LONG TERM OUTCOMES AT (?2 YEARS) OF ELBW INFANTS TREATED WITH EARLY LOW-DOSE HYDROCORTISONE (HC) TO PREVENT BRONCHOPULMONARY DYSPLASIA (BPD).  KL Watterberg for the PROPHET study group

 

Background:  360 mechanically ventilated ELBW infants were enrolled in a randomized, multicenter study of the short and long term effects of early HC prophylaxis of early to prevent adrenal insufficiency to prevent BPD.   Short term outcomes were reported in Pediatrics (114:1649, 2004).  HC-treated infants exposed to chorioamnionitis had significantly improved survival and survival without BPD.   

 

Objective:  To evaluate neurodevelopmental, growth and medical outcomes at 18 – 22 months corrected age in infants enrolled in the above study.

 

Methods:  All surviving infants ³ 18 months corrected age (n=294____) were eligible for evaluation by certified examiners masked to treatment assignment, including standardized neurologic exam & Bayley Scales of Infant Development II (BSID-II).  Neurodevelopmental impairment (NDI) = mental developmental index (MDI) or physical developmental index (PDI) <70, cerebral palsy (CP), blindness or deafness.  Treatment group comparisons are based on multiple linear regression models for continuous outcomes and multiple logistic regression models for binary and ordinal outcomes.  All analyses include adjustment for birth weight, gestational age, prenatal steroid use, outborn status, gender, motheraternal race (black vs. all other), method of delivery, and center where possible.  Additionally, gGrowth outcomes are adjusted for corrected age by computingusing z-scores based on the CDC 2000 growth charts for 2000.      Statistical results from multiple regression analysis…..

 

Results:  252 of 294___ survivors (86___%) were seen at a mean ± SD of 20.0____ ± 2.1___ months corrected age (mean ± SD, range 14.6__ - 28.0___).   Maternal education and household income were similar between groups.  All results are HC vs. placebo. There were no significant differences inResults were not different (HC vs. placebo) for length (80.7___ ± 3.5cm___ vs. 81.5 ___± 4.0cm)___, weight (10.6 ± 2.1kg vs. 10.9 ± 1.5kg),_______ or head circumference (47.1 ± 1.9cm vs. 47.3 ± 1.8cm)_______. or in   Similar numbers were receiving bronchodilators ___% vs. ___%.  Fewer HC patients were onreceiving  bronchodilators (17% vs. 23%) and or inhaled/systemic steroids (19__ % vs. 25___%), although not significantly different than placebo.  Functional gross motor level (normal 77% vs. 74%), independent normal gaitwalking (71% vs. 67%) and independent feeding (73% vs. 65%) were all  similar between groups (________).. 

 

 

Cerebral Palsy (CP)

Bayley MDI

Bayley PDI

MDI <70

PDI<70

NDI

HC-treated (n=126)

N, %16 (13%)

80.4 ± 19.1

82.8 ± 19.4

32 (27%)

31 (26%)

48

(39%)

Placebo

(n=126)

N, %18 (14%)

77.5 ± 19.3

83.9 ± 19.9

46 (37%)

29 (23%)

55

(44%)

Odds/RR/pp value

0.40

0.08

0.82

0.02*

0.94

0.14

 

Conclusions:  Early, low dose HC treatment was not associated with an increase in CP.  Treated infants had indicators of improved neurodevelopmental outcome.  In combination with the finding of improved survival without BPD in HC-treated infants exposed to chorioamnionitis, Tthese data support further, targeted  studies of HC treatment for of indicators of adrenal insufficiency in ELBW infants.