Elsevier

The Lancet

Volume 389, Issue 10079, 22–28 April 2017, Pages 1649-1659
The Lancet

Series
The evolution of modern respiratory care for preterm infants

https://doi.org/10.1016/S0140-6736(17)30312-4Get rights and content

Summary

Preterm birth rates are rising, and many preterm infants have breathing difficulty after birth. Treatments for infants with prolonged breathing difficulty include oxygen therapy, exogenous surfactant, various modes of respiratory support, and postnatal corticosteroids. In this Series paper, we review the history of neonatal respiratory care and its effect on long-term outcomes, and we outline the future direction of the research field. The delivery and monitoring of oxygen therapy remains controversial, despite being in use for more than 50 years. Exogenous surfactant replacement has been used for 25 years and has dramatically reduced mortality and morbidity, but more research on when and how it is administered is needed. Methods and techniques of neonatal respiratory support are evolving. Clinicians are moving away from routine intubation and ventilation, and new modes of non-invasive support are being investigated. Postnatal corticosteroids have a limited role in infants with evolving bronchopulmonary dysplasia, but more research is needed to identify the best timing, type, dose, and method of administration. Despite advances in neonatal care in the past 50 years, bronchopulmonary dysplasia, with all its adverse short-term and long-term consequences, is still a serious problem in neonatal care. The challenge remains to support breathing in preterm infants, with special attention to risk factors in the subpopulation of infants that are at highest risk of bronchopulmonary dysplasia, without damaging their lungs or adversely affecting their long-term health.

Introduction

Modern neonatal paediatrics started in the 1970s with the introduction of assisted ventilation. Before that time, respiratory distress syndrome, also known as hyaline membrane disease, was the commonest cause of death in preterm infants. Respiratory distress syndrome is caused by a lack of pulmonary surfactant to reduce surface tension at the air–liquid interface in the lung. Fetal surfactant production increases at 34–35 weeks' gestation, and surfactant deficiency is rare in infants born after that time.

Preterm infants born with insufficient pulmonary surfactant have respiratory distress that manifests clinically by laboured, rapid breathing, grunting, and central cyanosis. Respiratory distress typically becomes more severe during the first few days after birth as the airways progressively collapse because of increased surface tension. If infants survive the first few days, the lungs start to produce surfactant; the respiratory distress stabilises and then abates as the lungs reinflate. Before the 1970s, effective treatment for respiratory distress syndrome was limited to supplemental oxygen therapy.

The first attempts to mechanically assist breathing in these infants were often a desperate final attempt to avoid death and relied on the use of adult ventilators, but these early attempts were not very successful. Not until infant ventilators were developed and assistance could be provided earlier in the course of the disease did survival rates increase. Survival chances in infants weighing less than 1000 g at birth increased from less than 10% in the late 1960s (before assisted ventilation)1 to about 35% by the mid-1970s, when ventilation was widespread.1 However, morbidities improved at a slow pace; many extremely preterm infants who survive have neurodevelopmental disabilities or develop bronchopulmonary dysplasia—the so-called chronic lung disease of prematurity.

Other advances that improved survival of preterm infants included use of antenatal corticosteroids, first reported in 19722 and more widely used from the late-1970s onwards, and exogenous surfactant, which became available from the early 1990s. Another important advance leading to improved survival was a change in attitude, such that more of the most immature infants were offered active medical care.3

In this Series paper, we examine landmark developments in neonatal respiratory care. We describe the history of preterm respiratory support, the move towards gentler, non-invasive support, and the long-term effects of respiratory support given following preterm birth. We assess the lessons learned and areas for future research, focusing in particular on neonatal respiratory care provided in high-income countries.

Key messages

  • Oxygen is vital to life, but how much oxygen to give and how to accurately monitor oxygen saturation in preterm infants is controversial

  • Exogenous surfactant improves survival and morbidity in preterm infants, but more research on when and how it is administered is needed

  • Neonatal respiratory care is rapidly evolving; clinicians are moving away from routine intubation and ventilation and developing new modes of non-invasive support

  • Postnatal corticosteroids have a limited role in infants with evolving bronchopulmonary dysplasia

  • Despite many advances in neonatal intensive care, including widespread use of antenatal corticosteroids, exogenous surfactant, and gentler techniques for assisted ventilation, bronchopulmonary dysplasia remains a major problem in neonatal care

Section snippets

The use of oxygen in neonatology

The attitude towards the use of oxygen in prenatal respiratory care, once considered a panacea, has changed with time. Oxygen in unrestricted amounts is now understood to have contributed to the epidemic of retinopathy of prematurity and subsequent blindness. Restricted oxygen, however, causes death from hypoxia, so clinicians have had to find a middle ground.

The ability to monitor neonatal blood oxygen concentration is a relatively modern technical development, and supplemental oxygen was

The development of surfactants

Pulmonary surfactant deficiency was identified as the cause of respiratory distress syndrome in 1959.22 Soon after, the phospholipid dipalmitoyl phosphatidylcholine was identified as a major surfactant component.23 Nebulised dipalmitoyl phosphatidylcholine was initially trialled in infants in the 1960s,24 but the results were disappointing. In 1980, minced bovine lung enriched with synthetic lipids was instilled into the tracheas of ten infants with respiratory distress syndrome and was found

Conventional neonatal ventilation

Conventional neonatal ventilation has been in widespread use since the 1970s. Initially, mortality and air leak were common because surfactants and antenatal corticosteroids were not available and because of the effects of ventilation. Techniques have now evolved from non-synchronised, pressure-limited ventilation with unmeasured tidal volumes to synchronised, volume-targeted support. Synchronisation of ventilator inflations with spontaneous breathing reduces air leak and ventilation duration;43

Continuous positive airway pressure

The best known mode of non-invasive neonatal support is continuous positive airway pressure. First described for preterm infants in 1971, and delivered via endotracheal tube,50 continuous positive airway pressure improved oxygenation and survival. Many studies have described the physiological benefits of continuous positive airway pressure, which include chest wall and upper airway stabilisation, reduced apnoeas, lung resistance, and work of breathing, and improved tidal volume, oxygenation,

The widespread introduction of postnatal corticosteroids

Bronchopulmonary dysplasia in preterm infants is associated with poor neurodevelopmental outcomes. Clinicians have therefore postulated that if bronchopulmonary dysplasia could be reduced with corticosteroids, then neurodevelopmental outcomes would improve. The first randomised controlled trial63 of postnatal corticosteroid use in preterm infants took place in 1972, and the results showed no clinical benefits of hydrocortisone. In subsequent trials, use of hydrocortisone and prednisolone was

Bronchopulmonary dysplasia

Despite the use of antenatal corticosteroids, surfactant replacement, non-invasive respiratory support, and judicious use of supplemental oxygen and postnatal corticosteroids, bronchopulmonary dysplasia is still a major cause of childhood respiratory morbidity, affecting up to 50% of infants born less than 28 weeks' gestation—and the incidence continues to rise.89

Conclusions and future directions

We have described important advances in the respiratory care of preterm infants and highlighted remaining questions (table 2).

Many of the topics share a common theme; popular ideas and plausible therapies can cause harm, but discarding the therapies altogether might be worse. Neonatology is unfortunately peppered with examples of therapies that are enthusiastically embraced but subsequently proven to be harmful. It is imperative that we learn from this experience to improve preterm outcomes.

References (108)

  • AM Gibson et al.

    Respiratory outcomes for the tiniest or most immature infants

    Semin Fetal Neonatal Med

    (2014)
  • E Kajantie et al.

    Is very preterm birth a risk factor for adult cardiometabolic disease?

    Semin Fetal Neonatal Med

    (2014)
  • WH Kitchen et al.

    Changing outcome over 13 years of very low birthweight infants

    Semin Perinatol

    (1982)
  • GC Liggins et al.

    A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants

    Pediatrics

    (1972)
  • E Gultom et al.

    Changes over time in attitudes to treatment and survival rates for extremely preterm infants (23–27 weeks' gestational age)

    Aust N Z J Obstet Gynaecol

    (1997)
  • W Tin et al.

    Pulse oximetry, severe retinopathy, and outcome at one year in babies of less than 28 weeks gestation

    Arch Dis Child Fetal Neonatal Ed

    (2001)
  • Supplemental therapeutic oxygen for prethreshold retinopathy of prematurity (STOP-ROP), a randomized, controlled trial. I: primary outcomes

    Pediatrics

    (2000)
  • LM Askie et al.

    Oxygen-saturation targets and outcomes in extremely preterm infants

    N Engl J Med

    (2003)
  • LM Askie et al.

    NeOProM: Neonatal Oxygenation Prospective Meta-analysis Collaboration study protocol

    BMC Pediatr

    (2011)
  • WA Carlo et al.

    Target ranges of oxygen saturation in extremely preterm infants

    N Engl J Med

    (2010)
  • YE Vaucher et al.

    Neurodevelopmental outcomes in the early CPAP and pulse oximetry trial

    N Engl J Med

    (2012)
  • BA Darlow et al.

    Randomized controlled trial of oxygen saturation targets in very preterm infants: two year outcomes

    J Pediatr

    (2014)
  • BJ Stenson et al.

    Oxygen saturation and outcomes in preterm infants

    N Engl J Med

    (2013)
  • W Tarnow-Mordi et al.

    Outcomes of two trials of oxygen-saturation targets in preterm infants

    N Engl J Med

    (2016)
  • B Schmidt et al.

    Effects of targeting higher vs lower arterial oxygen saturations on death or disability in extremely preterm infants: a randomized clinical trial

    JAMA

    (2013)
  • BJ Stenson

    Oxygen saturation targets for extremely preterm infants after the NeOProM trials

    Neonatology

    (2016)
  • Guidelines for perinatal care

    (2012)
  • DG Sweet et al.

    European consensus guidelines on the management of neonatal respiratory distress syndrome in preterm infants—2013 update

    Neonatology

    (2013)
  • HA van Zanten et al.

    Compliance in oxygen saturation targeting in preterm infants: a systematic review

    Eur J Pediatr

    (2015)
  • H Hummler et al.

    Automated adjustments of inspired fraction of oxygen to avoid hypoxemia and hyperoxemia in neonates—a systematic review on clinical studies

    Klin Padiatr

    (2014)
  • SL Watkin et al.

    A comparison of pulse oximetry and near infrared spectroscopy (NIRS) in the detection of hypoxaemia occurring with pauses in nasal airflow in neonates

    J Clin Monit Comput

    (1999)
  • ME Avery et al.

    Surface properties in relation to atelectasis and hyaline membrane disease

    AMA J Dis Child

    (1959)
  • MH Klaus et al.

    Composition of surface-active material isolated from beef lung

    Proc Natl Acad Sci USA

    (1961)
  • E Robillard et al.

    Microaerosol administration of synthetic beta-gamma-dipalmitoyl-L-alpha-lecithin in the respiratory distress syndome: a preliminary report

    Can Med Assoc J

    (1964)
  • RF Soll et al.

    Prophylactic animal derived surfactant extract for preventing morbidity and mortality in preterm infants

    Cochrane Database Syst Rev

    (1997)
  • RF Soll

    Synthetic surfactant for respiratory distress syndrome in preterm infants

    Cochrane Database Syst Rev

    (1998)
  • Surfactant replacement therapy for severe neonatal respiratory distress syndrome: an international randomized clinical trial

    Pediatrics

    (1988)
  • N Seger et al.

    Animal derived surfactant extract for treatment of respiratory distress syndrome

    Cochrane Database Syst Rev

    (2009)
  • R Soll et al.

    Multiple versus single doses of exogenous surfactant for the prevention or treatment of neonatal respiratory distress syndrome

    Cochrane Database Syst Rev

    (2009)
  • S Ardell et al.

    Animal derived surfactant extract versus protein free synthetic surfactant for the prevention and treatment of respiratory distress syndrome

    Cochrane Database Syst Rev

    (2015)
  • N Singh et al.

    Comparison of animal-derived surfactants for the prevention and treatment of respiratory distress syndrome in preterm infants

    Cochrane Database Syst Rev

    (2015)
  • RH Pfister et al.

    Protein containing synthetic surfactant versus animal derived surfactant extract for the prevention and treatment of respiratory distress syndrome

    Cochrane Database Syst Rev

    (2007)
  • Guidelines for good practice in the management of neonatal respiratory distress syndrome

  • MX Rojas-Reyes et al.

    Prophylactic versus selective use of surfactant in preventing morbidity and mortality in preterm infants

    Cochrane Database Syst Rev

    (2012)
  • CJ Morley et al.

    Nasal CPAP or intubation at birth for very preterm infants

    N Engl J Med

    (2008)
  • TP Stevens et al.

    Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome

    Cochrane Database Syst Rev

    (2007)
  • J Kattwinkel et al.

    Technique for intrapartum administration of surfactant without requirement for an endotracheal tube

    J Perinatol

    (2004)
  • BG Sood

    Aerosolized surfactant in neonatal RDS

  • JM Pinheiro et al.

    Randomized trial of laryngeal mask airway versus endotracheal intubation for surfactant delivery

    J Perinatol

    (2016)
  • HG Kanmaz et al.

    Surfactant administration via thin catheter during spontaneous breathing: randomized controlled trial

    Pediatrics

    (2013)
  • Cited by (0)

    View full text