Benjamin S Brann

The Apgar score revisited: Influence of gestational age

We tested the hypothesis that Apgar scores are in part related to the newborn infants level of maturity. Seventy-three pregnant women with normal fetuses of gestational age 22 to 42 weeks were studied. Fetal well-being was documented by a prospectively designed recording of pregnancy history, labor complications, and birth outcome, including cord blood pH and base deficit measurements. The 1- and 5-minute Apgar scores were directly related to gestational age. Respiratory efforts, muscle tone, and reflex were the major determinants for a decreasing Apgar score with declining gestational age. We conclude that the 1- and 5-minute Apgar scores are influenced by the infants level of maturity and that our data may be useful in evaluating the true value of Apgar scores in assessing the fetal and neonatal condition of low birth weight infants.

Granulocyte colony-stimulating factor as a marker for bacterial infection in neonates

OBJECTIVE To evaluate granulocyte colony-stimulating factor (G-CSF) as an early marker of bacterial or fungal infection in neonates. STUDY DESIGN We measured G-CSF levels in infants of varying gestational and postnatal ages. We separated the infants into three groups: group 1, positive bacterial or fungal blood culture result; group 2, negative blood culture result but evidence of clinical sepsis; and group 3, negative blood culture result and no or weak evidence of sepsis. Comparison of mean G-CSF levels by group was accomplished by an analysis of variance. RESULTS One hundred seventy-six evaluations for sepsis were done for 156 infants with gestational ages ranging from 24 to 43 weeks; 50% of these infants were less than 35 weeks of gestational age. The mean G-CSF levels of groups 1 and 2 were significantly higher than those of group 3. The mean G-CSF level of each group was 2278 pg/ml (group 1), 1873 pg/ml (group 2), and 280 pg/ml (group 3) (p < 0.001). On the basis of a cutoff level of 200 pg/ml, the sensitivity of the test was 95%, specificity 73%, positive predictive value 40%, and negative predictive value 99%. CONCLUSION G-CSF levels represent a sensitive marker of infection in neonates of all gestational ages.

Neurologic and developmental status related to the evolution of visual-motor abnormalities from birth to 2 years of age in preterm infants with intraventricular hemorrhage**

We prospectively and longitudinally evaluated neurologic status, cognitive status, and visual-evoked responses in 63 premature infants with cerebral intraventricular hemorrhage, 27 premature infants without hemorrhage, and 22 full-term normal infants. We hypothesized that severe intraventricular hemorrhage (grades III and IV) is associated with impaired visual-motor function, in part because of compression-related injury of the periventricular white matter by ventricular dilation. Infants with grade III or IV hemorrhage had significantly more neurologic sequelae at term and at 3, 7, 12, and 24 months; lower Bayley mental and motor scores at 3, 7, and 12 months; more abnormality on Kohen-Raz subscales for eye-hand coordination, object manipulation, and object relations at 3, 7, and 12 months; and lower Mullen vision-receptive and vision-expressive coordination scores at 24 months. The 12-month visual-evoked response correlated with the 24-month vision-receptive and vision-expressive organization scores for infants with grade III or IV intraventricular hemorrhage (r = -0.49, p less than 0.01, and r = -0.40, p less than 0.05, respectively). The data confirm our hypotheses of increased cognitive and neurologic sequelae, and increased abnormality of visual-motor coordination, during the first 2 years of life in infants with severe (grade III or IV) intraventricular hemorrhage.

Behavioral characteristics and early temperament of premature infants with intracranial hemorrhage

Behavioral characteristics of 12 full-term and 44 premature infants with and without intracranial hemorrhage (ICH) were studied. Cranial ultrasonography prospectively documented Grade I-II ICH in 14, Grade III-IV in 19 and no ICH in 11 premature infants. Examination at corrected age of 40 +/- 2 weeks using the Neonatal Behavioral Assessment Scale showed that infants in the ICH groups had lower levels of arousal and more abnormal reflexes than full-terms. Infants with ICH III-IV displayed less optimal motor responses than full-term infants and diminished orientation responses, especially to visual stimuli. Thus, lower level of arousal, immature motoric processes, and poor visual orientation differentiated premature with ICH from full-term infants, although premature infants without these sequelae, did not differ significantly from full-term infants. The above may represent early manifestations of visual-perceptual and motor problems noted in the follow-up of ICH infants. Further, neonatal behavior was found to affect parent ratings of infant temperament (via the Bates Infant Characteristics Questionnaire) at 3 months corrected age, and the relationships between neonatal behavior and parental ratings differed depending upon the infants gestational age and severity of hemorrhage. We conclude that neonatal behaviors are less optimal in premature infants, and least optimal in premature infants with severe intracranial hemorrhage when compared to fullterm infants.

The in Vivo Effect of Bilirubin and Sulfisoxazole on Cerebral Oxygen, Glucose, and Lactate Metabolism in Newborn Piglets

ABSTRACT. Bilirubin inhibits in vitro oxidative phosphorylation and glycolysis. This study investigated the in vivo effect of bilirubin on cerebral oxygen, glucose, and lactate uptake in newborn piglets. Seventeen 2- to 4-day-old piglets were divided into three groups and examined as follows: group 1 = control (C); group 2 = control with sulfisoxazole; and group 3 = experimental, given bilirubin with sulfisoxazole. In the experimental group, bilirubin was infused for 4 h. The cerebral bilirubin content in the bilirubin-infused group was 11.0 ± 1.4 nmol/g of cerebral cortex (mean ± SEM), consistent with levels found in infants with kernicterus. However, this level of brain bilirubin had no major, acute effects on cerebral uptake of oxygen, glucose, or lactate despite producing lethargy and ataxia which were consistent with bilirubin intoxication. This suggests that mitochondrial changes may not be involved in vivo in acute bilirubin encephalopathy.

Cardiovascular effects of hypoxia/hypercarbia and tension pneumothorax in newborn piglets.

ObjectivesTo test the hypothesis that, in newborn piglets, the presence of a tension pneumothorax modifies the cardiovascular responses to hypoxia/hypercarbia. DesignProspective laboratory study. SettingPerinatal cardiovascular research laboratory at a university school of medicine. SubjectsSeven newborn piglets. InterventionsWe sequentially exposed the piglets to a baseline (control I) measure, hypoxia/hypercarbia, tension pneumothorax with normoxia/normocarbia, and tension pneumothorax with hypoxia/hypercarbia added. Measurements and Main ResultsBrain and systemic blood pressures and blood flow (radionuclide-microspheres) were measured. Hypoxia/hypercarbia resulted in increased brain perfusion (207 ± 61% of control, mean ± SEM, p < .05) and heart perfusion (176 ± 58% of control, p < .05) and decreased gastrointestinal perfusion (-37 ± 9% of control, p < .05). Tension pneumothorax with normoxia/normocarbia reduced the cardiac output (-70 ± 8% of control, p < .05), which was redistributed toward the brain (p < .05) at the expense of the gastrointestinal tract (p < .05). Although this redistribution in cardiac output persisted during tension pneumothorax with hypoxia/hypercarbia added, sustained reductions in cardiac output (-57 ± 11%, of control, p < .01) were associated with smaller increases in perfusion to brain (55 ± 54 vs. 207 ± 61% of control, tension pneumothorax with hypoxia/hypercarbia added, and hypoxia/hypercarbia time periods, respectively, p < .05) and heart (65 ± 49 vs. 176 ± 58% of control, tension pneumothorax with hypoxia/hypercarbia added, and hypoxia/hypercarbia time periods, respectively, p < .05) and larger decreases in blood flow to gastrointestinal tract, pancreas, and kidneys (p < .05) than with hypoxia/hypercarbia alone. ConclusionsTension pneumothorax-induced reductions in cardiac output limit the hypoxia/hypercarbia-mediated increases in perfusion to brain and heart and accentuate the hypoxia/hypercarbia-related decreases in perfusion to kidneys and splanchnic organs. (Crit Care Med 1994; 22:1453–1460)

Cerebral Cortical Blood Flow and Oxygen Metabolism in Normocythemic Hyperviscous Newborn Piglets

ABSTRACT: Our study tests the hypothesis that hyperviscosity independent of arterial O2 content reduces cerebral cortical blood flow, O2 delivery, and O2 uptake. After baseline determinations, ten 2− to 4-day-old awake spontaneously breathing piglets were given an intravenous infusion (5 ml · kg-1, body weight) of concentrated cyroprecipitate, whereas eight controls received normal saline. Cerebral cortical blood flow, arterial and superior sagittal sinus O2 content, whole blood viscosity, hematocrit, blood gases, and plasma fibrinogen concentrations were measured at baseline and 3 h after infusion. No significant changes were observed in the control group. Three hours after the infusion of concentrated cryoprecipitate the experimental group showed an increase in whole blood viscosity, whereas hematocrit and arterial O2 content were unchanged. There was a decrease in cerebral cortical blood flow and cerebral cortical O2 delivery, whereas cerebral cortical O2 uptake was unchanged. We conclude that hyperviscosity independent of arterial O2 content reduces cerebral cortical blood flow and that although O2 delivery was reduced in the newborn piglet cerebral cortical O2 uptake was maintained.

1349 IN VITRO EFFECT OF BILIRUBIN ON DOPAMINE SYNTHESIS IN ADULT RAT BRAIN SYNAPTOSOMES

Bilirubin (BR) can inhibit cyclic AMP-dependent protein kinase activity. To investigate the mechanism of BR neurotoxicity, we studied the effect of BR on production of dopamine, a neuro-transmitter whose synthesis is stimulated by cyclic AMP (c-AMP). We used a synaptosome (SYN) preparation to study dopamine synthesis rate (DSR); in vitro. SYNs, the biochemically functional units of synapses, were isolated by differential centrifugation from the corpus striatum of adult male Sprague-Dawley rats. DSR was quantitated by 14CO2 produced after addition of the labeled precursor, L-(l- 14C) tyrosine. The effect of BR was assessed at 4 different BR concentrations under 2 experimental conditions: basal DSR and 2mM dibutyryl c-AMP (db c-AMP) stimulated DSR. Results as noted in figures, were expressed as % of basal DSR and compared against matched controls. We conclude that while BR has no effect on basal DSR, it does dampen the db c-AMP stimulated synthesis of dopamine in vitro. The data provide evidence for an inhibitory effect of BR on protein kinase-mediated neuro-transmitter synthesis activation.

1360 THE APGAR SCORE REVISITED: DEVELOPMENTAL PATTERNS IN “OPTIMAL” NEWBORNS

The five objective criteria used in the Apgar score to assess the newborn include four signs (tone, reflex irritability, color, respiratory drive) that depend upon developmental maturity. The immature infant, with typically flaccid muscle tone is penalized by the Apgar method for developmental immaturity. We hypothesized that in nonasphyxiated fetuses, Apgar scores should correlate directly with gestational age (lower scores with decreasing maturity). 62 parturients (gestation: 23-42 weeks) were prospectively enrolled. By objective documentation of pregnancy history, labor complications, fetal heart rate tracings, cord blood pH & BE, their fetuses were judged as normal at the time of delivery. Direct relationship between Apgar scores and gestational age following a linear regression (y=.34x-4.8 at 1′, r=0.82; y=.28x-1.6 at 5′, r=0.77) was observed. Analysis of the total score into components reveals heart rate to be least influenced by maturity. Respiratory effort and muscle tone increase with increasing maturity. Skin color improves with development at the 5′ score. Reflex irritability trends upward but with more variability at 1′ than 5′. These data suggest that 1) the standard Apgar score may not be appropriate for the assessment of fetal well-being in premature infants, 2) scores thought representative of asphyxia in more mature newborns may not represent asphyxia in immature infants, and 3) these normative data are useful in the assessment of fetal status at various levels of maturity.

TEMPERAMENT CHARACTERISTICS OF PRETERM (PT) INFANTS AND CONCURRENT NEUROLOGICAL ABNORMALITIES

We have previously shown that prematurity and degree of Intraventricular Hemorrhage (IVH) are related to the temperamental characteristics of the infant at 3 months corrected age (CA). We hypothesized that similar results would be obtained at 7 months CA, and that these characteristics would be related to concurrent neurological abnormalities. Eighty-five infants (15 full-term (FT); 23 PT with no IVH; 20 PT with IVH Grade I-II; 27 PT with IVH Grade III-IV) were assessed with a laboratory behavioral observation of the infants temperament and a neurological examination performed by independent examiners. All PT infants were less positive (p<.05), less sociable (p<.05) and less active (p<.05) than FT infants, replicating our previous findings ac 3 months CA. Both cranial nerves and postural reflex abnormalitites were related to less positive, less active and less reactive behaviors (all p<.05). Head size and tone abnormalities as well as asymetries of tone or reflexes were also related to less reactivity (all p<.05). We conclude that both prematurity and neurological sequelae of IVH, rather than IVH itself, are related to the infants temperament.