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Perinatal strategies to prevent lung disease and promote lung development in the preterm lung – presented by Anna Lavizzari

Impact on lung development and lung health

Prematurity has been linked to an increased risk of Bronchopulmonary Dysplasia (BPD). On top of being a complex lung disease, multiple definitions exist in parallel – based on treatment strategies rather than physiopathology. The complexity of definitions is confounding the capability to predict long-term respiratory outcomes2.

Premature birth (week 17 -34) disrupts the normal lung development, as  alveoli have not yet been developed only primary respiratory bronchioles/saccules. Poor microvasculature development, no/low surfactant production and minimal matrix in tissue are other consequences, all impacting the baby’s future lung health.  

There are several known antennal and early postnatal risk factors for respiratory morbidity. Inflammations/infections and chorioamnionitis (CA, bacterial infection in membranes surrounding the foetus or amniotic fluid) were mentioned as increasing the risk for BPD but leading to a decreased risk for respiratory distress syndrome (RDS)3.

Foetal infections

According to a hypothesis by Watterberg et al, CA could lead to an accelerated functional lung maturation but also increase the vulnerability of the preterm lung to post-natal injury4. The effect of CA on foetal lungs depends on the type of  pathogen duration of foetal exposure, severity of lung exposure, interaction with post-natal risk factors, and interindividual susceptibility3. Even though research has shown that a history of of CA is associated with an increased risk of developing BPD, this association may be modulated by risk of RDS and gestational age5.

Other risk factors for BPD

Furthermore, vascular abnormalities in the placenta, preeclampsia and intra-uterine growth restriction are also risk factors for BPD and impaired lung function later in life6. There are also antenatal determinants of respiratory health for the babies7. Maternal smoking was mentioned as an increased risk for developing BPD after preterm birth and it has been shown to prolong the need for mechanical ventilation and respiratory support in the neonatal intensive care unit (NICU)7. Preterm infants whose mothers were still smoking, had higher rates of respiratory diseases later during childhood7.

Counteractions to reduce risk of BPD

So, what can be done to handle these challenges? At the NICU, there are some preventive strategies available, reducing the risk of lung damage. Early non-invasive respiratory support (Nasal CPAP) has been shown to decrease the risk of BPD and death8. The updated European guidelines on Neonatology9 contains recommendations om treatment strategies at the NICU.

Key points to consider for reducing burden of disease in prematurely born

  1. Lung disease associated with prematurity results from the complex interaction of different etiological factors that occur antenatally and postnatally.
  2. No single intervention is powerful enough to remove the burden of post-prematurity lung disease, but a multipronged preventive approach has the potential to reduce the burden of disease.
  3. Identifying infants at risk early and ensure lung function trajectory follow-up. Understanding clinical phenotyping may lead to targeted interventions and improved clinical outcomes.
  4. Close collaboration between neonatologists, paediatricians , and adult respiratory experts can improve and develop clinical practice and research in this field.

Following patients throughout life – presented by Lisbeth Duijts

Pulmonary lung disease has lifelong consequences and is seen in approximately 30% of preterm born babies during childhood10. Furthermore, they show poorer lung function, shown as 7-15% lower FEV1, stronger decline and for each week born earlier, more signs and symptoms of lung morbidity.

Good health is a team effort

Less is known about consequences in the span of a lifetime, but studies have shown an up to 2.9-fold increased risk for asthma/COPD10.

Early life events, including premature birth and low birth weight was included as a separate COPD classification (COPD-D) in the GOLD report 2023. The relationship between preterm birth and chronic respiratory diseases is not fully elucidated, but infants born preterm seem to have increased risks of respiratory morbidity across the life course10. Moreover, quite often there are related diagnoses and co-morbidities such as central dysregulated breathing, sleep disorders, and/or pulmonary hypertension, present. If so, the health outcomes may improve by the disease management by a multi-disciplinary team11. This team could include a pulmonologist, cardiologist/nephrologist, neonatologist/general practitioner, supporting staff (social worker) and an ophthalmologist. The team sets up a clear follow-up scheme from childhood to mid-adulthood, depending on individual needs – which may very well vary across life12. To ensure sustained multidisciplinary care may increase the chance to optimize the persons full potential.

Maria Messerer , PhD
Medical Director, Chiesi Nordic

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Referenser

  1. https://data.unicef.org/resources/born-too-soon-decade-of-action-on-preterm-birth).
  2. Katz TA, et al J pediatr. 2023 Katz TA, van Kaam AH, Schuit E, Mugie SM, Aarnoudse-Moens CSH, Weber EH, de Groof F, van Laerhoven H, Counsilman CE, van der Schoor SRD, Rijpert M, Schiering IA, Wilms J, Leemhuis AG, Onland W. Comparison of New Bronchopulmonary Dysplasia Definitions on Long-Term Outcomes in Preterm Infants. J Pediatr. 2023 Feb;253:86-93.e4. doi: 10.1016/j.jpeds.2022.09.022. Epub 2022 Sep 20. PMID: 36150504.
  3. Jobe AH. Effects of chorioamnionitis on the fetal lung. Clin Perinatol. 2012 Sep;39(3):441-57. doi: 10.1016/j.clp.2012.06.010. PMID: 22954262; PMCID: PMC3437038.
  4. Watterberg KL, Demers LM, Scott SM, Murphy S. Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics. 1996; 97:210–215. [PubMed: 8584379]
  5. Villamor-Martinez E, Álvarez-Fuente M, Ghazi A, et al. Association of Chorioamnionitis with Bronchopulmonary Dysplasia Among Preterm Infants; A Systematic Review, Meta-analysis, and Meta regression. JAMA Network Open, 2019; Nov 1;2(11):e1914611
  6. Mandell EW, Abman SH. Fetal Vascular Origins of Bronchopulmonary Dysplasia. J Pediatr. 2017 Jun;185:7-10.e1. doi: 10.1016/j.jpeds.2017.03.024. Epub 2017 Mar 27. PMID: 28359535.
  7. Morrow LA, Wagner BD, Ingram DA, Poindexter BB, Schibler K, Cotten CM, Dagle J, Sontag MK, Mourani PM, Abman SH. Antenatal Determinants of Bronchopulmonary Dysplasia and Late Respiratory Disease in Preterm Infants. Am J Respir Crit Care Med. 2017 Aug 1;196(3):364-374. doi: 10.1164/rccm.201612-2414OC. PMID: 28249118; PMCID: PMC5549867.
  8. Subramaniam P, Ho JJ, Davis PG. Prophylactic or very early initiation of continuous positive airway pressure (CPAP) for preterm infants. Cochrane Database Syst Rev. 2021 Oct 18;10(10):CD001243. doi: 10.1002/14651858.CD001243.pub4. PMID: 34661278; PMCID: PMC8521644.
  9. Sweet DG, Carnielli VP, Greisen G, Hallman M, Klebermass-Schrehof K, Ozek E, Te Pas A, Plavka R, Roehr CC, Saugstad OD, Simeoni U, Speer CP, Vento M, Visser GHA, Halliday HL. European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update. Neonatology. 2023;120(1):3-23. doi: 10.1159/000528914. Epub 2023 Feb 15. PMID: 36863329; PMCID: PMC10064400.
  10. Duijts L. Prematurity-related chronic respiratory disease across the life course. Eur Respir J. 2023 Jun 22;61(6):2300662. doi: 10.1183/13993003.00662-2023. PMID: 37348899.
  11. Miller, A. N., Shepherd, E. G., El-Ferzli, G., & Nelin, L. D. (2023). Multidisciplinary bronchopulmonary dysplasia care. Expert Review of Respiratory Medicine17(11), 989–1002. https://doi.org/10.1080/17476348.2023.2283120
  12. Simpson, S. J.,Du Berry, C., Evans, D et al . Unravelling the respiratory health path across the lifespan for survivors of preterm birth. The Lancet Respiratory Medicine, Volume 12, Issue 2p167-180 February 2024

ID 10029-12.09.2024