Risk Factors of Failure of Ibuprofen Treatment in Preterm Infants with Hemodynamically Significant Patent Ductus Arteriosus

Nam Hee Kwon; Ji Hoon Lee; Ga Won Jeon; Jong Beom Sin

doi:10.14734/kjp.2014.25.4.257

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Kwon, Lee, Jeon, and Sin: Risk Factors of Failure of Ibuprofen Treatment in Preterm Infants with Hemodynamically Significant Patent Ductus Arteriosus

Original Article

Korean J Perinatol 2014;25(4):257-265.

Published online: 21 December 2014

DOI: https://doi.org/10.14734/kjp.2014.25.4.257

Risk Factors of Failure of Ibuprofen Treatment in Preterm Infants with Hemodynamically Significant Patent Ductus Arteriosus

Nam Hee Kwon, M.D., Ji Hoon Lee, M.D., Ga Won Jeon, M.D., Ph.D., Jong Beom Sin, M.D., Ph.D.

Department of Pediatrics, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea

Received 7 August 201411 September 2014 Accepted 16 October 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

In this study, the risk factors of failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus (hsPDA) were investigated.

Methods

Among 403 preterm infants (<32 weeks gestation) born between January 2010 and December 2012, 125 infants treated with ibuprofen for hsPDA were retrospectively reviewed. The preterm infants were divided into the following groups according to their response to the 1^st and 2^nd cycles of ibuprofen treatment: responder groups I and II, closure of the ductus arteriosus after the 1^st and 2^nd cycles of ibuprofen treatment; and nonresponder groups I and II, persistency of hsPDA after the 1st and 2nd cycles of ibuprofen treatment.

Results

One hundred twenty five infants were enrolled in the study: 74 in responder group I, 51 in non-responder group I, 14 in responder group II, and 22 in non-responder group II. In non-responder group I, the gestational age and birth weight were smaller, the postnatal steroid treatment was more frequent, and the duration of mechanical ventilation and the days spent in the hospital were prolonged. In non-responder group II, the gestational age and birth weight were smaller, the diameters of the ductus arteriosus were larger, and the inotropics use was more frequent.

Conclusion

Failure of ibuprofen treatment of hsPDA is associated with the diameter of the ductus arteriosus and with inotropics use. Obtaining data regarding these is expected to help in determining if early direct surgical ligation is needed.

Keywords: Patent ductus arteriosus, Preterm infants, Ibuprofen

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Fig. 1.

Derivation of study groups.

Table 1.

Demographics and Obstetric Factors of Responder Goup I and Non-responder Group I

	Responder group I (n=74)	Non-responder group I (n=51)	P value	P value^*
Gestational age (wk^+day)	28⁺⁰±2⁺¹	26⁺¹±1⁺⁶	<0.001
Birth weight (g)	1,095±358	853±219	<0.001
Male, n (%)	29(39.2)	20(39.2)	1	0.588
Apgar score at 1 min	4.2+0.1	3.9+0.1	0.106	0.503
Apgar score at 5 min	6.8±0.1	6.4±0.1	0.016	0.471
Cesarean section, n (%)	49 (66.2)	39 (76.5)	0.238	0.014
Multiple birth, n (%)	18 (24.3)	15 (29.4)	0.542	0.982
Antenatal steroid, n (%)	56 (75.7)	36 (70.6)	0.542	0.899
Maternal PIH, n (%)	12 (16.2)	8 (15.7)	1	0.944
Maternal DM, n (%)	2 (2.7)	0 (0)	0.513	0.453
Histologic chorioamnionitis, n (%)	16 (21.6)	9 (17.6)	0.654	0.692
Small for gestational age, n (%)	8 (10.8)	4 (7.8)	0.76	0.293
Initial ductal size (mm)	2.59±0.77	2.81±0.57	0.027	0.159
Age at ibuprofen administration (days)	3.7±2.8	4.0±2.0	0.115	0.632

*P value, adjusted for gestational age and birth weight

Abbreviations : PIH, pregnancy-induced hypertension; DM, Diabetes mellitus.

Table 2.

Demographics and Obstetric Factors of Responder group II and Non-responder Group II

	Responder group II (n=14)	Non-responder group II (n=22)	P value	P value^*
Gestational age (wk^+day)	27⁺⁴±1⁺⁵	25⁺³±1⁺⁴	0.001
Birth weight (g)	1,031±221	768±189	<0.001
Male, n (%)	5 (35.7)	7(31.8)	1.0	0.922
Apgar score at 1 min	3.9+1.3	4.0+1.0	0.367	0.129
Apgar score at 5 min	6.5±1.1	6.3±1.0	0.181	0.010
Cesarean section, n (%)	11 (78.6)	16 (72.7)	1.0	0.911
Multiple birth, n (%)	4 (28.5)	8 (36.4))	1.0	0.471
Antenatal steroid, n (%)	11 (78.6)	13 (59.1)	0.292	0.625
Maternal PIH, n (%)	2 (14.3)	3 (13.6)	1.0	0.893
Maternal DM, n (%)	0 (0)	0 (0)
Histologic chorioamnionitis, n (%)	1 (7.1)	3 (22.7)	0.370	0.122
Small for gestational age, n (%)	1 (7.1)	2 (9.1)	1.0	0.708
Initial ductal size (mm)	2.51±0.64	2.96±0.43	<0.001	0.026
Age at ibuprofen administration (days)	4.5±2.2	3.8±1.8	0.179	0.333

^* P value, adjusted for gestational age and birth weight

Abbreviations : PIH, pregnancy-induced hypertension; DM, Diabetes mellitus.

Table 3.

Factors Associated with Patent Ductus Arteriosus of Responder Group I and Non-responder Group I

	Responder group I (n=74)	Non-responder group I (n=51)	P value	P value^*
RDS, n (%)	74 (100)	51 (100)	1	1
IVH (≥grade III), n (%)	10 (13.5)	11 (21.6	0.33	0.756
Sepsis, n (%)	13 (17.6)	13 (25.5)	0.37	0.851
NEC (≥grade II), n (%)	3 (4.1)	1 (2)	0.645	0.161
Duration of parenteral nutrition (days)	17.7±1.5	26.2±1.5	<0.001	0.266
ROP, n (%)	4 (5.4)	10 (19.6)	0.02	0.126
Inotropics use, n (%)	18 (24.3)	23 (45.1)	0.02	0.498
BPD (≥moderate), n (%)	5 (6.8)	11 (21.6)	0.027	0.123
Duration of mechanical ventilation (days)	16.5±18.1	36.8±20.3	<0.001	0.002
Postnatal steroid treatment, n (%)	13 (17.6)	31(60.8)	<0.001	<0.001
Hospital stay (days)	65±24	91±23	<0.001	<0.001
Death, n (%)	5 (6.8)	1(2.0)	0.339	0.022

^* P value, adjusted for gestational age and birth weight

Abbreviations : RDS, respiratory distress syndrome; IVH, intraventricular hemorrhage; NEC, Necrotizing enterocolitis; ROP, retinopathy of prematurity; BPD bronchopulmonary dysplasia.

Table 4.

Factors Associated with Patent Ductus Arteriosus of Responder Group II and Non-responder Group II

	Responder group II (n=14)	Non-responder group I (n=22)	II P value	P value^*
RDS, n (%)	14 (100)	22 (100)
IVH (≥ gradeIII), n (%)	2 (14.3)	4 (18.2)	1.0	0.282
Sepsis, n (%)	2 (14.3)	4 (18.2)	1.0	0.353
NEC (≥ stageII), n (%)	0 (0)	0 (0)
Duration of parenteral nutrition (days)	23.0±13.0	25.5±8.7	0.048	0.616
ROP, n (%)	1 (7.1)	5 (22.7)	0.370	0.353
Inotropics use, n (%)	1 (7.1)	16 (72.7)	<0.001	0.033
BPD (≥ moderate), n (%)	1 (7.1)	7 (31.8)	0.115	0.315
Duration of mechanical ventilaton (days)	36.5±21.8	46.9±18.2	<0.001	0.046
Postnatal steroid treatment, n (%)	6 (42.9)	14 (63.6)	0.307	0.955
Hospital stay (days)	91±26	98±25	0.007	0.561
Death, n (%)	0 (0)	1 (4.5)	1.0	0.714

^* P value, adjusted for gestational age and birth weight

Abbreviations : RDS, respiratory distress syndrome; IVH, intraventricular hemorrhage; NEC, Necrotizing enterocolitis; ROP, retinopathy of prematurity; BPD, bronchopulmonary dysplasia.

Table 5.

Risk Factors for Non-responder Group I

	Odds ratio	95% confidence interval	P value
Gestational age (wk^+day)	0.972	0.923–1.023	0.028
Birth weight (g)	1.001	0.998–1.003	0.683
Duration of mechanical ventilation (days)	1.001	0.964–1.041	0.940
Postnatal steroid treatment, n (%)	3.190	1.238– 8.221	0.016
Hospital stay (days)	1.036	1.014–1.057	0.001

Table 6.

Risk Factors for Non-responder Group II

	Odds ratio	95% confidence interval	P value
Gestational age (wk^+day)	0.966	0.811–1.152	0.700
Birth weight (g)	1.002	0.993–1.011	0.699
Duration of mechanical ventilation (days)	1.063	0.977–1.156	0.159
Initial ductal size (mm)	8.244	1.037–70.556	0.045
Inotropics use, n (%)	42.153	3.834–463.506	0.002

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