Search

Limits of viability of extremely premature infants have recently been addressed both in Europe and the United States. These reports, which demonstrate frequent adverse outcome of infants born before 26 weeks of gestation, have not considered the impact of surfactant therapy. We reviewed records of 445 infants born between 23 and 36 weeks gestation who were admitted to our nursery following the availability of surfactant treatment in 1986 through 1992. Two hundred and eighty-five infants were treated with surfactant (Survanta, Ross Laboratories) as part of controlled, prospective trials or as routine treatment under Food and Drug Administration approval. One hundred and fifty-six infants were unable to be treated with surfactant, as either they received placebo therapy during prospective trials or were born prior to approval of routine surfactant use in the United States. Four additional infants born following the commercial availability of surfactant did not receive surfactant therapy. Survival of untreated infants was 56% compared to 75% in treated infants (P < 0.001). Infants born at all gestational ages between 23 and 26 weeks had an increased likelihood of survival as a result of surfactant treatment. No differences in neurologic outcome between surfactant treated and non-treated infants were demonstrated at subsequent follow-up. We conclude that survival of extremely premature infants is improved following surfactant therapy and that subsequent neurologic outcome is not compromised as a result of this therapy.

Routine ACT tests cannot distinguish between prolonged blood clotting due to heparin effect or acquired abnormalities of the coagulation system after a loading dose of heparin. The purpose of this study was to examine an ACT test that inactivates heparin with Heparinase allowing for ACT assessment with and without heparin effect (HR-ACT with/without Heparinase, HemoTec, Inc.). The HR-ACT values were compared with the standard OR procedure that employed the Hemochron ACT. Twenty pediatric patients undergoing cardiopulmonary bypass for repair of cardiac defects were examined. All comparative ACT values were obtained from the same blood sample. Five sampling times were examined: 1) A baseline ACT was obtained before heparin had been administered; 2) A pre bypass ACT after a single heparin dose; 3) On bypass; 4) A post protamine ACT at the conclusion of surgery; and 5) In the Intensive Care Unit (PICU), 1 hour post protamine. The HemoTec HR-ACT with Heparinase and HR-ACT tests differentiated clotting time results that reflected coagulation status without the heparin effect. It identified those patients on bypass who were less than 5 kg, with prolonged ACTs that were due in part to hemodilution despite efforts at hemoconcentration.

A critical appraisal of four cohort studies examining the relationship between Ureaplasma urealyticum and chronic lung disease (CLD) of prematurity is presented. Three studies were concurrently conducted, but the fourth was conducted 4 years later when surfactant replacement was a widespread practice. Although infants were enrolled in all studies soon after birth before they had developed CLD, there were differences in patients population, the definition of colonization with U. urealyticum, neonatal management, and the definition of CLD of prematurity. Despite the differences, all four studies found an association between colonization and development of CLD of prematurity. A combined estimate of relative risk for the four studies was 1.91 (95% confidence interval, 1.54-2.37). When infants were categorized into groups by birth weight, the association was not observed in infants who weighed > 1,250 g. The association was also not observed in infants who weighed < 750 g, but the risk of CLD of prematurity in the uncolonized control group was already 82%. Because the cohort study design allows for the possibility that one or more additional factors associated with U. urealyticum may be the true cause(s) of CLD of prematurity, there is strong but not definitive evidence that U. urealyticum causes CLD of prematurity.

This study examined the association between Ureaplasma urealyticum colonization and the development of chronic lung disease (CLD) in 93 premature infants who were treated with surfactant and who had birth weights < 1251 g. Nasopharyngeal and tracheal cultures for U. urealyticum were obtained at 2 +/- 1 and at 14 +/- 1 days after birth and were positive in 17 (18%) of 93 patients. Infants born vaginally were 4.5 times more likely to be colonized than were those born by cesarean section. Colonization with U. urealyticum was associated with 1.66 (95% confidence interval, 1.24-2.20, P = .024) times the risk of developing CLD and with a greater incidence of > or = 2+ polymorphonuclear leukocytes in the tracheal aspirate at 2 +/- 1 days of age compared with uncolonized infants (P = .025). We conclude that U. urealyticum colonization is associated with CLD even after surfactant treatment. The presence of U. urealyticum is also associated with inflammatory cells in the tracheal aspirate.

This study measured Fc gamma receptor (FcR) expression on polymorphonuclear leukocytes (PMN) and monocytes from extremely premature infants. Flow cytometry was used to quantitate FcRIII [cluster of differention (CD) 16], FcRII (CD32), FcRI (CD64), CD14, and CD67 proteins on the PMN surface. Sixty-four premature infants with a mean gestational age +/- SD of 26 +/- 2 wk (birth weight = 847 +/- 217 g), 12 infants born at term (gestational age = 38 +/- 1 wk), and 37 adults were studied. Premature infants' PMN expressed less FcRIII, measured as mean log channel fluorescence (MCF), than did term infants or adults (MCF = 4.7 +/- 1.4, 6.1 +/- 1.0, and 8.8 +/- 1.8, respectively, p < 0.050). Premature infants also had a lower proportion of FcRIII-positive PMN than term infants or adults (mean +/- SEM = 0.83 +/- 0.02 versus 0.92 +/- 0.04 and 0.96 +/- 0.01, respectively, p < 0.050). FcRIII expression on PMN was positively associated with cell isolation procedures (p = 0.004), birth weight (p = 0.004), and postnatal age (p = 0.032). Premature infants also had lower PMN expression of FcRII when compared with adults and term infants (MCF = 2.4 +/- 0.6 versus 3.0 +/- 0.7 and 3.1 +/- 0.3, p < 0.050). Both premature and term infants had fewer FcRII positive PMN than did adults (mean +/- SEM = 0.90 +/- 0.09 and 0.89 +/- 0.07 versus 0.99 +/- 0.00, p < 0.050). Premature infants' monocytes also expressed significantly less FcRIII (MCF = 2.4 +/- 0.6 versus 3.4 +/- 0.9, p = 0.047) and FcRII (2.1 +/- 0.5 versus 2.9 +/- 0.6, p = 0.01) compared with adults. We conclude that extremely premature infants have decreased expression of FcRIII and FcRII on both their PMN and monocytes when compared with adults. The decrease in PMN FcRIII expression appears related to birth weight and chronologic age.

Previously reported activated clotting time (ACT) data in adults demonstrated higher values with the HemoTec LRACT (HT) and TriMed ACTivator (TM) techniques than with the Hemochron System P214/215 (HC) technique throughout a range of heparin concentrations. This study sought to determine if a difference exists in ACT values of neonatal patients receiving ECMO. ACTs were performed in nine neonatal ECMO patients using the HC, HT, and TM techniques. Techniques were compared for positive or negative direction of any prediction difference (bias), and the typical value of a difference (precision). Simultaneous, duplicate, morning, and afternoon ACT comparisons were obtained using all three techniques. Forty-six comparisons of HC values in the 180-240 sec range were analyzed. All techniques produced results different from the same sample. The HT and TM techniques were upwardly biased by 51 and 148 sec, respectively, when evaluated against HC. HT was negatively biased by 123 sec when evaluated against TM. Because ACT values vary among techniques, ACT target ranges should be technique specific. Future references to ACT data should identify the equipment and procedures employed.

Theoretical advantages and risks exist for the use of both the centrifugal and roller pump systems in neonatal extracorporeal membrane oxygenation (ECMO). The authors studied the pressure-volume-flow relationships in clinically configured ECMO systems using these two pumps and a simulated patient to characterize differences in the circuit mechanics of the two systems, and thereby improve the design of subsequent clinical comparative trials of the pumps themselves. The relationship between flow and pressure generated across the pump was identical for the two systems. Within the range of clinically used flows, there was a direct relationship between pump revolution and flow with the roller pump, and between pump revolution and pressure generated for the centrifugal pump. Flow was limited in both systems by restrictions on negative pressure generating capacity. In the roller pump circuit, the venous reservoir (bladder box) assembly interrupted flow when negative pressure exceeded -20 mmHg; in the centrifugal pump system, forward flow stopped when negative pressure exceeded -100 mmHg. Volume had no detectable effect on the patient-pump inlet pressure gradient until critically low volumes were reached. At that point, removal of a few milliliters of volume led to large increases in the pressure gradient. The authors conclude that differences in pressure-volume-flow relationships between roller and centrifugal pump ECMO systems are due to the presence of the bladder box in the roller pump circuit. The advantages and disadvantages of the greater negative pressure in the centrifugal pump system require further study.

From January 1986 through December 1988, we have seen 7 cases of isolated intestinal perforation in 250 infants with birth weights less than 1,000 g (3% incidence) without histological or clinical evidence of necrotizing enterocolitis (NEC). Patients had a mean birth weight of 670 g, gestational age of 25.1 weeks, and sustained a perforation at a chronological age of 10.4 days. No infants had been fed. A definite, blue-discolored abdomen was the only consistent clinical sign (n = 7). Free intraperitoneal air on radiograms was rarely observed (n = 1). Abdominal ultrasounds (n = 3) and metrizamide contrast studies (n = 3) were not diagnostic. The presence of an umbilical artery catheter (7/7), falling hematocrit (6/7), thrombocytopenia (5/7), and a positive diagnostic paracentesis were most commonly found. In 6 of 7 patients, this perforation was associated with coagulase-negative staphylococcal sepsis. Surgical or histological diagnosis showed focal perforation in either the terminal ileum (n = 4) or the transverse and descending colon (n = 3). Survival was 3 of 7; 2 patients died of intracranial hemorrhage and 2 died of Candida sepsis. We conclude that (1) intestinal perforation can occur in the absence of NEC; (2) bluish discoloration of the abdomen is the most reliable clinical finding; and (3) perforation may be associated with coagulase-negative staphylococcal infection.

This study compared the results of a commercially available, direct fluorescent antibody (DFA) test with viral culture in 880 specimens obtained from 690 patients by means of nasopharyngeal swabs. The two tests were congruent in 92.5% (814) of the specimens. The sensitivity of the DFA was 0.95, the specificity was 0.91, the positive predictive value was 0.82, and the negative predictive value was 0.98. Among 548 inpatients, there were 3 mixed infections (RSV and another virus), 8 RSV infections not identified by the DFA, and 35 positive DFA results not confirmed by cell culture. Use of the DFA test alone would have resulted in 502 (92%) correct patient-placement decisions. We conclude that the DFA test provides reliable evidence on which to base patient-placement decisions but that the error rate is too high to permit safe cohorting of high-risk patients, such as those with bronchopulmonary dysplasia.

Whole blood activated clotting time (ACT) can be determined by many different methods that use a variety of clotting cascade activators and end-points. This study compared the results of three whole blood ACT instruments at equivalent concentrations of heparin. Whole blood (9.8 ml) from 10 healthy adult volunteers without coagulation abnormalities was added to 0.2 ml of heparin solution producing heparin concentrations of 0, 0.1, 0.2, 0.4, 0.6, 0.8, and 1.0 U/ml. Coagulation status was determined in duplicate with the Hemochron 400 System (HC), the HemoTec Automated Coagulation Timer (HT), and the TriMed ACTivator (TM). Thrombin times or dilutions (TT) were also determined for each sample. Baseline values did not differ (p greater than 0.05); however, the HT and TM ACT values were significantly longer (p less than 0.05) than the HC ACT values at predicted heparin concentrations greater than 0.2 U/ml. Results from the HT and TM instruments were not significantly different. The HT and TM instruments both provided a greater ACT range over the heparin concentrations tested. Of the tests studied to monitor heparin therapy, mean scaled TTs showed the best correlation with predicted heparin concentrations.

This study compared six extracorporeal membrane oxygenation (ECMO) selection criteria in 42 neonates and analyzed factors influencing the accuracy of outcome predictions. The sensitivity of the criteria in identifying fatal cases varied from 0.44 to 0.94 and the specificity of predictions of survival ranged from 0.42 to 0.69. The criterion having the highest sensitivity had the lowest specificity and conversely the criterion with the lowest sensitivity had the highest specificity. Overall accuracy of the criteria, as measured by the total number of correct outcome predictions, differed little among the criteria (23/42 to 27/42 correct predictions). Three factors influenced predictive accuracy: 1) a primary diagnosis of congenital diaphragmatic hernia (CDH) was associated with a greater mortality (P less than 0.001) and a significantly higher positive predictive value (PPV) for all criteria (P = 0.0009-0.012) than that seen in patients with other primary diagnoses; 2) calculating the alveolar-arterial oxygen gradient using an assumed, rather than measured barometric pressure, or estimating oxygenation index using a calculated, rather than a measured, mean airway pressure, increased false positive mortality predictions in non-CDH patients; and 3) requiring a peak inspiratory pressure (PIP) of at least 50 cm H2O in the definition of maximal medical management, rather than a PIP of 20-49 cm H2O, significantly increased the PPV for three of four criteria examined (P = 0.02-0.04). Awareness of these factors may facilitate the identification of neonates who need ECMO to survive.

This study examined the effect of immunoglobulin A (IgA) and the IgA-binding lectin jacalin on the phagocytosis of type II group B streptococci (GBS). Strains possessing the trypsin-sensitive and trypsin-resistant components of the c protein (II/c) and type II GBS lacking the c protein (II) were examined by radiolabeled bacterial uptake, bactericidal assays, and electron microscopy. Type II/c GBS resisted phagocytosis by monocytes (4.9% +/- 0.8% uptake, mean +/- SE, n = 25) compared with type II GBS (8.5% +/- 1.4% uptake, n = 14, P = 0.03). Phagocytic killing by polymorphonuclear leukocytes was also less for the type II/c strain 78-471 than for the type II strain 79-176 (68% +/- 5% versus 86% +/- 4% reduction in CFU at 45 min, P = 0.03). IgA binding did not explain the resistance of type II/c GBS to phagocytosis. The uptake of type II/c GBS was not significantly different after opsonization in cord sera lacking endogenous IgA (5.93% +/- 1.4%) than in the same cord sera after addition of exogenous IgA (5.48% +/- 1.4%, P = 0.69, n = 9). Attempts to remove serum IgA with the IgA-binding lectin jacalin resulted in the binding of IgA-jacalin complexes to II/c GBS. This combination of nonspecific IgA and jacalin increased uptake of II/c GBS from 4.9% +/- 0.8% to 11.8% +/- 1.9% (P = 0.002). Jacalin also combined with specific, immune, monoclonal IgA bound to the surface of Haemophilus influenzae and promoted the uptake of these bacteria. Jacalin and IgA mediated phagocytosis of II/c GBS via receptors that were not dependent on divalent cations and that were not modulated by plating monocytes on antigen-antibody complexes.

The binding of 125I-labeled human myeloma immunoglobulin A (IgA) to four type II strains and one nontypable strain of group B streptococci was measured after streptococcal chains were broken by brief sonication. Some IgA binding was observed with all strains, but specific binding (binding that was inhibited by excess unlabeled IgA, was dose dependent, and was saturable) occurred only with those strains possessing the trypsin-sensitive beta component of the c protein. Similar amounts of binding were observed with myeloma IgA and IgA1 purified from normal serum. Specific binding was more rapid at 25 degrees C than at 0 or 37 degrees C and reached a plateau in 6 to 8 h. Binding was drastically reduced (85 to 90%) when streptococci had been heated (90 degrees C for 1 h). Most radioactivity bound to group B streptococci could be displaced (greater than 60% in 3 days) by the addition of excess unlabeled IgA. The binding capacity of one strain (10(8) streptococci in 1 ml of buffer) was saturated by approximately 24 micrograms of IgA. When transformed for Scatchard analysis, these data indicated that there was a specific binding capacity of 16,000 molecules of monomeric serum IgA per single streptococcal cell. The dissociation constant for IgA binding was 19.3 nM. Since enzyme-linked immunosorbent assay studies showed that the myeloma IgA used for the studies described above was IgA1, our quantitative data apply only to the binding of this subclass to group B streptococci. However, an enzyme-linked immunosorbent-filtration assay showed that both IgA1 and IgA2 bound to a type II group B streptococcus bearing the c protein.

Thirty-one type II and eight nontypable group B streptococcal isolates were categorized by the presence of the trypsin-resistant and trypsin-sensitive components of the Ibc protein antigen and studied for opsonization differences by using polymorphonuclear leukocyte chemiluminescence (CL). Type II strains varied in their ease of opsonization: strains possessing both components of the Ibc protein elicited a significantly lower mean CL peak (P less than or equal to .05) and a smaller CL integral (P less than or equal to .01) than did type II strains lacking both components or strains lacking type polysaccharide antigen but possessing the Ibc protein antigen. These strain differences were seen consistently with different sera and were also observed in an opsonophagocytic killing assay. Differences in opsonizing ability and bacterial killing were found for three standard test sera but could not be related to the concentration of type-specific antibody to capsular polysaccharide antigen. Our studies suggested that the Ibc protein antigen was one factor that contributed to the resistance to opsonization of strains of type II group B streptococci.

This study analyzed the clinical characteristics of 69 neonates who were admitted to the University of Minnesota Hospital between January, 1972, and June, 1984, with early onset Group B streptococcal infection (EOGBS) and determined those features associated with fatal infection. The incidence of EOGBS was 1.6 cases/1000 live births among 7960 inborn infants; the mortality rate for inborn and outborn infants was 28%. Multivariate analysis identified five features adequately predicting fatal outcome: birth weight less than 2500 g, absolute neutrophil count less than 1500 cells/mm3, hypotension, apnea and a pleural effusion on the initial chest radiographs. With these five variables and an initial blood pH less than 7.25, a clinical score was constructed that correctly predicted outcome in 93% of patients in this study (87% sensitivity, 95% specificity). Autopsy findings in 16 of 19 infants with fatal EOGBS suggested that surfactant deficiency respiratory distress syndrome was common in preterm infants with EOGBS and contributed to their higher mortality compared with term infants.

A 4-week-old, breast-fed female infant appeared healthy until signs and symptoms of CNS deterioration suddenly occurred. At presentation the infant was found to have a left-sided parietal intracerebral hematoma, markedly prolonged prothrombin time, and partial thromboplastin time, normal platelet count, and jaundice with a total and direct serum bilirubin level of 5.4 mg/dL and 2.6 mg/dL, respectively. Vitamin K1 and fresh frozen plasma returned the prothrombin time and partial thromboplastin time to normal values within 18 hours, suggesting that the infant had severe vitamin K deficiency complicated by intracerebral hemorrhage. Evaluation of the infant's direct hyperbilirubinemia led to the diagnosis of homozygous (pi-type ZZ [PiZZ] ) alpha-1-antitrypsin deficiency. The clinical circumstances predisposing to vitamin K deficiency in newborns and infants are discussed. Based on our observations in this case, we suggest that cholestatic liver disease should be suspected when unexplained vitamin K deficiency occurs in early infancy. The role of vitamin K in hemostasis and the laboratory diagnosis of vitamin K deficiency are discussed as they apply to the evaluation of hemorrhage in newborns and infants.

The influence of antibody and complement on the polymorphonuclear leukocytic uptake and killing of type II group B streptococci (GBS) was examined with 11 adult sera and three type II strains possessing the trypsin-resistant and trypsin-sensitive components (II/TR+TS) of the "c" (formerly Ibc) protein or two type II strains lacking both components (II/no c) of the c protein. All tested sera mediated a greater than 1 log10 reduction in colony-forming units (CFUR) of a type II/no c strain, even in the absence of measurable type-specific antibody (less than 1.08 micrograms/ml), but only 5 of 11 mediated a greater than 1 log10 CFUR of any type II/TR/TS strain, even in the presence of moderate levels of type-specific antibody. The classical pathway of complement activation appeared to be more important than the alternative pathway, and even absorbed or immunoglobulin G (IgG)-depleted serum (IgG, 10 mg/dl) mediated a greater than 1 log10 CFUR without magnesium ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (magnesium EGTA) chelation. Chelation with magnesium EGTA reduced the CFUR in 4 of 11 test sera and greatly reduced the CFUR in absorbed or IgG-depleted sera for type II/no c strains. Despite variation in the phagocytic killing of two representative strains of type II GBS, both strains were well phagocytized, as measured by radiolabeled bacterial uptake or electron microscopy. This study suggested that poorly killed type II/TR+TS GBS were easily phagocytized but apparently resisted intracellular killing.

Hemorrhage secondary to heparin therapy is one of the most serious risks of extracorporeal membrane oxygenation (ECMO). This study determined those variables which affect the precision of activated clotting time (ACT) measurements used to monitor heparin therapy. Heparin therapy of eight neonatal lambs was monitored during ECMO with two Hemochron 400 machines to determine the effects of intermachine variability, test volume, speed and direction of agitation, and interpersonnel variability on ACT values. Test volume (0.25 vs. 0.4 ml) and agitation speed (2 shakes/sec vs. one shake/sec) resulted in significantly different ACT values (p less than .05). The mean matched ACT values determined from different agitation directions (vertical vs. horizontal) or the use of a stepper pipette to measure test volume vs. visual estimation of test volume were not significantly different. Variability in ACT test results is significantly increased by variations in test volume or agitation (speed and direction), intermachine variability, and by interpersonnel technique. These variables should be considered when devising protocols for ACT monitoring and management of heparin therapy.