Lungenfunktion in Kindheit und Adoleszentenalter: Einfluss von Frühgeburtlichkeit und bronchopulmonaler Dysplasie

Zusammenfassung

Einleitung: Sterblichkeit und kurzfristige respiratorische Morbidität extrem Frühgeborener wurden durch Einsatz pränataler Steroide, die Surfactant-Substitutionstherapie und verbesserte Beatmungstechniken reduziert. Es gibt jedoch Hinweise, dass pränatale Faktoren, Grad der Frühgeburtlichkeit und bronchopulmonale Dysplasie (BPD) Einfluss auf die Lungenfunktion in Kindheit und Adoleszenz haben.

Methodik: Wir führten eine Literaturrecherche über langfristige Lungenfunktionsveränderungen bei Frühgeborenen (FG) unter 32 Gestationswochen in der Ära der Surfactant-Substitutionstherapie („Surfactant-Ära“) durch, um den langfristigen Einfluss von Frühgeburtlichkeit, BPD, Wachstumsverzögerung (IUGR), Chorioamnionitis oder maternalem metabolischem Syndrom auf die Lungenfunktion zu evaluieren.

Ergebnis: Frühgeburtlichkeit führt bei einem Teil der Betroffenen zu signifikanter Reduktion des maximalen Atemwegsflusses in Kindheit und Adoleszenz. Die bronchiale Obstruktion ist durch inhalative ß2-Mimetika nicht vollständig reversibel. Das Ausmaß der späteren Lungenfunktionsbeeinträchtigung korreliert teilweise mit den Schweregraden einer BPD. Eine Diffusionsrestriktion kommt besonders bei Kindern mit moderater bis schwerer BPD und extrem unreifen Frühgeborenen vor. Eine IUGR kann sich negativ auf die spätere Lungenfunktion auswirken. Der Einfluss einer Chorioamnionitis oder eines maternalen metabolischen Syndroms auf die Lungenfunktion Frühgeborener ist unzureichend untersucht.

Schlussfolgerung: Frühgeburtlichkeit vor 32 Gestationswochen ist auch in der in der Surfactant-Ära gehäuft mit einer persistierenden obstruktiven Atemwegserkrankung assoziiert, insbesondere nach einer BPD. Ehemalige Frühgeborene sollten auch pulmologisch in spezialisierten Nachsorgeeinrichtungen betreut werden.

Abstract

Introduction: The introduction of prenatal steroids, surfactant replacement therapy and gentle ventilation modes has reduced short term respiratory morbidity and increased survival of very preterm infants. However, there is some evidence that prenatal factors, the extend of prematurity and bronchopulmonary dysplasia (BPD) may affect pulmonary function in childhood and adolescence.

Methods: We have performed a comprehensive review on the outcome of pulmonary function after premature birth before 32 weeks of gestation in the era of surfactant replacement therapy and tried to evaluate the influence of chorioamnionitis, intrauterine growth retardation (IUGR), maternal metabolic syndrome, prematurity and BPD on long term pulmonary function.

Results: Some children and adolescents born very preterm may experience significant airflow reduction. The bronchial obstruction in these patients is not entirely reversible by inhalative ß2-mimetics. The degree of pulmonary function impairment is partly correlated with the degree of BPD. Abnormalities in pulmonary diffusion capacity may occur after extreme prematurity, but also in patients with moderate and severe BPD. IUGR may have a negative impact on later pulmonary function in very children. There is insufficient data to assess the preterm impact of chorioamnionitis or maternal metabolic syndrome on later lung function.

Conclusion: Infants born before 32 weeks of gestational age in the surfactant era still carry an increased risk to suffer an impaired pulmonary function in childhood and adolescence, particularly if they survived with BPD. Long term pulmonary care for these patients should take place in specialized centers.

Schlüsselwörter

Frühgeburtlichkeit - Lungenfunktion - bronchopulmonale Dysplasie - intrauterine Wachstumsverzögerung - Chorioamnionitis - metabolisches Syndrom

Key words

prematurity - pulmonary function - bronchopulmonary dysplasia - intrauterine growth retardation - chorioamnionitis - metabolic syndrome

• References

• 1 Joshi S, Kotecha S. Lung growth and development. Early Hum Dev 2007; 83: 789-794
• 2 Colin AA, McEvoy C, Castile RG. Respiratory Morbidity and Lung Function in Preterm Infants of 32 to 36 Weeks’ Gestational Age. Pediatrics 2010; 126: 115-128
• 3 Speer CP. Neonatal Respiratory Distress Syndrome: An Inflammatory Disease?. Neonatology 2011; 99: 316-319
• 4 Bersani I, Kunzmann S, Speer CP. Immunomodulatory properties of surfactant preparations. Expert Review of Anti-infective Therapy 2013; 11: 99-110
• 5 Nkadi PO, Merritt TA, Pillers DM. An overview of pulmonary surfactant in the neonate: Genetics, metabolism, and the role of surfactant in health and disease. Molecular Genetics and Metabolism 2009; 97: 95-101
• 6 Speer CP. Chorioamnionitis Postnatal Factors and Proinflammatory Response in the Pathogenetic Sequence of Bronchopulmonary Dysplasia. Neonatology 2009; 95: 353-361
• 7 WHO Media centre. Preterm birth: Fact sheet N°363. Updated November 2014, 2015, Feb. 14^th http://www.who.int/mediacentre/factsheets/fs363/en/
• 8 Baraldi E, Filippone M. Chronic lung disease after premature birth. N Engl J Med 2007; 357: 1946-1955
• 9 Harding R, Cock ML, Louey S et al. The compromised intra-uterine environment: implications for future lung health. Clin Exp Pharmacol Physiol 2000; 27: 965-974
• 10 Harding R. Sustained alterations in postnatal respiratory function following sub-optimal intrauterine conditions. Reprod Fertil Dev 1995; 7: 431-441
• 11 Radulescu L, Munteanu O, Popa F et al. The implications and consequences of maternal obesity on fetal intrauterine growth restriction. J Med Life 2013; 6: 292-298
• 12 Veerbeek J, Nikkels P, Torrance H et al. Placental pathology in early intrauterine growth restriction associated with maternal hypertension. Placenta 2014; 35: 696-701
• 13 Hay WW. Care of the Infant of the Diabetic Mother. Curr Diab Rep 2012; 12: 4-15
• 14 Northway WH, Rosan RC, Porter DY. Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia. N Engl J Med 1967; 276: 357-368
• 15 Philip AGS. Bronchopulmonary dysplasia: then and now. Neonatology 2012; 102: 1-8
• 16 Northway WH, Moss RB, Carlisle KB et al. Late pulmonary sequelae of bronchopulmonary dysplasia. N Engl J Med 1990; 323: 1793-1799
• 17 El Mazloum D, Moschino L, Bozzetto S et al. Chronic lung disease of prematurity: long-term respiratory outcome. Neonatology 2014; 105: 352-356
• 18 Kotecha SJ, Edwards MO, Watkins WJ et al. Effect of preterm birth on later FEV1: a systematic review and meta-analysis. Thorax 2013; 68: 760-766
• 19 Hallman M. The Story of Antenatal Steroid Therapy before Preterm Birth. Neonatology 2015; 107: 352-357
• 20 Speer CP, Sweet DG, Halliday HL. Surfactant therapy: past, present and future. Early Hum Dev 2013; 89 (Suppl. 01) S22-S24
• 21 Sweet DG, Carnielli V, Greisen G et al. European consensus guidelines on the management of neonatal respiratory distress syndrome in preterm infants--2013 update. Neonatology 2013; 103: 353-368
• 22 Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 163: 1723-1729
• 23 Thomas W, Speer CP. Nonventilatory strategies for prevention and treatment of bronchopulmonary dysplasia--what is the evidence?. Neonatology 2008; 94: 150-159
• 24 Been JV, Lugtenberg MJ, Smets E et al. Preterm Birth and Childhood Wheezing Disorders: A Systematic Review and Meta-Analysis. PLoS Med 2014; 11: e1001596
• 25 Broström EB, Thunqvist P, Adenfelt G et al. Obstructive lung disease in children with mild to severe BPD. Respiratory Medicine 2010; 104: 362-370
• 26 Korhonen P, Laitinen J, Hyödynmaa E et al. Respiratory outcome in school-aged, very-low-birth-weight children in the surfactant era. Acta Paediatr 2004; 93: 316-321
• 27 Halvorsen T, Skadberg BT, Eide GE et al. Characteristics of asthma and airway hyper-responsiveness after premature birth. Pediatr Allergy Immunol 2005; 16: 487-494
• 28 Baraldi E, Bonetto G, Zacchello F et al. Low exhaled nitric oxide in school-age children with bronchopulmonary dysplasia and airflow limitation. Am J Respir Crit Care Med 2005; 171: 68-72
• 29 Vollsaeter M, Roksund OD, Eide GE et al. Lung function after preterm birth: development from mid-childhood to adulthood. Thorax 2013; 68: 767-776
• 30 Clemm H, Roksund O, Thorsen E et al. Aerobic Capacity and Exercise Performance in Young People Born Extremely Preterm. Pediatrics 2011; 129: e97-e105
• 31 Hamon I, Varechova S, Vieux R et al. Exercise-induced bronchoconstriction in school-age children born extremely preterm. Pediatr Res 2012; 73: 464-468
• 32 Satrell E, Roksund O, Thorsen E et al. Pulmonary gas transfer in children and adolescents born extremely preterm. Eur Respir J 2013; 42: 1536-1544
• 33 Smith LJ, van Asperen PP, McKay KO et al. Reduced Exercise Capacity in Children Born Very Preterm. Pediatrics 2008; 122: e287-e293
• 34 Halvorsen T, Skadberg BT, Eide GE et al. Better care of immature infants; has it influenced long-term pulmonary outcome?. Acta Paediatr 2006; 95: 547-554
• 35 Robin B, Kim YJ, Huth J et al. Pulmonary function in bronchopulmonary dysplasia. Pediatr Pulmonol 2004; 37: 236-242
• 36 Balinotti JE, Chakr VC, Tiller C et al. Growth of Lung Parenchyma in Infants and Toddlers with Chronic Lung Disease of Infancy. Am J Respir Crit Care Med 2010; 181: 1093-1097
• 37 Sanchez-Solis M, Garcia-Marcos L, Bosch-Gimenez V et al. Lung function among infants born preterm, with or without bronchopulmonary dysplasia. Pediatr Pulmonol 2012; 47: 674-681
• 38 Wei MC, Yu JL, Liu XH et al. Characteristics of lung function in preterm infants with varying degrees of bronchopulmonary dysplasia. Zhonghua Yi Xue Za Zhi 2013; 93: 1716-1720
• 39 Hilgendorff A, Reiss I, Gortner L et al. Impact of airway obstruction on lung function in very preterm infants at term. Pediatric Critical Care Medicine 2008; 9: 629-635
• 40 Hjalmarson OSKL. Lung function at term reflects severity of bronchopulmonary dysplasia. J Pediatr 2005; 146: 86-90
• 41 Shao H, Sandberg K, Hjalmarson O. Impaired gas mixing and low lung volume in preterm infants with mild chronic lung disease. Pediatr Res. 1998; 43: 536-541
• 42 Hulskamp G, Lum S, Stocks J et al. Association of prematurity, lung disease and body size with lung volume and ventilation inhomogeneity in unsedated neonates: a multicentre study. Thorax 2009; 64: 240-245
• 43 Greenough A, Yuksel B, Cheeseman P. Effect of in utero growth retardation on lung function at follow-up of prematurely born infants. Eur Respir J 2004; 24: 731-733
• 44 Hjalmarson O, Brynjarsson H, Nilsson S et al. Persisting hypoxaemia is an insufficient measure of adverse lung function in very immature infants. Arch Dis Child Fetal Neonatal Ed 2014; 99: F257-F262
• 45 Fawke J, Lum S, Kirkby J et al. Lung Function and Respiratory Symptoms at 11 Years in Children Born Extremely Preterm. Am J Respir Crit Care Med 2010; 182: 237-245
• 46 Bolton CE, Stocks J, Hennessy E et al. The EPICure Study: Association between Hemodynamics and Lung Function at 11 Years after Extremely Preterm Birth. J Pediatr 2012; 161: 595.e2-601.e2
• 47 Lum S, Kirkby J, Welsh L et al. Nature and severity of lung function abnormalities in extremely pre-term children at 11 years of age. Eur Respir J 2011; 37: 1199-1207
• 48 Welsh L, Kirkby J, Lum S et al. The EPICure study: maximal exercise and physical activity in school children born extremely preterm. Thorax 2010; 65: 165-172
• 49 Ronkainen E, Dunder T, Peltoniemi O et al. New BPD predicts lung function at school age: Follow-up study and meta-analysis. Pediatr Pulmonol 2015; [Epub ahead of print]
• 50 Cazzato S, Ridolfi L, Bernardi F et al. Lung function outcome at school age in very low birth weight children. Pediatr Pulmonol 2013; 48: 830-837
• 51 Narayanan M, Beardsmore CS, Owers-Bradley J et al. Catch-up Alveolarization in Ex-Preterm Children. Evidence from 3 He Magnetic Resonance. Am J Respir Crit Care Med 2013; 187: 1104-1109
• 52 Joshi S, Powell T, Watkins WJ et al. Exercise-Induced Bronchoconstriction in School-Aged Children Who Had Chronic Lung Disease in Infancy. J Pediatr 2013; 162: 813-818.e1
• 53 Kaplan E, Bar-Yishay E, Prais D et al. Encouraging pulmonary outcome for surviving, neurologically intact, extremely premature infants in the postsurfactant era. Chest 2012; 142: 725-733
• 54 Vrijlandt EJLE, Boezen HM, Gerritsen J et al. Respiratory health in prematurely born preschool children with and without bronchopulmonary dysplasia. J Pediatr 2007; 150: 256-261
• 55 Hoo A, Gupta A, Lum S et al. Impact of ethnicity and extreme prematurity on infant pulmonary function. Pediatr Pulmonol 2014; 49: 679-687
• 56 Suursalmi P, Kopeli T, Korhonen P et al. Very low birthweight bronchopulmonary dysplasia survivors show no substantial association between lung function and current inflammatory markers. Acta Paediatr 2015; 104: 264-268
• 57 Vom Hove M, Prenzel F, Uhlig HH et al. Pulmonary outcome in former preterm, very low birth weight children with bronchopulmonary dysplasia: a case-control follow-up at school age. J Pediatr 2014; 164: 40.e4-45.e4
• 58 Hacking DF, Gibson A, Robertson C et al. Respiratory function at age 8-9 after extremely low birthweight or preterm birth in Victoria in 1997. Pediatr Pulmonol 2013; 48: 449-455
• 59 Schmalisch G, Wilitzki S, Roehr CC et al. Development of lung function in very low birth weight infants with or without bronchopulmonary dysplasia: Longitudinal assessment during the first 15 months of corrected age. BMC Pediatr 2012; 12: 37
• 60 Guimarães H, Rocha G, Pissarra S et al. Respiratory outcomes and atopy in school-age children who were preterm at birth, with and without bronchopulmonary dysplasia. Clinics (Sao Paulo) 2011; 66: 425-430
• 61 Schulzke SM, Hall GL, Nathan EA et al. Lung Volume and Ventilation Inhomogeneity in Preterm Infants at 15-18 Months Corrected Age. J Pediatr 2010; 156: 542.e2-549.e2
• 62 Filippone M. Childhood Course of Lung Function in Survivors of Bronchopulmonary Dysplasia. JAMA 2009; 302: 1418
• 63 Kairamkonda VR, Richardson J, Subhedar N et al. Lung function measurement in prematurely born preschool children with and without chronic lung disease. J Perinatol 2008; 28: 199-204
• 64 Doyle LW. Respiratory function at age 8-9 years in extremely low birthweight/very preterm children born in Victoria in 1991-1992. Pediatr Pulmonol 2006; 41: 570-576
• 65 Ronkainen E, Dunder T, Kaukola T et al. Intrauterine growth restriction predicts lower lung function at school age in children born very preterm. Arch Dis Child Fetal Neonatal Ed 2016; Jan 22 [Epub ahead of print]
• 66 Morsing E, Gustafsson P, Brodszki J. Lung function in children born after foetal growth restriction and very preterm birth. Acta Paediatr 2012; 101: 48-54
• 67 Kotecha SJ, Edwards MO, Watkins WJ et al. Effect of bronchodilators on forced expiratory volume in 1s in preterm-born participants aged 5 and over: a systematic review. Neonatology 107 2015; 231-240
• 68 Korhonen PH, Suursalmi PH, Kopeli T et al. Inflammatory activity at school age in very low birth weight bronchopulmonary dysplasia survivors. Pediatr Pulmonol 2015; 50: 683-690
• 69 Filippone M, Bonetto G, Corradi M et al. Evidence of unexpected oxidative stress in airways of adolescents born very pre-term. Eur Respir J 2012; 40: 1253-1259
• 70 Carraro S, Filippone M, Da Dalt L et al. Bronchopulmonary dysplasia: the earliest and perhaps the longest lasting obstructive lung disease in humans. Early Hum Dev 2013; 89 (Suppl. 03) S3-S5
• 71 Saarenpää H, Tikanmäki M, Sipola-Leppänen M et al. Lung Function in Very Low Birth Weight Adults. Pediatrics 2015; 136: 642-650
• 72 Landry JS, Tremblay GM, Li PZ et al. Lung Function and Bronchial Hyperresponsiveness in Adults Born Prematurely: A Cohort Study. Annals of the American Thoracic Society 2015; [Epub ahead of print]
• 73 Stern DA, Morgan WJ, Wright AL et al. Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study. Lancet 2007; 370: 758-764
• 74 Lange P, Celli B, Agustí A et al. Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease. N Engl J Med 2015; 373: 111-122
• 75 Bolton CE, Bush A, Hurst JR et al. Lung consequences in adults born prematurely. Thorax 2015; 70: 574-580
• 76 Thomas W, Speer CP. Management of infants with bronchopulmonary dysplasia in Germany. Early Hum Dev 2005; 81: 155-163
• 77 Baker CD, Alvira CM. Disrupted lung development and bronchopulmonary dysplasia. Current Opinion in Pediatrics 2014; 26: 306-314
• 78 O’Reilly M, Thébaud B. Cell-Based Strategies to Reconstitute Lung Function in Infants with Severe Bronchopulmonary Dysplasia. Clinics in Perinatology 2012; 39: 703-725
• 79 O’Reilly M, Thébaud B. Stem cells for the prevention of neonatal lung disease. Neonatology 2015; 107: 360-364
• 80 Nixon PA, Washburn LK, O’Shea TM. Antenatal steroid exposure and pulmonary outcomes in adolescents born with very low birth weight. J Perinatol 2013; 33: 806-810
• 81 Dalziel SR, Rea HH, Walker NK et al. Long term effects of antenatal betamethasone on lung function: 30 year follow up of a randomised controlled trial. Thorax 2006; 61: 678-683
• 82 Blennow M, Bohlin K. Surfactant and noninvasive ventilation. Neonatology 2015; 107: 330-336
• 83 Bassler D, Plavka R, Shinwell ES et al. Early Inhaled Budesonide for the Prevention of Bronchopulmonary Dysplasia. N Engl J Med 2015; 373: 1497-1506
• 84 Yeh TF, Chen CM, Wu SY et al. Intra-tracheal Administration of Budesonide/Surfactant to Prevent Bronchopulmonary Dysplasia. Am J Respir Crit Care Med 2015; Sep 9 [Epub ahead of print]
• 85 Curstedt T, Halliday HL, Speer CP. A unique story in neonatal research: the development of a porcine surfactant. Neonatology 2015; 107: 321-329
• 86 Glaser K, Fehrholz M, Curstedt T et al. Effects of the New Generation Synthetic Reconstituted Surfactant CHF5633 on Pro- and Anti-Inflammatory Cytokine Expression in Native and LPS-Stimulated Adult CD14+ Monocytes. PLoS One 2016; 11: e0146898