Proactive Diagnosis and Tailor-Made Treatment of Patent Ductus Arteriosus in Very Preterm Infants with Routine Echocardiography in Japan: A post hoc Analysis of the PLASE Study.

INTRODUCTION: A feature of the management of extremely preterm infants in Japan is proactive circulatory management using early routine echocardiography performed by neonatologists. METHODS: This study was a post hoc analysis of the Patent ductus arteriosus and Left Atrial Size Evaluation in preterm infants (PLASE) study, which is a prospective cohort study including preterm infants admitted to 34 tertiary neonatal intensive care units in Japan between October 2015 and December 2016. We described the details of the treatment strategy of patent ductus arteriosus (PDA) based on early routine echocardiography. RESULTS: In total, 613 preterm infants were included into the analysis. Twenty percent of infants with prophylactic indomethacin were switched to therapeutic cyclooxygenase inhibitor (COX-I) before the completion of the full prophylactic indomethacin course. Therapeutic COX-I was mostly administered based on echocardiographic findings before PDA became symptomatic or hemodynamically significant. Therapeutic COX-I was frequently discontinued after one or two doses before the full course (three doses) was completed. The proportion of infants requiring additional treatment (additional therapeutic COX-I course or surgical PDA closure) after discontinued COX-I courses (<3 doses) compared to infants after completed 3 doses course was significantly lower (after the first therapeutic COX-I course 46% vs. 68%, p < 0.001) or without a significant difference (after the second or third course). CONCLUSIONS: The clinical management of PDA in Japan featured (1) COX-I administration based on echocardiographic findings before symptomatic or hemodynamically significant PDA appeared and (2) frequent discontinuation of therapeutic COX-I before completing the standard three doses course.

Fluctuations in internal cerebral vein and central side veins of preterm infants.

BACKGROUND: Studies on the acute management of extremely low birthweight (ELBW) infants reveal a high incidence of intraventricular hemorrhage (IVH) in infants with high-grade internal cerebral vein perfusion waveform fluctuations. In this prospective observational study we investigated the Doppler perfusion waveform fluctuations in the great cerebral vein, straight sinus, and internal cerebral veins of ELBW infants. METHODS: We evaluated perfusion waveforms after birth every 12 h until 120 h in 73 ELBW infants (<1,000 g) at our hospital. Fluctuations were categorized into four patterns of increasing magnitude, Grades 0-3. RESULTS: The maximum grades of perfusion waveform fluctuations of the internal cerebral veins were 0, 1, 2, and 3 detected in 12, 38, 13, and 10 infants, respectively; those of the great cerebral vein were 0, 1, 2, and 3 detected in 5, 17, 20, and 31 infants, respectively; and those of the straight sinus were 0, 1, 2, and 3 detected in 1, 5, 17, and 50 infants, respectively. Only one of 803 simultaneous measurements of the Doppler perfusion waveforms showed stronger fluctuations of the peripheral vein than those of the central side veins. Intraventricular hemorrhage was associated with high-grade fluctuations in the internal cerebral veins but not in the great cerebral vein or straight sinus. CONCLUSIONS: Most infants had high-grade fluctuations in the great cerebral vein and straight sinus, with lower grade fluctuations in the internal cerebral vein, but IVH was not associated with those markers. Intraventricular hemorrhage was correlated with high-grade fluctuations only in the internal cerebral veins.

What echocardiographic indices are predictive of patent ductus arteriosus surgical closure in early preterm infants? A prospective multicenter cohort study.

BACKGROUND: No echocardiographic indices for predicting the need for preterm patent ductus arteriosus (PDA) surgery have been tested with an adequate sample size. We tested the hypothesis that some echocardiographic indices have better predictive ability for the need for PDA surgery. METHODS: We prospectively collected data from infants with gestational ages between 23 and 29 weeks at 34 Japanese neonatal intensive care units over 14 months. Data points were 1, 3, 7, and 14 days of age and, if applicable, before PDA surgery. We assessed five echocardiographic indices. Volume and dimension indices were adjusted for birth body weight (BBW). For each echocardiographic index, the worst value among all data points in nonsurgical patients or the value just before surgery in surgical patients was used. Multivariate logistic regression was applied with adjustment for clinical status. RESULTS: In total, 691 patients were analyzed, of whom 61 (8.8%) underwent surgery, as guided using the criteria in the protocol. The areas under the receiver-operating characteristic curve for PDA diameter (0.86) and PDA diameter/BBW (0.86) were the largest, followed by those of left pulmonary artery end-diastolic velocity (LPAedv) (0.80), and left atrial volume/BBW (0.80). CONCLUSIONS: Considering the measurement's easiness and independence of body size, PDA diameter and LPAedv may serve as useful indices for assessing the need for PDA surgery in early preterm infants.

Hemodynamics of infants with strong fluctuations of internal cerebral vein.

BACKGROUND: There is a high incidence of intraventricular hemorrhage in extremely low-birthweight (ELBW) infants of low gestational age with high-grade fluctuations in the perfusion waveform of the internal cerebral vein. This study investigated changes in the hemodynamic status of ELBW infants during initial strong fluctuations in the perfusion waveform of the internal cerebral vein. METHODS: We evaluated the perfusion waveform of the internal cerebral vein in 192 ELBW infants from birth, every 8 h for a total of 120 h. Sixty-seven infants had high-grade fluctuations. On the basis of the presence of patent ductus arteriosus (PDA), patients were subdivided into PDA(-) (n = 32) and PDA(+) (n = 35) groups. RESULTS: During the first high-grade fluctuation, the PDA(-) group had significant increases in systolic, diastolic, and mean blood pressure (P < 0.001 for all). The PDA(+) group did not have significant changes in blood pressure but did have significant increases in the number of interruptions or regurgitations of diastolic renal arterial blood flow (P = 0.04) and end-diastolic left pulmonary arterial flow velocity (P < 0.001), indicating increased left-to-right shunt. CONCLUSIONS: Blood pressure elevation may underlie fluctuations in the perfusion waveform of the internal cerebral vein and lead to the first high-grade increases during acute management of ELBW infants. When no elevation in blood pressure occurred, hemodynamically significant PDA was considered a potential underlying factor.

Changes in the perfusion waveform of the internal cerebral vein and intraventricular hemorrhage in the acute management of extremely low-birth-weight infants.

UNLABELLED: This prospective observational study aimed to investigate the association between changes in the Doppler perfusion waveform of the internal cerebral vein and risk of intraventricular hemorrhage (IVH) in extremely low-birth-weight (ELBW) infants. We evaluated the perfusion waveform of the internal cerebral vein every 8 h from immediately after birth to 144 h post-birth in 80 ELBW infants (<1,000 g) in our hospital. Fluctuations in the measured perfusion waveform were categorized into four patterns according to their increasing magnitude, from grade 0 (steady flow waveform) to grade 3; the IVH rate was investigated. Infants with grades 0-1 fluctuations of the perfusion waveform were classified as low grade (n = 55), and those with grades 2-3 fluctuations were classified as high grade (n = 25). The IVH rate was significantly higher in the high-grade group than the low-grade group (28 vs. 1%, p < 0.001). The IVH group (n = 8) showed a significantly greater rate of high-grade perfusion waveform than the non-IVH group (n = 72) (87 vs. 25%, p < 0.001). CONCLUSION: Changes in the perfusion waveform of the internal cerebral vein during the acute management of ELBW infants may be associated with IVH.