Hospitalization rates of premature and early term infants with RSV bronchiolitis. Leon Joseph MB ChB Pediatric Pumonology Shaare Zedek Medical Center

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1 Hospitalization rates of premature and early term infants with RSV bronchiolitis Leon Joseph MB ChB Pediatric Pumonology Shaare Zedek Medical Center

2 Conflicts of Interest Supported in part by an unrestricted grant from Abbott Laboratories

3 Respiratory Syncitial Virus Leading cause of hospitalization in infants with respiratory distress in the winter Palivizumab reduced morbidity and mortality in all premature infants

4 AAP Guidelines: Prematurity Palivizumab prophylaxis may be administered to infants born before 29 weeks, 0 days gestation Prophylaxis may be considered during the first year of life for preterm infants <32 weeks, 0 days who develop CLD of prematurity Infants with CLD of prematurity and who continue to require medical support during 6- months period before the start of the second RSV season (chronic systemic corticosteroid therapy, bronchodilators, diuretic therapy, or supplemental oxygen).

5 AAP Guidelines: CHD Those infants aged 12 months or younger with hemodynamically significant CHD may benefit from palivizumab prophylaxis. Prophylaxis is not recommended for primary asthma prevention or to reduce subsequent episodes of wheezing.

6 הנחיות משר"ב א. ילדים שנולדו פגים, הלוקים במחלת ריאות כרונית והזקוקים לטיפול בחמצן - עד לגיל שנתיים ב. ילדים שנולדו פגים, הלוקים במחלת הריאות ושנזקקו לטיפול באחד מאלה: חמצן, תרופות משתנות, קורטיקוסטרואידים או מרחיבי סימפונות - עד לגיל שנה ג. ילדים שנולדו בטרם מלאו 32 שבועות הריון + 6 ימים - עד לגיל שנה יקבל את החיסון ד. ילדים שנולדו בטרם מלאו 34 שבועות הריון + 6 ימים - עד לגיל חצי שנה יקבלו את החיסון.

7 הנחיות משר"ב - ה. ילדים הסובלים ממחלת לב מולדת עד לגיל שנה: ו. ילדים, ללא תלות בשבוע הלידה, שנולדו במשקל נמוך מ- 1 ק"ג עד - לגיל שנה. ז. ילדים, ללא תלות בשבוע הלידה, הסובלים ממחלת ריאות כרונית קשה - לעד גיל שנה.

8 What about the late premature infants Definition: weeks gestation 8-9% all births in USA Increased but low rates of RDS/BPD Increased rates of neurological morbidity Increased episodes of wheeze in later life? Kugelman and Colin. Pediatrics 2013;132:

9 Objectives Quantify rates of hospitalization in premature and term infants with RSV bronchiolitis in SZMC medical center.

10 Methods Prospective observational study two seasons Only those under 1 year of age included Bronchiolitis: acute respiratory distress, coryza, cough with clinical signs of lung crepitations with or without wheeze with or without fever. Nasal aspirate positive for RSV (direct immunoflourescence test [PathoDX]) Admission Criteria : required supplemental O2 significant respiratory distress feeding refusal poor general condition

11 Methods Control group- National birth rates by gestational age distribution Dollberg et al IMAJ 2005;7: Defined premature <34weeks late premature Early term birth term >38 weeks

12 Results 441 Admissions RSV proven bronchiolitis. 392 were under 1 year of age. 368 admitted to the ward 9 (2.4%) Preterm and 34 (9.2%) Late premature 24 admitted to the PICU. 1 (4.2%) Preterm and 7 (16.7%) Late premature 1 mortality (RSV and Adenovirus in potter s synd) 1 transfer (no available bed in PICU)

13 Gestational Age (weeks) Preterm <33+6 weeks National Birth % Ward cohort % admissions (n=9) LOS PICU (days) 12 Late Preterm ** 11.5* weeks (n=34) Late Preterm plus ** 9.7 Early term (n=66) Early Term **(n=28) Term >37 weeks (n=325) 6.6 ** p <0.001 * significantly greater than in term babies.

14 Results National birth cohort preterm < 33+6 late preterm term Late premature infants 5.0%

15 Results Admissions for bronchiolitis preterm < 33+6 late preterm term Late premature infants 9.2%

16 Results * general Israeli population * preterm < 32+6 weeks pretem < 33+6 weeks late preterm weeks late preterm weeks admissions for bronchiolitis single birth cohort ie. < 1 year old

17 Results Length of Stay * Late pretem weeks term weeks 0 ward PICU

18 Pavulizumab efficiency 5 Premature babies were hospitalized despite having receiving prophylaxis One became ill 4 weeks after last dose. She had concurrent, severe adenoviral infection and Potter s syndrome and died Four further cases were hospitalized to the ward and discharged after mean 5.5 days No cases of premature infants with RSV who did not receive prophylaxis

19 Discussion Over-expression of late-preterm (LP) and early term (ET) infants in a population of those admitted with RSV bronchiolitis. Late-preterm (LP) infants have longer LOS in PICU

20 Discussion Previous study: Helfrich et al showed that late premature infants weeks were: more likely to be hospitalized (8.5%) for longer periods of time required more respiratory support. Early Hum Dev Sep;91(9):541-6.

21 Discussion Both LP and ET are at an increased risk of receiving a diagnosis of asthma or recurrent wheezing and using inhaled corticosteroids at 18 months of age and at 5 years of age compared to controls. This dose dependant effect starts with extreme prematurity and persists in a continum to early term babies Goyal et al. Pediatrics 2011:128:e830 e838

22 Discussion Regarding RSV: increased prevalence of wheezing subsequent to RSV bronchiolitis At age 2 and 3 years of age, recurrent wheezing was reduced when RSV immunoprophylaxis was administered. Pérez-Yarza at al. Pediatr Infect Dis J. 2007;26: Régnier et al.pediatr Infect Dis J. 2013;32:820-6 Blanken et al. N Engl J Med. 2013;368: Yoshihara et al. Pediatrics. 2013;132:811-8.

23 Strengths Clearly defined cases Clear admission criteria Clear criteria for hospitalizations Only RSV proven cases included No cases of admissions for RSV without palivizumab

24 Limitations The control birth cohort was not specific to our institution and was performed several years prior to the study The local birth cohort had insufficient data to be used

25 Conclusions? What bearing do these data have upon RSV prophylaxis? Prevention of acute episodes of bronchiolitis Prevention of recurrent wheezing Continue to reduce indications for palivizumab like in the USA Increase the indications to influence patient well-being.