hospitalization rates of premature and early term infants ... filehospitalization rates of premature...

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.