近红外光谱技术对有血流动力学意义的动脉导管未闭早产儿肠道组织氧饱和度监测价值的前瞻性研究

目的 使用近红外光谱技术研究有血流动力学意义的动脉导管未闭（hemodynamically significant patent ductus arteriosus,hsPDA）早产儿肠道组织氧饱和度（regional oxygen saturation,rSO₂）的变化及规律,初步探索hsPDA早产儿肠道组织血氧水平变化的临床意义。 方法 前瞻性选取2017年10月至2020年10月深圳市龙岗中心医院新生儿科收治的胎龄<32周和/或出生体重<1 500 g的动脉导管未闭（patent ductus arteriosus,PDA）早产儿。按照hsPDA的诊断标准分为hsPDA组和无血流动力学意义的动脉导管未闭（non-hemodynamically significant patent ductus arteriosus,nhsPDA）组,将hsPDA组早产儿根据口服布洛芬后动脉导管关闭情况分为hsPDA关闭亚组和hsPDA未闭亚组。分别在诊断PDA时及治疗后测定血流动力学指标,持续监测患儿肠道组织rSO₂水平,分析其变化规律。 结果 共有241例PDA早产儿纳入研究,其中hsPDA组55例（22.8%）,nhsPDA组186例（77.2%）;hsPDA关闭亚组36例（65%）,hsPDA未闭亚组19例（35%）。hsPDA组左心房内径/主动脉根部内径值大于nhsPDA组,左室射血分数和短轴缩短率均低于nhsPDA组（P<0.05）。hsPDA组患儿肠道组织rSO₂在诊断后6 h内各时间点（1、2、4、6 h）均低于nhsPDA组（P<0.05）;hsPDA组早产儿肠道组织rSO₂随时间呈下降趋势（P<0.05）,至6 h时达最低值（0.448±0.014）。hsPDA关闭亚组左心房内径/主动脉根部内径值低于hsPDA未闭亚组,左室射血分数和短轴缩短率高于hsPDA未闭亚组（P<0.05）。hsPDA关闭亚组患儿肠道组织rSO₂在治疗后48~96 h内各时间点（48、72、96 h）均高于hsPDA未闭亚组（P<0.05）;hsPDA关闭亚组早产儿肠道组织rSO₂从治疗24 h后随时间呈上升趋势（P<0.05）,至96 h达最高值（0.578±0.031）。 结论 hsPDA对早产儿肠道组织氧合有影响,可通过近红外光谱技术持续监测hsPDA早产儿肠道组织rSO₂变化趋势指导临床管理。     

Cardiac output and ductal reopening during phototherapy in preterm infants

Left ventricular output (LVO), left pulmonary artery blood flow (LPA) and patency of the ductus arteriosus (PDA) were studied with 2D/pulsed Doppler ultrasound before, during and after phototherapy treatment in 27 preterm infants (gestational age < or =32 wk), who were exposed for a minimum of 12 h to phototherapy for non-haemolytic hyperbilirubinemia. In 14 infants (52%) the ductus arteriosus reopened during phototherapy, but ductal patency was not of haemodynamic importance. LVO initially decreased in preterm infants in whom the ductus did not reopen. From 12 h until discontinuation of phototherapy, LVO and LPA were higher than before phototherapy in all infants. After withdrawal of phototherapy, LVO and LPA returned to pre-phototherapy values.     

Abnormal blood flow patterns in renal arteries of small preterm infants with patent ductus arteriosus detected by Doppler ultrasonography

Blood flow velocities and pulsatory indices in both renal arteries (RAs) and in the internal carotid artery (CAI) were measured by pulsed Doppler ultrasonography in ten preterm infants with patent ductus arteriosus (PDA), before and after surgical ligation. The results obtained in the RAs were compared to those found in a reference group of 22 stable preterm infants. In the RAs the diastolic steal volume of the PDA led to a marked decrease in diastolic blood flow velocity (range 3 to-23 cm/s). Seven infants showed retrograde diastolic flow, whereas only three infants had these flow patterns in the CAI. In the RAs, the peak systolic blood flow velocities (range 56 to 135 cm/s) exceeded the values found in the reference group by 85% on average. The pulsatility indices reached values of above 1,00. In spite of the increase in systolic flow velocities before surgery, the time mean of maximum velocities was significantly lower than those measured after surgery and in the reference group. After PDA ligation, blood flow velocities normalized. The present study shows that a large PDA may induce abnormal flow patterns even in the RAs. These flow patterns may predispose to renal hypoperfusion and subsequent impairment of renal function.Abbreviations CAI internal carotid artery - NFC necrotizing enterocolitis - PDA patent ductus arteriosus - PI pulsatility index - RA renal artery - Vd end-diastolic velocity - V_max time mean of maximum velocity - Vs peak systolic velocity     

Cerebral and Abdominal Arterial Hemodynamics in Preterm Infants with Patent Ductus Arteriosus

Using Doppler echocardiography we evaluated the effect of ductal shunt flow on the cerebral and abdominal arterial blood flow in 25 preterm infants. Eligible for inclusion in this study were healthy preterm newborn infants. They were divided into two groups based on their gestational age: group A, 33-36 weeks (15 infants) and group B, 28–32 weeks (10 infants). Two-dimensional Doppler echocardiograms were obtained in each infant during the first 8 hours of life and repeated every 6–12 hours until no ductal shunt flow could be detected. Flow in the ductus arteriosus, the basilar artery and the coeliac artery were examined. Closure of the ductus arteriosus occurred significantly later(p< 0.05) in group B than in group A. Pulsatility indices of flow in the basilar and coeliac arteries were high when the ductus was patent, decreasing to a fixed level with closure. This study suggests that a shunt of the patent ductus arteriosus (PDA) adversely influences the cerebral and abdominal blood flow in preterm infants.     

Incidence and clinical features of patent ductus arteriosus in low-birthweight infants: a prospective analysis of 150 consecutively born infants.

The incidence of persistent patency of the ductus arteriosus beyond the third day of life was prospectively determined in 100 preterm infants with birthweights of 2,000 gm or less and 50 infants with birthweights of 2,001 to 2,500 gm. The overall incidence was 21% and was inversely related to increasing gestational age and birthweight. The data suggest that immaturity is the major determinant of the persistent patency of the ductus arteriosus. Spontaneous delayed closure of the ductus occurred in 79% of patients that survived the immediate neonatal period. There was a high degree of association between the presence of a patent ductus arteriosus (PDA) and respiratory distress syndrome (RDS). Eight infants with severe RDS and PDA developed heart failure and four required surgical ligation of the ductus. None of the infants with birthweights greater than 2,000 gm who had PDA developed heart failure or required surgical ligation of the ductus arteriosus.     

Factors affecting successful closure of hemodynamically significant patent ductus arteriosus with indomethacin in extremely low birth weight infants

Background  The incidence of patent ductus arteriosus (PDA) is high in extremely low birth weight (ELBW) infants. Indomethacin has been widely used in the prophylaxis and treatment of hemodynamically significant PDA. This retrospective study was undertaken to identify factors such as birth weight, gestational age, gender, fetal growth retardation, ductal size, timing of the first dose of indomethacin and side effects of indomethacin, which may affect the successful closure of the PDA with indomethacin in ELBW infants. Methods  A cohort of 139 ELBW infants who had received indomethacin treatment for PDA during a consecutive period of more than three years (September 2000 to December 2003) was retrospectively analyzed. Results  Administration of indomethacin was associated with closure of PDA in 108 (77.7%) of 139 ELBW infants, and only 19.4% of infants required surgical ligation of the ductus eventually. There was no significant relationship between closure of PDA with gestational age, gender, fetal growth retardation, and ductal size. A higher birth weight and early use of indomethacin after birth could significantly increase the closure rate of PDA (P<0.05). Side effects of indomethacin such as transient oliguria and hyponatremia during indomethacin therapy did not affect PDA closure. Conclusions  Indomethacin is effective for the treatment of PDA in ELBW infants. A higher rate of ductal closure is related to the increase of birth weight. PDA closure with indomethacin is age-related, and early administration of indomethacin could increase PDA closure and reduce the incidence of hyponatremia. There is no significant difference in major morbidities such as bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and retinopathy of prematurity (ROP) after early treatment. Early screening for hemodynamically significant PDA in ELBW infants and early treatment with indomethacin are recommended.     

Stroke volume and left ventricular output in preterm infants with patent ductus arteriosus

To assess the effect of patent ductus arteriosus (PDA) on left ventricular output (LVO) we studied stroke volume (SV), LVO, and heart rate (HR) in 21 very low birth wt preterm neonates with clinically symptomatic PDA before and after surgical ligation. Six additional infants were also studied before PDA with left-to-right shunt was detectable by the pulsed Doppler technique. Gestational age (median and range) was 28 (24-32) wk. SV was measured by duplex Doppler and M-mode echocardiography, and LVO was calculated as product of SV and HR. LVO was 419 (305-562) mL/min/kg during symptomatic PDA. It decreased to 246 (191-292) mL/min/kg after ligation (n = 21, p less than 0.001). SV was 2.69 (1.98-4.10) mL/kg during symptomatic PDA decreasing to 1.63 (1.22-1.98) mL/kg after ductal closure (n = 21, p less than 0.001). HR did not change after ductal closure. In the six infants with three examinations, LVO and SV were normal before detectable ductal left-to-right shunt and after ligation, but LVO was increased by 59.5 +/- 23% (mean +/- SD) (p less than 0.05), and SV by 60 +/- 32% (p less than 0.05) during symptomatic PDA. In conclusion, preterm neonates with RDS, requiring mechanical ventilation, increased LVO during symptomatic PDA by increasing their SV, and not by changing their HR.     

Recovery of prostaglandin production associated with reopening of the ductus arteriosus after indomethacin treatment in preterm infants with respiratory distress syndrome

Increased PGE production has been demonstrated in 9 of 17 preterm infants with patent ductus arteriosus (PDA) associated with respiratory distress syndrome (RDS). Inhibition of PGE production in eight preterm infants with PDA and RDS was associated with marked improvement in the respiratory and circulatory function of all of them. However, in six of them this effect was only transient. In the posttreatment period of five and a half days reopening of the ductus arteriosus was frequently associated with increased PGE production and a drop of indomethacin serum levels. Three of these six infants were transferred for surgical ligation whereas the other three were successfully treated with a second course of indomethacin. However, the margin between closure of the ductus arteriosus and the deterioration of kidney function in preterm infants treated with a presently recommended indomethacin dosage was narrow. In conclusion, until an acceptable therapeutic serum level of indomethacin for ductal closure in preterm infants has been established and the duration of effective prostaglandin synthesis inhibition is known, it is too early for a general recommendation of a dosage regime of indomethacin for the pharmacological closure of PDA in infants with RDS.     

Failure of a repeat course of cyclooxygenase inhibitor to close a PDA is a risk factor for developing chronic lung disease in ELBW infants

Background  

The optimal treatment regimen or protocol for managing a persistent patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants has not been well established. This study was aimed at evaluating the failure rate of a cyclooxygenase (COX) inhibitor (COI) for PDA closure and to determine the incidence of a PDA requiring ligation in ELBW infants. We examined the clinical characteristics and risk factors that may predict the clinical consequences of failure of PDA closure by COI.     

生后早期床旁心脏超声预测极低出生体重儿动脉导管持续开放的研究(英文翻译)

目的 探讨出生早期床旁心脏超声预测极低出生体重儿（very low birth weight infant,VLBWI）动脉导管持续开放的价值。 方法 回顾性选取2020年3月至2021年6月收治的51例VLBWI为研究对象,入院时日龄≤3 d并且住院时间≥14 d。根据出生14 d及28 d动脉导管未闭（patent ductus arteriosus,PDA）直径大小分为3组：大PDA组（PDA直径≥2 mm）、小PDA组（PDA直径<2 mm）和PDA关闭组（PDA直径=0 mm）,比较3组间生后72 h的心脏超声参数。采用受试者工作特征（receiver operating characteristic,ROC）曲线评估生后72 h心脏超声参数预测生后14 d和28 d动脉导管持续开放（PDA直径≥2 mm）的价值。 结果 生后14 d时,大PDA组有17例,小PDA组11例,PDA关闭组23例;生后28 d时,大PDA组有14例,小PDA组9例,PDA关闭组26例。3组患儿间胎龄、出生体重、肺泡表面活性物质应用及低血压发生率的比较差异有统计学意义（P<0.05）。生后72 h的PDA直径、左肺动脉舒张末期流速、左心室输出量、左心室输出量/上腔静脉血流与生后14 d及28 d时动脉导管持续开放有关（P<0.05）;左心房/主动脉根部直径与生后28 d时动脉导管持续开放有关（P<0.05）。ROC曲线结果显示,生后72 h PDA直径预测生后14 d及28 d动脉导管持续开放的曲线下面积最大,分别为0.841和0.927;其次是左肺动脉舒张末期流速,其曲线下面积分别为0.793和0.833。 结论 生后72 h的床旁心脏超声指标,尤其是PDA直径及左肺动脉舒张末期流速,可预测VLBWI生后14 d和28 d动脉导管持续开放,为后续PDA早期目标性治疗策略的实施提供依据。     

Antenatal Calcium Channel Blocker Exposure and Subsequent Patent Ductus Arteriosus in Extremely Low-Birth-Weight Infants

This study aimed to assess whether tocolytic fetal exposure to antenatal calcium channel blockers (aCCB) increases the risk for hemodynamically significant patent ductus arterioses (hsPDA) in extremely low-birth-weight (ELBW) infants. This case-control study investigated ELBW infants (<1,000 g) without cardiac defects in a level 3 neonatal intensive care unit who had survived at least 7 days. Nifedipine was the only aCCB used for this study population. The measurements included the history of aCCB exposure, selected maternal data, hsPDA diagnosis, gestational age at birth, birth weight, mode of delivery, sex, maternal race, location of birth, Apgar scores, and selected neonatal morbidities. The end point of the study was hsPDA, defined as an echocardiographically confirmed PDA with clinical symptoms. A total of 180 infants met the study criteria. The diagnosis was hsPDA for 56% of these patients, 20% of whom had aCCB exposure. Of the infants without hsPDA, 11% had aCCB exposure (p = 0.09). No statistically significant associations were found between aCCB exposure and hsPDA after adjustment for gestational age (odds ratio [OR], 1.5; 95% confidence interval [CI], 0.6–3.7) or for gestational age and cumulative aCCB exposure of 100 mg or more (OR, 2.0; 95% CI, 0.6–6.5). A history of aCCB exposure does not appear to increase hsPDA risk in ELBW infants. Studies using neonatal serum nifedipine concentrations after antenatal exposure should be performed to confirm this conclusion.     

Severity of the ductal shunt: a comparison of different markers

BACKGROUND: When the ductus arteriosus (DA) is patent, the ductal shunt is proportional to the ratio of left ventricular output (LVO) to systemic blood flow. Systemic blood flow can be estimated by measuring flow in the superior vena cava (SVC). OBJECTIVE: To re-evaluate the accuracy of standard echocardiographic markers of patent ductus arteriosus (PDA) using LVO/SVC flow ratio. METHODS: Prospective study. Preterm infants of 24-30 weeks gestational age and postnatal age less than 48 hours. The following echocardiographic criteria were measured: left atrial to aortic root ratio (LA/Ao); DA diameter by B mode and colour Doppler; mean and end diastolic flow velocity of the left pulmonary artery (LPA); LVO; SVC flow. RESULTS: Twenty three preterm infants were enrolled (median gestational age 28 weeks (range 24-30), median birth weight 840 g (500-1440)). The DA was closed in eight (mean (SD) LVO/SVC 2.4 (0.3)) and open in 15 (mean (SD) LVO/SVC 4.5 (0.6)). An LA/Ao ratio > or =1.4, a DA diameter > or =1.4 mm/kg, and a mean and end diastolic flow velocity of LPA respectively > or =0.42 and > or =0.20 m/s identified an LVO/SVC > or =4 with a sensitivity and a specificity above 90%. CONCLUSION: This study indicates that LA/Ao ratio, DA diameter, and mean and end diastolic flow velocity of the LPA are accurate markers of PDA. These standard echocardiographic variables are easy to measure and need less skill and resources than direct measurements of ductal shunt.     

极低出生体重儿动脉导管未闭转归的影响因素分析

目的分析极低出生体重儿动脉导管未闭(PDA)转归的影响因素。方法以2012年1月至2014年12月收治的194例极低出生体重儿为研究对象,根据心脏超声检查及治疗转归情况分为无PDA组,PDA自然关闭组、药物关闭组、手术关闭组,分析其临床及超声心动图特征。结果 PDA自然关闭率58.7%。自然关闭组的出生胎龄、出生体重、小于胎龄儿比例均大于药物和手术关闭组,药物及手术关闭组的新生儿呼吸窘迫综合征发生率及肺表面活性物质(PS)应用比例高于自然关闭组(P0.05)。不同时间段自然关闭组的动脉导管直径均明显小于药物和手术关闭组(P0.05)。多因素logistic回归分析示出生胎龄、PS应用及48 h动脉导管直径与PDA转归显著相关。自然关闭组PDA分流类型均以关闭型为主,而药物及手术关闭组在48 h以肺高压型及进展型为主,在4 d、7 d时均以进展型为主。结论极低出生体重儿PDA自然关闭率较高,出生胎龄越小以及应用PS的患儿自然关闭率越低;动脉导管直径越大且分流类型为进展型或脉冲型的PDA不易自然关闭。     

Early functional closure of the ductus arteriosus associated with decreased severity of respiratory distress syndrome in preterm infants

It has been shown that a patent ductus arteriosus may complicate the course of the respiratory distress syndrome (RDS) in preterm infants. In this study, an attempt is made to answer the question: Is there any relationship between RDS and patency of the ductus arteriosus in preterm infants, that is, do preterm infants without the RDS have early functional closure of the ductus arteriosus? Clinical observations were made on 144 preterm infants 25 to 34 weeks' gestation. Infants were included in the study if the status of the ductus arteriosus (open or closed) could be established either by clinical examination or retrograde aortography. The ductus arteriosus was closed in 59 infants within 48 hours of birth and open in 85. None of the infants with a closed ductus had severe RDS and only three had mild RDS. In contrast, 50% (43 of 85) of infants with open ductus had severe RDS. These findings suggest that early functional closure of the ductus can occur even in very immature infants, and this early closure appears to be associated with a decreased incidence of RDS.     

Patent ductus arteriosus treated with ligation or indomethacin: a follow-up study.

The course and complications of fifty-two infants with patent ductus arteriosus requiring closure were assessed prospectively. Twenty-six infants with a PDA received indomethacin for pharmacologic closure of the PDA, and 26 underwent ligation. The current study analyzes and compares the longitudinal follow-up with respect to somatic growth, neurologic function, psychomotor and mental development, and renal, ophthalmologic, and audiologic function in 21 infants in each group who entered the follow-up. No selective morbidity was attributable to PDA closure with indomethacin when compared to surgically treated infants.     

The effects of caffeine on the preterm sheep ductus arteriosus

Caffeine and other methyl xanthines are widely used in the neonatal period. A recent, randomized, placebo-controlled, multicenter trial found that infants who were randomly assigned to caffeine treatment had less need for pharmacologic and/or surgical closure of a patent ductus arteriosus (PDA). We hypothesized that the decreased need for pharmacologic and surgical closure of the PDA after caffeine treatment might be due to a direct effect of caffeine on ductus contractility. We examined preterm fetal lamb ductus arteriosus (from 24 fetuses, 105 +/- 4 d of gestation, term = 147 d), in vitro to determine the direct effects of caffeine on the isometric tension of the ductus arteriosus. Caffeine (0.003-0.3 mM) had no direct effect on ductus arteriosus tension, nor did it affect the contractile response of the ductus arteriosus to increasing oxygen concentrations. Caffeine's lack of effect was observed in both the presence and absence of indomethacin and NG-nitro-L-arginine methyl ester (L-NAME) (inhibitors of prostaglandin and nitric oxide production). In conclusion, we found no evidence of a direct effect of therapeutic caffeine concentrations on ductus contractility.     

Supplemental Nitrogen Inhalation Therapy in Very Low-Birth-Weight Infants with Patent Ductus Arteriosus

Very low-birth weight infants with patent ductus arteriosus (PDA) accompanied by severe heart failure do not respond to indomethacine therapy. It is essential to stabilize the general condition of these infants until surgical intervention. We tried to regulate the pulmonary blood flow to control congestive heart failure by administering supplemental nitrogen inhalation therapy to six very low-birth-weight infants with PDA. After the inhalation of supplemental nitrogen gas was begun, the arterial oxygen saturation and partial oxygen pressure immediately decreased. Furthermore, the blood pH, systolic pressure, and urine output significantly increased. The infants were well stabilized. Furthermore, there were no complications related to nitrogen gas inhalation. Supplemental nitrogen inhalation therapy is an effective and feasible therapy for severe congestive heart failure in very low-birth-weight infants with PDA.     

Paracetamol Therapy for Patent Ductus Arteriosus in Premature İnfants: A Chance Before Surgical Ligation

Patent ductus arteriosus (PDA) remains a common problem in premature infants. Treatment options include pharmacologic therapy and surgical ligation, but these are associated with potentially significant adverse effects. This report describes the effect of administering oral paracetamol to premature neonates with PDA. The study enrolled seven premature neonates followed up with the diagnosis of hemodynamically significant PDA (hsPDA) between February and December 2012 and treated with oral paracetamol. Patients with hsPDA were given at least two or more courses of ibuprofen treatment. If this therapy failed to promote ductal closure, the patients with clinical symptoms who had hsPDA defined by echocardiography were treated with oral paracetamol (15 mg/kg every 6 h). If these patients did not respond to paracetamol therapy, the PDA was closed by surgical ligation. The mean gestational age of the seven patients in this study was 26.1 weeks, and their mean birth weight was 936 g. Paracetamol treatment was started at 36.2 ± 11.6 days. The mean internal ductal diameter was 2.0 ± 0.2 mm, and the left atrium-to-aorta ratio was 1.5 ± 0.2. All the patients were administered oral paracetamol because of no response to ibuprofen treatment. The hsPDA was successfully closed with oral paracetamol in five (71.4 %) of the seven patients. The remaining two patients had surgical ligation performed, but one of them died. No side effects related to paracetamol were observed. Oral paracetamol may be used as an alternative drug for the management of hsPDA in premature neonates when ibuprofen treatment is unsuccessful and the only other therapeutic option is surgery.     

Changes in cerebral,renal and mesenteric blood flow velocity during continuous and bolus infusion of indomethacin

Vasoconstriction induced by bolus injection of indomethacin reduces organ perfusion and has been related to the well-known side effects of indomethacin given for closure of the patent ductus arteriosus (PDA). The aim of the study was to compare the changes in cerebral, renal and mesenteric blood flow velocities after continuous infusion versus bolus injection of indomethacin for closure of the PDA. Thirty-two preterm infants (range 26-35 wk gestational age) with PDA were randomly assigned to receive the same amount of indomethacin either as three bolus injections (n = 14) or as a continuous infusion (n = 18) over 36 h. Blood flow velocities were measured in the internal carotid, right renal and superior mesenteric arteries at baseline and serially at 10, 30, 60 and 120 min and 12, 24, 36 and 48 h after the start of indomethacin treatment. There were no differences in blood flow velocities between both groups at baseline. During continuous infusion of indomethacin there was no significant change in the cerebral, renal and mesenteric blood flow velocities, whereas the flow velocities in the infants receiving bolus injections decreased significantly during the first 2 h after indomethacin administration in all arteries measured. There was a transient, but significant reduction in urine output after bolus injection of indomethacin. Conclusion: In contrast to bolus injections, decrease of organ blood flow and impairment of urine output do not accompany continuous infusion of indomethacin over 36 h.     

N-terminal-pro-brain natriuretic peptide: a guide for early targeted indomethacin therapy for patent ductus arteriosus in preterm Infants

Aim: To determine whether N‐terminal‐pro‐brain natriuretic peptide (NT‐proBNP) level could be an effective guide for early targeted indomethacin therapy for patent ductus arteriosus (PDA) in preterm infants. Methods: An interventional study involved preterm infants, born at <33 weeks of gestation, who had plasma NT‐proBNP levels obtained at day 2 of life. Indomethacin therapy was given if plasma NT‐proBNP level was ≥10 180 pg/mL, the cut‐off for predicting hemodynamic significant PDA (hsPDA). Echocardiograms were performed within 6 h at the time of plasma NT‐proBNP collection and again at day 7, or whenever clinical hsPDA was suspected. Primary outcomes were the incidence of later hsPDA and unnecessary exposure rate to indomethacin. Results: Fifty infants were enrolled. On day 2, 19 (38%) infants had plasma NT‐proBNP above the cut‐off and received indomethacin therapy; none of them developed later hsPDA, while 1 of 31 infants with NT‐proBNP below the cut‐off level developed clinical hsPDA. Unnecessary exposure to indomethacin occurred in two infants (11%). Overall, no enrolled infants had either reopening of ductus or PDA ligation. Conclusion: Using NT‐proBNP level on day 2 as a guide for early targeted indomethacin therapy reduced later onset of hsPDA and the number of unnecessary exposures to indomethacin.