Cerebral Resistive Indices and Intraventricular Hemorrhage in Premature Neonates <29 weeks’ gestation: A Pilot Prospective Cohort Study

Cerebral Resistive Indices and Intraventricular Hemorrhage in Premature Neonates <29 weeks’ gestation: A Pilot Prospective Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cerebral Resistive Indices and Intraventricular Hemorrhage in Premature Neonates <29 weeks’ gestation: A Pilot Prospective Cohort Study Abhinav Pal, Dan Stewart, Kshama Ojha, Vesna Kriss, Craig Ziegler, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6422565/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Oct, 2025 Read the published version in BMC Pediatrics → Version 1 posted 12 You are reading this latest preprint version Abstract Background: In extremely preterm newborns, intraventricular hemorrhage (IVH) greatly influences neurodevelopmental outcomes. Preterm newborns who later develop IVH might have altered cerebral blood flow (CBF) as measured by resistive index (RI) on Doppler ultrasound. Knowledge regarding RI in extremely premature infants remains limited. Objective: This pilot prospective cohort study aimed to evaluate the association between early cerebral RI (within the first 36 hours of life) and the occurrence of IVH in preterm infants born at < 29 weeks' gestation. Methods: Prospective cohort study in which cranial Doppler was performed in preterm infants < 29 weeks at < 36 hours of age and between 5–7 days of age. CBF velocities and RI were measured. Clinical and demographic factors were also assessed. Results: Of the 30 enrolled infants, 27% developed an IVH. RI measured at < 36 hours of life for the neonates with IVH was significant higher compared to those who did not have IVH (0.70(± 0.04) vs 0.65(± 0.05); p = 0.02). Multiple regression showed RI amongst babies with IVH was higher by 0.05, when controlled for other clinical variables (p = 0.01). These differences were not statistically significant when measured at 5–7 days. RI had no significant correlation with antenatal steroid use, delayed cord clamping, or presence of hemodynamically significant patent ductus arteriosus. Conclusion: Higher cerebral RI measured within the first 36 hours of life was associated with IVH in this pilot study. These early results draw attention to the requirement for bigger, sufficiently powered research to assess RI as a possible early sign for IVH risk stratification in very preterm newborns. Figures Figure 1 Figure 2 Figure 3 Impact Statement The key message of this article is that abnormal Doppler ultrasound is associated with intraventricular hemorrhage and perhaps can be used to predict intraventricular hemorrhage in premature neonates. What is already known on this topic: Doppler indices like resistive index can detect fluctuations in cerebral blood flow which in turn may result in an intraventricular hemorrhage. Resistive index is well studied in term neonates but has not been well studied in preterm neonates. What this study adds: This is a pilot study done early in life in very low birthweight infants. It adds to existing literature to try and understand neonatal cranial blood flow changes. How this study might affect research, practice or policy: highlights utility of duplex Doppler in premature neonates and paves way for future research. Introduction In the United States, 20–25% of all infants born at < 1500g develop intraventricular hemorrhage (IVH).( 1 ) Developing an IVH represents a major neonatal morbidity, as well as a public health concern as approximately 50–75% of preterm survivors IVH develop cerebral palsy, intellectual disability, and/or hydrocephalus.( 2 ) Premature infants are prone to development of IVH due to the presence of a highly vascular subependymal germinal matrix. This area is a rich network of immature vessels, poorly supported by connective tissue.( 3 ) In addition, they are also particularly sensitive to changes in cerebral blood flow (CBF) because they may have impaired autoregulation. Lack of autoregulation results in a pressure-passive circulation in which the infant cannot compensate for fluctuations in systemic blood pressure.( 4 ) Other factors that contribute to the fluctuation of CBF include severe respiratory distress syndrome, hypercarbia, patent ductus arteriosus and systemic hypotension.( 5 ) This fragility of the germinal matrix along with fluctuations in CBF, particularly in the first day of life, serves as the basis of developing hemorrhage in this population.( 3 , 6 ) Identifying newborns at higher risk of IVH early on could revolutionize clinical treatment by allowing focused therapies meant to lower long-term neurological damage.( 3 ) Cerebral blood flow can be examined via transfontanellar color Doppler in neonates, using the anterior fontanelle as an acoustic window. This quick and easy diagnostic tool, neither exposes newborn infants to the complications of ionizing radiation, nor requires their sedation.( 7 , 8 ) Doppler indices measured include: peak systolic velocity and end diastolic velocity, and using these, the resistive index (RI) is calculated. An elevated RI corresponds to vasoconstriction and low blood flow velocity, whereas a low RI is related to vasodilation and high blood flow velocity.( 8 ) Duplex Doppler indices for CBF have been extensively studied in term neonates and a well-established correlation exists between abnormal RIs and the development of white matter injury in asphyxiated term newborns.( 9 , 10 ) However, Doppler indices have not been well studied in premature infants. ( 11 ) Therefore, few values exist for Doppler indices in extreme preterm infants and very few clinical parameters have been studied for comparison.( 12 , 13 ) The American Academy of Neurology and the American Academy of Pediatrics recommends routine screening ultrasonography on all preterm neonates of less than 30 weeks' gestation.( 14 , 15 ) Currently, there are no current recommendations for the use of Doppler CBF measurement in preterm infants. The primary aim of this study was to prospectively measure and compare the RI values in the middle cerebral arteries of preterm infants born at less than 29 weeks’ gestation that develop IVH with those who did not develop IVH. Our hypothesis was twofold: ( 1 ) an alteration in CBF in very low birth weight infants born less than 29 weeks’ gestation could be detected by changes in cranial duplex Doppler measurements performed within 36 hours of birth and these changes could be used to predict the subsequent development of IVH, and ( 2 ) clinically unstable infants, as measured by high score for neonatal acute physiology with perinatal extension (SNAPPE-II scores), will have an abnormal cerebral blood flow and resistive index.( 16 ) Methods A prospective cohort study design was used. The patient population consisted of all infants born at < 29 weeks gestation admitted to Norton Children’s Hospital neonatal intensive care unit (NICU) in Louisville, KY between August 2017 and July 2018. This pilot study was approved by the institutional medical ethics board. Patients or the public were not involved in the design, or conduct, or reporting, or dissemination plans of our research. Inclusion criteria consisted of gestational age < 29 weeks and postnatal age at the time of enrollment of < 36 hours. Exclusion criteria included any infant with known prenatally diagnosed IVH, any infant with known IVH prior to enrollment, known cyanotic or hemodynamically significant congenital heart disease (not including patent ductus arteriosus), infants not expected to survive beyond 5 days of life and prenatal diagnosis of hydrocephalus or other congenital neurologic abnormality. Written informed consent was obtained from parent(s). Imaging protocol: Our unit policy is to maintain a neutral/midline position of the head for the first 72 hours of age after birth in all infants < 1500g to reduce incidence of IVH.( 17 ) All the patients remained in a comfortable supine position in the incubator with the head in the midline position during the scanning period. Measurements were obtained at bedside with the General Electric LOGIQ E ultrasound machine with the 7MHz linear phased array probe using a trans-fontanelle approach via the anterior fontanelle. Sonographic imaging was performed in the coronal plane of the right and left middle cerebral artery (MCA) using color and duplex Doppler. Average peak systolic velocity (PSV) and end diastolic velocity (EDV) were obtained from at least three sequential stable waveforms per patient. Resistive index (RI) was calculated by the following formula: RI = (PSV-EDV)/PSV.( 18 ) Mean RI was calculated by averaging the left and right MCA resistive index; previous studies have shown no difference between the resistive index of left and right arteries.( 13 , 19 ) Average peak systolic velocity divided by the end diastolic velocity (S/D) ratio were also obtained for each measurement. Two cranial ultrasounds were performed. The initial cranial ultrasound was performed at < 36 hours of age and the second between 5–7 days of age. We chose to perform ultrasound at < 36 hours of life as we wanted to assess whether changes in cerebral blood flow during the transition to extra uterine life after birth would impact the development of IVH as majority of IVH occurs within the first day.( 20 ) We repeated the study at 5–7 days of age to assess the changing patterns of cerebral circulation. All patients tolerated the procedure without any changes in vital signs and the need for sedation. If signs of stress/agitation were seen, then the procedure was stopped briefly and then resumed once infant was more comfortable. All the measurements were obtained by a single investigator (author A.P.). The images were stored and then independently reviewed by the same pediatric radiologist (author V.M.K.). Data collected from this study were not utilized in clinical decision making in the care of the patient. These ultrasounds were performed separately from the routine screening sonographic studies ordered by the clinical team. Also, at our institution, routine Doppler studies are not performed for preterm infants. Demographics, prenatal and postnatal data were obtained from the maternal and infant’s medical records. Prenatal/maternal factors studied included: maternal age, risk factors present at the time of delivery, exposure to antenatal steroids, use of antenatal magnesium sulfate for neuroprotection, medications/drugs used during pregnancy, prolonged rupture of membranes and presence or absence of chorioamnionitis. Postnatal and delivery factors studies included: gestational age, Apgar scores, performance of delayed cord clamping, small for gestational age (birth weight < 10th percentile), vitals at the time of study, presence or absence of hemodynamically significant patent ductus arteriosus (PDA) (if an ECHO was ordered by the clinical team), presence of IVH, use of vasopressors, need for blood transfusion and SNAPPE-II score.( 16 ) IVH was graded from grade I to grade IV per Volpe classification.( 6 ) Infants were considered to have an IVH If any grade of IVH was detected before 7 days of age. PDA was classified as hemodynamically significant (hs-PDA) if the left atrium to aortic root diameter ratio was > 1.5 and patient had clinical signs of hemodynamically significant PDA as judged by the clinical team. RI values used for comparison from a previous study in 24–28 weeks’ gestation were 0.76 (0.69–0.83).( 13 ) Delayed cord clamping in our practice is any delay in clamping of cord by more than 30 seconds. Complete antenatal steroid course was defined as two doses of steroids given at least 24 hours prior to delivery. Mothers who did not receive any doses of antenatal steroids, or received a partial steroid course or doses < 24 hours prior to delivery were considered to have an incomplete antenatal steroid course for the purpose of this study. Statistical tests used included the Pearson’s chi-square test, independent sample t-test, multiple regression and the Pearson’s correlation coefficient for most variables. The distribution of all continuous variables was checked for normality; and nonparametric statistics such as the Mann-Whitney U and the Spearman’s correlation coefficient were used when the variables were deemed non-normally distributed. Data presented include frequency and percentages, means and standard deviations, along with correlation coefficients and scatterplots. All p -values were two-tailed. Statistical significance was set by convention at p < 0.05. Also, Bonferroni correction was used where required and the p-value for that data was set at 0.025. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 25. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement cohort reporting guidelines were used.( 21 ) Results Although 58 infants met inclusion criteria during enrollment period, 30 infants were ultimately successfully enrolled in the study. ( Fig. 1 ) Demographics and clinical characteristics The gestational age range was 23 6/7 weeks to 28 3/7 weeks with a mean of 26.4 ± 1.52 weeks. The birth weight ranged from 460g to 1440g with a mean of 899g ± 242g. Eight neonates developed IVH [8/30 (27%)] and two of these eight developed severe IVH (grade III & grade IV). Neonates were first divided into the IVH group (n = 8) and the non-IVH group (n = 22). There was no statistically significant difference in gestational age, birth weight, delayed cord clamping, antenatal steroid use, chorioamnionitis, magnesium sulfate use, presence of hs-PDA or SNAPPE-II scores between the IVH and the non-IVH group. ( Table 1 ) Duplex Doppler ultrasound Duplex Doppler ultrasound was performed at two time periods in all the infants: first one performed at < 36 hours of life was at a mean age of 17 ± 9 hours of life. Second ultrasound performed between 5–7 days of age at mean age of 5.7 ± 0.8 days. It typically took about 10–15 minutes to perform the study. Mean resistive index performed < 36 hours of life (RI-1) was 0.66 ± 0.05. Mean resistive index performed between 5–7 days of age (RI-2) was 0.70 ± 0.04. None of the babies had IVH during the first Doppler ultrasound per the limited views performed and analyzed. Various clinical parameters were analyzed in relationship to the resistive index. There was no significant difference in the resistive index values when compared with gender, birthweight, antenatal steroid use, use of antenatal magnesium sulfate, presence of hs-PDA, performance of delayed cord clamping, maternal chorioamnionitis, use of pressors or need for blood transfusion within the first 24 hours of life. We also performed Pearson and Spearman’s correlation for our continuous variables and found no significant correlation for both RI-1 and RI-2 when compared with gestational age, APGAR score at 5 minutes and SNAPPE-II scores. There was a statistically significant negative correlation between the RI-1 and mean arterial blood pressure (R=-0.387, p = 0.034). However, this correlation was not significant for RI-2. ( Table 2 and Fig. 2 ) Doppler indices, specifically RI, PSV, EDV and S/D ratio were significantly higher when measured at 5–7 days of age compared to when measured early in life at < 36 hours of age. ( Fig. 3 ) Doppler and IVH When comparing IVH and duplex Doppler indices, we found that when measured at < 36 hours of age, the resistive index in the IVH group was significantly higher compared to the non-IVH group (IVH group, mean = 0.70; non-IVH group, mean = 0.65, p = 0.022). The peak systolic velocity / end diastolic velocity (S/D) ratio was also significantly higher for the IVH group at < 36 hours of life (IVH group, mean = 3.37; non-IVH group, mean = 2.91, p = 0.01). This difference is not significant when duplex Doppler ultrasound is performed at 5–7 days. ( Table 3 ) Resistive index measured < 36 hours of life did have a positive correlation with the grade of IVH, but the result was not statistically significant (Spearman’s R = 0.05, p = 0.9). Subjects who developed IVH had a significantly higher systolic velocity (IVH group, mean = 12.34 cm/s; non-IVH group, mean = 10.36 cm/s, p = 0.01) and also consistently noted a more continuous, uninterrupted cerebral blood flow pattern in the ultrasounds at < 36 hours as seen by the duplex Doppler blood flow pattern. Table 1: Demographics and Perinatal Characteristics Any IVH < DOL 7 Yes (8) No (22) P- Value Gender Female (%) 4 (50%) 8 (36%) 0.678 Male (%) 4 (50%) 14 (64%) Gestational age in weeks [Mean (SD)] 25.98 (1.69) 26.55 (1.46) 0.313 Birth weight in grams [Mean (SD)] 933.63 (239.39) 887.05 (248.41) 0.650 Apgar 5 minutes [Median (Minimum-Maximum)] 8.00 (5-9) 8.000 (2-9) 0.982 Birth weight 999 grams or less (%) 6 (75%) 13 (59%) 0.672 Delayed cord clamping Yes (%) 4 (50%) 12 (55%) 1.000 Maternal chorioamnionitis Yes (%) 3 (38%) 4 (19%) 0.357 Antenatal steroids Yes (%) 3 (38%) 17 (77%) 0.078 Magnesium sulfate Yes (%) 6 (75%) 19 (86%) 0.589 hs-PDA Yes (%) 3 (38%) 10 (45%) 1.000 Use of vasopressors in 1 st 24 hours Yes (%) 2 (25%) 4 (18%) 1.000 Blood transfusion in 1 st 24 hours Yes (%) 0 (0%) 2 (9%) 0.595 SNAPPE-II scores [Median (Minimum-Maximum)] 24.0 (0-69) 25.5 (0-68) 0.881 RI-1: Resistive index at <36 hours of life RI-2: Resistive index at 5-7 days of life IVH: Intraventricular hemorrhage hs-PDA: hemodynamically significant patent ductus arteriosus SNAPPE-II: Score for neonatal acute physiology with perinatal extension II Unequal variance t-test used, unless specified *:Mann-Whitney-Wilcoxon test ^: Spearman’s r RI-1: Resistive index at <36 hours of life RI-2: Resistive index at 5-7 days of life hs-PDA: hemodynamically significant patent ductus arteriosus SNAPPE-II: Score for neonatal acute physiology with perinatal extension II Table 3 Doppler Indices and IVH Doppler Indices IVH group (n = 8) Non-IVH group (n = 22) Mean (SD) Mean (SD) P Value RI-1 .70 (.04) .65 (.05) 0.022* PSV-1 (cm/s) 12.34 (1.97) 10.36 (1.84) 0.018* EDV-1 (cm/s) 3.66 (.25) 3.57 (.48) 0.600 S/D-1 3.37 (.46) 2.91 (.39) 0.011* RI-2 .72 (.04) .70 (.04) 0.480 PSV-2 (cm/s) 17.15 (5.26) 13.70 (3.07) 0.115 EDV-2 (cm/s) 4.73 (1.01) 4.00 (.75) 0.041 S/D-2 3.59 (.56) 3.43 (.48) 0.444 *p < 0.025 (Bonferroni correction) RI-1 = Resistive Index < 36 hours of life; PSV-1 = Peak systolic velocity < 36 hours of life EDV-1 = end diastolic velocity < 36 hours of life; S/D-1 = Peak systolic velocity/ end diastolic velocity < 36 hours of life; RI-2 = Resistive Index at 5–7 days of age; PSV-2 = Peak systolic velocity at 5–7 days of age EDV-2 = end diastolic velocity at 5–7 days of age; S/D-2 = Peak systolic velocity/ end diastolic velocity at 5–7 days of age; IVH: Intraventricular hemorrhage A multiple regression was performed where Resistive index measured < 36 hours of life was regressed on presence of IVH, birthweight, antenatal steroid administration, and presence of hemodynamically significant PDA. The results show that a significant relationship exists between IVH and the resistive index < 36 hours of life (B = 0.054, t = 2.51, p = 0.019), after controlling for birthweight, antenatal steroid administration, and presence of hemodynamically significant PDA. This indicates that babies with IVH have an average resistive index greater than 0.05 than those not having IVH. Discussion Although, the first routine cranial ultrasound in preterm infants < 30 weeks gestation is recommended anytime within the first week of life, the majority of IVH occurs within the first day of life. Only about 38% of IVH cases are seen after the first 24 hours.( 14 , 20 ) If these preterm infants survive, they may develop adverse neurodevelopmental outcomes. Therefore, in our prospective pilot study, we explored the relationship of CBF to IVH in this critical time period. Among infants less than 29 weeks’ gestation, resistive index and S/D ratio at < 36 hours of age were higher in infants who developed IVH than those who did not. This high RI seen in the hemorrhage group translates to high vascular resistance to blood flow, and hence, a low CBF.( 8 ) Higher RI in our cohort also correlated with lower mean arterial blood pressure. Hence, we speculate that this difference in CBF in the hemorrhage group seen in the first 36 hours of life may be due to impaired autoregulation early in life. Our findings are consistent with other studies that show a pattern of altered CBF in extremely preterm infants via indirect measurement of CBF, using cerebral regional oxygen saturation measured via near infrared spectroscopy (NIRS).( 22 ) Utilizing NIRS, Meek et al. and Sorensen et al. found significantly lower CBF on the first postnatal day, in infants that developed severe IVH. Verhagen et al. had similar findings but also suggested that CBF remains persistently low for two weeks following IVH.( 23 – 25 ) In contrast, Alderliesten et al. suggested a higher CBF being associated with IVH.( 4 ) Noori et al. showed that amongst the neonates who develop IVH, CBF is initially low but subsequently increased towards normal just before development of IVH.( 26 ) More recent work by Farag et al. also demonstrates correlation of IVH and RI at less than 24 hours of life using doppler indices of the anterior cerebral artery.( 27 ) These studies support that impaired autoregulation leading to an ischemia-reperfusion injury precedes and perhaps contributes to development of IVH which is consistent with the suggestion of impaired autoregulation and lower CBF in our observations in the IVH group early in life. This difference in CBF pattern in the hemorrhage group was not found when the RI was measured between 5–7 days of age. This is perhaps due to improved autoregulation later in life as evidenced by lack of correlation between RI and mean arterial blood pressure and statistically significant increase in PSV and EDV over time, when measured later in life. Previous work by other authors has also showed MCA velocity to be increasing overtime during the first 48 hours, and volumetric ultrasonographic data suggests a gradual increase in CBF over the first two weeks.( 28 , 29 ) This indicates temporal/developmental changes in the cerebral blood flow over the first week of life that may predispose certain high risk infants to development of IVH. Measuring Doppler indices more frequently over time might delineate the course of these changes and provide further guidance for predicting the infants at high risk of developing IVH. Similar to our findings, Elhameed et al. also noted increased resistive index when Doppler was performed later in life. However, they did not find any association between resistive index and IVH. But they did find high end diastolic velocity (EDV > 9.2 cm/s) to be a predictor of IVH. This is different from our study as we found positive correlation between high RI and presence of IVH and none with EDV. Their study differed from ours as they had very few very low birth weight (VLBW) neonates (only 10 neonates < 32 weeks gestation) and they averaged measurements from the anterior cerebral artery along with middle cerebral artery. ( 30 ) Farag et al found correlation of high RI and EDV with IVH but also has older infants in study with a mean gestational age of 29 weeks.( 27 ) Besides IVH, in our study, we also looked at multiple other clinical factors such as PDA, chorioamnionitis, SNAPPE-II scores and delayed cord clamping and their relationship with resistive index. Lipman et al. showed an association between high resistive index and PDA, attributed to decreased diastolic flow.( 31 ) The decreased diastolic flow could be due to the presence of the ductal steal phenomenon in the presence of the large PDA. Ecury-Goossen et al. showed that infants with hemodynamically significant PDA have a higher RI compared to those without PDA, but this was only seen in the anterior cerebral artery and the internal carotid artery and not corroborated in the other cerebral arteries. The authors of this study concluded that the presence of hemodynamically significant PDA does not always significantly affect cerebral perfusion.( 12 ) We did not find any difference between a hemodynamically significant PDA and MCA RI, which is similar to the conclusion of the previous study by Ecury-Goossen et al.. Perhaps, this difference was not seen because of the lack of a clear definition of hemodynamically significant PDA across various institutions.( 32 ) We expected to find a relationship between SNAPPE-II scores and resistive index as infants with high SNAPPE-II scores are sicker leading to abnormal CBF, but we found no significant relationship between RI and SNAPPE-II scores. This could be explained by SNAPPE-II scores measuring physiology within the first 12 hours and we measured Doppler flow at a mean age of 17 hours and again at 5.7 days of life, a finding similar to a previous study.( 12 ) Effects of delayed cord clamping have been clearly demonstrated in preterm infants with an increase peak hematocrit and the reduced need of blood transfusion, however its effect on IVH remains unclear.( 33 ) In one study of 60 infants, delaying clamping cord by 45 seconds showed a clear reduction in incidence of IVH.( 34 ) On the other hand, in a large trial of 1566 preterm infants (GA 60 seconds on incidence of severe IVH.( 35 ) We found no relationship between delaying of cord clamping and incidence of IVH and RI in our cohort. Our study differs from the previous as in our center cord clamping is delayed only up to 30 seconds when indicated, and only 16/30 infants in our cohort received delayed cord clamping. Also, multiple regression suggested a difference in RI of 0.05 was statistically significant in predicting IVH in our study of VLBW infants (n = 30). Our findings are similar to another larger study of 147 infants by Farag et al., which using logistic regression also suggests a higher RI > 0.75 to be predictive of IVH.( 27 ) Limitations: Besides a small sample size, our study had other limitations as well. The exclusion of eligible infants and dropout rates may introduce selection bias, limiting generalizability. Also, studies of cerebral blood flow are limited because velocity measurements are difficult to compare as they depend on the angle of the probe to the intracerebral vessel.( 19 ) This variability was reduced by having the same investigator perform all the duplex Doppler studies, using the same technique. Any further differences are mitigated by the fact that RI is reproducible and has inter-observer reliability( 12 ), and thus was the measurement of choice for our study. However, we acknowledge that duplex Doppler measurements only give us a snapshot of time and further corroboration with serial Doppler measurements would further support our findings. Conclusion and Future Directions: In summary, our pilot study indicates that an elevated resistive index at < 36 hours is associated with IVH in VLBW infants < 29 weeks’ gestation. The use of RIs as a prediction tool needs to be validated in a large, multicentered study. Identifying this at-risk group, could perhaps lead to additional interventions to prevent an IVH. At the present time, the clinicians may use midline head positioning, gentle caretaking, indomethacin and avoiding fluid bolus administration with modest improvements in the incidence of severe IVH in this subset of preterm infants.( 3 , 17 , 36 ) Bedside ultrasound in the NICU remains underutilized, though the use is rapidly expanding and its impact on clinical management has been well demonstrated.( 37 , 38 ) Future studies could use serial ultrasound measurements or perhaps use newer modalities such as ultrafast plane-wave Doppler imaging( 39 ) in order to validate our findings in a larger population. Abbreviations IVH: Intraventricular hemorrhage; CBF: cerebral blood flow; RI: Resistive Index; SNAPPE-II: score for neonatal acute physiology with perinatal extension; NICU: neonatal intensive care unit; MCA: middle cerebral artery; PSV: peak systolic velocity; EDV: end diastolic velocity; hs-PDA: hemodynamically significant PDA; SPSS: Statistical Package for Social Sciences; STROBE: Strengthening the Reporting of Observational Studies in Epidemiology; NIRS: near infrared spectroscopy; VLBW: very low birth weight Declarations Ethics approval and consent to participate: This pilot study was approved by the institutional medical ethics board at University of Louisville. IRB number 17.0654 Consent for publication: Not applicable Availability of data and materials: All data generated or analyzed during this study are included in this published article [and its supplementary information files]. Competing interests: The authors declare that they have no competing interests. Funding: No financial assistance was received for this study. Authors' contributions: -Abhinav Pal, Dan Stewart, Vesna Kriss and Hannah Fischer: Substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; Drafting the article and revising it critically for important intellectual content; and final approval of the version to be published. -Kshama Ojha and Craig Ziegler: analysis and interpretation of data, revising article critically Acknowledgements: We acknowledge the division of neonatology and the department of pediatrics for the encouragement and support; and the UofL GME office for statistical support. Clinical trial number: not applicable References Siffel C, Kistler KD, Sarda SP. Global incidence of intraventricular hemorrhage among extremely preterm infants: a systematic literature review. J Perinat Med. 2021;49(9):1017-26. Luu TM, Ment LR, Schneider KC, Katz KH, Allan WC, Vohr BR. 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Journal of clinical neonatology. 2014;3(2):76-88. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61(4):344-9. Noori S, Seri I. Hemodynamic antecedents of peri/intraventricular hemorrhage in very preterm neonates. Seminars in Fetal and Neonatal Medicine. 2015;20(4):232-7. Meek JH, Tyszczuk L, Elwell CE, Wyatt JS. Low cerebral blood flow is a risk factor for severe intraventricular haemorrhage. Archives of Disease in Childhood - Fetal and Neonatal Edition. 1999;81(1):F15. Sorensen LC, Maroun LL, Borch K, Lou HC, Greisen G. Neonatal cerebral oxygenation is not linked to foetal vasculitis and predicts intraventricular haemorrhage in preterm infants. Acta Paediatrica. 2008;97(11):1529-34. Verhagen Elise A, ter Horst Hendrik J, Keating P, Martijn A, Van Braeckel Koenraad NJA, Bos Arend F. Cerebral Oxygenation in Preterm Infants With Germinal Matrix–Intraventricular Hemorrhages. Stroke. 2010;41(12):2901-7. Noori S, McCoy M, Anderson MP, Ramji F, Seri I. Changes in cardiac function and cerebral blood flow in relation to peri/intraventricular hemorrhage in extremely preterm infants. The Journal of pediatrics. 2014;164(2):264-70. e3. Farag MM, Gouda MH, Almohsen AMA, Khalifa MA. Intraventricular hemorrhage prediction in premature neonates in the era of hemodynamics monitoring: a prospective cohort study. European Journal of Pediatrics. 2022;181(12):4067-77. Evans N, Kluckow M, Simmons M, Osborn D. Which to measure, systemic or organ blood flow? Middle cerebral artery and superior vena cava flow in very preterm infants. Archives of disease in childhood Fetal and neonatal edition. 2002;87(3):F181-F4. Kehrer M, Blumenstock G, Ehehalt S, Goelz R, Poets C, Schoning M. Development of cerebral blood flow volume in preterm neonates during the first two weeks of life. Pediatr Res. 2005;58(5):927-30. Elhameed AMA, Fouda EM. Transcranial ultrasound Doppler parameters in cerebral vessels may predict intracerebral hemorrhage in preterm newborns. The Egyptian Journal of Radiology and Nuclear Medicine. 2011;42(1):69-75. Lipman B, Serwer GA, Brazy JE. Abnormal cerebral hemodynamics in preterm infants with patent ductus arteriosus. Pediatrics. 1982;69(6):778-81. El-Khuffash A, Levy PT, Gorenflo M, Frantz ID. The definition of a hemodynamically significant ductus arteriosus. Pediatric Research. 2019;85(6):740-1. Fogarty M, Osborn DA, Askie L, Seidler AL, Hunter K, Lui K, et al. Delayed vs early umbilical cord clamping for preterm infants: a systematic review and meta-analysis. Am J Obstet Gynecol. 2018;218(1):1-18. Chiruvolu A, Tolia VN, Qin H, Stone GL, Rich D, Conant RJ, et al. Effect of delayed cord clamping on very preterm infants. Am J Obstet Gynecol. 2015;213(5):676.e1-7. Tarnow-Mordi W, Morris J, Kirby A, Robledo K, Askie L, Brown R, et al. Delayed versus Immediate Cord Clamping in Preterm Infants. N Engl J Med. 2017;377(25):2445-55. Fowlie PW, Davis PG, McGuire W. Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. The Cochrane database of systematic reviews. 2010(7):Cd000174. Harabor A, Soraisham AS. Utility of Targeted Neonatal Echocardiography in the Management of Neonatal Illness. J Ultrasound Med. 2015;34(7):1259-63. Kluckow M. Use of ultrasound in the haemodynamic assessment of the sick neonate. Arch Dis Child Fetal Neonatal Ed. 2014;99(4):F332-7. Demene C, Pernot M, Biran V, Alison M, Fink M, Baud O, et al. Ultrafast Doppler reveals the mapping of cerebral vascular resistivity in neonates. J Cereb Blood Flow Metab. 2014;34(6):1009-17. Additional Declarations No competing interests reported. Supplementary Files DeidentifiedCompleteDatasheet.xlsx Cite Share Download PDF Status: Published Journal Publication published 03 Oct, 2025 Read the published version in BMC Pediatrics → Version 1 posted Editorial decision: Revision requested 17 Jun, 2025 Reviews received at journal 01 Jun, 2025 Reviewers agreed at journal 22 May, 2025 Reviews received at journal 22 May, 2025 Reviewers agreed at journal 22 May, 2025 Reviews received at journal 22 May, 2025 Reviewers agreed at journal 19 May, 2025 Reviewers invited by journal 19 May, 2025 Editor assigned by journal 13 May, 2025 Editor invited by journal 24 Apr, 2025 Submission checks completed at journal 18 Apr, 2025 First submitted to journal 18 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6422565","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":458958014,"identity":"edb5f428-b3a9-4c3f-9fe1-794a2be6a4b4","order_by":0,"name":"Abhinav Pal","email":"","orcid":"","institution":"Stormont Vail Health","correspondingAuthor":false,"prefix":"","firstName":"Abhinav","middleName":"","lastName":"Pal","suffix":""},{"id":458958015,"identity":"eaa9e154-6ab3-476c-9805-ecce036a7a56","order_by":1,"name":"Dan Stewart","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDUlEQVRIie3QsUrEMBjA8a8E6hI690Cur5Cjo0Vf5QuFc2nFsYNwPYSbDm49cfAVzjeIFK5LtGvGdL+hY13UBBFBW3V0yH9oQpofHy2Ay/UfE59bT2sAatal0F9efSdoH4QwfCelwD8SP8SPw59IUD8K77lP+Oa22RdYVMfRNjVTCpgGCgfJRF4goTjn26fUVygryhQ3REI8GSFMZIwAVnkpia/4yhD6UAq+Ar4bI82BeT2+5neGXFoSrS15gcUoURkDiiLfGQKWQL00pARkY9+iDqyi83RxL0kcojynzBLch7MbqYf/WJPN2j45jafSa7uuODmLro9a3V0lUVAPT7GJocNw9LrL5XK5fu8NdOFsR4VcWhgAAAAASUVORK5CYII=","orcid":"","institution":"University of Louisville","correspondingAuthor":true,"prefix":"","firstName":"Dan","middleName":"","lastName":"Stewart","suffix":""},{"id":458958016,"identity":"816f685b-9142-4a59-a9bf-bc70ac5dad75","order_by":2,"name":"Kshama Ojha","email":"","orcid":"","institution":"Children’s Mercy Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kshama","middleName":"","lastName":"Ojha","suffix":""},{"id":458958017,"identity":"75f45a70-4451-4311-a614-d90bc6df86e5","order_by":3,"name":"Vesna Kriss","email":"","orcid":"","institution":"Norton Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Vesna","middleName":"","lastName":"Kriss","suffix":""},{"id":458958018,"identity":"5fbb5704-c030-48a4-bbc8-102df48a63c0","order_by":4,"name":"Craig Ziegler","email":"","orcid":"","institution":"University of Louisville","correspondingAuthor":false,"prefix":"","firstName":"Craig","middleName":"","lastName":"Ziegler","suffix":""},{"id":458958019,"identity":"293bf596-a170-4151-a045-935cc163ea45","order_by":5,"name":"Hannah Fischer","email":"","orcid":"","institution":"University of Louisville","correspondingAuthor":false,"prefix":"","firstName":"Hannah","middleName":"","lastName":"Fischer","suffix":""}],"badges":[],"createdAt":"2025-04-10 18:23:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6422565/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6422565/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12887-025-06119-0","type":"published","date":"2025-10-03T15:57:45+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":83279725,"identity":"100c9be3-a6f0-41ec-ba56-45b2a4f4b93b","added_by":"auto","created_at":"2025-05-22 10:04:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":192654,"visible":true,"origin":"","legend":"\u003cp\u003eEnrollment of infants during enrollment period\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6422565/v1/eb3cd02ee78ef3db2ef40d5f.png"},{"id":83279727,"identity":"f3a568d3-2d89-40c4-b29a-3d682cd526e2","added_by":"auto","created_at":"2025-05-22 10:04:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":51566,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation Between Mean Blood Pressure and RI \u003cbr\u003e\n RI-1: Resistive index at \u0026lt;36 hours of life\u003cbr\u003e\nRI-2: Resistive index at 5-7 days of life\u003cstrong\u003e\u003cbr\u003e\n \u003c/strong\u003eMBP: Mean arterial blood pressure in mmHg\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6422565/v1/aa674ef6a98731471b459a7f.png"},{"id":83279728,"identity":"0c5aa44a-3045-4d3e-bbf6-d9fa411d096a","added_by":"auto","created_at":"2025-05-22 10:04:53","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":168987,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of Various Doppler Indices at the Two Different Points of Examination\u003cbr\u003e\n RI-1= Resistive Index \u0026lt;36 hours of life; PSV-1= Peak systolic velocity \u0026lt;36 hours of life EDV-1= end diastolic velocity \u0026lt;36 hours of life; S/D-1= Peak systolic velocity/ end diastolic velocity \u0026lt;36 hours of life; RI-2= Resistive Index at 5-7 days of age; PSV-2= Peak systolic velocity at 5-7 days of age EDV-2= end diastolic velocity at 5-7 days of age; S/D-2= Peak systolic velocity/ end diastolic velocity at 5-7 days of age\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-6422565/v1/b212b7c0bf0b198c2a4a400d.png"},{"id":92883776,"identity":"4eb1d389-319f-4721-86ab-7cddc355a06a","added_by":"auto","created_at":"2025-10-06 16:09:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1502948,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6422565/v1/d792aefc-6087-4185-886e-23e249af6ff6.pdf"},{"id":83279723,"identity":"daf57e70-267e-475f-bb0b-b4682d8fbe04","added_by":"auto","created_at":"2025-05-22 10:04:53","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":35890,"visible":true,"origin":"","legend":"","description":"","filename":"DeidentifiedCompleteDatasheet.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6422565/v1/af1e0108e212807a9c7c381b.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cerebral Resistive Indices and Intraventricular Hemorrhage in Premature Neonates \u003c29 weeks’ gestation: A Pilot Prospective Cohort Study","fulltext":[{"header":"Impact Statement","content":"\u003cul\u003e\n \u003cli\u003eThe key message of this article is that abnormal Doppler ultrasound is associated with intraventricular hemorrhage and perhaps can be used to predict intraventricular hemorrhage in premature neonates.\u003c/li\u003e\n \u003cli\u003eWhat is already known on this topic: Doppler indices like resistive index can detect fluctuations in cerebral blood flow which in turn may result in an intraventricular hemorrhage. Resistive index is well studied in term neonates but has not been well studied in preterm neonates.\u003c/li\u003e\n \u003cli\u003eWhat this study adds: This is a pilot study done early in life in very low birthweight infants. It adds to existing literature to try and understand neonatal cranial blood flow changes.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eHow this study might affect research, practice or policy: highlights utility of duplex Doppler in premature neonates and paves way for future research.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003eIn the United States, 20\u0026ndash;25% of all infants born at \u0026lt;\u0026thinsp;1500g develop intraventricular hemorrhage (IVH).(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Developing an IVH represents a major neonatal morbidity, as well as a public health concern as approximately 50\u0026ndash;75% of preterm survivors IVH develop cerebral palsy, intellectual disability, and/or hydrocephalus.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003ePremature infants are prone to development of IVH due to the presence of a highly vascular subependymal germinal matrix. This area is a rich network of immature vessels, poorly supported by connective tissue.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) In addition, they are also particularly sensitive to changes in cerebral blood flow (CBF) because they may have impaired autoregulation. Lack of autoregulation results in a pressure-passive circulation in which the infant cannot compensate for fluctuations in systemic blood pressure.(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Other factors that contribute to the fluctuation of CBF include severe respiratory distress syndrome, hypercarbia, patent ductus arteriosus and systemic hypotension.(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) This fragility of the germinal matrix along with fluctuations in CBF, particularly in the first day of life, serves as the basis of developing hemorrhage in this population.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Identifying newborns at higher risk of IVH early on could revolutionize clinical treatment by allowing focused therapies meant to lower long-term neurological damage.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eCerebral blood flow can be examined via transfontanellar color Doppler in neonates, using the anterior fontanelle as an acoustic window. This quick and easy diagnostic tool, neither exposes newborn infants to the complications of ionizing radiation, nor requires their sedation.(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) Doppler indices measured include: peak systolic velocity and end diastolic velocity, and using these, the resistive index (RI) is calculated. An elevated RI corresponds to vasoconstriction and low blood flow velocity, whereas a low RI is related to vasodilation and high blood flow velocity.(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eDuplex Doppler indices for CBF have been extensively studied in term neonates and a well-established correlation exists between abnormal RIs and the development of white matter injury in asphyxiated term newborns.(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) However, Doppler indices have not been well studied in premature infants. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) Therefore, few values exist for Doppler indices in extreme preterm infants and very few clinical parameters have been studied for comparison.(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe American Academy of Neurology and the American Academy of Pediatrics recommends routine screening ultrasonography on all preterm neonates of less than 30 weeks' gestation.(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) Currently, there are no current recommendations for the use of Doppler CBF measurement in preterm infants.\u003c/p\u003e \u003cp\u003eThe primary aim of this study was to prospectively measure and compare the RI values in the middle cerebral arteries of preterm infants born at less than 29 weeks\u0026rsquo; gestation that develop IVH with those who did not develop IVH.\u003c/p\u003e \u003cp\u003eOur hypothesis was twofold: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) an alteration in CBF in very low birth weight infants born less than 29 weeks\u0026rsquo; gestation could be detected by changes in cranial duplex Doppler measurements performed within 36 hours of birth and these changes could be used to predict the subsequent development of IVH, and (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) clinically unstable infants, as measured by high score for neonatal acute physiology with perinatal extension (SNAPPE-II scores), will have an abnormal cerebral blood flow and resistive index.(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eA prospective cohort study design was used. The patient population consisted of all infants born at \u0026lt;\u0026thinsp;29 weeks gestation admitted to Norton Children\u0026rsquo;s Hospital neonatal intensive care unit (NICU) in Louisville, KY between August 2017 and July 2018. This pilot study was approved by the institutional medical ethics board. Patients or the public were not involved in the design, or conduct, or reporting, or dissemination plans of our research.\u003c/p\u003e \u003cp\u003eInclusion criteria consisted of gestational age\u0026thinsp;\u0026lt;\u0026thinsp;29 weeks and postnatal age at the time of enrollment of \u0026lt;\u0026thinsp;36 hours. Exclusion criteria included any infant with known prenatally diagnosed IVH, any infant with known IVH prior to enrollment, known cyanotic or hemodynamically significant congenital heart disease (not including patent ductus arteriosus), infants not expected to survive beyond 5 days of life and prenatal diagnosis of hydrocephalus or other congenital neurologic abnormality. Written informed consent was obtained from parent(s).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eImaging protocol:\u003c/h2\u003e \u003cp\u003eOur unit policy is to maintain a neutral/midline position of the head for the first 72 hours of age after birth in all infants\u0026thinsp;\u0026lt;\u0026thinsp;1500g to reduce incidence of IVH.(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) All the patients remained in a comfortable supine position in the incubator with the head in the midline position during the scanning period.\u003c/p\u003e \u003cp\u003eMeasurements were obtained at bedside with the General Electric LOGIQ E ultrasound machine with the 7MHz linear phased array probe using a trans-fontanelle approach via the anterior fontanelle. Sonographic imaging was performed in the coronal plane of the right and left middle cerebral artery (MCA) using color and duplex Doppler. Average peak systolic velocity (PSV) and end diastolic velocity (EDV) were obtained from at least three sequential stable waveforms per patient. Resistive index (RI) was calculated by the following formula: RI = (PSV-EDV)/PSV.(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) Mean RI was calculated by averaging the left and right MCA resistive index; previous studies have shown no difference between the resistive index of left and right arteries.(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) Average peak systolic velocity divided by the end diastolic velocity (S/D) ratio were also obtained for each measurement.\u003c/p\u003e \u003cp\u003eTwo cranial ultrasounds were performed. The initial cranial ultrasound was performed at \u0026lt;\u0026thinsp;36 hours of age and the second between 5\u0026ndash;7 days of age. We chose to perform ultrasound at \u0026lt;\u0026thinsp;36 hours of life as we wanted to assess whether changes in cerebral blood flow during the transition to extra uterine life after birth would impact the development of IVH as majority of IVH occurs within the first day.(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) We repeated the study at 5\u0026ndash;7 days of age to assess the changing patterns of cerebral circulation. All patients tolerated the procedure without any changes in vital signs and the need for sedation. If signs of stress/agitation were seen, then the procedure was stopped briefly and then resumed once infant was more comfortable. All the measurements were obtained by a single investigator (author A.P.). The images were stored and then independently reviewed by the same pediatric radiologist (author V.M.K.). Data collected from this study were not utilized in clinical decision making in the care of the patient. These ultrasounds were performed separately from the routine screening sonographic studies ordered by the clinical team. Also, at our institution, routine Doppler studies are not performed for preterm infants.\u003c/p\u003e \u003cp\u003eDemographics, prenatal and postnatal data were obtained from the maternal and infant\u0026rsquo;s medical records.\u003c/p\u003e \u003cp\u003ePrenatal/maternal factors studied included: maternal age, risk factors present at the time of delivery, exposure to antenatal steroids, use of antenatal magnesium sulfate for neuroprotection, medications/drugs used during pregnancy, prolonged rupture of membranes and presence or absence of chorioamnionitis.\u003c/p\u003e \u003cp\u003ePostnatal and delivery factors studies included: gestational age, Apgar scores, performance of delayed cord clamping, small for gestational age (birth weight\u0026thinsp;\u0026lt;\u0026thinsp;10th percentile), vitals at the time of study, presence or absence of hemodynamically significant patent ductus arteriosus (PDA) (if an ECHO was ordered by the clinical team), presence of IVH, use of vasopressors, need for blood transfusion and SNAPPE-II score.(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIVH was graded from grade I to grade IV per Volpe classification.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Infants were considered to have an IVH If any grade of IVH was detected before 7 days of age. PDA was classified as hemodynamically significant (hs-PDA) if the left atrium to aortic root diameter ratio was \u0026gt;\u0026thinsp;1.5 and patient had clinical signs of hemodynamically significant PDA as judged by the clinical team. RI values used for comparison from a previous study in 24\u0026ndash;28 weeks\u0026rsquo; gestation were 0.76 (0.69\u0026ndash;0.83).(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) Delayed cord clamping in our practice is any delay in clamping of cord by more than 30 seconds. Complete antenatal steroid course was defined as two doses of steroids given at least 24 hours prior to delivery. Mothers who did not receive any doses of antenatal steroids, or received a partial steroid course or doses\u0026thinsp;\u0026lt;\u0026thinsp;24 hours prior to delivery were considered to have an incomplete antenatal steroid course for the purpose of this study.\u003c/p\u003e \u003cp\u003eStatistical tests used included the Pearson\u0026rsquo;s chi-square test, independent sample t-test, multiple regression and the Pearson\u0026rsquo;s correlation coefficient for most variables. The distribution of all continuous variables was checked for normality; and nonparametric statistics such as the Mann-Whitney U and the Spearman\u0026rsquo;s correlation coefficient were used when the variables were deemed non-normally distributed. Data presented include frequency and percentages, means and standard deviations, along with correlation coefficients and scatterplots. All \u003cem\u003ep\u003c/em\u003e-values were two-tailed. Statistical significance was set by convention at \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Also, Bonferroni correction was used where required and the p-value for that data was set at 0.025. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 25. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement cohort reporting guidelines were used.(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e)\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eAlthough 58 infants met inclusion criteria during enrollment period, 30 infants were ultimately successfully enrolled in the study. \u003cstrong\u003e(\u003c/strong\u003eFig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n\u003ch3\u003eDemographics and clinical characteristics\u003c/h3\u003e\n\u003cp\u003eThe gestational age range was 23 6/7 weeks to 28 3/7 weeks with a mean of 26.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.52 weeks. The birth weight ranged from 460g to 1440g with a mean of 899g\u0026thinsp;\u0026plusmn;\u0026thinsp;242g. Eight neonates developed IVH [8/30 (27%)] and two of these eight developed severe IVH (grade III \u0026amp; grade IV).\u003c/p\u003e\n\u003cp\u003eNeonates were first divided into the IVH group (n\u0026thinsp;=\u0026thinsp;8) and the non-IVH group (n\u0026thinsp;=\u0026thinsp;22). There was no statistically significant difference in gestational age, birth weight, delayed cord clamping, antenatal steroid use, chorioamnionitis, magnesium sulfate use, presence of hs-PDA or SNAPPE-II scores between the IVH and the non-IVH group. \u003cstrong\u003e(\u003c/strong\u003eTable \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n\u003ch3\u003eDuplex Doppler ultrasound\u003c/h3\u003e\n\u003cp\u003eDuplex Doppler ultrasound was performed at two time periods in all the infants: first one performed at \u0026lt;\u0026thinsp;36 hours of life was at a mean age of 17\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;9 hours of life. Second ultrasound performed between 5\u0026ndash;7 days of age at mean age of 5.7\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.8 days. It typically took about 10\u0026ndash;15 minutes to perform the study. Mean resistive index performed\u0026thinsp;\u0026lt;\u0026thinsp;36 hours of life (RI-1) was 0.66\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05. Mean resistive index performed between 5\u0026ndash;7 days of age (RI-2) was 0.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04.\u003c/p\u003e\n\u003cp\u003eNone of the babies had IVH during the first Doppler ultrasound per the limited views performed and analyzed.\u003c/p\u003e\n\u003cp\u003eVarious clinical parameters were analyzed in relationship to the resistive index. There was no significant difference in the resistive index values when compared with gender, birthweight, antenatal steroid use, use of antenatal magnesium sulfate, presence of hs-PDA, performance of delayed cord clamping, maternal chorioamnionitis, use of pressors or need for blood transfusion within the first 24 hours of life. We also performed Pearson and Spearman\u0026rsquo;s correlation for our continuous variables and found no significant correlation for both RI-1 and RI-2 when compared with gestational age, APGAR score at 5 minutes and SNAPPE-II scores. There was a statistically significant negative correlation between the RI-1 and mean arterial blood pressure (R=-0.387, p\u0026thinsp;=\u0026thinsp;0.034). However, this correlation was not significant for RI-2. \u003cstrong\u003e(\u003c/strong\u003eTable \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e \u003cstrong\u003eand\u003c/strong\u003e Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv\u003e\u003cbr\u003e\u003c/div\u003e\n\u003cp\u003eDoppler indices, specifically RI, PSV, EDV and S/D ratio were significantly higher when measured at 5\u0026ndash;7 days of age compared to when measured early in life at \u0026lt;\u0026thinsp;36 hours of age. \u003cstrong\u003e(\u003c/strong\u003eFig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n\u003ch3\u003eDoppler and IVH\u003c/h3\u003e\n\u003cp\u003eWhen comparing IVH and duplex Doppler indices, we found that when measured at \u0026lt;\u0026thinsp;36 hours of age, the resistive index in the IVH group was significantly higher compared to the non-IVH group (IVH group, mean\u0026thinsp;=\u0026thinsp;0.70; non-IVH group, mean\u0026thinsp;=\u0026thinsp;0.65, p\u0026thinsp;=\u0026thinsp;0.022). The peak systolic velocity / end diastolic velocity (S/D) ratio was also significantly higher for the IVH group at \u0026lt;\u0026thinsp;36 hours of life (IVH group, mean\u0026thinsp;=\u0026thinsp;3.37; non-IVH group, mean\u0026thinsp;=\u0026thinsp;2.91, p\u0026thinsp;=\u0026thinsp;0.01). This difference is not significant when duplex Doppler ultrasound is performed at 5\u0026ndash;7 days. \u003cstrong\u003e(\u003c/strong\u003eTable \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cstrong\u003e)\u003c/strong\u003e Resistive index measured\u0026thinsp;\u0026lt;\u0026thinsp;36 hours of life did have a positive correlation with the grade of IVH, but the result was not statistically significant (Spearman\u0026rsquo;s R\u0026thinsp;=\u0026thinsp;0.05, p\u0026thinsp;=\u0026thinsp;0.9). Subjects who developed IVH had a significantly higher systolic velocity (IVH group, mean\u0026thinsp;=\u0026thinsp;12.34 cm/s; non-IVH group, mean\u0026thinsp;=\u0026thinsp;10.36 cm/s, p\u0026thinsp;=\u0026thinsp;0.01) and also consistently noted a more continuous, uninterrupted cerebral blood flow pattern in the ultrasounds at \u0026lt;\u0026thinsp;36 hours as seen by the duplex Doppler blood flow pattern.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1: Demographics and Perinatal Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"678\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 327px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 273px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAny IVH \u0026lt; DOL 7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes (8)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo (22)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP- Value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(50%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(36%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.678\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(50%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e14\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(64%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 336px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGestational age in weeks [Mean (SD)]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e25.98\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(1.69)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e26.55\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(1.46)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.313\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 336px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBirth weight in grams [Mean (SD)]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e933.63\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(239.39)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e887.05\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(248.41)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.650\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 336px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eApgar 5 minutes [Median (Minimum-Maximum)]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e8.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(5-9)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e8.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(2-9)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.982\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBirth weight\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e999 grams or less (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(75%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e13\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(59%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.672\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDelayed cord clamping\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(50%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e12\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(55%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMaternal chorioamnionitis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(38%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(19%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.357\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAntenatal steroids\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(38%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e17\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(77%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.078\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMagnesium sulfate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(75%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e19\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(86%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.589\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ehs-PDA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(38%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e10\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(45%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUse of vasopressors in 1\u003csup\u003est\u003c/sup\u003e 24 hours\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(25%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(18%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBlood transfusion in 1\u003csup\u003est\u003c/sup\u003e 24 hours\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(0%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(9%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.595\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 336px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSNAPPE-II scores [Median (Minimum-Maximum)]\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e24.0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(0-69)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e25.5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(0-68)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.881\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;RI-1: Resistive index at \u0026lt;36 hours of life\u003cbr\u003e\u0026nbsp;RI-2: Resistive index at 5-7 days of life\u003cbr\u003e\u0026nbsp;IVH: Intraventricular hemorrhage\u003cbr\u003e\u0026nbsp;hs-PDA: hemodynamically significant patent ductus arteriosus\u003cbr\u003e\u0026nbsp;SNAPPE-II: Score for neonatal acute physiology with perinatal extension II\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\"\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Unequal variance t-test used, unless specified\u003cbr\u003e\u0026nbsp;*:Mann-Whitney-Wilcoxon test\u003cbr\u003e\u0026nbsp;^: Spearman\u0026rsquo;s r\u003cbr\u003e\u0026nbsp;RI-1: Resistive index at \u0026lt;36 hours of life\u003cbr\u003e\u0026nbsp;RI-2: Resistive index at 5-7 days of life\u003cbr\u003e\u0026nbsp;hs-PDA: hemodynamically significant patent ductus arteriosus\u003cbr\u003e\u0026nbsp;SNAPPE-II: Score for neonatal acute physiology with perinatal extension II\u0026nbsp;\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDoppler Indices and IVH\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eDoppler Indices\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eIVH group (n\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eNon-IVH group (n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e(SD)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e(SD)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP Value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRI-1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.022*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePSV-1 (cm/s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(1.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(1.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.018*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEDV-1 (cm/s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.600\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eS/D-1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.011*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRI-2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.480\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePSV-2 (cm/s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(5.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(3.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.115\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEDV-2 (cm/s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eS/D-2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.444\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003e*p\u0026thinsp;\u0026lt;\u0026thinsp;0.025 (Bonferroni correction)\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003eRI-1\u0026thinsp;=\u0026thinsp;Resistive Index\u0026thinsp;\u0026lt;\u0026thinsp;36 hours of life; PSV-1\u0026thinsp;=\u0026thinsp;Peak systolic velocity\u0026thinsp;\u0026lt;\u0026thinsp;36 hours of life EDV-1\u0026thinsp;=\u0026thinsp;end diastolic velocity\u0026thinsp;\u0026lt;\u0026thinsp;36 hours of life; S/D-1\u0026thinsp;=\u0026thinsp;Peak systolic velocity/ end diastolic velocity\u0026thinsp;\u0026lt;\u0026thinsp;36 hours of life;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003eRI-2\u0026thinsp;=\u0026thinsp;Resistive Index at 5\u0026ndash;7 days of age; PSV-2\u0026thinsp;=\u0026thinsp;Peak systolic velocity at 5\u0026ndash;7 days of age EDV-2\u0026thinsp;=\u0026thinsp;end diastolic velocity at 5\u0026ndash;7 days of age; S/D-2\u0026thinsp;=\u0026thinsp;Peak systolic velocity/ end diastolic velocity at 5\u0026ndash;7 days of age;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003eIVH: Intraventricular hemorrhage\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eA multiple regression was performed where Resistive index measured\u0026thinsp;\u0026lt;\u0026thinsp;36 hours of life was regressed on presence of IVH, birthweight, antenatal steroid administration, and presence of hemodynamically significant PDA. The results show that a significant relationship exists between IVH and the resistive index\u0026thinsp;\u0026lt;\u0026thinsp;36 hours of life (B\u0026thinsp;=\u0026thinsp;0.054, t\u0026thinsp;=\u0026thinsp;2.51, p\u0026thinsp;=\u0026thinsp;0.019), after controlling for birthweight, antenatal steroid administration, and presence of hemodynamically significant PDA. This indicates that babies with IVH have an average resistive index greater than 0.05 than those not having IVH.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAlthough, the first routine cranial ultrasound in preterm infants\u0026thinsp;\u0026lt;\u0026thinsp;30 weeks gestation is recommended anytime within the first week of life, the majority of IVH occurs within the first day of life. Only about 38% of IVH cases are seen after the first 24 hours.(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) If these preterm infants survive, they may develop adverse neurodevelopmental outcomes. Therefore, in our prospective pilot study, we explored the relationship of CBF to IVH in this critical time period.\u003c/p\u003e \u003cp\u003eAmong infants less than 29 weeks\u0026rsquo; gestation, resistive index and S/D ratio at \u0026lt;\u0026thinsp;36 hours of age were higher in infants who developed IVH than those who did not. This high RI seen in the hemorrhage group translates to high vascular resistance to blood flow, and hence, a low CBF.(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) Higher RI in our cohort also correlated with lower mean arterial blood pressure. Hence, we speculate that this difference in CBF in the hemorrhage group seen in the first 36 hours of life may be due to impaired autoregulation early in life.\u003c/p\u003e \u003cp\u003eOur findings are consistent with other studies that show a pattern of altered CBF in extremely preterm infants via indirect measurement of CBF, using cerebral regional oxygen saturation measured via near infrared spectroscopy (NIRS).(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) Utilizing NIRS, Meek et al. and Sorensen et al. found significantly lower CBF on the first postnatal day, in infants that developed severe IVH. Verhagen et al. had similar findings but also suggested that CBF remains persistently low for two weeks following IVH.(\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) In contrast, Alderliesten et al. suggested a higher CBF being associated with IVH.(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Noori et al. showed that amongst the neonates who develop IVH, CBF is initially low but subsequently increased towards normal just before development of IVH.(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e) More recent work by Farag et al. also demonstrates correlation of IVH and RI at less than 24 hours of life using doppler indices of the anterior cerebral artery.(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e) These studies support that impaired autoregulation leading to an ischemia-reperfusion injury precedes and perhaps contributes to development of IVH which is consistent with the suggestion of impaired autoregulation and lower CBF in our observations in the IVH group early in life.\u003c/p\u003e \u003cp\u003eThis difference in CBF pattern in the hemorrhage group was not found when the RI was measured between 5\u0026ndash;7 days of age. This is perhaps due to improved autoregulation later in life as evidenced by lack of correlation between RI and mean arterial blood pressure and statistically significant increase in PSV and EDV over time, when measured later in life. Previous work by other authors has also showed MCA velocity to be increasing overtime during the first 48 hours, and volumetric ultrasonographic data suggests a gradual increase in CBF over the first two weeks.(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e) This indicates temporal/developmental changes in the cerebral blood flow over the first week of life that may predispose certain high risk infants to development of IVH. Measuring Doppler indices more frequently over time might delineate the course of these changes and provide further guidance for predicting the infants at high risk of developing IVH.\u003c/p\u003e \u003cp\u003eSimilar to our findings, Elhameed et al. also noted increased resistive index when Doppler was performed later in life. However, they did not find any association between resistive index and IVH. But they did find high end diastolic velocity (EDV\u0026thinsp;\u0026gt;\u0026thinsp;9.2 cm/s) to be a predictor of IVH. This is different from our study as we found positive correlation between high RI and presence of IVH and none with EDV. Their study differed from ours as they had very few very low birth weight (VLBW) neonates (only 10 neonates\u0026thinsp;\u0026lt;\u0026thinsp;32 weeks gestation) and they averaged measurements from the anterior cerebral artery along with middle cerebral artery. (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e) Farag et al found correlation of high RI and EDV with IVH but also has older infants in study with a mean gestational age of 29 weeks.(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eBesides IVH, in our study, we also looked at multiple other clinical factors such as PDA, chorioamnionitis, SNAPPE-II scores and delayed cord clamping and their relationship with resistive index.\u003c/p\u003e \u003cp\u003eLipman et al. showed an association between high resistive index and PDA, attributed to decreased diastolic flow.(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e) The decreased diastolic flow could be due to the presence of the ductal steal phenomenon in the presence of the large PDA. Ecury-Goossen et al. showed that infants with hemodynamically significant PDA have a higher RI compared to those without PDA, but this was only seen in the anterior cerebral artery and the internal carotid artery and not corroborated in the other cerebral arteries. The authors of this study concluded that the presence of hemodynamically significant PDA does not always significantly affect cerebral perfusion.(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) We did not find any difference between a hemodynamically significant PDA and MCA RI, which is similar to the conclusion of the previous study by Ecury-Goossen et al.. Perhaps, this difference was not seen because of the lack of a clear definition of hemodynamically significant PDA across various institutions.(\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eWe expected to find a relationship between SNAPPE-II scores and resistive index as infants with high SNAPPE-II scores are sicker leading to abnormal CBF, but we found no significant relationship between RI and SNAPPE-II scores. This could be explained by SNAPPE-II scores measuring physiology within the first 12 hours and we measured Doppler flow at a mean age of 17 hours and again at 5.7 days of life, a finding similar to a previous study.(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eEffects of delayed cord clamping have been clearly demonstrated in preterm infants with an increase peak hematocrit and the reduced need of blood transfusion, however its effect on IVH remains unclear.(\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e) In one study of 60 infants, delaying clamping cord by 45 seconds showed a clear reduction in incidence of IVH.(\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e) On the other hand, in a large trial of 1566 preterm infants (GA\u0026thinsp;\u0026lt;\u0026thinsp;30 weeks), there was no effect of delaying cord clamping by \u0026gt;\u0026thinsp;60 seconds on incidence of severe IVH.(\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e) We found no relationship between delaying of cord clamping and incidence of IVH and RI in our cohort. Our study differs from the previous as in our center cord clamping is delayed only up to 30 seconds when indicated, and only 16/30 infants in our cohort received delayed cord clamping.\u003c/p\u003e \u003cp\u003eAlso, multiple regression suggested a difference in RI of 0.05 was statistically significant in predicting IVH in our study of VLBW infants (n\u0026thinsp;=\u0026thinsp;30). Our findings are similar to another larger study of 147 infants by Farag et al., which using logistic regression also suggests a higher RI\u0026thinsp;\u0026gt;\u0026thinsp;0.75 to be predictive of IVH.(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eLimitations:\u003c/p\u003e \u003cp\u003eBesides a small sample size, our study had other limitations as well. The exclusion of eligible infants and dropout rates may introduce selection bias, limiting generalizability. Also, studies of cerebral blood flow are limited because velocity measurements are difficult to compare as they depend on the angle of the probe to the intracerebral vessel.(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) This variability was reduced by having the same investigator perform all the duplex Doppler studies, using the same technique. Any further differences are mitigated by the fact that RI is reproducible and has inter-observer reliability(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), and thus was the measurement of choice for our study. However, we acknowledge that duplex Doppler measurements only give us a snapshot of time and further corroboration with serial Doppler measurements would further support our findings.\u003c/p\u003e \u003cp\u003eConclusion and Future Directions:\u003c/p\u003e \u003cp\u003eIn summary, our pilot study indicates that an elevated resistive index at \u0026lt;\u0026thinsp;36 hours is associated with IVH in VLBW infants\u0026thinsp;\u0026lt;\u0026thinsp;29 weeks\u0026rsquo; gestation. The use of RIs as a prediction tool needs to be validated in a large, multicentered study. Identifying this at-risk group, could perhaps lead to additional interventions to prevent an IVH. At the present time, the clinicians may use midline head positioning, gentle caretaking, indomethacin and avoiding fluid bolus administration with modest improvements in the incidence of severe IVH in this subset of preterm infants.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e) Bedside ultrasound in the NICU remains underutilized, though the use is rapidly expanding and its impact on clinical management has been well demonstrated.(\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e) Future studies could use serial ultrasound measurements or perhaps use newer modalities such as ultrafast plane-wave Doppler imaging(\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e) in order to validate our findings in a larger population.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eIVH: Intraventricular hemorrhage; CBF: cerebral blood flow; RI: Resistive Index; SNAPPE-II: score for neonatal acute physiology with perinatal extension; NICU: neonatal intensive care unit; MCA: middle cerebral artery; PSV: peak systolic velocity; EDV: end diastolic velocity; hs-PDA: hemodynamically significant PDA; SPSS: Statistical Package for Social Sciences; STROBE: Strengthening the Reporting of Observational Studies in Epidemiology; NIRS: near infrared spectroscopy; VLBW: very low birth weight\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cul\u003e\n \u003cul type=\"disc\"\u003e\n \u003cli\u003eEthics approval and consent to participate: This pilot study was approved by the institutional medical ethics board at University of Louisville. IRB number 17.0654\u003c/li\u003e\n \u003cli\u003eConsent for publication: Not applicable\u003c/li\u003e\n \u003cli\u003eAvailability of data and materials:\u0026nbsp;All data generated or analyzed during this study are included in this published article [and its supplementary information files].\u003c/li\u003e\n \u003cli\u003eCompeting interests: The authors declare that they have no competing interests.\u003c/li\u003e\n \u003cli\u003eFunding: No financial assistance was received for this study.\u003c/li\u003e\n \u003cli\u003eAuthors\u0026apos; contributions:\u003cbr\u003e\u0026nbsp;-Abhinav Pal, Dan Stewart, Vesna Kriss and Hannah Fischer: Substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; Drafting the article and revising it critically for important intellectual content; and final approval of the version to be published.\u003cbr\u003e\u0026nbsp;-Kshama Ojha and Craig Ziegler: analysis and interpretation of data, revising article critically\u003c/li\u003e\n \u003cli\u003eAcknowledgements: We acknowledge the division of neonatology and the department of pediatrics for the encouragement and support; and the UofL GME office for statistical support.\u003c/li\u003e\n \u003cli\u003eClinical trial number: not applicable\u003cstrong\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003c/li\u003e\n \u003c/ul\u003e\n\u003c/ul\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSiffel C, Kistler KD, Sarda SP. Global incidence of intraventricular hemorrhage among extremely preterm infants: a systematic literature review. J Perinat Med. 2021;49(9):1017-26.\u003c/li\u003e\n\u003cli\u003eLuu TM, Ment LR, Schneider KC, Katz KH, Allan WC, Vohr BR. Lasting effects of preterm birth and neonatal brain hemorrhage at 12 years of age. Pediatrics. 2009;123(3):1037-44.\u003c/li\u003e\n\u003cli\u003eBallabh P. Pathogenesis and prevention of intraventricular hemorrhage. Clin Perinatol. 2014;41(1):47-67.\u003c/li\u003e\n\u003cli\u003eAlderliesten T, Lemmers PM, Smarius JJ, van de Vosse RE, Baerts W, van Bel F. Cerebral oxygenation, extraction, and autoregulation in very preterm infants who develop peri-intraventricular hemorrhage. J Pediatr. 2013;162(4):698-704.e2.\u003c/li\u003e\n\u003cli\u003eMullaart RA, Hopman JC, Rotteveel JJ, Daniels O, Stoelinga GB, De Haan AF. Cerebral blood flow fluctuation in neonatal respiratory distress and periventricular haemorrhage. Early Hum Dev. 1994;37(3):179-85.\u003c/li\u003e\n\u003cli\u003eVolpe JJ. Neurology of the newborn. Philadelphia: Saunders/Elsevier; 2008. p. 157.\u003c/li\u003e\n\u003cli\u003eKehrer M, Goelz R, Krageloh-Mann I, Schoning M. Measurement of volume of cerebral blood flow in healthy preterm and term neonates with ultrasound. Lancet. 2002;360(9347):1749-50.\u003c/li\u003e\n\u003cli\u003eArgollo N, Lessa I, Ribeiro S. Cranial Doppler resistance index measurement in preterm newborns with cerebral white matter lesion. J Pediatr (Rio J). 2006;82(3):221-6.\u003c/li\u003e\n\u003cli\u003eGerner GJ, Burton VJ, Poretti A, Bosemani T, Cristofalo E, Tekes A, et al. Transfontanellar duplex brain ultrasonography resistive indices as a prognostic tool in neonatal hypoxic-ischemic encephalopathy before and after treatment with therapeutic hypothermia. J Perinatol. 2016;36(3):202-6.\u003c/li\u003e\n\u003cli\u003ePinto PS, Tekes A, Singhi S, Northington FJ, Parkinson C, Huisman TA. White-gray matter echogenicity ratio and resistive index: sonographic bedside markers of cerebral hypoxic-ischemic injury/edema? J Perinatol. 2012;32(6):448-53.\u003c/li\u003e\n\u003cli\u003eWindschall D, Hoekstra K, Haase R. Doppler Sonography of Blood Flow Velocity in the Vertebral Arteries of Preterm and Term Neonates. J Ultrasound Med. 2016;35(9):1941-7.\u003c/li\u003e\n\u003cli\u003eEcury-Goossen GM, Raets MM, Camfferman FA, Vos RH, van Rosmalen J, Reiss IK, et al. Resistive indices of cerebral arteries in very preterm infants: values throughout stay in the neonatal intensive care unit and impact of patent ductus arteriosus. Pediatr Radiol. 2016;46(9):1291-300.\u003c/li\u003e\n\u003cli\u003ePezzati M, Dani C, Biadaioli R, Filippi L, Biagiotti R, Giani T, et al. Early postnatal doppler assessment of cerebral blood flow velocity in healthy preterm and term infants. Dev Med Child Neurol. 2002;44(11):745-52.\u003c/li\u003e\n\u003cli\u003eMent LR, Bada HS, Barnes P, Grant PE, Hirtz D, Papile LA, et al. Practice parameter: neuroimaging of the neonate: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2002;58(12):1726-38.\u003c/li\u003e\n\u003cli\u003eHand IL, Shellhaas RA, Milla SS, FETUS CO, NEWBORN SON, SECTION ON RADIOLOGY, Cummings JJ, et al. Routine Neuroimaging of the Preterm Brain. Pediatrics. 2020;146(5).\u003c/li\u003e\n\u003cli\u003eRichardson DK, Corcoran JD, Escobar GJ, Lee SK. SNAP-II and SNAPPE-II: Simplified newborn illness severity and mortality risk scores. The Journal of Pediatrics. 2001;138(1):92-100.\u003c/li\u003e\n\u003cli\u003eCarteaux P, Cohen H, Check J, George J, McKinley P, Lewis W, et al. Evaluation and development of potentially better practices for the prevention of brain hemorrhage and ischemic brain injury in very low birth weight infants. Pediatrics. 2003;111(4 Pt 2):e489-96.\u003c/li\u003e\n\u003cli\u003eLowe LH, Bailey Z. State-of-the-art cranial sonography: Part 1, modern techniques and image interpretation. AJR Am J Roentgenol. 2011;196(5):1028-33.\u003c/li\u003e\n\u003cli\u003eSeibert JJ, McCowan TC, Chadduck WM, Adametz JR, Glasier CM, Williamson SL, et al. Duplex pulsed Doppler US versus intracranial pressure in the neonate: clinical and experimental studies. Radiology. 1989;171(1):155-9.\u003c/li\u003e\n\u003cli\u003eAl-Abdi SY, Al-Aamri MA. A Systematic Review and Meta-analysis of the Timing of Early Intraventricular Hemorrhage in Preterm Neonates: Clinical and Research Implications. Journal of clinical neonatology. 2014;3(2):76-88.\u003c/li\u003e\n\u003cli\u003evon Elm E, Altman DG, Egger M, Pocock SJ, G\u0026oslash;tzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61(4):344-9.\u003c/li\u003e\n\u003cli\u003eNoori S, Seri I. Hemodynamic antecedents of peri/intraventricular hemorrhage in very preterm neonates. Seminars in Fetal and Neonatal Medicine. 2015;20(4):232-7.\u003c/li\u003e\n\u003cli\u003eMeek JH, Tyszczuk L, Elwell CE, Wyatt JS. Low cerebral blood flow is a risk factor for severe intraventricular haemorrhage. Archives of Disease in Childhood - Fetal and Neonatal Edition. 1999;81(1):F15.\u003c/li\u003e\n\u003cli\u003eSorensen LC, Maroun LL, Borch K, Lou HC, Greisen G. Neonatal cerebral oxygenation is not linked to foetal vasculitis and predicts intraventricular haemorrhage in preterm infants. Acta Paediatrica. 2008;97(11):1529-34.\u003c/li\u003e\n\u003cli\u003eVerhagen Elise A, ter Horst Hendrik J, Keating P, Martijn A, Van Braeckel Koenraad NJA, Bos Arend F. Cerebral Oxygenation in Preterm Infants With Germinal Matrix\u0026ndash;Intraventricular Hemorrhages. Stroke. 2010;41(12):2901-7.\u003c/li\u003e\n\u003cli\u003eNoori S, McCoy M, Anderson MP, Ramji F, Seri I. Changes in cardiac function and cerebral blood flow in relation to peri/intraventricular hemorrhage in extremely preterm infants. The Journal of pediatrics. 2014;164(2):264-70. e3.\u003c/li\u003e\n\u003cli\u003eFarag MM, Gouda MH, Almohsen AMA, Khalifa MA. Intraventricular hemorrhage prediction in premature neonates in the era of hemodynamics monitoring: a prospective cohort study. European Journal of Pediatrics. 2022;181(12):4067-77.\u003c/li\u003e\n\u003cli\u003eEvans N, Kluckow M, Simmons M, Osborn D. Which to measure, systemic or organ blood flow? Middle cerebral artery and superior vena cava flow in very preterm infants. Archives of disease in childhood Fetal and neonatal edition. 2002;87(3):F181-F4.\u003c/li\u003e\n\u003cli\u003eKehrer M, Blumenstock G, Ehehalt S, Goelz R, Poets C, Schoning M. Development of cerebral blood flow volume in preterm neonates during the first two weeks of life. Pediatr Res. 2005;58(5):927-30.\u003c/li\u003e\n\u003cli\u003eElhameed AMA, Fouda EM. Transcranial ultrasound Doppler parameters in cerebral vessels may predict intracerebral hemorrhage in preterm newborns. The Egyptian Journal of Radiology and Nuclear Medicine. 2011;42(1):69-75.\u003c/li\u003e\n\u003cli\u003eLipman B, Serwer GA, Brazy JE. Abnormal cerebral hemodynamics in preterm infants with patent ductus arteriosus. Pediatrics. 1982;69(6):778-81.\u003c/li\u003e\n\u003cli\u003eEl-Khuffash A, Levy PT, Gorenflo M, Frantz ID. The definition of a hemodynamically significant ductus arteriosus. Pediatric Research. 2019;85(6):740-1.\u003c/li\u003e\n\u003cli\u003eFogarty M, Osborn DA, Askie L, Seidler AL, Hunter K, Lui K, et al. Delayed vs early umbilical cord clamping for preterm infants: a systematic review and meta-analysis. Am J Obstet Gynecol. 2018;218(1):1-18.\u003c/li\u003e\n\u003cli\u003eChiruvolu A, Tolia VN, Qin H, Stone GL, Rich D, Conant RJ, et al. Effect of delayed cord clamping on very preterm infants. Am J Obstet Gynecol. 2015;213(5):676.e1-7.\u003c/li\u003e\n\u003cli\u003eTarnow-Mordi W, Morris J, Kirby A, Robledo K, Askie L, Brown R, et al. Delayed versus Immediate Cord Clamping in Preterm Infants. N Engl J Med. 2017;377(25):2445-55.\u003c/li\u003e\n\u003cli\u003eFowlie PW, Davis PG, McGuire W. Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. The Cochrane database of systematic reviews. 2010(7):Cd000174.\u003c/li\u003e\n\u003cli\u003eHarabor A, Soraisham AS. Utility of Targeted Neonatal Echocardiography in the Management of Neonatal Illness. J Ultrasound Med. 2015;34(7):1259-63.\u003c/li\u003e\n\u003cli\u003eKluckow M. Use of ultrasound in the haemodynamic assessment of the sick neonate. Arch Dis Child Fetal Neonatal Ed. 2014;99(4):F332-7.\u003c/li\u003e\n\u003cli\u003eDemene C, Pernot M, Biran V, Alison M, Fink M, Baud O, et al. Ultrafast Doppler reveals the mapping of cerebral vascular resistivity in neonates. J Cereb Blood Flow Metab. 2014;34(6):1009-17.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6422565/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6422565/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003eIn extremely preterm newborns, intraventricular hemorrhage (IVH) greatly influences neurodevelopmental outcomes. Preterm newborns who later develop IVH might have altered cerebral blood flow (CBF) as measured by resistive index (RI) on Doppler ultrasound. Knowledge regarding RI in extremely premature infants remains limited.\u003c/p\u003e\u003ch2\u003eObjective:\u003c/h2\u003e \u003cp\u003eThis pilot prospective cohort study aimed to evaluate the association between early cerebral RI (within the first 36 hours of life) and the occurrence of IVH in preterm infants born at \u0026lt;\u0026thinsp;29 weeks' gestation.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eProspective cohort study in which cranial Doppler was performed in preterm infants\u0026thinsp;\u0026lt;\u0026thinsp;29 weeks at \u0026lt;\u0026thinsp;36 hours of age and between 5\u0026ndash;7 days of age. CBF velocities and RI were measured. Clinical and demographic factors were also assessed.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eOf the 30 enrolled infants, 27% developed an IVH. RI measured at \u0026lt;\u0026thinsp;36 hours of life for the neonates with IVH was significant higher compared to those who did not have IVH (0.70(\u0026plusmn;\u0026thinsp;0.04) vs 0.65(\u0026plusmn;\u0026thinsp;0.05); p\u0026thinsp;=\u0026thinsp;0.02). Multiple regression showed RI amongst babies with IVH was higher by 0.05, when controlled for other clinical variables (p\u0026thinsp;=\u0026thinsp;0.01). These differences were not statistically significant when measured at 5\u0026ndash;7 days. RI had no significant correlation with antenatal steroid use, delayed cord clamping, or presence of hemodynamically significant patent ductus arteriosus.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eHigher cerebral RI measured within the first 36 hours of life was associated with IVH in this pilot study. These early results draw attention to the requirement for bigger, sufficiently powered research to assess RI as a possible early sign for IVH risk stratification in very preterm newborns.\u003c/p\u003e","manuscriptTitle":"Cerebral Resistive Indices and Intraventricular Hemorrhage in Premature Neonates \u0026lt;29 weeks’ gestation: A Pilot Prospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-22 10:04:49","doi":"10.21203/rs.3.rs-6422565/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-17T15:21:38+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-01T18:32:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"197199863736983113939886389030006795796","date":"2025-05-22T18:25:24+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-22T09:47:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"245880620546944539774043676598208804131","date":"2025-05-22T07:04:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-22T06:03:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"243352307302728035764483745722150823020","date":"2025-05-19T21:07:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-19T15:13:42+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-13T18:11:35+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-04-24T06:00:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-18T05:32:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2025-04-18T05:31:46+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"664bf130-bf15-419d-803f-fd33f8ea07e5","owner":[],"postedDate":"May 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-06T16:02:50+00:00","versionOfRecord":{"articleIdentity":"rs-6422565","link":"https://doi.org/10.1186/s12887-025-06119-0","journal":{"identity":"bmc-pediatrics","isVorOnly":false,"title":"BMC Pediatrics"},"publishedOn":"2025-10-03 15:57:45","publishedOnDateReadable":"October 3rd, 2025"},"versionCreatedAt":"2025-05-22 10:04:49","video":"","vorDoi":"10.1186/s12887-025-06119-0","vorDoiUrl":"https://doi.org/10.1186/s12887-025-06119-0","workflowStages":[]},"version":"v1","identity":"rs-6422565","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6422565","identity":"rs-6422565","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}