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Ibuprofen treatment for patent ductus arteriosus in preterm infants: a retrospective cohort study in a leading Chinese center
doi: 10.2478/fzm-2021-0013
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Abstract:
Objective There is a dilemma of ibuprofen treatment with patent ductus arteriosus (PDA) as to how and when to treat. We aimed to clarify this issue in very preterm infants (VPIs; < 32 weeks). Methods: This retrospective study included 1 659 VPIs who were diagnosed with PDA according to echocardiographic examinations and cardiovascular dysfunction scoring system (the CVD scoring). The VPIs were classified into six groups (A1, A2, A3, B1, B2, and B3) based on CVD scores (A, < 3, and B, ≥ 3), and treatment with ibuprofen for PDA (1, conservational management; 2, early ibuprofen treatment; and 3, late ibuprofen treatment). Treatment was stopped when PDA was closed, CVD score was zero or PDA needed ligation. Results: VPIs with CVD scores < 3 had most PDA closure without surgery, and early ibuprofen treatment did not significantly affect PDA closure. VPIs with CVD scores ≥ 3 had some PDA closure after 2 courses of treatment, but closure rates decreased linearly with ibuprofen course (1st 75.2%, 2nd 62.3%, 3rd 50.0%, P < 0.0001), and early ibuprofen treatment (group B2) did not increase PDA closure compared to late ibuprofen treatment (group B3). In these same infants, the longer they were in CVD scores ≥ 3, the more the complications of preterm were increased (retinopathy of prematurity ROP 1st 16.5%, 2nd 23.8%, 3rd 29.6%, P = 0.016; bronchopulmonary dysplasia BPD 1st 15.5%, 2nd 26.7%, 3rd 33.8%, P < 0.0001; intraventricular hemorrhage IVH 1st 20.4%, 2nd 32.4%, 3rd 23.8%, P = 0.015). Conclusion: Ibuprofen is suggested for PDA closure when the PDA reopens or has developed into the stage when the CVD score ≥ 3.
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Key words:
- preterm infants /
- ibuprofen /
- patent ductus arteriosus /
- cohort study /
- CVD score
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Table 1. Clinical outcomes according to CVD scores
Variables PDA χ2/t P value CVD < 3 CVD ≥ 3 n=1019 n=640 Surgery(PDA ligation)(n/%) 0 16.5 - - PDA closure (n/%) 75.0(772) 66.5(426) 16.201 < 0.0001 1st course of ibuprofen (n/%) 86.1(179) 75.2(313) 9.439 0.002 2nd course of ibuprofen (n/%) 91.3(21) 62.3(76) 1.136 0.287 3rd course of ibuprofen (n/%) 73.9(17) 50.0(36) 4.041 0.044 RDS (n/%) 66.8(679) 83.5(533) 56.219 < 0.0001 ROP (n/%) 7.7(77) 20.7(131) 59.941 < 0.0001 IVH (n/%) 17.4(179) 25(159) 12.881 < 0.0001 NEC (n/%) 1.1(10) 1.2(8) 0.264 0.607 BPD(n/%) 8.9(90) 22.4(143) 59.539 < 0.0001 Death (n/%) 8.8(75) 6.8(41) 0.538 0.463 PDA closure time (d) 10.8±0.8 14.5±1.4 7.015 < 0.0001 PDA diameter (mm) 2.2±0.5 2.4±0.6 6.280 < 0.0001 Ibuprofen (n/%) 24.9(254) 95.3(610) 779.560 < 0.0001 Ibuprofen after 24h (n/%) 66.5(169) 98.1(598) 178.508 < 0.0001 BPD, pulmonary dysplasia; ROP, retinopathy of prematurity; IVH. intraventricular hemorrhage; NEC, Necrotizing enterocolitis. 
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Table 2. Clinical outcomes according to CVD scores ≥ 3
Variables CVD≥3 B1 vs B2 B1 vs B3 B2 vs B3 B2+B3 vs B1 PDA ligation (%) < 0.0001 < 0.0001 0.053 < 0.0001 (96.7 vs 33.3) (96.7 vs 12.2) (33.3 vs 12.2) (12.6 vs 86.6) PDA closure (%) 0.192 < 0.0001 < 0.001 < 0.0001 (6.7 vs 16.7) (6.7 vs 70.9) (16.7 vs 70.9) (69.8 vs 6.7) ROP (%) 0.730 0.048 0.056 0.057 (34.5 vs 41.7) (34.5 vs 19.4) (41.7 vs 19.4) (19.9 vs 34.5) IVH (%) 0.729 0.010 0.318 0.11 (44.8 vs 33.3) (44.8 vs 23.7) (33.3 vs 23.7) (23.9 vs 44.8) NEC(%) - - - - (0 vs 0) (0 vs 0) (0 vs 1.3) (1.3 vs 0) BPD(%) 0.005 < 0.0001 0.442 < 0.0001 (72.4 vs 25) (72.4 vs 19.9) (25 vs 19.9) (20.0 vs 72.4) Death(%) 1.000 0.947 0.551 1.000 (6.7 vs 8.3) (6.7 vs 6.4) (8.3 vs 6.4) (6.4 vs 6.7) PDA closure time(d) 0.307 0.028 0.554 0.026 (19.2±6.2 vs 11.4±0.2) (19.2±6.2 vs 14.3±1.1) (11.4±0.2 vs 14.3±1.1) (19.2±6.2 vs 14.3±1.1) PDA diameter (mm) 0.622 0.612 0.463 0.625 (2.4±0.5 vs 2.5±0.5) (2.4±0.5 vs 2.3±0.7) (2.5±0.5 vs 2.4±0.7)) (2.4±0.5 vs 2.3±0.7) BPD, pulmonary dysplasia; ROP, retinopathy of prematurity; IVH, intraventricular hemorrhage; NEC, Necrotizing enterocolitis.
B1, non-ibuprofen intervention; B2, ibuprofen intervention was conducted within 24 h; B3, ibuprofen intervention was conducted after 24h; B2+B3, ibuprofen intervention
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Table 3. Clinical outcomes according to ibuprofen course and intervention timing
CVD score Time Course ≥3 B2(< 24h) B3(≥24h) 1 2 ≥3 P 1 2 ≥3 P Antenatal 66.7 50 0 - 37.0 39.7 39.4 0.828 Corticosteroid(%) NRDS (%) 66.7 100 100 0.513 79.9 89.3 90.1 0.012 Pneumonia (%) 77.8 100 0 - 29.5 46.7 31.0 0.002 Closure (%) 22.2 0 0 - 76.4 63.3 50.7 < 0.0001 Ligation (%) 33.3 50.0 0 - 8.6 27 16.9 < 0.0001 ROP (%) 44.4 50 0 - 16.5 23.8 29.6 0.016 IVH (%) 11.1 10.0 1 0.018 20.4 32.4 23.8 0.015 NEC (%) 0 0 0 - 1.7 0.8 0 - BPD (%) 33.3 - - - 15.5 26.7 33.8 < 0.0001 Death (%) 11.1 - - - 6.9 5.0 5.6 0.743 RDS, respiratory distress syndrome; BPD, pulmonary dysplasia; ROP, retinopathy of prematurity; IVH, intraventricular hemorrhage; NEC, Necrotizing enterocolitis.
B2, ibuprofen intervention was conducted within 24 h; B3, ibuprofen intervention was conducted after 24h
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