansoura University Children’s Hospital, Mansoura, Egypt.

Hesham Abdel-Hady
Professor of Pediatrics,
Department of Pediatrics/Neonatology, Mansoura University Children’s Hospital, Mansoura, Egypt.

TYPE OF INVESTIGATION: 

Prevention

QUESTION: 

(P) In preterm infants born ≤ 36 weeks of gestation, (I) does thermal care interventions in delivery room (C) compared to usual care, (O) affect core body temperature and incidence of moderate to severe hypothermia (T) on admission or within the first 2 hours of life.

METHODS: 

• Design: Systematic review and network meta-analysis
• Type of studies: Randomized clinical trials (RCTs) and quasi-RCTs.
• Blinding: Participants and therapist were not blinded for all studies; the outcome assessors were masked in 2 trials (6%).
• Follow-up period: Two hours post-intervention up to discharge.
• Setting: All studies were conducted in a hospital setting.
• Patients:
  • Inclusion criteria: preterm neonates born ≤36weeks of gestation
  • Exclusion criteria: term infants or infants with birth weight greater than 2500 g
• Intervention:
  • The following nine thermal care interventions in the delivery room were included: (1) plastic bag or plastic wrap covering the torso and limbs with the head uncovered or covered with a cloth cap; (2) plastic cap covering the head; (3) skin-to-skin contact; (4) thermal mattress; (5) plastic bag or plastic wrap covering the torso and limbs with the head covered with a plastic cap (6) plastic bag or plastic wrap covering the torso and limbs along with use of a thermal mattress; (7) plastic bag or plastic wrap covering the torso and limbs along with heated humidified gas for resuscitation or for initiating invasive or noninvasive respiratory support in the delivery room; (8) plastic bag or plastic wrap covering the torso and limbs along with an incubator for transporting from the delivery room; and (9) routine care, including drying and covering the body with warm blankets, with or without a cloth cap.
• Outcomes:
  • Primary outcome: core body temperature and incidence of moderate to severe hypothermia (defined as body temperature <36 °C) on admission or within the first 2 hours of life.
  • Secondary outcomes: incidence of hyperthermia (defined as body temperature >37.5 °C), major brain injury (grade 3 or 4 intraventricular hemorrhage or periventricular leukomalacia), and mortality before discharge.
• Analysis and Sample Size:
  • The authors performed network meta-analysis with bayesian random effects model
  • Ranking of interventions was done with surface under the cumulative ranking curve (SUCRA) plots. SUCRA values ranging from 0% to 100%.
  • The authors did the following sensitivity analyses:(1) neonates born at 30 weeks’ gestation or less; (2) plastic bag and plastic wrap as separate interventions; (3) drying versus no drying before application of plastic bag or wrap; and (4) incidence of any hypothermia defined as a core body temperature<36.5 °C at admission or within the first 2 hours of life.

MAIN RESULTS:

• A total of 34 trials with 3688 infants were included with a mean gestational age 29 weeks and mean birth weight of 1200 grams.
• Plastic bag or wrap with a thermal mattress (MD, 0.98 °C; 95% CrI, 0.60-1.36 °C; low certainty of evidence), plastic cap (MD, 0.83 °C; 95%CrI, 0.28-1.38 °C; moderate certainty of evidence), plastic bag or wrap with heated humidified respiratory gas (MD, 0.76 °C; 95% CrI, 0.38-1.15 °C; moderate certainty of evidence), plastic bag or wrap with a plastic cap(MD,0.62 °C; 95% CrI,0.37-0.88°C; moderate certainty of evidence), thermal mattress (MD,0.62 °C; 95% CrI, 0.33-0.93 °C), and plastic bag or wrap alone (MD, 0.56 °C; 95% CrI, 0.44-0.69 °C; moderate certainty of evidence) were associated with significantly higher axillary or rectal temperature recordings at admission or within 2 hours of life compared with routine care.
• Three interventions were associated with a reduced risk of moderate to severe hypothermia at admission or within 2 hours of life compared with routine care, including: Plastic bag or wrap alone (RR, 0.23; 95% CrI, 0.04-0.55; moderate certainty of evidence), thermal mattress (RR, 0.12; 95% CrI, 0.00-0.62 ; low certainty of evidence), and plastic bag or wrap with heated humidified gas (RR, 0.12; 95% CrI, 0.00-0.47; low certainty of evidence).
• Only direct evidence from pairwise meta-analysis revealed an increased risk of hyperthermia for plastic bag or wrap alone vs routine care (RR, 3.39; 95%CrI, 1.84-6.25) as well as for plastic bag or wrap with a thermal mattress vs plastic bag or wrap alone (RR, 2.25; 95%CrI, 1.13-4.50).When compared with routine care, plastic bag or wrap with heated humidified gas was associated with decreased risk of major brain injury compared with routine care (RR, 0.23; 95% CrI, 0.03-0.67; moderate certainty of evidence).
• Plastic bag or wrap with a plastic cap was associated with decreased risk of mortality before discharge when compared with routine care (RR,0.19; 95%CrI,0.02-0.66; low certainty of evidence).

CONCLUSION:

The authors conclude that moderate certainty evidence denotes most of the thermal care interventions at delivery room were associated with improved core body temperature. Use of a plastic bag or wrap with heated humidified gas was associated with reduced risk of major brain injury (with moderate certainty of evidence) and a plastic bag or wrap with a plastic cap was associated with lower risk of mortality (with low certainty of evidence).

COMMENTARY:

Preterm neonates are at increased risk for hypothermia after birth which is an independent predictor for neonatal mortality and morbidity. (1,2) Maintaining normal temperature is a key initial step in stabilization of the newborn at birth. (3) Several interventions to prevent hypothermia in the delivery room have been studied either solely or in combinations. (4–7) The neonatal life support task force suggested using a combination of different interventions to prevent hypothermia on neonatal admission to the NICU. (3)  However, this suggestion was based on relatively old evidence with weak recommendations and very low-certainty.

This network meta-analysis was conducted on 34 randomized and quasi-randomized controlled trials including 3688 preterm, ≤ 36 weeks gestation, infants aiming to identify thermal care intervention in the delivery room that can best reduce neonatal hypothermia and improve clinical outcomes. The researchers compared eight interventions to routine care and found that most of the interventions were associated with higher core body temperature. They found that plastic bag or wrap alone, thermal mattress, and plastic bag or wrap with heated humidified gas were associated with reduced risk of moderate to severe hypothermia compared with routine care. The SUCRA analysis showed that the combination of plastic bag or wrap with a thermal mattress was the best intervention to improve core body temperature at admission but direct evidence from pair-wise comparisons indicated that this combination increases the risk of hyperthermia. In sensitivity analyses, plastic bag and plastic wrap were equally good at maintaining core body temperature, the effect of interventions in improving temperature was consistent among preterm infants ≤ 30 weeks gestation, and drying did not make a difference compared to no drying before the application of plastic bag or wrap. Authors found that the use of a plastic bag or wrap with heated humidified gas was associated with reduced risk of major brain injury and a plastic bag or wrap with a plastic cap was associated with lower risk of mortality.

Major strengths of this study are the use of network meta-analysis which can inform comparative effectiveness in the presence multiple interventions, the systematic search strategy, and clinically relevant interventions and outcomes. However, the study is limited by wide differences in the method of temperature measurement between included trials, inability to perform analysis of some secondary outcomes due to data limitation, small sample size of the included trials and low event rates for the primary outcome leading to possible selective reporting and publication bias, and inability to access unpublished data from the included studies. (5)

Although, the majority of thermal care interventions were associated with better core body temperature and decreased risk of moderate to severe hypothermia at admission or within the first 2 hours of life compared with routine care, the certainty of evidence ranged from very-low to moderate for the primary and secondary outcomes. Future, adequately powered, randomized controlled trials are needed to determine the best combination of interventions to prevent hypothermia with no risk of hyperthermia and to assess quality-improvement bundle of hypothermia preventive measures to assess the individual benefit for each newborn.

REFERENCES:

1. 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.
2. de Almeida MFB, Guinsburg R, Sancho GA, Rosa IRM, Lamy ZC, Martinez FE, et al. Hypothermia and Early Neonatal Mortality in Preterm Infants. J Pediatr 2014; 164:271–275.e1.
3. Wyckoff MH, Wyllie J, Aziz K, de Almeida MF, Fabres J, Fawke J, et al. Neonatal Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation 2020; 142:S185–221.
4. Li S, Guo P, Zou Q, He F, Xu F, Tan L. Efficacy and Safety of Plastic Wrap for Prevention of Hypothermia after Birth and during NICU in Preterm Infants: A Systematic Review and Meta-Analysis. Baud O, ed. PLoS One 2016; 11:e0156960.
5. McCall EM, Alderdice F, Halliday HL, Vohra S, Johnston L. Interventions to prevent hypothermia at birth in preterm and/or low birth weight infants. Cochrane Database Syst Rev 2018; 2:CD004210.
6. Oatley HK, Blencowe H, Lawn JE. The effect of coverings, including plastic bags and wraps, on mortality and morbidity in preterm and full-term neonates. J Perinatol 2016; 36 Suppl 1:S83-9.
7. Meyer MP, Owen LS, te Pas AB. Use of Heated Humidified Gases for Early Stabilization of Preterm Infants: A Meta-Analysis. Front Pediatr 2018; 6:319.