Characteristics of Bronchopulmonary Dysplasia in Very Low Birth Weight Infants according to the Timing of Dexamethasone Administration

Hae Yun Lee; Hyoung Jin Lee; Ji Won Koh; In Gu Song; Sae Yun Kim; Young Hwa Jung; Seung Han Shin; Chang Won Choi; Ee-Kyung Kim; Han-Suk Kim; Beyong Il Kim; Jung-Hwan Choi

doi:10.14734/kjp.2015.26.4.321

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Lee, Lee, Koh, Song, Kim, Jung, Shin, Choi, Kim, Kim, Kim, and Choi: Characteristics of Bronchopulmonary Dysplasia in Very Low Birth Weight Infants according to the Timing of Dexamethasone Administration

Original Article

Korean J Perinatol 2015;26(4):321-328.

Published online: 20 December 2015

DOI: https://doi.org/10.14734/kjp.2015.26.4.321

Characteristics of Bronchopulmonary Dysplasia in Very Low Birth Weight Infants according to the Timing of Dexamethasone Administration

Hae Yun Lee, M.D.¹, Hyoung Jin Lee, M.D.¹, Ji Won Koh, M.D.¹, In Gu Song, M.D.¹, Sae Yun Kim, M.D.¹, Young Hwa Jung, M.D.¹, Seung Han Shin, M.D.^1,^3,, Chang Won Choi, MD., Ph.D.^2,³, Ee-Kyung Kim, M.D., Ph.D.^1,³, Han-Suk Kim, M.D., Ph.D.^1,³, Beyong Il Kim, M.D., Ph.D.^2,³, Jung-Hwan Choi, M.D., Ph.D.^1,³

¹Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea

²Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Korea

³Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea

Correspondence to: Seung Han Shin, M.D. Department of Pediatrics, Seoul National University College of Medicine, 101 Daehak-ro Jongno-gu, Seoul 110-799, Korea Tel: +82-2-2072-7230, Fax: +82-2-2072-0590, E-mail: revival421@snu.ac.kr

Received 23 September 2015 Revised 17 October 2015 Accepted 28 October 2015

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

Corticosteroids has been used for treatment and prophylaxis of bronchopulmonary dysplasia (BPD) in preterm infants. However, administration of corticosteroids could be delayed due to its potential harmful effects on neurodevelopment. The aim of this study was to evaluate the adequate dexamethasone administration timing in very low birth weight infants.

Methods

Medical records of 56 VLBW infants who were admitted to neonatal intensive care unit of Seoul National University Children's Hospital and Seoul National University Bundang Hospital between January 2008 and September 2014 were collected retrospectively. Study population were divided into early administration group (dexamethasone administration before 4 weeks of postnatal days) and late administration group (after 4 weeks) and respiratory morbidities were compared between groups.

Results

There were no significant differences in clinical characteristics between early administration group (n=30) and late administration group (n=26). Respiratory severity score and oxygen needs at 7 days after birth and before administering dexamethasone were comparable. Extubation was done earlier postnatal days in early administration group. Incidence of severe BPD was higher in the late administration group. There was no significant difference in diagnosed with cerebral palsy (CP) at 12 months of corrected age. When adjusting for multiple risk factors, administration of dexamethasone 4 weeks after birth and severe of BPD showed a significant association (adjusted OR 17.14 [1.29–227.52], P=0.031).

Conclusion

Administration of dexamethasone in order to minimize ventilator care and to reduce severe BPD might be done between 1 week and 4 weeks after birth in very low birth weight infants.

Keywords: Very low birth weight, Bronchopulmonary dysplasia, Dexamethasone, Cerebral palsy

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Table 1.

Demographics of Study Population

Median (range) or number (%)	DXM administration		P-value
Median (range) or number (%)	<4 wks (n=30)	≥4 wks (n=26)	P-value
Gestational age (wks)	26⁺⁶ (23⁺²-29⁺²)	26⁺³ (23⁺⁴-32)	0.576
Gestational age (wks)
Birth weight (g)	783 (530–1,260)	750 (370–1,630)	0.831
AS
1 min	3 (1–8)	2 (0–8)	0.561
5 min	5 (2–9)	5 (1–9)	0.785
Female	15 (50.0)	9 (34.6)	0.288
C/S	18 (60.0)	16 (61.5)	1.000
Multiple birth	20 (66.7)	14 (53.8)	0.414
SGA	8 (26.7)	11 (42.3)	0.265
Oligohydramnios	4 (13.3)	8 (30.8)	0.175
Chorioamnionitis	16 (53.3)	9 (34.6)	0.407
Prenatal Steroid	17 (56.7)	12 (46.2)	0.593
RDS	27 (90.0)	23 (88.5)	1.000
NEC	2 (6.7)	5 (19.2)	0.231
IVH≥3	2 (6.7)	2 (7.7)	1.000
PVL	3 (10.0)	4 (15.4)	0.693
Culture proven sepsis	6 (20.0)	11 (42.3)	0.087
PDA operation	13 (43.3)	14 (53.8)	0.592
ROP operation	21 (70.0)	14 (53.8)	0.273

Abbreviations: DXM, dexamethasone; AS, apgar score; C/S, cesarean section; SGA, small for gestational age; RDS, respiratory distress syndrome; NEC, necrotizing enterocolitis; IVH, intraventricular hemorrhage; PVL, periventricular leukomalacia; PDA, patent ductus arteriosus; ROP, retinopathy of prematurity

Table 2.

Clinical Settings of Study Population according to Timing of Dexamethasone Treatment

Median (range) or number (%)	DXM administration		P-value
Median (range) or number (%)	<4 wks (n=30)	≥4 wks (n=26)	P-value
At postnatal 7 days
FiO²	0.23 (0.21–1.00)	0.23 (0.21–0.90)	0.792
HFOV, n (%)	8 (26.7)	6 (23.1)	1.000
Before DXM started
RSS	6.7 (3.5–14)	4.55 (2.5–6.6)	0.080
FiO²	0.4 (0.21–1.0)	0.25 (0.4–1.0)	0.888
HFOV, n (%)	9 (30.0)	5 (19.2)	0.537
DXM started
Postnatal day DXM started	21 (9–27)	52 (28–158)	<0.001
Post conceptional age DXM started	29⁺⁵ (26⁺²-32⁺¹)	34⁺² (28⁺⁴-49⁺²)	<0.001
First cycle DXM dose (mg/kg)	0.84 (0.35–1.25)	1.1 (0.2–3.24)	0.019
Cumulative DXM dose (mg/kg)	1.2 (0.43–25.31)	1.1 (0.45–7.41)	0.600
Multiple cycle DXM^∗, n (%)	12 (40.0)	15 (57.7)	1.000
DXM total cycle, median (range)	2 (1–10)	1 (1–7)	0.104
After DXM started
Post FiO₂	0.3 (0.21–0.85)	0.28 (0.21–0.8)	0.133
Pre-post FiO₂ †	0.05 (0.45∼-0.37)	0.1 (0.77∼-0.5)	0.362

^∗ Multiple cycles DXM was defined as two or more times administration.

^† The difference before and after dexamethasone administion oxygen demand Abbreviations: DXM, dexamethasone; RSS, respiratory severity score; FiO₂, fraction of inspiration oxygen; HFOV, high frequency oscillation ventilation.

Table 3.

Respiratory Morbidity and Mortality during Hospital Stay and Cerebral Palsy at 12 Months of Corrected Age

Median (range) or number (%)	DXM administration		P-value
Median (range) or number (%)	<4 wks (n=30)	≥4 wks (n=26)	P-value
From DXM started until extubation (days)	8 (1–721)	9 (1–41)	0.786
From Birth until extubation (days)	32 (16–732)	63.5 (27–170)	0.001
Length of stay (days)	101 (30–562)	115 (81–435)	0.158
Death before discharge	3 (10.0)	1 (3.8)	0.615
Severe BPD	13 (43.3)	22 (84.6)	0.040
Death or severe BPD	14 (46.7)	22 (84.6)	0.005
CP	2 (6.7)	3 (11.5)	0.652
Death or CP	5 (16.7)	4 (15.4)	1.000
Tracheostomy	3 (10.0)	5 (19.2)	0.455

Abbreviations: DXM, dexamethasone; BPD, bronchopulmonary dysplasia; CP, cerebral palsy.

Table 4.

Association of Severe BPD with Clinical Findings

Variables	Univariable OR (95%CI)	P-value	Mutivariable OR (95%CI)	P-value
GA ≥ 26 wks	0.57 (0.18–1.84)	0.347	0.94 (0.12–7.43)	0.954
SGA	4.25 (1.05–17.20)	0.043	9.47 (0.33–273.49)	0.19
Oligohydramnios	7.77 (0.88–68.44)	0.065	4.24 (0.16–111.38)	0.386
hCAM	1.92 (0.63–5.88)	0.285	1.73 (0.18–16.73)	0.637
Prenatal DXM	2.06 (0.66–6.41)	0.211	3.68 (0.40–34.22)	0.253
PDA operation	3.11 (0.97–10.00)	0.057	5.12 (0.57–45.67)	0.144
Before DXM start HFOV apply	4.13 (0.82–20.97)	0.088	8.55 (0.57–129.32)	0.121
DXM ≥ 4 wks	6.77 (1.86–24.65)	0.004	17.14 (1.29–227.52)	0.031

Abbreviations: BPD, bronchopulmonary dysplasia; GA, gestational age; SGA, small for gestational age; hCAM, histological chorioamnionitis; DXM, dexamethasone; PDA, patent ductus arteriosus; HFOV, high frequency oscillation ventilation.

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