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Neonatal Respiratory Distress Syndrome: Tackling A Worldwide Problem

Janet Dyer

It’s the 21st century, yet newborn infants are still at risk for a deadly condition that robs them of their first breaths: neonatal respiratory distress syndrome (NRDS), also known as infant respiratory distress syndrome and hyaline membrane disease (see videos listed in Box 1: Can You Identify NRDS?). In countries with large pockets of poverty, mortality rates run roughly 10 times higher. than in wealthier countries. But even in developed countries, the mortality rate reaches as high as 60%.1 In the U.S., respiratory distress syndrome is among the most common causes of death in the first month of life.2

NRDS is also a threat for different reasons. For example, in one recent study, 1.9% of premature babies who had NRDS later developed cerebral palsy, compared with 0.5% of premature babies who did not have NRDS.3 A 2018 study found premature infants had a higher risk of childhood epilepsy..4

Can You Identify NRDS?

Video: Respiratory Distress in the Newborn by Megan Connelly for OPENPediatrics. Differential diagnosis, epidemiology, pathophysiology, presentation, diagnosis, management 9:54 min

https://www.youtube.com/watch?v=j3ypUlLMRLs.

Video: Recognizing Respiratory Distress by Monica Kleinman, MD, for OPENPediatrics.

Identifying signs and symptoms in the pediatric patient 17:24 min

https://www.youtube.com/watch?v=Fmt6JB-W_M8.

Newborn Respiratory Disorders–CRASH! Medical Review Series 30:12 min

https://www.youtube.com/watch?v=KEd0EvbKjf8.

The Stats on NRDS

  • About 1% of newborn infants develop respiratory distress syndrome.
  • About 12% of babies born in the U.S. are born prematurely–a higher rate than in other developed countries.
  • Preterm birth is the world’s number-one cause of newborn deaths (almost 30%).
  • Neonatal respiratory distress syndrome is the leading cause of death in premature infants.
  • The risk of RDS depends on gestational age: > 50% at < 28 weeks; < 5% at > 37 weeks.
  • Between 2003 and 2013, the number of deaths due to NRDS dropped from 20.5 per 100,000 live births to 13.4.
  • NRDS accounted for 2.3% of all infant deaths in the U.S. in 2013.

Sources:

AMBOSS.com. Neonatal Respiratory Distress Syndrome March of Dimes Peristats.18

American Thoracic Society.. Respiratory Distress Syndrome of the Newborn, Chapter 19

Moreover, the treatments for NRDS have risks of their own. Mechanical ventilation, for instance, which helps keep infants alive, also puts them at risk for bronchopulmonary dysplasia (BPD.). An estimated 5,000 to 10,000 newborns develop BPD or other form of chronic lung disease.5

However, more babies are surviving RDS. A main breakthrough has been the development of surfactant replacement, now the go-to therapy. Its use has meant an astounding drop in mortality, from nearly 100% to less than 10%.5,6 Various researchers seek to polish that gold standard by finding the best timing, best dose, and best methods of delivering surfactant treatment to maximize effect and minimize risks.7 A 2017 study., for instance, found early treatment with pulmonary surfactant—within 12 hours of birth—combined with mechanical ventilation could “remarkably improve lung oxygenation and compliance.”8

Another mainstay of treatment for NRDS, inhaled nitric oxide, improves oxygenation and reduces pulmonary inflammation. Begun soon after birth in premature infants, it relieves acute symptoms and helps reduce the risk of chronic lung disease.5 It’s indicated for term and near-term (> 34 weeks’ gestation) infants,9 but some physicians are prescribing it for extremely premature infants. That practice has caused debate; in one study, giving iNO off-label. did not reduce in-hospital mortality.10

Curious about current protocols? The American Academy of Pediatrics Committee on Fetus and Newborn. has a list of guidelines, including those citing Cochrane Neonatal Reviews.11

WHAT’S NEXT? TRENDS IN TREATMENT

A review of the state of the art in treatment. for NRDS says there’s more work to be done. Recently, research has focused more on making treatment less invasive and more targeted. For example, new evidence has demonstrated that selective use of surfactant, rather than prophylactic use, reduces BPD and/or death.7

Another proposition is to administer surfactant differently: Using a small catheter, for instance, instead of an endotracheal tube for infants breathing spontaneously may combine the benefits of continuous positive airway pressure (CPAP) (thus avoiding mechanical ventilation) and early surfactant treatment.7 Other research suggests that nebulized surfactant may reduce the need for intubation. in preterm infants treated with nasal CPAP.12

Researchers are also looking to revise protocols on mechanical ventilation and oxygenation. A small pilot study published earlier this year suggests that even a short period under invasive mechanical ventilation at higher oxygen levels can lead to lung inflammation: higher IL-6, IL-8, and TNF-α levels and lower IL-10 levels.13

Some research is focusing on nutrition. Vitamin D, for instance, has been shown to help stimulate fetal lung maturation; deficiency in the vitamin lowers oxygenation and reduces survival time in preterm neonates.14 Vitamin A, important to cell growth, has been shown to reduce BPD.4

Other recent trends in modern neonatology include revisiting standard ideas. Some of the questions being considered include:

But while treatments have improved by leaps and bounds, they have not been able to keep up with the ever-growing incidence of preterm birth, by far the biggest risk factor for NRDS. According to the American Thoracic Society, “Preventing premature births could nearly eliminate RDS..”5

In the meantime, research and experimentation continue around the globe, especially in countries that are high in preterm births and low in resources like ventilators and CPAP. In those places, desperate times are leading to innovative measures. In Malawi, for instance, where babies with RDS have only a 25% chance of survival, the existing medical devices tend to break down under the harsh conditions of African health care settings. So, doctors there competed in a design challenge and created a more affordable and durable bubble-CPAP. Their prototype? A plastic shoebox from Target and two fish-tank pumps. It cost a fraction of the price of the real CPAP but proved just as effective. With the help of engineering professors from Rice University, they perfected their device and called it Pumani—Malawian for “breathe restfully.”17

Pioneer in Treatment of Neonatal Respiratory Distress Dies

In 1963, Jacqueline Kennedy gave birth to a baby nearly six weeks early. Within minutes, the baby, Patrick Bouvier, began struggling to breathe. He was rushed to Boston Children’s Hospital, where he was placed in a hyperbaric chamber–a revolutionary treatment at the time.

Standing by was William F. Bernhard., a cardiovascular surgeon at Children’s Hospital, and already a leader in the use of hyperbaric chambers in medicine. Bernhard made more medical history as he and the medical team attempted to save the baby’s life.

Patrick died two days later of hyaline membrane disease, now called neonatal respiratory distress syndrome. The case, with all the media attention, heightened public awareness of the disease and spurred further research.

Patrick Kennedy’s obituary in The New York Times read, in part: “[T]he battle for the Kennedy baby was lost only because medical science had not yet advanced far enough to accomplish as quickly as necessary what the body can do by itself in its own time.”5

Dr. Bernhard died on October 29, 2018, aged 93.19

Author bio: 
Janet Dyer is a freelance writer living in New York.

References

  1. Hubbard RM, Choudhury KM, Lim G. Treatment patterns and clinical outcomes in neonates diagnosed with respiratory distress syndrome in a low-income country: a report from Bangladesh. Anesth Analg 2018;5;(126):1684–1686.10.1213/ANE.0000000000002865
  2. Jacob J, Kamitsuka M, Clark RH, Kelleher AS, Spitzer AR. Etiologies of NICU deaths [published online December 8, 2014]. Pediatrics 2015;135;(1):e59–e65.10.1542/peds.2014-2967
  3. Thygesen SK, Olsen M, Østergaard JR, et al. Respiratory distress syndrome in moderately late and late preterm infants and risk of cerebral palsy: a population-based cohort study. BMJ Open 2016;6:e011643 Available at: https://bmjopen.bmj.com/content/6/10/e011643. Accessed January 9, 2019
  4. Thygesen SK, Olsen M, Pedersen L, et al. Respiratory distress syndrome in preterm infants and risk of epilepsy in a Danish cohort [published online September 8, 2017]. Eur J Epidemiol 2018;33;(3):313–321.10.1007/s10654-017-0308-1
  5. American Thoracic Society. Respiratory distress syndrome of the newborn  Available at: https://www.thoracic.org/patients/patient-resources/breathing-in-america/resources/chapter-19-respiratory-distress-syndr.pdf. Accessed January 4, 2019
  6. Mandile O. Neonatal respiratory distress syndrome and its treatment with artificial surfactant. The embryo project encyclopedia The embryo project at Arizona State University. July 3, 2018; Available at: https://embryo.asu.edu/pages/neonatal-respiratory-distress-syndrome-and-its-treatment-artificial-surfactant. Accessed January 4, 2019
  7. Niemarkt HJ, Hütten MC, Kramer BW. Surfactant for respiratory distress syndrome: new ideas on a familiar drug with innovative applications. Neonatology 2017;111;(4):408–414.10.1159/000458466
  8. Wang L-P, Mao Q-H, Yang L. Effect of pulmonary surfactant combined with mechanical ventilation on oxygenation functions and expressions of serum transforming growth factor-beta1 (TGF-β1) and bone morphogenetic protein 7 (BMP-7) of neonatal respiratory distress syndrome. Eur Rev Med Pharmacol Sci 2017;21;(19):4357–4361. Accessed January 9, 2019.
  9. Inomax (nitric oxide) prescribing information Hazelwood, Montana: INO Therapeutics LLC. 2015;
  10. Carey WA, Weaver AL, Mara KC, Clark RH. Inhaled nitric oxide in extremely premature neonates with respiratory distress syndrome [published online February 2, 2018]. Pediatrics 2018;141;(3):e2017310810.1542/peds.2017-3108
  11. Cochrane Neonatal. American Academy of Pediatrics Committee on Fetus and Newborn January 2019; Available at: https://neonatal.cochrane.org/our-work/guidelines/american-academypediatrics-committee-fetus-and-newborn#surfactant. Accessed January 4, 2019
  12. Minocchieri S, Berry CA, Pillow JJ. Nebulised surfactant to reduce severity of respiratory distress: a blinded, parallel, randomised controlled trial [July 26, 2018]. Arch Dis Child Fetal Neonatal Ed 2018; pii: fetalneonatal-2018-315051 10.1136/archdischild-2018-315051
  13. Carvalho CG, Procianoy RS, Neto EC, Silveira RC. Preterm neonates with respiratory distress syndrome: ventilator-induced lung injury and oxidative stress. J Immunol Res 2018; 6963754 10.1155/2018/6963754
  14. Gatera VA, Abdulah R, Musfiroh I, et al. Updates on the status of vitamin D as a risk factor for respiratory distress syndrome. Adv Pharmacol Sci 2018; 8494816 10.1155/2018/8494816
  15. Kugelman A, Borenstein-Levin L, Jubran H, et al. Less is more: modern neonatology [July 30, 2018]. Rambam Maimonides Med J 2018;9;(3):e002310.5041/RMMJ.10344
  16. Doyle LW, Carse E, Adams A-M, et al. Ventilation in extremely preterm infants and respiratory function at 8 years. N Engl J Med 2017;377;(4):329–337.10.1056/NEJMoa1700827
  17. Dahl C. The vital role of early-innovation funders. Stanford Social Innovation Review 2019; Available at: https://ssir.org/articles/entry/the_vital_role_of_early_innovation_funders. Accessed January 4, 2019
  18. March of Dimes. Peristats  Available at: https://www.marchofdimes.org/search-results.aspx?search-text=Peristats. Accessed January 4, 2019
  19. Marquard BDr.WilliamF. Bernhard, innovative surgeon who treated baby Patrick Kennedy, dies at 93 Boston Globe. November 2, 2018; Available at: https://www.bostonglobe.com/metro/obituaries/2018/11/01/william-bernhard-innovative-surgeon-who-treated-baby-patrick-kennedy-dies/qBKotnya3xxj90TmKCZHAI/story.html. Accessed January 4, 2019