[MA 2023 29] Development of surfactant treatment for respiratory distress syndrome in preterm infants using high resolution vital parameters
Amsterdam UMC, location AMC, Department of Neonatology
Proposed by: Wes Onland [w.onland@amsterdamumc.nl]
Introduction
Respiratory distress syndrome (RDS) is a lung disease in preterm infants caused by deficiency of surfactant. RDS is an important complication of preterm birth with increased risk of a need for invasive mechanical ventilation, prolonged respiratory support and even increased risk of mortality if not treated with exogeneous surfactant (1, 2). Many high-quality studies have shown that administration of surfactant is effective and safe. Randomized controlled trials have shown that compared with prophylactic surfactant administration, selective surfactant in preterm infants with evolving signs of RDS lead to a reduced risk of death or bronchopulmonary dysplasia (BPD), the chronic lung disease of the premature at 36 weeks postmenstrual age (3-5). The Cochrane reviews showed that early selective surfactant was the best approach for preterm infants with RDS compared to late rescue, and that this administration was most optimal within two hours after birth. However, the studies did not answer the dilemma what parameters or what threshold should be used for surfactant treatment when given early selective rescue (6, 7).
Although a large population cohort study from Sweden (8) showed that infants with lower gestational age received more often received surfactant within 2h after birth. However, 38.9% of infants received surfactant >2h of life overall, which might be too late and have clinical consequences. In order to solve this dilemma, studies focused on predicting the need for surfactant treatment in order that clinicians treat these infants in the same way. Several parameters have been associated with the need for surfactant. A study by de Jaegere (9) showed that birth weight <800 gram, gender and FiO2>0.25 were predictors of treatment failure, whereas two other studies showed that a FiO2 of 0.3, was predictive for treatment failure (10, 11). However, a recent study, with a strict FiO2 criterion for treatment failure of 0.3 showed that a FiO2>0.23 in the first two hours of life has a high predictive value (12). The European guideline advises a threshold of FiO2>0.3 after delivery room stabilization (2) in contrast with the Canadian guideline (13) (FiO2>0.50), whereas both the American Academy of Paediatrics (AAP) and National Institute (14) for Health and Care Excellence (NICE) guideline (15) do not state a FiO2 threshold.
In summary, an established prediction model for severe respiratory distress syndrome needing surfactant therapy is not available yet. The optimal threshold or which parameters should be used for early selective surfactant administration is not known. The objective of this research project is to develop and internally validate a prediction rule for surfactant administration at birth with static parameters, and investigate the additional value of adding temporal data to this prediction model two hours after birth.
Description of the SRP Project/Problem
Development of prediction model for early selective surfactant treatment within two hours after birth for RDS in preterm infants. The prediction model should be based on clinical parameters, should have good discriminating and calibrating. But the research question is whether incorporating high resolution vital parameters data (SpO2, FiO2, ratio SpO2/FiO2, breathing frequency, heart rate) every 20 sec at one and two hours after birth would increase these performances. The temporal data and clinical data are already available in an existing database including admitted patients with a gestational age < 30 weeks born between 2016 and 2023. In the upcoming period, another database will be formed expanding this database by including patients born between 2009 and 2016.
Research questions
a) What is the discriminating and calibrating performance of a clinical prediction model for early treatment with surfactant?
b) What is the added value of incorporating high resolution data in terms of these predicting performances?
Expected results
This project is expected to include the following results:
a) pre-processing high resolution data (all infants born between 2009 and 2023).
b) develop and validation of a RDS prediction model.
c) updating prediction model with high resolution vital parameters.
Time period:
May – November
Contact:
Wes Onland
NICU Amsterdam UMC, Kamer H4-139
w.onland@amsterdamumc.nl
06-55184397
References
1. Bhandari V, Black R, Gandhi B, Hogue S, Kakkilaya V, Mikhael M, et al. RDS-NExT workshop: consensus statements for the use of surfactant in preterm neonates with RDS. J Perinatol. 2023.
2. Sweet DG, Carnielli VP, Greisen G, Hallman M, Klebermass-Schrehof K, Ozek E, et al. European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update. Neonatology. 2023;120(1):3-23.
3. Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet JM, Carlin JB, Investigators CT. Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med. 2008;358(7):700-8.
4. Network SSGotEKSNNR, Finer NN, Carlo WA, Walsh MC, Rich W, Gantz MG, et al. Early CPAP versus surfactant in extremely preterm infants. N Engl J Med. 2010;362(21):1970-9.
5. Dunn MS, Kaempf J, de Klerk A, de Klerk R, Reilly M, Howard D, et al. Randomized trial comparing 3 approaches to the initial respiratory management of preterm neonates. Pediatrics. 2011;128(5):e1069-76.
6. Bahadue FL, Soll R. Early versus delayed selective surfactant treatment for neonatal respiratory distress syndrome. Cochrane Database Syst Rev. 2012;11(11):CD001456.
7. Rojas-Reyes MX, Morley CJ, Soll R. Prophylactic versus selective use of surfactant in preventing morbidity and mortality in preterm infants. Cochrane Database Syst Rev. 2012(3):CD000510.
8. Challis P, Nydert P, Hakansson S, Norman M. Association of Adherence to Surfactant Best Practice Uses With Clinical Outcomes Among Neonates in Sweden. JAMA Netw Open. 2021;4(5):e217269.
9. De Jaegere AP, van der Lee JH, Cante C, van Kaam AH. Early prediction of nasal continuous positive airway pressure failure in preterm infants less than 30 weeks gestation. Acta Paediatr. 2012;101(4):374-9.
10. Dargaville PA, Aiyappan A, De Paoli AG, Dalton RG, Kuschel CA, Kamlin CO, et al. Continuous positive airway pressure failure in preterm infants: incidence, predictors and consequences. Neonatology. 2013;104(1):8-14.
11. Gulczynska E, Szczapa T, Hozejowski R, Borszewska-Kornacka MK, Rutkowska M. Fraction of Inspired Oxygen as a Predictor of CPAP Failure in Preterm Infants with Respiratory Distress Syndrome: A Prospective Multicenter Study. Neonatology. 2019;116(2):171-8.
12. Dell'Orto V, Nobile S, Correani A, Marchionni P, Giretti I, Rondina C, et al. Early nasal continuous positive airway pressure failure prediction in preterm infants less than 32 weeks gestational age suffering from respiratory distress syndrome. Pediatr Pulmonol. 2021;56(12):3879-86.
13. Ng EH, Shah V. Guidelines for surfactant replacement therapy in neonates. Paediatr Child Health. 2021;26(1):35-49.
14. Polin RA, Carlo WA, Committee on F, Newborn, American Academy of P. Surfactant replacement therapy for preterm and term neonates with respiratory distress. Pediatrics. 2014;133(1):156-63.
15. Banerjee S, Fernandez R, Fox GF, Goss KCW, Mactier H, Reynolds P, et al. Surfactant replacement therapy for respiratory distress syndrome in preterm infants: United Kingdom national consensus. Pediatr Res. 2019;86(1):12-4.