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The outcomes of hypoxic-ischemic encephalopathy vary between death and intact survival. The spectrum of long-term morbidity in survivors ranges from mild motor and cognitive deficits to cerebral palsy and severe cognitive deficits. Our literature review reinforces the notion that the spectrum of hypoxic-ischemic encephalopathy outcomes represents a continuum, which has important implications for the prediction of outcome and the indications for intervention. We summarize predictive criteria at 3 time points: the first 6 hours of life, 6-72 hours of life, and at hospital discharge. In this era of neuroprotection, predictive models that aid therapeutic decision making, including the withdrawal of support, need to be revised.

We sought to analyze associations between aberrant hematologic counts and adverse outcome in neonates with hypoxic ischemic encephalopathy (HIE) due to various intrapartum asphyxial insult types and to describe the postnatal changes in counts. Hematologic counts between 0 and 120 hours of age of 316 consecutively admitted neonates with HIE were collected retrospectively. Asphyxial insult types were categorized as acute near-total, prolonged partial, or "mixed." Associations between hematologic counts and adverse outcome by 2 years of age were analyzed. No associations were found between patterns of hematologic counts in the first 12 hours and adverse outcome. Lymphocyte counts peaked in the first 2 hours of age in all insult types (46% had values > 10.0 x 10 (9)/L) and by 4 to 6 hours reached normal levels. Nucleated red blood cell counts peaked between 6 and 8 hours of age and fell to normal levels by 36 to 72 hours of age (56% had values > 1860 x 10 (6)/L). Relatively few subjects had low platelet counts by age 12 hours; the nadir occurred on days 2 to 3. No associations were found between hematologic counts and adverse outcome. The characteristic hematologic changes found are attributable to the asphyxial insults, not to brain injury. Because of inconsistent changes, hematologic counts cannot be used on their own to time asphyxial insults.

We compared neonatal characteristics and adverse outcome rates of neonates with hypoxic-ischemic encephalopathy following (1) prolonged partial asphyxia, (2) acute near-total intrapartum asphyxia, and (3) the two combined. The time course of the insult was determined individually by two authors from obstetric data and neonatal charts. "Severe adverse outcome" was defined as death or severe disability detectable by age 2 years. The asphyxial time course was prolonged partial asphyxia in 167 (45%), acute near-total asphyxia in 96 (26%), combined in 78 (21%), and indeterminate in 34 (8%) patients. Among patients with known time course and outcomes, 212 (67%) had severe adverse outcome and 103 (33%) were free of severe adverse outcome. Severe adverse outcome rates were 61% for prolonged partial asphyxia, 67% for acute near-total asphyxia, and 79% for combined time course asphyxia ( P = 0.025). Long-term outcomes differ according to the time course of the insult; infants with combined time course had the worst outcome.

Aims To describe the base deficit (BD) values and the rate of postnatal recovery of the BD of infants with hypoxic ischemic encephalopathy due to intrapartum asphyxia; and to explore the relationships between the rate of recovery of BD, severe adverse outcome and different time patterns (acute total vs prolonged partial) of asphyxia. Methods Clinical and laboratory data were collected from the neonatal period (n = 244) and outcome data to a minimal age of 1 y (n = 218). Rates of recovery of BD were described in four 60 min blocks of time. The values of rate of recovery were compared between the outcome groups, ignoring correlation structure within subjects and with adjustment by the generalized estimating equations method. Results The BD normalized within 4 h of birth in all but 9 of 244 infants. The rates of recovery of BD in infants with good and severe adverse outcome respectively were 0.11 [95% confidence interval (95% CI) 0.07, 0.14] and 0.09 (95% CI 0.07, 0.12) mmol l(-1) min(-1) over the first 4 h after birth. The rates of recovery were similar with or without buffer therapy, and after acute near-total and prolonged partial asphyxia. Conclusion The BD in the great majority of infants with severe intrapartum asphyxia normalizes within 4 h of birth. The BD recovery rate of infants with adverse outcomes was similar to those with relatively good outcome. The different time patterns of asphyxial episode were not associated with differential recovery profiles.

Objective To evaluate bronchopulmonary dysplasia (BPD), serious brain injury, and severe retinopathy of prematurity (ROP) as predictors of poor long-term outcome in very low birth weight infants. Study design We examined the associations between counts of the 3 morbidities and long-term outcomes in 1514 of 1791 (85%) infants with birth weights of 500-1250 g who were enrolled in the Caffeine for Apnea of Prematurity trial from October 1999, to October 2004, had complete morbidity data, and were alive at 36 weeks postmenstrual age (PMA). BPD was defined as use of supplemental oxygen at 36 weeks PMA. Serious brain injury on cranial ultrasound included grade 3 and 4 hemorrhage, cystic periventricular leucomalacia, porencephalic cysts, or ventriculomegaly of any cause. Poor long-term outcome was death after 36 weeks PMA or survival to 5 years with 1 or more of the following disabilities: motor impairment, cognitive impairment, behavior problems, poor general health, deafness, and blindness. Results BPD, serious brain injury, and severe ROP occurred in 43%, 13%, and 6% of the infants, respectively. Each of the 3 morbidities was similarly and independently correlated with poor 5-year outcome. Rates of death or disability (95% CI) in children with none, any 1, any 2, and all 3 morbidities were 11.2% (9.0%-13.7%), 22.9% (19.6%-26.5%), 43.9% (35.5%-52.6%), and 61.5% (40.6%-79.8%), respectively. Conclusions In very low birth weight infants who survive to 36 weeks PMA, a count of BPD, serious brain injury, and severe ROP predicts the risk of a late death or survival with disability at 5 years.

The contribution of electroencephalogram (EEG) findings early in the course of neonatal bacterial meningitis to the prediction of severe adverse outcome was assessed in a retrospective cohort study. Infants had known outcomes to 1 year of age and an EEG performed during the first week of illness. EEGs were subclassified as follows: overall EEG description, background activity, presence of positive rolandic sharp waves, presence of seizure activity, and presence of focal abnormal activity. EEG patterns predictive of severe adverse outcome were identified by univariate and multivariate analyses. Of 101 infants admitted with bacterial meningitis, 37 had an EEG performed. Of the 37 infants, 21 had adverse outcomes; nine infants died, and 12 infants had moderate or severe disability. EEG background activity and overall EEG description were identified as predictors of adverse outcome; multivariate analysis indicated that the latter was a stronger predictor (sensitivity 88%, specificity 90%). Infants with normal or mildly abnormal EEGs had good outcomes whereas those with moderate to markedly abnormal EEGs died or survived with adverse outcome. The accuracy of predictions increased when EEGs were repeated. In a high-risk population of infants with bacterial meningitis, moderate-to-markedly abnormal EEG reliably predicts adverse outcome.

Objective. To build predictive models of severe adverse outcome at various times in the course of neonatal bacterial meningitis. Study Design. Retrospective cohort study with follow-up to a minimum age of 1 year of term and near-term infants, admitted between 1979 and 1998 to a regional tertiary care center. Predictors of adverse outcome detectable at 1 year of age (death or moderate or severe neurosensory impairment) were identified by univariate analysis. Independent predictors of adverse outcome were identified by multivariate analysis. Predictive tree models were constructed at 12, 24, 48, and 96 hours after admission and at discharge. Results. Of 101 infants admitted with definitive bacterial meningitis, 13 died and 17 had moderate or severe disability at 1 year of age. Outcomes are known for all patients, to 1 year of age. Twelve hours after admission the important predictors of adverse outcome were presence of seizures, presence of coma, use of inotropes, and leukopenia (sensitivity: 68%; specificity: 100%). At 96 hours the predictors were seizure duration of >72 hours, presence of coma, use of inotropes, and leukopenia (sensitivity: 88%; specificity: 99%). Conclusions. Most infants at risk for adverse outcome can be identified within 12 hours of admission. Duration of seizures for >72 hours, presence of coma, use of inotropes, and leukopenia were the most important predictors of adverse outcome. Although these models have good predictive accuracy, they need to be validated in a contemporary cohort in large multicenter studies. bacterial meningitis, neonate, prognostic model.

On the basis of opinions of problematic evidence, Kirpalani et al1 stated that the “standard of care” criteria for adopting hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE) had not been met. They argued for a “conservative approach.” Clinicians who are “impressed” by their evidence are not mandated to offer cooling and can ethically continue to randomly assign patients “into ongoing, or new trials.” Yet, the authors considered the evidence to be “certainly” sufficiently strong for cautious use of this treatment by clinicians who are “impressed with the results.” These apparently conflicting statements are reinforced by previous confusing statements by co-author Barks2: “Many of us, including this author and the lead author [Dr Shankaran] of the Network trial,[3] who caution against uncontrolled adoption of cooling, have lost equipoise, and we are now cooling babies who meet the eligibility criteria of our original trials,” and the semantically elusive, “In a small number of experienced centers, it is a novel therapy that has become ‘standard care’ (without randomization), but it is not yet the ‘standard of care’ (emphasis in the original). Evolution in this field has outdated this conservative approach. One cooling trial (Infant Cooling Evaluation [ICE])4 was stopped prematurely, the research protocol of another has been altered,5 a third trial (Trial of Whole Body Hypothermia for Perinatal Asphyxia [TOBY])6 was stopped at the end of the funding period before achieving its revised sample size, and 3 independent systematic reviews4,7,8 have confirmed the efficacy and safety of cooling. Today's question is whether it is acceptable for individual hospitals or physicians to withhold from parents … Address correspondence to Max Perlman, MB, BS, FRCPC, FRCP, 1711/175 Cumberland St, Toronto, Ontario, Canada M5R 3M9. E-mail: max.perlman{at}sympatico.ca

Objectives: (1) To develop methods to describe autopsy utilization patterns in a neonatal intensive care unit. (2) To identify classes of patients likely to have clinicopathologic concordance or discordance. Methods: Five hundred forty-five consecutive neonatal intensive care unit deaths (338 autopsied, rate 62%) in a regional tertiary/quaternary care neonatal intensive care unit for referred infants (65,000 annual births) were classified in six clinical diagnostic groups (anomalies, cardiac anomalies, hypoxic ischemic encephalopathy, prematurity and its complications, infections, and other) and rated in three levels of certainty of clinical diagnosis as "gold standard" certainty, almost complete certainty, and less certain than the latter. Clinicopathologic discordances were rated in three classes using clinical, pathologic, and multidisciplinary mortality conference records. The proportions of autopsied cases, cases with major discordances, and cases with no discordances were compared and analyzed in relation to diagnostic group and level of certainty. Results: Performance of autopsy was associated with clinical diagnostic uncertainty ( p = 0.008). Major discordances with implications for outcome (Class I) were found in 3%, and without implications for outcome (Class II) in 15% of cases; 42% of cases had no discordances. Major discordance rate varied inversely with the degree of diagnostic certainty ( p = 0.000) and varied among clinical groups. Conclusions: (1) Autopsy was used most for cases with potential for high yields. (2) Clinicopathologic discordances were more frequent and important in certain clinical diagnostic groups (prematurity, other) and with high levels of diagnostic uncertainty. When the diagnostic "gold standard" is available during life, autopsy will provide little information. (J Pediatr 1998;132:75-9)

Objective: To build models that predict severe adverse outcome within 4 hours of birth in patients with postasphyxial hypoxic-ischemic encephalopathy. The goal was to develop models for selecting patients for therapeutic trials of neuroprotective medications. Study design: Retrospective cohort study with follow-up to a minimum age of 12 months of 164 “outborn” term infants admitted to a tertiary neonatal intensive care unit, and 14 “inborn” term infants in the two tertiary perinatal centers in a regionalized setting. After performing univariate screening tests, multivariate models of association between risk factors and “severe adverse outcome” (death or major neurosensory impairment) were constructed. Results: Of 178 infants with postasphyxial hypoxic-ischemic encephalopathy of defined severity admitted consecutively between 1985 and 1992, 48 died, 40 survived with major neurosensory impairment, and 13 were lost to follow-up. The important predictors of severe adverse outcome in the first 4 hours were delayed onset of breathing, administration of chest compressions, and seizures. At 60 minutes of age, based on predicted probabilities of >0.50, the sensitivity of the predictive model was 85% and specificity 68%. The parameter estimates of the predictive models are reported. Conclusion: Age of onset of breathing, administration of chest compressions, and age of onset of seizures were the most important variables predictive of adverse outcome in this study. Although fairly sensitive and specific, these predictive models should be applied with caution. To build more accurate models, a template for the conduct of a large, multicenter prospective study is provided. (J Pediatr 1997;131:613-7)

Multiorgan dysfunction (MOD) is a consistent feature of the postasphyxial newborn infant. MOD is related to the diving reflex which, when activated by asphyxia, shunts blood from the skin and splanchnic region to the heart, adrenal glands, and brain. The presumed goal is to protect these vital organs from hypoxic-ischemic injury. This study examined patterns of involvement of major organ/systems and combinations of these in infants with postasphyxial hypoxic-ischemic encephalopathy (HIE), and associations between dysfunction and the long-term outcome. Outcome data were available for 130 infants who met 1 or more of 4 eligibility criteria: 1) a 5-minute Apgar score below 5, metabolic acidosis, and/or a lack of respiration for 5 minutes or longer; 2) a need for mechanical ventilation at birth; 3) evidence of encephalopathy (altered consciousness and/or seizures); and/or 4) complete functional assessment of the kidneys, cardiovascular system, lungs, and liver. Severe adverse outcomes (death from postasphyxial HIE, severe cerebral palsy diagnosed in the first year of life, mild or moderate cerebral palsy with blindness or deafness in the first year; moderate cerebral palsy with developmental delay at 21-24 months of age) were noted for 80 of 130 infants, 62% of the total. All infants had at least one organ dysfunction in addition to HIE. The incidence of renal, cardiovascular, pulmonary, and hepatic dysfunction ranged from 58% to 88% of infants having a good outcome and from 64% to 86% of those with an adverse outcome. Pulmonary and hepatic dysfunctions were most frequent. The rate of adverse outcomes increased from 1 to 3 as the number of additional organs involved increased from 1 to 3, but decreased when an additional 4 organs were involved. MOD was universally present in these infants with severe postasphyxial HIE, but was not associated with long-term outcomes.

Objective. To study the effect of a single dose of exogenous bovine surfactant on oxygen and ventilatory requirements of neonates with early chronic lung disease. Study design. Prospective pilot study. Setting. Three regional neonatal intensive care units. Methods. Infants 7 to 30 days old with birth weights less than 1500 g were eligible if they required a fraction of inspired oxygen (FIO2) of more than 0.4, had stable ventilatory requirements for 24 hours before study entry, and showed diffuse haziness on chest radiographs. Those with patent ductus arteriosus or active infection or those receiving steroid therapy were excluded. After treatment with the surfactant, differences in FIO2 and the ventilator efficiency index were analyzed using the Wilcoxon signed rank test. Results. Ten patients were recruited. Median values (range): birth weight, 693 g (530 to 1100 g); gestation, 25 weeks (24 to 27 weeks); and postnatal age at study entry, 13 days (9 to 30 days). The FIO2 decreased significantly between 0 and 1 hour after surfactant administration, from a median (range) of 0.67 (0.47 to 0.88) to 0.39 (0.28 to 0.63). This effect was sustained for 24 hours (median FIO2, 0.36). Although the FIO2 subsequently increased to 0.49 (range, 0.35 to 0.88) at 72 hours, it was significantly lower than that entry before the study. There was a trend toward an increase in the ventilator efficiency index at 24 and 48 hours. Conclusions. A single dose of surfactant is effective in reducing oxygen requirements in neonates with early chronic lung disease. Surfactant replacement may be useful adjunctive therapy in these neonates.

Objectives: To analyze secular changes in the rates of death and of major impaired outcome in surviving outborn infants who weighed ≤ 800 gm at birth and were admitted in 1980 to 1989, with adjustment for changes in risk factors and severity of illness around the time of birth; and to identify changes in these factors that might explain changes in outcomes. Design: Retrospective cohort study with follow-up to a minimum of 18 months of postterm age. After preliminary screening, multivariate models of association between risk/severity of illness factors and outcomes were constructed, validated, and used to adjust outcomes (death and major impairment to 18 to 24 months of age). Setting: Regional neonatal intensive care unit for referral of “outborn” infants. Patients: Two hundred eighty-seven consecutively admitted infants who weighed ≤ 800 gm at birth (97% follow-up). Results: The death rate during the 1980s did not fall significantly (p adjusted for risk factors = 0.115). The major impairment rate fell (odds ratio, 0.24 [95% confidence interval, 0.10, 0.60]; p = 0.002, adjusted for delivery route and respiratory failure measures), mainly because of a reduced rate of blindness, not attributable to cryotherapy. The risk factors that improved and were possibly related to the reduced impairment rate were blood pH and glucose concentration, and serum sodium concentration in the first 48 hours of life. Conclusions: Despite an increasing selection for referral of less mature and more severely ill outborn babies near the “limit of viability,” and despite more aggressive care, the rate of major impairment fell significantly during the 1980s. This trend was enhanced by adjustment for severity of illness. The fall was attributable to a reduced rate of blindness, and was associated with evidence of improved control of physiologic balance after birth. (J P EDIATR 1995;126:75-87)

Outcomes at 18-24 months corrected age of very low-birth-weight infants admitted to our Neonatal Intensive Care Unit in 1984-1987 (period 2) were compared with the outcomes of infants admitted in 1980-1983 (period 1) (total 1357 infants). In the 500-750-g birth-weight subgroup, the survival rate increased from 32 to 54% (p = 0.002). Rates of moderate and severe impairment at 18-24 months (neurosensory deficit, or Bayley corrected mental developmental index < or = 68) in this subgroup decreased from 41 to 15% (p = 0.005), and in those without severe impairment, mean mental Bayley scores in periods 1 and 2 were 84 +/- 18 and 90 +/- 16, respectively (p = 0.20). Analysis after exclusion of small-for-gestational-age infants gave similar results. In the small-for-gestational-age infants of birth weight 500-750 g, the survival rate increased but the impairment rate was unchanged between periods. It is concluded that outcomes improved in 1984-1987 compared with 1980-1983 only for infants with birth weight of 500-750 g.

Objective. In light of the paucity of published data on the use of surfactant in full-term infants with respiratory failure due to meconium aspiration syndrome and respiratory distress syndrome, we report our experience with this therapy. Our goal was to explore possible justification for randomized controlled trials of surfactant treatment in similar patients at an earlier, less severe stage of the disease. Methods. Retrospective consecutive case series of 20 infants with severe meconium aspiration syndrome and 29 infants with severe respiratory distress syndrome who received bovine surfactant between March 1990 and December 1992 in three neonatal intensive care units in a regionalized setting. Outcome of treatment was assessed by comparing changes in several respiratory indices including the oxygenation index, between 4 and 6 hours and 1 and 3 hours before and after the first dose of surfactant. Differences were analyzed using analysis of variance for repeated measures, with treatment and time as co-variates. Results. In the meconium aspiration group the mean oxygenation index decreased from 36 ± 12 at 1 to 3 hours presurfactant to 24 ± 14 at 1 to 3 hours postsurfactant (P < .001). In the patients with respiratory distress syndrome the mean oxygenation index fell from 30 ± 17 at 1 to 3 hours presurfactant to 12 ± 6 at 1 to 3 hours postsurfactant (P = .0001). Three of 20 patients with meconium aspiration syndrome and 3 of 29 patients with respiratory distress syndrome received extracorporeal membrane oxygenation. Conclusions. Surfactant therapy in full-term infants with respiratory failure due to the meconium aspiration and respiratory distress syndromes is often effective in improving gas exchange. A randomized controlled trial of surfactant therapy at an earlier stage in the course of the illness should be performed.

Does ‘observational research’ need the approval of a research ethics committee? When is patient or client consent needed? These questions are raised in the correspondence (page 87) arising from the study of feeding problems in neonates with meconium-stained amniotic fluid reported in Paediatrics & Child Health(1). The goal of the study was to determine whether feeding problems are more frequent in neonates with meconium-stained amniotic fluid. To ensure unbiased reporting of problems, the nurses who supervised infant feeding were masked to the maternal and delivery details of the infants, and were not informed of the purpose of the study, and attempts were made to wash off the meconium from the babies with stained skin. Babies recognized by physicians at birth to have contraindications to early feeding were excluded from the study. First, the terms ‘observational study’, ‘research’ and ‘routine care’ should be defined. Observation is the basis for all clinical research, but randomized, controlled, therapeutic trials are usually perceived to be in a unique category, namely, ‘true’ experiments. Observational studies may be based on documentation in archived health records or patient databases maintained by states, insurers, departments or researchers, or may be created prospectively. Nonroutine interventions may have been unplanned or designed prospectively. The observations may be reported individually, or in aggregated and analyzed forms. An observational paper may take the form of a case series, case-control study or cohort study. In the research by Narchi and Kulaylat (1), the authors’ description of their work as a prospective observational study is accurate. Masking of the nursing staff was a planned intervention, not routine practice (see next paragraph). “Research refers to a class of activities designed to develop or contribute to generalizable knowledge” (2). Markers of research, as opposed to routine care, include the gathering of data beyond those required solely for clinical purposes, the alteration of clinical practices in a way that is instrumental for the research, and the intent to publish the results. The present study had all three ‘prospective’ markers. On the other hand, ’routine care’ or ‘practice’ “refer [sic] to a class of activities designed solely to enhance the well-being of an individual patient” (2). The boundary between practice and research may be fuzzy, as suggested by the response of the authors to Dr Springate’s letter (page 87). Space does not permit consideration of all ethical aspects of prospective observational research. Below, the author discusses how, as a member of a research ethics board (REB), he would deal with the questions raised by this study. The ‘policy statement’ on Ethical Conduct for Research Involving Humans (3) forms the basis for the policies and practices of Canadian researchers. Firstly, is REB approval needed for this research? In Canada, “all research that involves living subjects requires review and approval by an REB ... before the research is started” (Article 1.1 [a]) (3). This even includes research involving review of patient records (Article 1.6) (3); in Minnesota, informed consent is also required to review records (4). Research proposals undergo independent scientific and ethical review, owing to the recognition that researchers have an inherent conflict of interest. Scientific review is performed by scientific peers. The determination of compliance with the ethical principles of research in humans must be independent, and the REB membership should include experts in research ethics and the law. Readers who find the notion of independent review superfluous will find an explanation for these demands in the signal paper of Beecher (5) about research completed by some of our older contemporaries and teachers. Would an REB require parental consent for this research? The principle of “respect for free and informed consent” can be waived by the REB in Canada under specific conditions. Among other criteria, the research should involve no more than minimal risk (roughly, the risk associated with everyday life) and not involve a therapeutic intervention (3). Does masking of the nurses represent a therapeutic intervention? In the author’s opinion, yes. Would it have been practical for the researcher to request free and informed consent from nearly 3000 subjects in one year? Probably not. In defining and implementing their responsibilities, nurses increasingly see themselves, and are seen by governments and the law, to be independent of physicians. For example, according to the “Medication Administration Standards” of the College of Nurses of Ontario, the nurse “will assess the appropriateness of the medication as prescribed for the client in the particular situation given” and will “follow up with the physician if the order is believed to be inappropriate” (6). The same would apply to a feeding regimen. Clearly in Ontario, it would not be possible to withhold the clinical information that is needed to evaluate patients or clients from nursing staff. Research ethics questions are difficult to answer, especially when policies and practices are in evolution. Two recent articles about proposed changes to the Helsinki code illustrate the differences of opinion that can exist (7,8). The perceived need to change the code is based to some extent on international variation in approaches to research ethics (7). Moreover, according to one of the commentators: “The right to informed consent does not resonate with all subjects in all cultures” (7). Do standards for research cross national borders? Ethically, probably yes, or at least the World Medical Association thinks so (9). This does not apply to most legal standards, which are, by definition, national. Could an alternative research design, such as a retrospective case-control study, have answered the authors’ question? Given their level of ‘routine’ nursing surveillance of feeding and documentation, probably yes. If the ‘actions of meconium inside the stomach should be studied further’, would a randomized control trial of gastric lavage for infants born with meconium-stained amniotic fluid be feasible? The current state of knowledge as reflected in the paper of Narchi and Kulaylat (1) provides little or no support for such a trial. In summary, as a REB member relying on the Canadian Tri-Council Policy Statement, my answers to the two questions posed at the beginning of this commentary would be as follows. First, consent by the patient, client, parent or guardian would be required in Canada for the conduct of this research, primarily owing to the change made in clinical practice for the purpose of the study. Blinding of the nursing staff “to remove any potential bias in reporting observation of feeding patterns” is undoubtedly an intervention in the Canadian context in which nurses accept and are legislated to have responsibility for their actions. Second, the conduct of ‘observational’ research in which consent is not required, retrospective as well as prospective, has required the approval of a REB since October 1999, but not before that date. These answers may not apply to research conducted in other jurisdictions.

A randomized, controlled trial was conducted to evaluate a new noninvasive system for placement of the endotracheal tube, based on a magnetic field interference-sensing technique. Seventy-two neonates treated by the standard technique were compared with 70 treated by the new system (TRACH MATE), with radiographic localization as the standard. As judged by the author(s) on the morning after the intubation, correct initial placement was achieved in 69 (78%) of 88 intubations using the new system, compared with 71 (66%) of 107 using the standard technique (Fisher's Test, one-tailed, P = .044). Repositioning was actually done in 23 (26%) of 88 TRACH MATE intubations, compared with 42 (39%) of 107 standard intubations (Fisher's test, one-tailed; P = .037). Intubation of the right main bronchus occurred in 7 standard intubations, but in none of the TRACH MATE intubations (Fisher's test, one-tailed; P = .014). Endotracheal tube position (high, low, or appropriate) was correctly determined by TRACH MATE in 77 (90%) of 85 intubations; the position was not recorded on three occasions. No differences in the number of complications (eg, unplanned extubations, distal displacement, subglottic stenosis) were found between the two groups. It is concluded that the TRACH MATE technique is superior to the standard clinical method in initial placement of the endotracheal tube.

Transient symptomatic neonatal hypoglycemia, a diagnosis that is made in the neonatal nursery, is not usually associated with apparently normal infants who have been discharged from hospital. We describe 3 such cases that presented at home on day 3 of life with seizures or life-threatening apneas. We postulate that early discharge of apparently normal infants with marginal nutritional or metabolic adaptation, may expose some infants to postdischarge (but still neonatal) hypoglycemia and its attendant risks.

Platelet counts were studied in preterm infants with the respiratory distress syndrome (RDS), excluding patients with significant perinatal and postnatal hypoxia. Counts fell to a nadir on day 4 (p < 0.000). Exploratory analysis indicated that severity of RDS (levels of FiO2 and mean airway pressure), airleak syndrome, grade of intraventricular hemorrhage (IVH) and low platelet count on day 1 were correlated with low platelet count on days 4 and 5. Further analysis by stepwise removal of each variable demonstrated statistically that FiO2 exerted a unique influence on the change in platelet count between day 1 and days 4/5 (p < 0.002). It is concluded that the severity of RDS is strongly associated with the fall in platelet count in the first few postnatal days. The effect of IVH on platelet count may be secondary to the effect of the RDS.

Objectives To systematically review the effectiveness, as determined by survival without moderate to severe neurodevelopmental disability in infancy and childhood, and the safety of hypothermia vs normothermia in neonates with postintrapartum hypoxic-ischemic encephalopathy and to perform subgroup analyses based on severity of encephalopathy (moderate or severe), type of hypothermia (systemic or selective head cooling), and degree of hypothermia (moderate [≤32.0-33.5°C] or mild [≥33.6°C]). Data Sources MEDLINE, EMBASE, CINAHL (Cumulative Index for Nursing and Allied Health Literature), the Cochrane Library, abstracts of annual meetings of the Pediatric Academic Societies, and bibliographies of identified articles. Study Selection Randomized and quasi-randomized controlled trials without language restriction were assessed by 2 reviewers independently and discrepancies were resolved by involving a third reviewer. Quality of the trials was assessed on the basis of concealment of allocation, method of randomization, masking of outcome assessment, and completeness of follow-up. Intervention Systemic or selective head hypothermia compared with normothermia. Main Outcome Measure Death or moderate to severe neurodevelopmental disability. Results Eight studies of acceptable quality were included. The combined outcome of death or neurodevelopmental disability in childhood was reduced in infants receiving hypothermia compared with control infants (4 studies including 497 infants; relative risk, 0.76, 95% confidence interval, 0.65-0.88; number needed to treat, 6; 95% confidence interval, 4-14), as were death and moderate to severe neurodevelopmental disability when analyzed separately. Cardiac arrhythmias and thrombocytopenia were more common with hypothermia; however, they were clinically benign. Conclusions In neonates with postintrapartum asphyxial hypoxic-ischemic encephalopathy, hypothermia is effective in reducing death and moderate to severe neurodevelopmental disability either in combination or separately and is a safe intervention.

OBJECTIVE: To determine the extent that social variables influence cognitive development of very low birth weight (VLBW) infants across the preschool years. STUDY DESIGN: Participants were VLBW (500-1250 g) children enrolled in the Caffeine for Apnea of Prematurity randomized trial between 1999 and 2004. We investigated the relationships between 4 potential social advantages: higher maternal education, higher paternal education, caregiver employment, and 2 biologic parents in the same home--and gain in cognitive scores. Cognitive assessments were performed at the corrected ages of 18 months (Mental Development Index score on the Bayley Scales of Infant Development II) and 5 years (Full Scale IQ on the Wechsler Preschool and Primary Scale of Intelligence III). Cognitive gain was computed by subtracting each individual 18-month Mental Development Index score from the corresponding Full Scale IQ at 5 years. RESULTS: Data were available for 1347 children. Mean (SD) cognitive scores were 90.8 (15.7) at 18 months and 98.9 (14.5) at 5 years. Multivariable regression showed that higher maternal education, higher paternal education, and caregiver employment had independent and additive effects of similar size on cognitive gain (P < .001); the mean cognitive gain between 18 months and 5 years increased by 3.6 points in the presence of each of these advantages. When all 3 were present, cognitive scores improved on average by 10.9 points compared with children without any of these advantages. CONCLUSION: In VLBW children, a count of 3 social advantages strongly predicts gains in cognitive scores across the preschool years.

Objectives To construct and validate a model and derive a simple rule that is usable in any birth location for the prediction of outcome of term infants with severe asphyxia. Design Retrospective cohort study. Setting Regional outborn neonatal intensive care unit. Participants Infants with postintrapartum asphyxial hypoxic-ischemic encephalopathy (n = 375). Main Exposures Clinical and laboratory predictors available at age 4 hours. Main Outcome Measures A logistic regression model was developed and internally validated (with random sampling and based on the year of birth) for severe adverse outcome, which was defined as death or severe disability (severe cerebral palsy, severe developmental delay, sensorineural deafness, or cortical blindness singly or in combination). A simple prediction rule was derived from 3 variables. Results Complete data were available for 302 (92%) of the 345 infants with known outcomes (204 infants with severe adverse outcome). Six independent predictors of outcomes were identified. Using the 3 most significant predictors (chest compressions, age at onset of respiration, and base deficit), severe adverse outcome rates were 46% (95% confidence interval, 33%-58%) with none of the 3 predictors, 64% (95% confidence interval, 54%-73%) with any 1 predictor, 76% (95% confidence interval, 66%-85%) with any 2 predictors, and 93% (95% confidence interval, 81%-99%) with all of the 3 predictors present. The internal validations revealed a robust model. Conclusions This predictive model for neonatal hypoxic-ischemic encephalopathy provides a sliding scale of probabilities that could be used for prognostication and to design eligibility criteria for decision making including neuroprotective therapy.

While the number of survivors of term hypoxic-ischemic encephalopathy (HIE) is lower than the number of survivors of extreme prematurity, the proportion of neonates with long-term sequelae is higher. All neonates with Sarnat stages 2 (moderate) and 3 (severe) should be enrolled in follow-up programs. The present paper discusses the clinical and imaging diagnostic criteria for HIE, which are essential to decisions about follow-up. Prognostic indicators are also summarized. The recommendations for follow-up and intervention are based on the clinical condition of the baby at the time of discharge from intensive care, including an assessment of feeding, vision, hearing and whether seizures continue to be present. Early assessments (at four to eight months) focus on head growth, general health and motor neurodevelopment. Assessments at 12 to 24 months focus on cognitive skills and language development. Preschool assessments are also strongly recommended to provide for the identification of children requiring early education programs. Knowledge of long-term outcome and its secular changes enhance prognostication, and the evaluation of new preventive and therapeutic approaches.

Objectives. 1) To assess pathology in the heart, kidneys, lungs, liver, and intestine in babies dying of postasphyxial hypoxic ischemic encephalopathy (HIE), and their suitability for organ transplantation. 2) To analyze the correlation between in vivo clinical markers of collateral organ damage and autopsy findings. Study Design. Retrospective cohort study of 58 infants who died of postasphyxial HIE and had autopsies during 1985 to 1994. Collateral organ damage was evaluated clinically and pathologically, and the results compared. Results. Severe pathological changes were observed in 6% to 62% of the five organs studied; 59% of the four major organs had either minor or no pathology. The sensitivity of the clinical predictors ranged from 69% to 100%, and specificity from 50% to 97%. Conclusions. The organs of newborns dying of severe HIE may be suitable for use as donor organs; predictions of their suitability were most accurate for liver, kidney, and lungs, and least accurate for the heart.

Objective To determine clinical outcomes and the prevalence of prothrombotic conditions in patients who had neonatal renal venous thrombosis (RVT). Study design A retrospective cohort of neonates with RVT who were admitted to 4 pediatric centers from 1980 to 2001 was identified. Information on clinical presentation, laboratory and radiological investigation, and treatment were abstracted. Survivors were evaluated for renal status and prothrombotic conditions. Results Forty-three patients with neonatal RVT were identified. RVT was unilateral in 24 patients (56%) and associated with 2thrombi at other sites in 32 patienets (74%). Clinical presentations included renal failure in 24 patients (56%), thrombocytopenia, anemia, or both in 22 patients (51%), and renal mass in 21 patients (49%). Neonatal interventions included anti-coagulants in 28 patients (65%), antihypertensive medications in 9 patients (21%), peritoneal dialysis in 2 patients (5%), and nephrectomy in 2 patients (5%). The median age at follow-up was 3.7 years (range, 0.5-20.2 years). Thirteen patients (34%) had hypertension, and 11 patients (29%) had renal failure. End-stage renal disease developed in 3 patients, and they underwent live-related renal transplants. Twelve of the 28 patients (43%) examined had prothrombotic abnormalities. Conclusion Neonatal RVT is associated with significant renal morbidity and a high prevalence of prothrombotic abnormalities.

Background: Multiorgan dysfunction (MOD) is one of four consensus based criteria for the diagnosis of intrapartum asphyxia. The theoretical concept behind MOD is the diving reflex (conservation of blood flow to vital organs at the cost of non-vital organs). Objectives: To assess the patterns of involvement of each major organ/system and combinations of involvement in infants with post-asphyxial hypoxic-ischaemic encephalopathy (HIE), and to describe this in relation to long term outcome. Design: Retrospective cohort study. Setting: Regional tertiary neonatal intensive care unit at the Hospital for Sick Children, Toronto, Canada. Patients: Term neonates with post-intrapartal asphyxial HIE assessed for kidney, cardiovascular system, lung, and liver function. Outcome: Death and presence or absence of severe neurodevelopmental disability. Results: Out of 130 of 144 eligible infants with outcome data, 80 (62%) had severe adverse outcome and 50 (38%) had good outcome. All infants had evidence of MOD (at least one organ dysfunction in addition to HIE). Renal, cardiovascular, pulmonary, and hepatic dysfunction was present in 58–88% of infants with good outcome and 64–86% of infants with adverse outcome. Conclusions: MOD was present in all the infants with severe post-asphyxial HIE. However, there was no association between MOD and outcome in these infants. No relation between individual or combinations of organ involvements and long term outcomes was observed.

Publication represents the convergence of the activities of researchers, research subjects, research ethics boards, sponsors (industrial, government and others), officials of research institutions, editors, peer reviewers and publishers. For many of these players and their representatives, publication builds careers and leads to personal financial gains. For research subjects and consumers of health care, publication in peer-reviewed journals validates the introduction of new beneficial treatments and new clinical standards. Each of the above groups has its own interests and its own conventional values, as does each individual within each group. Each group and individual may have ethical blind spots, conflicts of interest and temptations, which may lead to violations of ethical principles and practices. Of the examples of misconduct that have marred publication, those that are based on conflicts of interest have attracted much recent attention (1). Here I will focus on violations by researcher-physicians of the privacy of research subjects. The scope of invasions of privacy that can result from publication is illustrated by the three anecdotes below.

Objectives. To analyze, in extremely low birth weight infants, associations between peak bilirubin concentration and evidence of brain damage, and between peak bilirubin concentration and blindness attributable to retinopathy of prematurity. Methods. Retrospective study of 128 infants of ≤800 g birth weight and ≤27 weeks gestation born between 1980 and 1989 and discharged from a tertiary neonatal intensive care unit. After screening analyses, multivariable analyses were conducted to identify associations between blindness and peak bilirubin concentration (dichotomized at different levels to create 3 binary variables), and between severe adverse neurodevelopmental outcome at 18 months postterm age and peak bilirubin levels. Results. Of 128 18-month survivors, 15 had severe visual loss attributable to retinopathy of prematurity, 21 had neurodevelopmental deficit, and 5 were deaf. Visual loss was significantly associated with low-peak serum bilirubin concentration ( Conclusions. In these infants, prolonged phototherapy and low-peak serum bilirubin concentrations were associated with severe visual loss attributable to retinopathy of prematurity. The findings should be interpreted with caution until the evidence is reinforced in other patient populations.

Objective: A recent rapid decrease in the duration of neonatal hospital stay in Ontario, Canada, enabled us to study the association between healthy infants' age at neonatal hospital discharge and subsequent readmission rates. Design: (1) Population-based and (2) single hospital-based retrospective studies. Setting and study population: (1) A total of 920,554 healthy infants with a birth weight of 2500 gm or more, born in Ontario from 1987 to 1994. (2) Infants with a birth weight of 2500 gm or more, born during the same period, and readmitted before 15 days from home to the Hospital for Sick Children for jaundice or dehydration. Measurement: Duration of neonatal stay in the hospital and readmission rates were measured, and diagnostic codes were analyzed. Severity of illness was evaluated in infants readmitted to our hospital. Results: In Ontario the mean length of stay decreased from 4.5 days to 2.7 days ( p = 0.000), and the readmission rate during the first 2 weeks of life increased from 12.9 to 20.7 per 1000 ( p = 0.000). Increased rates of readmission were most marked for jaundice and dehydration. The infants readmitted to our hospital had evidence of increased severity of illness as indicated by higher serum bilirubin and sodium concentrations. Two deaths occurred in infants with hypernatremic dehydration, one in 1992-1993 and another in 1993-1994. Conclusions: In Ontario, shorter neonatal hospital stay was associated with increased readmission rates for conditions that may not give rise to symptoms or signs on days 1 to 3 of life. In our hospital the severity of jaundice and dehydration in readmitted infants increased. The severity-of-illness data raise the question of whether shorter neonatal hospital stay of apparently healthy infants is always safe. Decisions to discharge infants should be based on rigorous evaluation of individual infants. (J PEDIATR 1995;127:758-66)

This study presents an overview of 2515 consecutive autopsies performed on newborn infants who died during the first 28 days of life at The Hospital for Sick Children, Toronto, during the period 1970–89. The infants were grouped into two categories according to their gestational age, then subdivided into groups of early (0–6 days) and late (7–28 days) neonatal death. Trends in the occurrence of neuropathologic observation were documented. For each 5-year period and each gestational group, the following diagnoses were recorded: hypoxic-ischemic neuronal changes, periventricular leukomalacia, infarction, kernicterus, meningitis, and hemorrhage (subependymal, parenchymal, choroidal). Over these 20 years, our results show that death in preterm infants decreased because of a drop in the incidence of subependymal hemorrhage/intraventricular hemorrhage, kernicterus, and meningitis but increased in term infants as a result of a higher frequency of hypoxic-ischemic neuronal necrosis and choroid plexus hemorrhage.

Sixty-one parents of 43 neonates in a neonatal intensive care unit were interviewed within 3 days of their first conference with the neonatologist to assess their needs for medical information. The conference with the physician and the interview with the investigator were audiotaped. Information given by the physician and information recalled by the parents was categorized and rated by the investigator. The physicians gave very detailed information about diagnosis in 77% of cases whereas 39% of the parents recalled diagnostic information in great detail. Respective percentages for prognosis were 16 and 33; for current management (eg, investigation, therapy), 28 and 66; and for cause of illness, 16 and 18. The statistical significance of the differences between the very detailed information in the physician-parent conferences and in the parent-investigator interviews was, by category

* Abbreviations: ICU = : intensive care unit • NTISS = : Neonatal Therapeutic Intervention Scoring System • SNAP = : Score for Neonatal Acute Physiology • VLBW = : very low birth weight • NICU = : neonatal intensive care unit Severity of illness scores, based on deranged physiology, are used to compute the probability of the risk of death of severely ill patients. An original goal was to use these predictions to “provide a reproducible and empiric basis for decisions to forgo treatment.”1 This goal has not been realized.2–5 A second use of severity scores is to compare outcomes such as mortality rate between intensive care units (ICUs), physicians, or periods. By adjusting outcome rates for initial severity of illness at or soon after admission or birth (zero-time), the rates can be compared “on a level playing field.”6 The adjusted rates might be used as putative indicators of health care provider quality, or “report cards.”7 These could “inform revisions in health care financing and structure.”1 Richardson et al pioneered models of risk adjustment for neonates, based on therapeutic (Neonatal Therapeutic Intervention Scoring System [NTISS]) as well as pathophysiologic measures (Score for Neonatal Acute Physiology [SNAP]).8 They now report a reduction in risk-adjusted mortality rate of very low birth weight (VLBW) infants between 1989–1990 and 1995.9 The first outcome year … Address correspondence to Max Perlman, MB, BS, FRCP, Division of Neonatology, Department of Paediatrics, Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8.

Based on limited anecdotal evidence, glucagon is used for the management of intractable neonatal hypoglycemia persisting in the face of high glucose administration rates.To evaluate the short-term response of blood glucose levels to an intravenous infusion of glucagon.A retrospective observational study in which all newborns who received glucagon infusions (usual dose, 0.5-1 mg/d) during a 5-year period were identified (N = 55). The common causes of hypoglycemia were perinatal stress, intrauterine growth restriction, prematurity, and maternal diabetes mellitus. Laboratory blood glucose measurements made between 24 hours before and 72 hours after the start of the glucagon infusion and the rates of glucose administration during the same period were analyzed. The effects of glucagon on sodium and platelet levels were also examined.University referral hospital.A statistically and clinically significant rise in blood glucose concentration, from a mean of 36.3 to 93.0 mg/dL (2.02-5.17 mmol/L), was observed within 4 hours of starting glucagon administration. The change was unrelated to the cause of the hypoglycemia. The frequency of hypoglycemic episodes was significantly reduced, and no further episodes of severe hypoglycemia (glucose level,20 mg/dL [1.1 mmol/L]) occurred. Five patients, 4 of whom were preterm newborns with intrauterine growth restriction, required additional glycemic treatment. Seventy-five percent of newborns were thrombocytopenic before starting glucagon infusion, and in 9 newborns platelet counts decreased following glucagon infusion. There was no hyponatremia attributable to glucagon.Glucagon infusions appear to be beneficial for problematic neonatal hypoglycemia of different causes.

(2001) BMJ 323, 533. Bedford H, de Louvois J, Halket S . , et al. . Meningitis in infancy in England and Wales: follow up at age 5 years. . Sep 8; . : . –6 . [OpenUrl][1][Abstract/FREE Full Text][2] QUESTION: In children who survived meningitis during their first year of life, what are the sequelae at 5 years of age? Inception cohort of children who survived an acute attack of meningitis in their first year compared with children who did not have meningitis. General practices in England and Wales, UK. 1717 children who contracted meningitis during their first year. Sex- and age-matched children from the same general practice as the index child formed the control group. Data at 5 years of age were available for 1584 children (92%) who had had meningitis and 1391 in the control group (94%). General practitioners completed questionnaires on children that described any problems in neuromotor development, learning, vision, hearing, speech and language, and behaviour, and the presence of seizure disorders. Parents completed questionnaires on their child's health, development, and schooling. Gestational age, birthweight, the organism that caused the meningitis, and age at … [1]: {openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DBedford%26rft.auinit1%253DH.%26rft.volume%253D323%26rft.issue%253D7312%26rft.spage%253D533%26rft.epage%253D533%26rft.atitle%253DMeningitis%2Bin%2Binfancy%2Bin%2BEngland%2Band%2BWales%253A%2Bfollow%2Bup%2Bat%2Bage%2B5%2Byears%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fbmj.323.7312.533%26rft_id%253Dinfo%253Apmid%252F11546697%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=bmj&resid=323/7312/533&atom=%2Febmed%2F7%2F2%2F60.atom

Source Citation Moyer VA, Ahn C, Sneed S. Accuracy of clinical judgment in neonatal jaundice. Arch Pediatr Adolesc Med. 2000 Apr;154:391-4. 10768679

Association between Timing of Asphyxial Episode and Distribution of Central Nervous System (CNS) Injury in Human Infants

Variability of serum AST and ALT measurements in infants with moderate to severe post-asphyxial hypoxic-ischemic encephalopathy (PA-HIE) suggests variable efficiency of the Diving Reflex 1112

Delayed diagnosis of the cause of severe CNMD with MVD prolongs parental uncertainty, delays decision making, and increases NICU costs. Objective: To compare time to diagnosis in patients with CNMD and MVD with “ideal” time to diagnosis based on a diagnostic algorithm. Methods: The time to diagnosis of a consecutive series of patients (1987-1996) with CNMD and MVD admitted on day 1 was compared to the“ideal” time to diagnosis using a diagnostic algorithm. Our“ideal” investigation consists of pertinent workups for sepsis, congenital infections, chromosome and metabolic disorders on day 1, MRI(CT) and testing mother for myotonic dystrophy (MD) on day 2, and if a clear diagnostic pathway is not established, EMG and DNA test for MD on day 3. All investigations including a muscle biopsy, if indicated, can be completed by day 8. Exclusions: apneic episodes without MVD, cervical spinal cord injury, and acute encephalopathies. Results: Of 22 patients admitted, therapy was withdrawn in 19, of which 16 died. 2 had dysgenetic brain, 1 Zellweger's syndrome, 1 nemaline rod, 1 centronuclear, and 1 myotubular myopathy. The chromosome disorders were not suspected before test results were received. Numbers in brackets in the table refer to numbers of patients. Using the algorithm, mean age of diagnosis could have been shortened by 7d for a central cause, by 16d for a chromosomal (Chrom) disorder, by 19d for a myopathy, and by 15d for MD. Of the patients who died, the sum of hospital days to diagnosis was 259. Conclusion: Time to diagnosis can be shortened by implementing a diagnostic algorithm. Of the patients who died, the total hospital days to diagnosis could have been reduced by 66%.

Decreased Placental Transfusion may Lead to Persistent Pulmonary Hypertension of the Newborn (PPHN) 1156

Rationale: Data in the perinatal animal and adult trauma patient suggest that the timing and severity of blood volume (BV) loss and rapidity and degree of BV replacement are important determinants of outcome in HS. Objective: To identify and analyze the importance of risk factors for adverse outcome. Methods: Retrospective data collection on 34 cases admitted from 1985-1994 (HSC) and 10 cases from 1988-1994 (MSH, WCH). Inclusion criteria: ≥34 wks gestation and HS at birth defined as severe pallor with reduced or absent pulses despite a HR of >100 bpm and a calculated BV loss of >25% (21 mls/kg). Exclusions: internal hemorrhage, chronic blood loss, or hemolysis. Adverse outcome included death or survival with severe neurological disability. Univariate analyses compared groups by adverse or good outcome. Results: Are expressed as median values(interquartile range). GA was 40 (37-40) wks, BW 3135 (2707-3535) g and the calculated BV loss was 48 (39-57) mls/kg. Five patients were lost to follow up and 19 of 39 (49%) had adverse outcomes: 11 died, 6 had severe CP and 2 had severe cognitive delay. Etiology of HS (cases with adverse outcome/total) included: placental abruption (5/14), fetomaternal hemorrhage (3/5), vasa praevia (4/4), umbilical cord tears (2/2), twin-to-twin transfusion (2/2), placenta praevia (1/2), tight nuchal cord (0/2), placental incision (0/2) and indeterminate (2/10). Group differences in Obstetrical factors (presence and timing of CTG abnormalities, occurrence of APH), and volume and timing of BV replacement were not statistically significant. Patients with adverse outcomes had greater blood losses of 54 vs. 44 mls/kg (p=0.03), a lower 5 minute Apgar score of 1 vs. 4 (p=0.006), greater base deficit of 21 vs. 12 mmol/l(p=0.006), and tended to have a longer interval from onset of HS to first volume replacement of 410 vs. 106 mins (p=0.19). Severe encephalopathy, seizures, DIC, myocardial ischemia, and severe renal dysfunction were strongly associated with adverse outcomes. Conclusions: Risk factors for adverse outcome included the magnitude of blood loss, severity of metabolic acidosis and depression at birth, and the presence of severe organ dysfunction. Length of time from onset of HS to first volume replacement, although not statistically significant, is likely to be a risk factor for adverse outcome.