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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 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. 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.

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.

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.

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

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.

Hyperoxia and Hypocarbia in the Immediate Postnatal Period are Associated with Adverse Outcomes of Post-asphyxial HypoxicIschemic Encephalopathy(PA-HIE) † 1047

Peak Serum Bilirubin Levels, Duration of Phototherapy and Adverse Outcome in Extremely Low Birth Weight Infants

HEMORRHAGIC SHOCK IN THE NEWBORN: ANALYSIS OF BLOOD VOLUME LOSS, REPLACEMENT STRATEGY AND OUTCOME. 921

SERUM TRANSAMINASE MEASUREMENTS IN POST-ASPHYXIAL (PA) HYPOXIC ISCHEMIC ENCEPHALOPATHY (HIE). 1743

High-frequency oscillatory ventilation (HFOV) was used to treat 41 infants with persistent pulmonary hypertension of the newborn (PPHN). Of the 37 patients who showed early improvement on HFOV, three died. The remaining 34 patients demonstrated, within one hour of the switchover to HFOV, a rise in mean arterial/alveolar oxygen tension ratio (PaO2/PaO2) from 0.093 +/- 0.041 (SD) to 0.132 +/- 0.051 (p less than .001), and a fall in mean PaCO2 from 42 +/- 10 to 34 +/- torr 9 (p less than .01). Mean airway pressure (Paw) fell significantly (p less than .01) within 12 h. The mean duration of conventional mechanical ventilation before starting HFOV was longer in 13 patients who developed bronchopulmonary dysplasia (BPD) than in 21 non-BPD patients (44.7 +/- 32.3 vs. 19.1 +/- 15.6 h, p less than .002), as was the duration of exposure to Paw greater than 15 cm H2O during that treatment mode (31.8 +/- 21.3 vs. 9.5 +/- 6.0 h, p less than .001). HFOV is often effective in the treatment of patients with PPHN, and early initiation of this type of mechanical ventilation may be associated with a reduced incidence of BPD.

From January 1983 to September 1984 our neonatal ICU (NICU) treated eight endotracheally intubated infants who had suspected airway obstruction characterized by hypercarbia dissonant with severity of lung disease and difficulty in ventilation with lack of chest movement, both on conventional intermittent mandatory ventilation and high-frequency oscillation. Bronchoscopic removal of necrotic tissue was possible in six infants, two of whom survived. Bronchoscopy showed desquamation of epithelial surfaces, leaving encrusted exudations considered to be characteristic of necrotizing tracheobronchitis (NTB). The four nonsurvivors of bronchoscopy and one of the infants not submitted to bronchoscopy had NTB confirmed at autopsy. NTB was not associated with any specific lung disease, humidifier, or ventilator. The autopsy frequency of NTB during this period was 5 per 160 NICU admissions. A separate chart review of unselected autopsied cases in 1981 and 1982 showed that 12 of 284 neonates admitted to the NICU had NTB. NTB appears to be a rediscovered condition related to endotracheal intubation and mechanical ventilation using high mean airway pressures.

Fifteen preterm infants who weighed 0.7 to 2.0 kg and had clinical evidence of a patent ductus arteriosus (PDA) were studied by combined 2-dimensional and Doppler echocardiography before and after the administration of indomethacin. In 10 patients the PDA was widely patent at the time of the study and in 5 the lumen was narrow. In this latter group, the PDA was narrow at the pulmonary artery end in 2 patients, in the middle in 2 patients and at the aortic end and the middle in 1 patient. After the administration of intravenous indomethacin, the PDA closed completely in 12 patients and constricted in 3. The patterns of closure could be documented in those in whom serial studies were performed. In 3 patients, closure occurred after a single dose of indomethacin, in 3 after 2 doses and in the rest after a full course of 3 doses. Doppler interrogation at the aortic and pulmonary artery end of the PDA demonstrated the shunting patterns and provided a reliable assessment of patency after the ductal lumen was outside the range of lateral resolution following constriction. In no case did the PDA reopen after the course of indomethacin. This combined approach is a reliable method of assessing a PDA before and after a course of indomethacin. It should provide the means to answer many of the questions regarding the effect of various manipulations on the PDA in the preterm infant.

Injection of aminoglycosides into a filter chamber was compared with retrograde injection into i.v. tubing for delivery of intermittent drug dosages at low infusion rates in neonates. In 50 infants receiving gentamicin sulfate and 21 receiving amikacin sulfate for at least two days by retrograde i.v. infusion, peak and trough concentrations of the drugs were obtained. A subsequent dose was administered using the filter device, and peak and trough concentrations were obtained. For each infant, the difference between trough and peak concentration (delta C) was compared for the two methods. In vitro testing for gentamicin concentration was performed using the same infusion systems (10 trials for each system). For both in vivo and in vitro testing, the infusion flow rate was 10 mL/hr. For infants receiving gentamicin, delta C was greater for the filter device in 32, greater for retrograde infusion in 13, and equal in 5. The mean gentamicin delta C was significantly greater for the filter chamber method than for retrograde infusion. The in vitro studies showed significantly better gentamicin recovery with the filter device than with retrograde infusion. For amikacin, delta C was greater for the filter device in 15 infants, but the mean amikacin delta C was not significantly different for the two methods. At low flow rates commonly used in infants, the infusion system using the filter device was equal to or superior to retrograde infusion for ensuring complete delivery of intermittent drug doses.