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

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.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.