Department of Pharmacy, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen, 518102, China.
Department of Hospital Infection Control, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen, 518102, China.
Clin Res Hepatol Gastroenterol. 2021 Mar;45(2):101495. doi: 10.1016/j.clinre.2020.06.019. Epub 2020 Jul 25.
Hemodynamically significant patent ductus arteriosus (hsPDA) in very low birth weight (VLBW) infants is routinely treated in many countries with oral ibuprofen. This study retrospectively assessed whether the risk of cholestatic liver disease (CLD) increased due to oral ibuprofen administration in VLBW infants.
A total of 122 VLBW preterm infants (26∼32 weeks, birth weight<1500g) diagnosed with patent ductus arteriosus (PDA) admitted to our neonatal intensive care unit (NICU) between September 2016 to August 2018 were included. Sixty-four infants were diagnosed with hs-PDA and received ibuprofen treatment. VLBW infants with PDA untreated with ibuprofen served as controls. Soybean oil and fat emulsions were routinely added to parenteral nutrition (PN). Once CLD was diagnosed, the fat emulsions were immediately replaced with multi-oil fat emulsion injections. To assess the independent association of treatment and duration of ibuprofen with CLD and duration of fasting and PN, binary logistic regression or multivariate linear regression analyses were conducted, adjusting for major confounders (birth weight, gestational age, Clinical Risk Index for Babies, and cholestasis-associated risk factors).
The duration of PN increased due to ibuprofen treatment for 6.559 days (95% CI: 1.769, 11.349; P=0.008), and the risk of prolonged fasting (cutoff>5 days) might have increased due to ibuprofen treatment (OR: 3.043, 95% CI: 0.965, 9.594; P=0.057). Furthermore, CLD was influenced by ibuprofen treatment (OR: 6.730; 95% CI: 1.279, 35.41; P=0.024), early thrombocytopenia 7 days postnatal (OR: 6.996; 95% CI: 1.769, 27.658; P=0.004), and late onset sepsis (OR: 6.976; 95% CI: 1.561, 31.169; P=0.011). Further analysis adjusting for cholestasis-associated risk factors revealed that CLD was influenced by the duration of ibuprofen treatment (OR: 2.864; 95% CI: 1.104, 7.422; P=0.030), Platlets counts 7 days postnatal (OR: 0.971; 95% CI: 0.950, 0.994; P=0.013), and duration of antibiotics (OR: 1.134; 95% CI: 1.002, 1.282; P=0.046).
This retrospective study indicated oral ibuprofen duration-dependently increased the risk of CLD in VLBW infants with PDA, and early thrombocytopenia served as the critical risk factor.
在许多国家，对于极低出生体重儿（VLBW）中存在的临床显著动脉导管未闭（hsPDA），常采用口服布洛芬进行治疗。本研究回顾性评估了 VLBW 婴儿口服布洛芬是否会增加胆汁淤积性肝病（CLD）的风险。
共纳入 2016 年 9 月至 2018 年 8 月期间在我院新生儿重症监护病房（NICU）诊断为动脉导管未闭（PDA）的 122 例 VLBW 早产儿（26～32 周，出生体重<1500g）。其中 64 例被诊断为 hs-PDA，并接受布洛芬治疗。未用布洛芬治疗的 PDA 早产儿作为对照组。静脉营养（PN）中常规添加大豆油和脂肪乳剂。一旦诊断出 CLD，立即将脂肪乳剂替换为多油脂肪乳剂注射。为评估治疗和布洛芬使用时间与 CLD 及禁食和 PN 时间的独立相关性，采用二项逻辑回归或多元线性回归分析，对主要混杂因素（出生体重、胎龄、婴儿临床风险指数和胆汁淤积相关危险因素）进行调整。
布洛芬治疗导致 PN 时间延长 6.559 天（95%CI：1.769，11.349；P=0.008），且由于布洛芬治疗，延长禁食时间（>5 天）的风险可能增加（OR：3.043，95%CI：0.965，9.594；P=0.057）。此外，CLD 受到布洛芬治疗的影响（OR：6.730；95%CI：1.279，35.41；P=0.024）、出生后第 7 天血小板减少症（OR：6.996；95%CI：1.769，27.658；P=0.004）和晚发性败血症（OR：6.976；95%CI：1.561，31.169；P=0.011）。进一步调整胆汁淤积相关危险因素后分析显示，CLD 与布洛芬治疗时间（OR：2.864；95%CI：1.104，7.422；P=0.030）、出生后第 7 天血小板计数（OR：0.971；95%CI：0.950，0.994；P=0.013）和抗生素使用时间（OR：1.134；95%CI：1.002，1.282；P=0.046）有关。
本回顾性研究表明，口服布洛芬时间依赖性增加了 VLBW 伴有 PDA 婴儿发生 CLD 的风险，且早期血小板减少症是关键的危险因素。
