Published online August 1, 2007
PEDIATRICS
Vol. 120
No. 2
August 2007, pp.
372-380
(doi:10.1542/peds.2006-3398)
Low Superior Vena Cava Flow and Effect of Inotropes on Neurodevelopment to 3 Years in Preterm Infants
David A. Osborn, MM, FRACP, PhDa,b,
Nick Evans, MRCPCH, MDa,b,
Martin Kluckow, FRACP, PhDb,c,
Jennifer R. Bowen, FRACPb,c and
Ingrid Rieger, FRACPa,b
a Royal Prince Alfred Newborn Care, Royal Prince Alfred Hospital, Camperdown, Australia
b Department of Obstetrics and Gynaecology, University of Sydney, Sydney, Australia
c Department of Neonatology, Royal North Shore Hospital, St Leonards, Australia
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ABSTRACT
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OBJECTIVE. The goal was to report the 1- and 3-year outcomes of preterm infants with low systemic blood flow in the first day and the effect of dobutamine versus dopamine for treatment of low systemic blood flow.
METHODS. A cohort of 128 infants born at <30 weeks of gestation underwent echocardiographic measurement of superior vena cava flow at 3, 10, and 24 hours of age. Forty-two infants with low superior vena cava flow (<41 mL/kg per minute) were assigned randomly to dobutamine or dopamine. Surviving infants underwent blinded neurodevelopmental assessments at corrected ages of 1 and 3 years.
RESULTS. Seventy-six of 87 surviving infants were seen at 1 year and 67 at 3 years. Forty-four infants had low superior vena cava flow. At 3 years, with adjustment for perinatal risk factors, death was predicted by low superior vena cava flow, lower gestational age, and low 5-minute Apgar score. Substantial reductions in the Griffiths General Quotient were associated with low superior vena cava flow and birth weight of <10th percentile. Infants with low flow had significant reductions in personal-social, hearing and speech, and performance subscales. Death or disability at 3 years was predicted by low superior vena cava flow and lower gestational age. For infants treated with inotropes, no significant differences were found in clinical outcomes, except for reduced rates of late severe periventricular/intraventricular hemorrhage in the dobutamine group. At 3 years, infants in the dopamine group had significantly more disability and a lower Griffiths General Quotient. At the latest time measured, however, combined rates of death or disability were similar.
CONCLUSIONS. Early low superior vena cava flow was associated with substantial rates of death, morbidity, and developmental impairments. No difference was found in combined rates of death and disability for infants assigned randomly to dopamine or dobutamine.
Key Words: premature infant • developmental disability • cardiac output • dopamine • dobutamine
Abbreviations: GQ—General Quotient • OR—odds ratio • PIVH—periventricular/intraventricular hemorrhage • SBF—systemic blood flow • SGA—small for gestational age • SVC—superior vena cava • CI—confidence interval
More than 30% of infants born at <30 weeks of gestation develop low systemic blood flow (SBF) in the first day after birth.1,2 However, the usual echocardiographic measures of SBF (ventricular outputs) are unreliable3 at this time, because of frequent shunts (ductus arteriosus4 and foramen ovale5) between systemic and pulmonary circulations. To overcome this problem, we studied 2 cohorts of infants for whom superior vena cava (SVC) flow was used as a measure of SBF. For the first cohort,2 physicians were blinded with respect to echocardiographic flow measures, and treatments (volume and inotropes) were targeted at blood pressure. In this cohort, lower average SVC flow on the first day was associated with increased risk of late periventricular/intraventricular hemorrhage (PIVH),2 death or disability, and abnormal motor findings (motor delay or cerebral palsy) but not overall developmental scores at 3 years.6 However, significantly reduced developmental scores were associated with the number of times SVC flow of <31 mL/kg per minute was detected during the first day.6
For the second cohort1 reported here, 128 infants born before 30 weeks were screened echocardiographically, from soon after birth until 24 hours of age, for failure of early ductal constriction and development of low SBF (SVC flow of <41 mL/kg per minute). The subgroup of infants with failure of early ductal constriction were entered into a short-term, double-blind, randomized, crossover trial of indomethacin and placebo.7 The subgroup of infants who developed low SVC flow were entered into a double-blind, randomized trial of dopamine versus dobutamine with short-term, crossover rescue for infants for whom SVC flow failed to improve.8 Those studies were designed and powered to explore short-term hemodynamic effects, and the details of the methods and results were reported previously.1,7,8 The published literature on circulatory support in preterm infants is characterized by a complete lack of data about effects on neurodevelopmental outcomes. The aim of this article is to report the neurodevelopmental outcomes of the second cohort and the outcomes of the survivors of the subgroup of infants with low SVC who were assigned randomly to dopamine or dobutamine.
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METHODS
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Cohort Study
This was a 2-center, prospective cohort study conducted between October 1998 and December 1999 (Australian Clinical Trials Registry No. ACTRN012607000152426). The short-term outcomes for the original cohort have already been reported.1 The ethics committees of Central Sydney and Northern Sydney Area Health Services approved the study. Informed consent was obtained from all parents. Infants who were born at <30 weeks of gestation and who were <24 hours of age were eligible. Infants were excluded if a major congenital or cardiac abnormality was identified, if the infant was considered by the attending clinician to be nonviable, or if inotropes or indomethacin had been administered previously. Methods for recording of clinical and physiologic variables were reported previously.1,7,8 Echocardiographic monitoring was performed routinely at 3, 5 to 10, and 24 hours of age.
Infants in the cohort were eligible for inclusion in 2 sequential, blinded, intervention studies of echocardiographically directed cardiovascular treatments. The first intervention study7 was a crossover study that examined the hemodynamic effects of indomethacin given before 12 hours of age to infants with a large ductus arteriosus (color Doppler diameter: >1.6 mm). The second intervention study (described below) examined the effects of volume and inotropes given to infants with low SBF (SVC flow: <41 mL/kg per minute).8
Randomized Trial of Dobutamine Versus Dopamine
Forty-two infants with low SVC flow (<41 mL/kg per minute) were enrolled in a blinded, randomized trial of volume and dobutamine versus volume and dopamine; the effects on SBF were reported previously.8 After administration of normal saline solution at 10 mL/kg, infants were assigned randomly to receive dobutamine or dopamine, initially at 10 µg/kg per minute and then at 20 µg/kg per minute if SVC flows failed to be maintained at >40 mL/kg per minute in the first 24 hours. Infants crossed to the other inotrope if SVC flow of >40 mL/kg per minute was not maintained in the first 24 hours. Echocardiographic assessment was performed immediately before and after normal saline solution administration and before and 30 minutes after commencement of inotrope administration or changes in the dose or type of inotrope. All measurements were performed in a blinded manner with respect to treatment allocation. SVC flow was determined as described previously,9 and low SBF was defined as SVC flow of <41 mL/kg per minute at any time in the first 24 hours, on the basis of previous data for healthy preterm infants.9
Neurodevelopmental Follow-up Assessments
Surviving infants were assessed with the Griffiths Mental Development Scales and physical examination in the Royal Prince Alfred Hospital and Royal North Shore Hospital Newborn Follow-up Clinics at corrected ages of 1 and 3 years. These assessments were performed by developmental pediatricians who were blinded with respect to early hemodynamic observations and treatment allocation. At corrected ages of 1 and 3 years, infants were assessed for delayed development, with delayed development defined as a Griffiths General Quotient (GQ) >2 SDs below the population mean, cerebral palsy, deafness (requiring hearing aids), blindness (visual acuity of <6/60), and disability (any of previous). For corrected age of 3 years, the subscales of locomotor, personal-social, hearing and speech, eye-hand coordination, performance, and practical reasoning are reported. The SDs for the Griffiths GQ were 12.0 at corrected age of 1 year10 and 12.7 at corrected age of 3 years.11 In addition, rates of death or disability at corrected age of 3 years and at the latest time measured (corrected age of 1 or 3 years) are reported.
Statistical Analyses
Data were analyzed by using SPSS 14.0 for Windows (SPSS, Chicago, IL), with the independent-sample t test, 
2 test, or Fisher's exact test as appropriate. Nonparametric variables were analyzed by using the Mann-Whitney U test. Multivariate analyses were performed to determine perinatal predictors of death before follow-up assessment, Griffiths GQ >1 SD below the mean (logistic regression), Griffiths GQ (linear regression), and death or disability at 3 years (logistic regression), after adjustment for perinatal confounders. Variables eligible in the models included maternal use of antihypertensive drugs, ex utero transfer, any prenatal steroid use, complete prenatal steroid use (>48 hours), labor, cesarean delivery, gestational age, birth weight, birth weight percentile, small for gestational age (SGA) (<10th percentile), 1-minute Apgar score of 
4, 5-minute Apgar score of <7, respiratory distress syndrome, low SVC flow in the first day, ductus arteriosus diameter of >1.6 mm in the first day, and average mean airway pressure in the first 12 hours. Infants with an early large-diameter ductus arteriosus received early targeted indomethacin treatment. Backward stepwise regression was used, with variables included in the base model if they were not considered to be an intervening variable, they were significant in univariate analyses (P < .2), and the estimate of effect was stable in direction between univariate and multivariate analyses. Potential confounders were retained in the model if they affected the estimate of effect of the explanatory variable (low SVC flow) by 
10%. The Nagelkerke R2 statistic was used to express the proportion of variance of the dependent variable explained by the model. The analyses of outcomes at the latest time measured (corrected age of 1 or 3 years) were performed to determine whether the results were sensitive to losses at 3 years among infants whose developmental outcomes had been assessed previously.
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RESULTS
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Cohort Study
Overall Findings
Echocardiographic and clinical monitoring in the first 24 hours was performed for 128 infants (Fig 1). Thirty-six (28%) of 128 infants died before discharge. Another 5 infants died after discharge and before developmental follow-up assessment, leaving 87 survivors. Losses to follow-up monitoring among survivors included 11 infants (12%) at corrected age of 12 months and 20 infants (23%) by 3 years. At 12 months, 3 infants had incomplete assessments (2 developmentally delayed and 1 uncooperative); at 3 years, 5 infants had incomplete assessments (3 developmentally delayed and 2 uncooperative). These infants underwent pediatrician examinations for cerebral palsy and neurosensory impairments.
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FIGURE 1 Flowchart of 128 infants enrolled in the cohort study with follow-up assessments at corrected ages of 1 and 3 years. Infants with low SVC flow (<41 mL/kg per min) were assigned randomly to volume and dobutamine versus volume and dopamine. a Losses were not cumulative at each time period; b total number of infants assessed at corrected ages of 1 and 3 years with low SVC flow.
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A total of 44 infants (34%) had SVC flow of <41 mL/kg per minute detected in the first 24 hours. Perinatal characteristics and neonatal outcomes of infants with low flow were reported previously.1 Briefly, infants with low flow were of significantly lower gestational age (normal flow: 27.4 ± 1.6 weeks; low flow: 25.8 ± 1.8 weeks; P < .001) and birth weight (normal flow: 1027 ± 276 g; low flow: 916 ± 271 g; P = .03), were less likely to have been exposed prenatally to steroids (normal flow: 96%; low flow: 84%; P = .03), and were unlikely to have been born to a mother receiving antihypertensive agents (normal flow: 25%; low flow: 5%; P = .004). There was no significant association between labor or mode of delivery, but infants with low flow were more likely to be in poor condition at birth, as indicated by increased incidence of 5-minute Apgar scores of <7 (normal flow: 18%; low flow: 34%; P = .04). All infants with low flow received ventilation (normal flow: 85%; low flow: 100%; P = .04). There was a significant association between low SVC flow and higher average mean airway pressure in the first 12 hours (normal flow: 6.7 ± 3.2 cm H2O; low flow: 8.7 ± 2.4 cm H2O; P < .001) but not a larger-diameter (>1.6-mm) ductus arteriosus in the first day (normal flow: 65%; low flow: 75%; P = .3). However, the 80 infants with a large-diameter ductus arteriosus received early targeted indomethacin therapy. Low SVC flow was associated with significant increases in rates of PIVH (normal flow: 20%; low flow: 48%; P < .001), grade 3 or 4 PIVH (normal flow: 6%; low flow: 27%; P = .001), death before discharge (normal flow: 13%; low flow: 57%; P < .001), necrotizing enterocolitis (normal flow: 0%; low flow: 9%; P = .01), and grade 3 or 4 retinopathy of prematurity in survivors (normal flow: 7 of 75 infants, 9%; low flow: 6 of 20 infants, 30%; P = .03). There was no significant association with periventricular leukomalacia (normal flow: 3 of 75 infants, 4%; low flow: 3 of 24 infants, 13%; P = .2).
Neurodevelopment at Corrected Ages of 1 and 3 Years
Of infants with normal SVC flow, 15 died (11 before discharge and 4 after discharge), leaving 69 survivors. Of those, 60 were assessed at corrected age of 1 year and 54 at corrected age of 3 years. Of infants with low SVC flow, 26 died (25 before discharge and 1 after discharge), leaving 18 survivors. Of those, 16 were assessed at 1 year and 13 at 3 years. At 1 year, there was no significant association between low SVC flow and Griffiths GQ or locomotor quotient, the presence of cerebral palsy, or sensorineural impairments (Table 1). Disability was diagnosed for 24% of infants with normal flow and 31% of infants with low SVC flow in the first day.
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TABLE 1 Neurodevelopmental Outcomes at Corrected Ages of 1 and 3 Years, Comparing Infants With Low (<41 mL/kg per minute) and Normal SVC Flows in the First Day
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In univariate analyses at 3 years, low SVC flow was associated significantly with a development quotient >1 SD below the mean for population normative values, a lower mean Griffiths GQ (normal flow: 103.7; low flow: 82.5; P = .005) (Table 1 and Fig 2), and lower quotients for the personal-social, hearing and speech, and performance scales. Trends toward reduced quotients for locomotor, eye-hand coordination, and practical reasoning scales were not significant. Infants with low SVC flow were at substantial and significantly increased risk of death or disability at 3 years (normal flow: 37%; low flow: 79%; P < .001). An assessment for death or disability was possible at 1 or 3 years for 92% of all infants. Low SVC flow was highly predictive of combined death or disability (normal flow: 28 of 75 infants, 37%; low flow: 32 of 43 infants, 74%; P < .001). There were nonsignificant trends toward increased rates of cerebral palsy, hearing impairment, disability, and Griffiths GQ >2 SD below population normative values.
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FIGURE 2 Box plots of Griffiths Mental Development Scale scores at corrected ages of 1 year (A) and 3 years (B) for surviving infants with normal and low SVC flows. Box plots represent the median (line), interquartile range (box ends), and range (whiskers). At corrected age of 3 years, the mean Griffiths GQ for infants maintaining normal SVC flow was 103.7 (SD: 18.2; median: 108.0; interquartile range: 88.1–117.0), compared with 82.5 (SD: 33.0; median: 83.5; interquartile range: 66.4–107.5) for infants with low SVC flow; the adjusted difference in means was –16.53 (95% CI: –29.45 to –3.60; P = .01).
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Multivariate analyses were performed to assess associations between low SVC flow and death (analysis included 128 infants), Griffiths GQ >1 SD below population normative values (66 infants), Griffiths GQ (66 infants), and death or disability at 3 years (107 infants), after correction for perinatal variables (Table 2). Death was predicted by low SVC flow (odds ratio [OR]: 3.89; 95% confidence interval [CI]: 1.23–12.13), gestational age, and 5-minute Apgar score of <7. A Griffiths GQ >1 SD below population normative values was predicted by low SVC flow (OR: 4.36; 95% CI: 1.01–18.83) and SGA status (<10th percentile), and the Griffiths GQ was predicted by low SVC flow (mean difference: –16.53; 95% CI: –29.45 to –3.60) and SGA status (<10th percentile). Death or disability was predicted by low SVC flow (OR: 3.67; 95% CI: 1.19–11.41) and gestational age. The final models explained 61% (Nagelkerke R2) of the variability for death, 23% of the variability for Griffiths GQ >1 SD below population normative values, 24% of the variability for the developmental quotient, and 49% of the variability for death and disability.
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TABLE 2 Regression Analyses for Prediction of Death and Developmental Outcomes at Corrected Ages of 1 and 3 Years
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Dobutamine Versus Dopamine
Overall Findings
Twenty-two infants were initially assigned randomly to volume and dobutamine and 20 to volume and dopamine. Perinatal and baseline cardiorespiratory variables for the 2 groups were reported previously.8 Briefly, the infants were of similar gestational age, birth weight, and gender; prenatal factors and postnatal respiratory morbidity rates were similar between the 2 groups. Baseline hemodynamic variables showed a slightly but significantly lower mean blood pressure (dobutamine: 29.9 mm Hg; dopamine: 26.0 mm Hg) in the dopamine group, a difference that was not reflected in the baseline flow measurements. There were no significant differences for overall clinical outcomes between infants initially assigned randomly to volume and dobutamine, compared with volume and dopamine (Table 3). However, there was a significant reduction in the rate of late grade 3 or 4 PIVH in the dobutamine group (dobutamine: 5%; dopamine: 35%; P = .02).
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TABLE 3 Neonatal Outcomes of Infants With Low SVC Flow Assigned Randomly to Volume and Dobutamine Versus Volume and Dopamine
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Neurodevelopment at Corrected Ages of 1 and 3 Years
By corrected age of 1 year (Table 4), 1 additional infant with severe cerebral palsy and development delay had died after discharge, resulting in infant mortality rates of 64% in the dobutamine group and 50% in the dopamine group. At 1 year, 1 infant in each group was lost to follow-up monitoring. At that time, there were no significant differences in rates of cerebral palsy, Griffiths GQ values (mean: dobutamine: 89.1; dopamine: 83.4), locomotor quotients (mean: dobutamine: 83.1; dopamine: 88.6), or rates of Griffiths GQ >2 SD below population normative values. Rates of disability were similar.
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TABLE 4 Developmental Outcomes at Corrected Ages of 1 and 3 Years for Infants With Low SVC Flow Assigned Randomly to Volume and Dobutamine Versus Volume and Dopamine
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At 3 years, 5 of 18 infants did not attend follow-up assessments, of whom 1 infant in the dopamine group had cerebral palsy diagnosed at 1 year and 2 infants in the dobutamine group were considered to have no disability at 1 year. Of 13 survivors assessed at 3 years, infants in the dopamine group had significantly more disability (dobutamine: 0 of 6 infants; dopamine: 5 of 7 infants; P = .02) and lower Griffiths GQ (dobutamine: 104.2; dopamine: 60.7; P = .02). There were trends toward lower scores for all subscales, with the personal-social scale being the only one to reach statistical significance (dobutamine: 108.8; dopamine: 70.4; P = .01). Combined rates of death or disability at 3 years (dobutamine: 70%; dopamine: 88%) or at the latest time of assessment (dobutamine: 71%; dopamine: 75%; relative risk: 0.95; 95% CI: 0.66–1.38) were not different.
Eighteen infants (43%) failed to increase or maintain SVC flows at >40 mL/kg per minute in response to the initial inotrope to which the infant was assigned randomly (dobutamine: 7 of 22 infants, 32%; dopamine: 11 of 20 infants, 55%; P = .2). Fifteen of these infants crossed over to the other inotrope. The rates of death (responders: 48%; nonresponders: 71%; P = .5) or combined death or disability at 3 years (responders: 64%; nonresponders: 87%; P = .2) or at the latest time of assessment (responders: 64%; nonresponders: 88%; P = .2) were not significantly different for infants who responded, compared with those who failed to respond.
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DISCUSSION
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In very preterm infants, this study found significant associations between low SBF in the first day and death, morbidity, and neurodevelopmental impairments at corrected age of 3 years, despite targeting of infants with low SVC flow (<41 mL/kg per minute) with volume expansion and inotropes, with the goal of improving and maintaining SVC flows throughout the first day. A previous cohort study2,6,9 involved treatment of infants with symptomatic ductus arteriosus with indomethacin and hypotension with inotropes, by physicians blinded to echocardiographic information. That study found that many infants with normal blood pressure had unrecognized low SVC flow and that targeting hypotension resulted in a considerable delay in treatment with inotropes for infants who developed low SVC flow. In the cohort reported here, infants were targeted with early indomethacin therapy for a large-diameter ductus arteriosus and underwent echocardiographic monitoring for low SVC flow. These low flows were treated with normal saline solution and inotrope (dopamine or dobutamine) titrated from 10 to 20 µg/kg per minute, with the goal of maintaining normal SVC flow. Infants crossed over to the other inotrope if the first one failed to maintain SVC flows at >40 mL/kg per minute. The rates of overall death and disability at 3 years were nearly identical for the 2 cohorts (1995–1996: 52%; 1998–1999: 49%), with very similar enrollment criteria and follow-up assessments.
SVC flow was used in this study as the best estimate of SBF, because it was shown previously that shunts between the systemic and pulmonary circulations (ductus arteriosus and foramen ovale) result in ventricular outputs being unreliable estimates of SBF in the first day. SVC flow has also been shown to be a significant predictor of late PIVH,1,2 subsequent motor impairments, and developmental disability.6 The cardiovascular protocol used in this study was designed to compare the effects of commonly used inotropes (dopamine and dobutamine) in infants with low SVC flow. We reported8 that dopamine produced significantly greater increases in blood pressure at both 10 and 20 µg/kg per minute but little change in SVC flow, whereas dobutamine produced little change in blood pressure but a significantly greater increase in SVC flow at the highest dose reached. More than 40% of infants receiving inotropes failed to maintain SVC flows in the first day and crossed over to the other inotrope. In long-term follow-up assessments, infants with low SVC flow in the first day were at substantial and significantly increased risk of death and disability. The developmental impairments were not restricted to motor impairments, as reported previously, but included significant reductions in the personal-social, hearing and speech, and performance quotients. The overall adjusted Griffiths GQ averaged 16.53 points lower (>1 SD) for infants with low flow, representing a substantial important effect on infant development. The analyses of outcomes at the latest time measured (corrected age of 1 or 3 years) was performed to determine whether the results were sensitive to losses at 3 years among infants whose developmental outcome had been assessed previously. That analysis supported the aforementioned conclusions.
Although dobutamine increased blood flow to a greater extent than dopamine,8 there does not seem to have been any obvious clinical benefit, in terms of death or PIVH. Reduced rates of late severe PIVH in infants receiving dobutamine were balanced by no significant difference in rates of PIVH overall. In longer-term, neurodevelopmental, follow-up assessments, there was no significant difference in combined rates of death or disability at any period, with trends toward increased rates of death in the dobutamine group being balanced by trends toward increased rates of disability in the dopamine group. Caution should be used in interpreting the clinical outcomes of this study, in view of the crossover design, which resulted in one third of infants receiving both inotropes, and the small sample size. In addition, dopamine was not titrated to blood pressure, as is usual practice. However, this study was targeting low SBF, not hypotension, and the dose regimen was chosen to reflect commonly used dose ranges and to facilitate blinding of study interventions. The crossover design was used to explore the effects of the inotropes on blood flow and to ensure that each infant received the inotrope that best improved blood flow. A meta-analysis of previous studies that enrolled infants with hypotension also showed no difference in neonatal morbidity or mortality rates between infants assigned randomly to either dobutamine or dopamine.10 However, the small sample size of this study and the limited number of infants included in the meta-analysis limit the power of current data to detect small but potentially clinically important differences in clinical outcomes.
The failure of SBF and organ blood flow in the first 24 hours in extremely premature infants is now becoming well recognized.1,2,12–15 The failure of researchers to demonstrate that standard cardiovascular treatments improve most outcomes for preterm infants12,16–18 may be attributed to a number of factors. Treatments have not been targeted to infants most likely to benefit, including very preterm infants with a hemodynamically significant ductus arteriosus in the first hours, who are most at risk of low SBF.1,2 Instead, indomethacin and ibuprofen have been administered prophylactically to infants, irrespective of spontaneous ductus arteriosus constriction.16 When volume expansion and inotropes have been used, they have almost always been used to treat infants with hypotension,17,18 which is a sign of low vascular resistance, especially after the first day,19 but also occurs late in the pathogenesis of decompensated shock in the first day.1,2,20 Targeting hypotension has the potential to centralize blood flow to vital organs but it does not address the underlying problem of poor myocardial contractility20 and high vascular resistance,1,2,20 which are associated with low SVC flows in the first hours in very premature infants. It may be that treatment of low SBF once it has developed is too late to prevent the associated adverse outcomes. Future studies should consider targeting infants most at risk of low SBF or organ blood flow, to prevent these low flows from occurring.
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CONCLUSIONS
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Low SVC flow in the first day in very preterm infants was associated with substantial mortality and morbidity rates, including late PIVH, necrotizing enterocolitis, and severe retinopathy of prematurity. Developmental follow-up assessments at corrected age of 1 year failed to detect developmental impairments associated with low SVC flow. At 3 years, low flow was associated with substantial delays in a number of areas, as measured with the Griffiths personal-social, hearing and speech, and performance subscales, with overall developmental delay persisting after adjustment for perinatal confounders. Although dobutamine was associated with greater increases in SVC flow and reduced rates of late severe PIVH, there was no significant difference in combined death and disability rates at 3 years, compared with infants receiving dopamine. Studies are required to determine the underlying factors associated with low SBF and to determine effective strategies for prevention of these low flow states.
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ACKNOWLEDGMENTS
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The North Shore Heart Research Foundation and the Australian Government National Health and Medical Research Council provided grants in support of this research.
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FOOTNOTES
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Accepted Mar 27, 2007.
Address correspondence to David A. Osborn, MM, FRACP, PhD, Royal Prince Alfred Newborn Care, Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales 2050, Australia. E-mail:david.osborn{at}email.cs.nsw.gov.au
The authors have indicated they have no financial relationships relevant to this article to disclose.
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PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics
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J Miletin and E M Dempsey
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Arch. Dis. Child. Fetal Neonatal Ed.,
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ABSTRACT
METHODS
