1. Is Patent Ductus Arteriosus Ligation Responsible for Adverse Outcome in Very Low Birth Weight (VLBW) Infants?
 MJ. Qureshi, MD1*, M. Bamehrez, MD1, F. Al-Sufayan, MD1, K. Kwiatkowski, RN1, D. Moddemann, MD1,
J. Baier, MD1 and M. Seshia, MB.ChB1
1Department of Pediatrics and Child Health, University of Manitoba, Winnipeg
ABSTRACT
INTRODUCTION: Surgical ligation of Patent Ductus Arteriosus in VLBW infants has been shown to increase the risk of neurodevelopmental impairment.
HYPOTHESIS: Preterm infants weighing <1250g, undergoing ductal ligation, have an increased incidence of adverse neurodevelopmental outcomes.
METHODS: A retrospective chart review of all infants with BW <1250g admitted to 2 NICUs in Manitoba between 2000 and 2005, with ECHO diagnosis of PDA. PDA severity was scored at the time the decision to treat (and how to treat) from 1 (incidental PDA) to 5 (PDA with a significant increase in ventilator support (need for HFV, increase in MAP ≥ 2 cm H2O, increase in FiO2 ≥ 0.2, pulmonary hemorrhage). The relationships between clinical characteristics, disease severity, outcomes and PDA treatments were examined by univariate and multivariate analysis. Primary outcome was a composite of death before a corrected age of months &/or survival with ≥1 neurodevelopmental impairments: cerebral palsy, cognitive delay (Bayley Scales of Infant Development MDI <70 or Revised Gesell Developmental Scales adaptive DQ <70), hearing loss requiring amplification, or bilateral blindness (corrected visual acuity <20/200). RESULTS:176 VLBW infants with PDA (BW 924  15g, GA 26.7  0.1weeks) were studied. PDA treatment was: 26 (14.8%) none, 84 (47.7%) indomethacin (indo) alone, 19 (10.8%) primary surgery, and 47 (26.7%) indo and subsequent surgery. BW and gestation varied significantly according to treatment category. Infants having PDA surgery (primary & after indo) were less mature and smaller than infants not treated for their PDAs(25.5  0.3, 26.3  0.2 vs wks; p<0.001, p=0.006 and 808  47, 894  30 vs. 903  36 g; p=0.097, p=0.001). 27 surviving infants (15%) were lost to follow up. 88 (53%) died or survived with major neurodevelopmental impairment at follow up at months corrected age. PDA and SNAPPE-II scores were higher in infants with PDA ligation (3.66 vs. 2.08; p=0.013, 51 vs.32; p<0.001) and correlated with outcome. In multivariate models PDA score was a positive predictor for death or adverse Neurodevelopmental outcome and PDA treatment group was negative predictor.
CONCLUSION: Surgical treatment of PDA was a marker for death or poor ND outcome. However, underlying immaturity and clinical condition at time of PDA ligation may be responsible for the adverse outcome observed.
Patient Characteristics
METHODS
Retrospective chart review of infants admitted between 2000 and 2005 to NICU Children’s Hospital or St. Boniface General Hospital, with BW <1250g and diagnosed by ECHO to have a PDA.
A PDA severity score was developed
Primary outcome: composite of death prior to corrected age of months and/or survival with ≥1 neurodevelopmental impairments (NDI): cerebral palsy, cognitive delay, hearing loss requiring amplification, or bilateral blindness
Statistical Analysis: stepwise logistic regression (SPSS® version 15)
No Treatment (n=26)
Indomethacin
Alone (n=84)
Primary Surgery (n=19)
Indomethacin plus surgery (n=47)
GA(wks) * †
27.4  0.4
27  0.2
25.5  0.3
26.3  0.2
Birth weight(g)* †
903  36
976  19
808  47
894  30
Male
13(50%)
49(58%)
7(37%)
25(53%)
SNAPPE-II score *
35  1.6#
23  4.7
48  6.4†
40  5.2 §
IUGR<3rd %ile
10(39%)
12(14%)
3(16%)
4(9%)
BPD
3(18%)
27(37%)
10(63%)
18(40%)
P=0.00
Score
Criteria 1
No tachypnea, tachycardia or feeding intolerance
Non ventilated, PDA diagnosed incidentally 2
Tolerant of weaning from ventilator
Ventilated 3
Intolerant of weaning from ventilator 4
Ventilated: escalating support (Increase MAP ≤ 2 cm H2O, increase FiO2 ≤ 0.2) 5
Ventilated: HFV, increase MAP ≥ 2 cmH2O, increase FiO2 ≥ 0.2, and/or pulmonary hemorrhage
p<0.001
No Death/NDI Death/NDI
Conditional model of Death or ND impairment
*Mean  SEM # p<0.05 No treatment vs. primary surgery †p< 0.05 Primary Surgery vs. all other groups
p<0.05 Indomethacin alone vs. Primary surgery & Indo + surgery § p< 0.05 Indo + surgery vs. Indo alone & primary surgery
Outcomes
Factor
Risk
95% CI
p value
Gestation
1.15
0.022
Birth Weight
0.99
0.024
PDA treatment group
0.61
0.033
PDA score
1.46
0.013
Max IVH grade
1.56
0.005
Hypotension in 1st week
0.22
0.003
Out of 176, 34 infants died and 27 were lost to follow up. For the primary outcome, 149 infants
were included in the analysis
No Rx
(n=25)
Indomethacin only
(n=69)
Surgery only
(n=18)
Indomethacin + Surgery (n=37)
Death /NDI
14(56%)
32(46.4%)
12(67%)
18(49%)
Cerebral Palsy*
2 (15%)
5 (10%)
3 (21%)
4 (13%)
Blindness*
0 (0%)
3 (5%)
2 (14%)
6 (17%)
Cognitive delay*
13 (24%)
7 (54%)
12 (39%)
Hearing impairment*
1 (7%)
5 (14%)
BACKGROUND
Persistent patency of the ductus arteriosus, unresponsive to Prostaglandin Synthetase inhibitors (PSI) administration(~40%) is a frequent problem in VLBW infants.
Surgical ligation has been associated with higher pulmonary morbidity, impaired LV diastolic function and impaired neurodevelopmental outcome.
OBJECTIVE
To compare the neurodevelopmental outcome of preterm infants, weighing <1250g and diagnosed with a PDA, according to therapeutic management.
* Percentages expressed as % of survivors excluding lost to follow up
Distribution of PDA scores among the treatment groups
CONCLUSIONS
Surgical treatment of PDA was a marker for death or poor ND outcome.
However underlying immaturity and clinical condition at the time of PDA ligation may be responsible for the adverse outcome observed.
RESULTS
Infants with
PDA
N=176
Not Treated
n=26
Treated
n=150
Indomethacin
Alone
n=84
Primary Surgery
n=19
+ surgery
n=47
Supported by the Manitoba Institute of Child Health