Clinical Comparison Study of Oral Ibuprofen on Neonatal Patent Ductus Arteriosus

doi:10.3877/cma.j.issn.1673-5250.2013.02.011

Objective

To investigate rate of spontaneous closure, efficacy and safety of oral ibuprofen on neonatal patent ductus arteriosus (PDA).

Methods

From October 2008 to September 2011, a total of 96 neonates admitted to department of pediatrics with premature infants, neonate pneumonia or cyanosis associated with PDA confirmed by echocardiography from 15 h to 24 d after delivery. They were divided into two groups based on different treatment strategies: Treatment group (n=61, treatment by oral ibuprofen suspension 10 mg/kg, 5 mg/kg at 24 h and 48 h, respectively, and echocardiography examination after treatment 72 h to 96 h); placebo group (n=35, treatment by oral physiological saline 1 mL/kg, 0.5 mL/kg at 24 h and 48 h, respectively, echocardiography examination after treatment 72 h to 96 h. They were treatment by oral ibuprofen suspension as strategies of treatment group if PDA persistence, and echocardiography examination again after treatment by ibuprofen 72 h to 96 h. There had no significance difference between two groups among general clinical data and results of echocardiography of heart before treatment etc.(P>0.05). Data of reexamine results of echocardiography of heart and incidence of adverse reactions were analysis between two groups by statistics. Informed consent was obtained from the parents of each participating neonate.

Results

①The PDA closing rates of overall, full term infants, asymptomatic infants, without others cardiopathy infants, PDA confirmed born within 72 h in treatment group (88.5%, 91.3%, 92.9%, 89.6%, 93.0%) were significant higher than those in placebo group (62.9%, 50.0%, 68.0%, 60.7%, 66.7%)(P<0.05). There were no significant difference in PDA closing rates of preterm infants, symptomatic infants, with other cardiopathy infants, PDA confirmed born after 72 h between treatment group (86.8%, 78.9%, 84.6%, 77.8%) and placebo group (71.4%, 50.0%, 71.4%, 50.0%)(P>0.05). ②There were no significant difference between two groups in closing rates of PDA of preterm infants and full term infants, symptomatic and asymptomatic, with and without others cardiopathy, PDA confirmed born within and after 72 h (P>0.05). ③ In placebo group, PDA disappear spontaneously in 22/35 (62.9%) cases after treatment by placebo, and PDA were closed in 8/13 (61.5%) cases after treatmen by strategies as that of treatment group.④There were 4 cases premature infants born after 10 d treatment by ibuprofen, closed in 2/4 cases, and diameter reduced in the other 2/4 cases.⑤Oliguria occurred in 6 cases (9.8%) in treatment group, and 2 cases (5.7%) in placebo group. ⑥Another 3 cases treatment by ibuprofen who had been excluded by this study, occurred serious decrease of platelet (PLT), upper gastrointestinal hemorrhage, and hematochezia one case, respectively.

Conclusions

Oral ibuprofen is effective in closing PDA in preterm infants within 10 days of life. It is effective in closing PDA in full term infants with neonate pneumonia or cyanosis and preterm infants after 10 days of life, too. It is safe to clinical use.

Key words: ibuprofen, patent ductus arteriosus, infant, newborn

表1 96例PDA新生儿一般临床资料比较(±s)

Table 1 Comparison of general clinical data among 96 cases PDA neonates (±s)

组别	n	性别[n(%)]					Apgar评分(分)
组别	n	男性	女性	胎龄(孕周)	出生体重(g)	早产儿比例[n(%)]	1 min	5 min	合并其他心脏病比例[n(%)]
治疗组	61	33(54.1)	28(45.9)	36.5±2.9	2761±730	38(62.3)	7.2±1.3	8.6±0.6	13(21.3)
安慰剂组	35	19(54.3)	16(45.7)	36.6±3.0	2577±586	21(60.0)	7.7±1.2	8.8±0.7	7(20.0)
χ²/t		0.000		－0.149	1.273	0.049	－1.627	－0.977	0.023
P		0.986		0.882	0.206	0.824	0.107	0.331	0.879

表1 96例PDA新生儿一般临床资料比较(±s)

Table 1 Comparison of general clinical data among 96 cases PDA neonates (±s)

组别	n	性别[n(%)]					Apgar评分(分)
组别	n	男性	女性	胎龄(孕周)	出生体重(g)	早产儿比例[n(%)]	1 min	5 min	合并其他心脏病比例[n(%)]
治疗组	61	33(54.1)	28(45.9)	36.5±2.9	2761±730	38(62.3)	7.2±1.3	8.6±0.6	13(21.3)
安慰剂组	35	19(54.3)	16(45.7)	36.6±3.0	2577±586	21(60.0)	7.7±1.2	8.8±0.7	7(20.0)
χ²/t		0.000		－0.149	1.273	0.049	－1.627	－0.977	0.023
P		0.986		0.882	0.206	0.824	0.107	0.331	0.879

表2 96例PDA新生儿治疗前心脏彩超检查结果比较(±s)

Table 2 Comparison of results of echocardiography before treatment among 96 cases PDA neonates (±s)

组别	n	彩超确诊时患儿日龄(d)^a	导管直径(mm)^a	导管直径的平方/出生体重(mm²/kg)^a	导管水平左向右分流峰值流速(m/s)^b	导管两端压差(mm Hg)^b	闻及2/6级及以上收缩期杂音比例[n(%)]	脉压差(mm Hg)^b
治疗组	61	2.0(2.0～4.0)	2.0(2.0～2.0)	1.5(1.2～2.0)	2.4±0.8	25.3±14.6	23(37.7)	19.7±6.4
安慰剂组	35	3.0(2.0～3.0)	2.0(2.0～2.0)	1.7(1.3～2.7)	2.3±0.8	22.6±15.0	12(34.3)	20.9±6.9
z/t		－0.153	－0.794	－1.123	0.682	0.853	χ²＝0.112	0.904
P		0.878	0.427	0.261	0.497	0.396	0.738	0.368

表2 96例PDA新生儿治疗前心脏彩超检查结果比较(±s)

Table 2 Comparison of results of echocardiography before treatment among 96 cases PDA neonates (±s)

组别	n	彩超确诊时患儿日龄(d)^a	导管直径(mm)^a	导管直径的平方/出生体重(mm²/kg)^a	导管水平左向右分流峰值流速(m/s)^b	导管两端压差(mm Hg)^b	闻及2/6级及以上收缩期杂音比例[n(%)]	脉压差(mm Hg)^b
治疗组	61	2.0(2.0～4.0)	2.0(2.0～2.0)	1.5(1.2～2.0)	2.4±0.8	25.3±14.6	23(37.7)	19.7±6.4
安慰剂组	35	3.0(2.0～3.0)	2.0(2.0～2.0)	1.7(1.3～2.7)	2.3±0.8	22.6±15.0	12(34.3)	20.9±6.9
z/t		－0.153	－0.794	－1.123	0.682	0.853	χ²＝0.112	0.904
P		0.878	0.427	0.261	0.497	0.396	0.738	0.368

表3 两组治疗(72～96)h后复查心脏彩超的动脉导管关闭率比较

Table 3 Comparison of results of the closing rates of ductus arteriosus during 72 h to 96 h after oral ibuprofen suspension therapy or placebo

组别	n	总关闭率[n(%)]	PDA早产儿	PDA足月儿	症状性PDA患儿	非症状性PDA患儿	合并其他心脏病患儿	不合并其他心脏病患儿	出生72 h内确诊患儿	出生72 h后确诊患儿
治疗组	61	154(88.5)	86.8%(33/38)	91.3%(21/23)	78.9%(15/19)	92.9%(39/42)	84.6%(11/13)	89.6%(43/48)	93.0%(40/43)	77.8%(14/18)
安慰剂组	35	22(62.9)	71.4%(15/21)	50.0% ( 7/14)	50.0% ( 5/10)	68.0%(17/25)	71.4% ( 5/ 7)	60.7%(17/28)	66.7%(18/27)	50.0% ( 4/ 8)
Pearson χ²/Continuity
Correction χ²		8.884	1.224	5.978	－	5.368	－	8.868	6.362	－
P		0.003	0.269	0.014	Fisher's ExactTest 0.205	0.021	Fisher's ExactTest 0.587	0.003	0.012	Fisher's ExactTest 0.197

表3 两组治疗(72～96)h后复查心脏彩超的动脉导管关闭率比较

Table 3 Comparison of results of the closing rates of ductus arteriosus during 72 h to 96 h after oral ibuprofen suspension therapy or placebo

组别	n	总关闭率[n(%)]	PDA早产儿	PDA足月儿	症状性PDA患儿	非症状性PDA患儿	合并其他心脏病患儿	不合并其他心脏病患儿	出生72 h内确诊患儿	出生72 h后确诊患儿
治疗组	61	154(88.5)	86.8%(33/38)	91.3%(21/23)	78.9%(15/19)	92.9%(39/42)	84.6%(11/13)	89.6%(43/48)	93.0%(40/43)	77.8%(14/18)
安慰剂组	35	22(62.9)	71.4%(15/21)	50.0% ( 7/14)	50.0% ( 5/10)	68.0%(17/25)	71.4% ( 5/ 7)	60.7%(17/28)	66.7%(18/27)	50.0% ( 4/ 8)
Pearson χ²/Continuity
Correction χ²		8.884	1.224	5.978	－	5.368	－	8.868	6.362	－
P		0.003	0.269	0.014	Fisher's ExactTest 0.205	0.021	Fisher's ExactTest 0.587	0.003	0.012	Fisher's ExactTest 0.197

表4 治疗组4例PDA早产儿生后10 d予布洛芬治疗的一般临床资料比较

Table 4 Comparison of general clinical data among 4 cases PDA preterm infants born after 10 d treatment by ibuprofen

No.	胎龄(孕周)	出生体重(g)	Apgar评分(分)		治疗时日龄(d)	治疗前导管内径(mm)	治疗后导管内径(mm)	导管直径的平方/出生体重(mm²/kg)	导管水平左向右分流峰值流速(m/s)	导管两端压差(mm Hg)	肌钙蛋白I (μg/L)	闻及2/6级及以上收缩期杂音	脉压差(mm Hg)
No.	胎龄(孕周)	出生体重(g)	1 min	5 min	治疗时日龄(d)	治疗前导管内径(mm)	治疗后导管内径(mm)	导管直径的平方/出生体重(mm²/kg)	导管水平左向右分流峰值流速(m/s)	导管两端压差(mm Hg)	肌钙蛋白I (μg/L)	闻及2/6级及以上收缩期杂音	脉压差(mm Hg)
1	28^＋4	1200	3	8	11	2.0	0.0	3.3	1.73	25	0.10	否	17
2	29	1450	6	8	22	2.0	0.0	2.8	3.20	41	0.05	是	29
3	31^＋3	1300	7	7	24	3.5	1.0	9.4	2.94	34	0.03	是	10
4	31^＋4	1750	8	9	12	2.0	1.0	2.3	1.28	18	0.04	否	26

表4 治疗组4例PDA早产儿生后10 d予布洛芬治疗的一般临床资料比较

Table 4 Comparison of general clinical data among 4 cases PDA preterm infants born after 10 d treatment by ibuprofen

No.	胎龄(孕周)	出生体重(g)	Apgar评分(分)		治疗时日龄(d)	治疗前导管内径(mm)	治疗后导管内径(mm)	导管直径的平方/出生体重(mm²/kg)	导管水平左向右分流峰值流速(m/s)	导管两端压差(mm Hg)	肌钙蛋白I (μg/L)	闻及2/6级及以上收缩期杂音	脉压差(mm Hg)
No.	胎龄(孕周)	出生体重(g)	1 min	5 min	治疗时日龄(d)	治疗前导管内径(mm)	治疗后导管内径(mm)	导管直径的平方/出生体重(mm²/kg)	导管水平左向右分流峰值流速(m/s)	导管两端压差(mm Hg)	肌钙蛋白I (μg/L)	闻及2/6级及以上收缩期杂音	脉压差(mm Hg)
1	28^＋4	1200	3	8	11	2.0	0.0	3.3	1.73	25	0.10	否	17
2	29	1450	6	8	22	2.0	0.0	2.8	3.20	41	0.05	是	29
3	31^＋3	1300	7	7	24	3.5	1.0	9.4	2.94	34	0.03	是	10
4	31^＋4	1750	8	9	12	2.0	1.0	2.3	1.28	18	0.04	否	26

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