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Hospitalization rates of premature and early term
infants with RSV bronchiolitis
Leon Joseph MB ChB
Pediatric Pumonology
Shaare Zedek Medical Center
Conflicts of Interest
• Supported in part by an unrestricted grant from Abbott
Laboratories
Respiratory Syncitial Virus
• Leading cause of hospitalization in infants with respiratory distress in the winter
• Palivizumab reduced morbidity and mortality in all premature infants
AAP Guidelines: Prematurity
• Palivizumab prophylaxis may be administeredto 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 secondRSV season (chronic systemic corticosteroid therapy, bronchodilators, diuretic
therapy, or supplemental oxygen).
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.
ב"משרהנחיות
הלוקים במחלת ריאות , ילדים שנולדו פגים. א•
עד לגיל שנתיים-כרונית והזקוקים לטיפול בחמצן
הלוקים במחלת הריאות , ילדים שנולדו פגים. ב•
תרופות , חמצן: ושנזקקו לטיפול באחד מאלה
קורטיקוסטרואידים או מרחיבי סימפונות , משתנות
עד לגיל שנה-
6+ שבועות הריון 32ילדים שנולדו בטרם מלאו . ג•
עד לגיל שנה יקבל את החיסון-ימים
+ שבועות הריון 34ילדים שנולדו בטרם מלאו . ד•
.עד לגיל חצי שנה יקבלו את החיסון-ימים 6
ב"משרהנחיות
:עד לגיל שנה-ילדים הסובלים ממחלת לב מולדת . ה•
ג "ק1-שנולדו במשקל נמוך מ, ללא תלות בשבוע הלידה, ילדים. ו•
.לגיל שנה-עד
הסובלים ממחלת ריאות כרונית , ללא תלות בשבוע הלידה, ילדים. ז•
.לעד גיל שנה-קשה
What about the late premature infants
• Definition: 34 - 36+6 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;132:741–751
Objectives
• Quantify rates of hospitalization in premature and term infants with RSV bronchiolitis in SZMC medical center.
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 distressfeeding refusal
poor general condition
Methods
• Control group-
– National birth rates by gestational age distribution – Dollberg et al IMAJ 2005;7:311-314
• Defined premature <34weeks
late premature 34-36+6
Early term birth 37-37+6
term >38 weeks
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)
LOS PICU (days)% Ward
admissions
National Birth
cohort %
Gestational Age
(weeks)
12 2.4 (n=9)1.8Preterm
<33+6 weeks
11.5*9.2 **
(n=34)
5.0Late Preterm
34-36+6 weeks
9.7 17.9 **
(n=66)
10.1Late Preterm plus
Early term 34-37+6
7.38.8 **(n=28)5.1Early Term
37- 37+6
6.6 88.3 (n=325)93.2Term >37 weeks
** p <0.001
* significantly greater than in term babies.
ResultsNational birth cohort 1993-2001
preterm <33+6
late preterm34-36+6
term 37-42
Late premature infants 5.0%
Results
Admissions for bronchiolitis
preterm <33+6
late preterm34-36+6
term 37-42
Late premature infants 9.2%
Results
0
2
4
6
8
10
12
14
16
18
20
preterm < 32+6
weeks
pretem < 33+6
weeks
late preterm 34-
36+6 weeks
late preterm 34-
37+6 weeks
general Israelipopulation
admissionsforbronchiolitissingle birthcohort ie. < 1year old
*
*
ResultsLength of Stay
0
2
4
6
8
10
12
14
ward PICU
Latepretem34-36+6weeks
term 37-42weeks
*
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
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
Discussion
• Previous study:
• Helfrich et al showed that late premature infants 33-36+6 weeks were:– more likely to be hospitalized (8.5%)
– for longer periods of time
– required more respiratory support.
• Early Hum Dev. 2015 Sep;91(9):541-6.
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
• Edwards et al. J Allergy Clin Immunol 2015;136:581-7
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;26:733-9.
• Régnier et al .Pediatr Infect Dis J. 2013;32:820-6
• Blanken et al. N Engl J Med. 2013;368:1791-9.
• Yoshihara et al. Pediatrics. 2013;132:811-8.
Strengths
• Clearly defined cases
– Clear admission criteria
– Clear criteria for hospitalizations
– Only RSV proven cases included
• No cases of admissions for RSV without palivizumab
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
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.