Association with Ductus Arteriosus Closure by Ibuprofen and Intrauterine Inflammation in Very Low Birth Weight Infants

Han-Su Seon; Jung-Bae Lee; In-Uk Kim; Soo-Hyun Kim; Jung-Ha Lee; Do-Hyun Kim; Hee-Sup Kim

doi:10.14734/kjp.2013.24.3.158

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Seon, Lee, Kim, Kim, Lee, Kim, and Kim: Association with Ductus Arteriosus Closure by Ibuprofen and Intrauterine Inflammation in Very Low Birth Weight Infants

Original Article

Korean J Perinatol 2013;24(3):158-167.

Published online: 19 June 2013

DOI: https://doi.org/10.14734/kjp.2013.24.3.158

Association with Ductus Arteriosus Closure by Ibuprofen and Intrauterine Inflammation in Very Low Birth Weight Infants

Han-Su Seon, M.D., Jung-Bae Lee, M.D., In-Uk Kim, M.D., Soo-Hyun Kim, M.D., Jung-Ha Lee, M.D., Do-Hyun Kim, M.D., Hee-Sup Kim, M.D.

Department of Pediatrics, Dongguk University Ilsan Hospital, Goyang, Korea

주관책임자 : 김도현, 410-774 경기도 고양시 일산동구 식사동 814 동국대학교 일산병원 소아청소년과 전화 : 031)961-7184, Fax : 031)961-7188 E-mail : dayeong1@dumc.or.kr

Received 25 July 2013 Revised 9 August 2013 Accepted 16 August 2013

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 :

Ibuprofen is an inhibitor of prostaglandin synthesis and used to close a patent ductus arteriosus (PDA) of preterm infants. This study investigated the association between the response to ibuprofen treatment for PDA and maternal intrauterine inflammation in preterm infants.

Methods :

We retrospectively reviewed the medical records of very low birth weight (VLBW) infants diagnosed with PDA, who are admitted immediately after birth in the neonatal intensive care unit at Dongguk University Ilsan Hospital between March 2010 and May 2013. After the first cycle of ibuprofen therapy, infants whose ductus arteriosus was closed and not closed were classified as Responders and Non-responders I, respectively. After the second cycle of ibuprofen therapy, infants with persistent PDA were classified as Non-responders II. We performed multiple logistic regression analysis to determine the most important factor associated with persistent PDA.

Results :

After the first cycle of ibuprofen therapy, the numbers of Responders and Non-responders I were 40 and 14, respectively. Rate of cesarean section was significantly lower in Non-responders I than that of Responders (P=0.023). In addition, Rate of maternal amnionitis in Non-responder I was significantly higher than that of Responders (P=0.016). By multiple logistic regression analysis, maternal amnionitis was found to be a significant risk factor of the failure of ductus arteriosus closure after the first cycle of ibuprofen treatment (P=0.039).

Conclusion :

The present study shows that maternal amnionitis is an independent risk factor for the treatment failure after the first cycle of ibuprofen therapy in VLBW infants with PDA.

Keywords: Patent ductus arteriosus, Intrauterine inflammation, Amnionitis, Very low birth weight infant

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Table 1.

Characteristics of the Study Infants

Characteristics	Success of PDA closure Responder N=40	Failure o of PDA closure
		Non-Responder I		Non-Respponder II
		N=14	P-value	N=4	P-value
GA, weeks	27.6±2.4	26.3±1.9	0.077	25.1±1.5	0.054
Bwt, g	965.0 ± 276.3	933.8±270.4	0.717	798.2±244.3	0.253
Male, N (%)	23 (57.5)	6 (42.9)	0.344	3 (75)	0.634
Multiple births, N (%)	18 (45.0)	5 (35.7)	0.755	2 (50)	1.000
Cesarean section, N (%)	31 (77.5)	6 (42.9)	0.023	2 (50)	0.256
Apgar score at 1min	5.1±1.9	4.6±1.9	0.427	4.8±2.6	0.722
Apgar score at 5min	7.2±1.6	6.7±1.6	0.350	6.0±2.9	0.192
Initial CRP, mg/dL	0.12±0.46	0.11±0.34	0.946	0.37±0.62	0.327
PDA size, mm	2.3±0.9	2.6±1.2	0.321	2.7±1.1	0.484
Diuretics use, N (%)	12 (30.0)	6 (42.9)	0.512	3 (75)	0.107
Phototherapy, N (%)	36 (90.0)	14 (100)	0.563	4 (100)	1.000
Fluid, mL/kg/day	57.6±4.2	59.0±4.2	0.284	59.0±2.2	0.484
RDS, N (%)	33 (82.5)	11 (78.6)	0.708	4 (100)	1.000
NEC, N (%)	5 (12.5)	0 (0)	0.311	0 (0)	1.000
Late onset sepsis, N (%)	5 (12.5)	4 (28.6)	0.216	1 (25)	0.456

Abbreviations: N, number; GA, gestational age; Bwt, birth weight; CRP, C-reactive protein; PDA, patent ductus arteriosus; Fluid, fluid volume at first day after birth; RDS, respiratory distress syndrome; NEC, necrotizing enterocolitis.

Table 2.

Maternal Characteristics of the Study Infants

Characteristics	Success of PDA closure Responder N=40	Failure o of PDA closure
		Non-Responder I		Non-Respponder II
		N=14	P-value	N=4	P-value
Age, yrs	32.1±3.7	31.1±4.1	0.387	30.5±3.3	0.389
PROM, N (%)	12 (30.0)	6 (42.9)	0.512	1 (25.0)	1.000
Preeclampsia, N (%)	5 (12.5)	0 (0)	0.311	0 (0)	1.000
Prenatal antibiotics, N (%)	23 (57.5)	5 (35.7)	0.657	3 (75.0)	0.634
HCAM, N (%)	22 (55.0)	10 (71.4)	0.354	4 (100)	0.133
Amnionitis, N (%)	8 (20.0)	8 (57.1)	0.016	4 (100)	0.004
Funisitis, N (%)	9 (22.5)	5 (35.7)	0.479	2 (50.0)	0.256
	N=23	N=12		N=4
CRP	1.4±1.3	1.5±1.5	0.946	1.9±1.7	0.327
CRP >0.5, N (%)	14 (56.5)	9 (75.0)	0.476	4 (100)	0.268

Abbreviations: N, number; PROM, premature rupture of membrane; HCAM, histologic chorioamnionitis; CRP, C-reactive protein.

Table 3.

Risk Factors for the Failure of PDA Closure after First Cycle of Ibuprofen Treatment by Logistic Regression Analysis

Risk factor	Odd ratio	95% Confidence Interval		P-value
Risk factor	Odd ratio	Lower	Upper	P-value
Cesarean section	3.555	0.906	13.950	0.069
Maternal amnionitis	4.235	1.075	16,692	0.039

Adjusted for cesarean section and maternal amnionitis in all subjects included in this study.

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