Measurement of intragastric oxygen concentration for the diagnosis of H-type tracheoesophageal fistula.

The demonstration of an H-type tracheoesophageal fistula before surgical correction is frequently difficult. Currently utilized procedures are so irregularly successful that surgical exploration is sometimes necessary without prior demonstration of the fistula. A case is reported in which the diagnosis was made by measurement of intragastric oxygen concentration, which increased and declined in response to the endotracheal insuffation of 100% oxygen and room air, respectively. The fistula was subsequently demonstrated by barium esophagram and was successfully treated surgically. In the presence of the classic clinical triad (choking during feedings, abdominal distention, and pneumonitis), a positive intragastric oxygen test may be sufficient indication for surgical exploration.

Indwelling umbilical arterial catheter: a preferred sampling site for blood culture.

Indwelling umbilical arterial catheter was evaluated prospectively as an alternative site for blood culture sampling. In 282 infants, 318 paired blood cultures were obtained from the peripheral vein and from the indwelling umbilical arterial line. Duration of umbilical catheter placement ranged from 0.5 to 196 hours; in 17% of the infants, catheters were in place for between 24 and 196 hours. In 13 blood culture pairs the same pathogens were found and had been obtained from the peripheral vein and the umbilical arterial line. Two pairs were positive for discrepant organisms. A total of 11 pairs were positive in one site only, with five positive from peripheral vein only and the other six from the umbilical arterial catheter. However, most of these single-site positive blood cultures were apparently true positives based on supporting laboratory data for infection. Contamination rates were 1.3% and 0.9% for peripheral vein and umbilical arterial catheter blood cultures, respectively. Thus, in sick neonates, the indwelling umbilical arterial line was an alternative and perhaps a preferred site for blood culture sampling.

Significance of serial C-reactive protein responses in neonatal infection and other disorders.

OBJECTIVE: This study was performed to determine prospectively whether, in the presence of proved or presumed bacterial infection, the sensitivity of serum C-reactive protein (CRP) response could be enhanced by serial rather than single determinations. We also sought to assess CRP responses to clinically identified noninfectious disorders. DESIGN: The CRP responses of 491 infants on 691 occasions of suspected infection were assessed. CRP levels were measured initially and twice again at 12-hour intervals (rate immunonephelometry). Assessments also included a blood culture, complete blood cell count, and chest radiograph and culture of spinal fluid when appropriate. CRP responses were correlated with four designated clinical groups: (1) positive blood or cerebrospinal fluid cultures (n = 190); (2) negative blood culture-definite infection (necrotizing enterocolitis stages 2 and 3, pneumonia, subcutaneous abscess) (n = 52); (3) negative blood culture-possible infection (antenatal risk factors, meconium aspiration, positive urine group B streptococcus antigen, necrotizing enterocolitis stage 1, febrile infants) (n = 287); and (4) negative blood culture-no infection (respiratory distress syndrome, transient tachypnea of the newborn, patent ductus arteriosus, tissue trauma) (n = 160). Diagnoses were made before CRP results were known. RESULTS: In all, 187 (27%) of the blood cultures were positive. A single organism was recovered from 174 of these; two organisms from 13. Among the single-organism cultures, 50 (29%) were Gram-negative, 120 (69%) were Gram-positive, and 4 (2%) were budding yeasts. CRP levels were elevated in various groups as follows: in the positive blood culture group (by organism), Gram-negative rods, 92% (46/50); group B streptococcus, 92% (12/13); Staphylococcus aureus, 89% (8/9); group D streptococcus, 71% (10/14); Streptococcus viridans, 60% (6/10); Staphylococcus epidermidis, 55% (40/73). In the negative blood culture-definite infection group, CRP levels were abnormal in 88%; in the negative culture-possible infection group, CRP was elevated in 33%; and in the negative blood culture-no infection group, CRP was elevated in 9%. Serial determinations of CRP resulted in enhanced sensitivity in the positive blood culture group, the negative blood culture-definite infection group, and the negative blood culture-possible infection group. Initial determinations by themselves were inadequately sensitive. Serial determinations did not enhance sensitivity of the negative blood culture-no infection group. High specificity (91%) is suggested by the low incidence of abnormal CRP levels among infants who were not infected. CONCLUSIONS: These data suggest that it would be appropriate to conduct a cautious, controlled trial to assess the safety of discontinuing antibiotic therapy if three serial CRP measurements are normal and if there are no other clinical factors suggestive of infection. The data also indicate the necessity for serial determinations of CRP for optimal sensitivity.

A decreased incidence of necrotizing enterocolitis after prenatal glucocorticoid therapy.

In a large multicentered, collaborative randomized and blinded trial utilizing antenatal corticosteroids, the goals included determining the effectiveness of these agents in accelerating lung maturation, as well as monitoring any short-term or long-term adverse effects of this treatment on the parturient, fetus, and/or infant. More than 100 specific items, pertaining to diagnoses, complications, and outcomes were recorded for the 696 mothers enrolled in the study and their 745 infants. A significantly decreased incidence of necrotizing enterocolitis (P = .002) was found in the infants treated with steroids. The possibility of accelerated intestinal maturation induced by antenatal maternal steroid therapy exists. This treatment regimen is particularly attractive as adverse aspects of steroid therapy at the dosage utilized have not been demonstrated.

Blood pressure increases, birth weight-dependent stability boundary, and intraventricular hemorrhage.

The blood pressure (BP) and transcutaneous PO2 (TcPO2) changes associated with intensive care procedures were evaluated to determine whether responses differ between babies with and without periventricular-intraventricular hemorrhage (PV-IVH). Fifty-three inborn babies less than or equal to 1500 g were studied using a microcomputer-based monitoring system. With almost any procedure including a seemingly benign one such as a diaper change, peak systolic BP increased and TcPO2 decreased. However, responses to interventions did not differ between babies with PV-IVH and those without PV-IVH. Neither did these responses differ between those with birth weight less than or equal to 1000 g and greater than 1000 g. When each baby's record was scanned for the highest peak systolic BP before diagnosis of PV-IVH or within 48 hours in those with no PV-IVH and their BP points plotted against birth weight, a stable region was evident wherein PV-IVH occurred at a lower incidence (13%). When peak systolic BP was beyond this stable region, the incidence of PV-IVH was significantly higher, 70% (P less than .0001). The stability boundary for the maximum systolic BP is birth weight-dependent; the limit for the highest tolerable peak systolic BP is lower for the low-birth-weight infant. In over 70% of instances the highest peak systolic BP was associated with motor activities either induced by nursery procedures or spontaneous. We speculate that decreasing the frequency of intensive care interventions may decrease episodic BP increases to levels beyond the birth weight-dependent stability boundary where PV-IVH is likely to occur.

Longitudinal growth of hospitalized very low birth weight infants.

BACKGROUND: The interpretation of growth rates for very low birth weight infants is obscured by limited data, recent changes in perinatal care, and the uncertain effects of multiple therapies. OBJECTIVES: To develop contemporary postnatal growth curves for very low birth weight preterm infants and to relate growth velocity to birth weight, nutritional practices, fetal growth status (small- or appropriate-for-gestational-age), and major neonatal morbidities (chronic lung disease, nosocomial infection or late-onset infection, severe intraventricular hemorrhage, and necrotizing enterocolitis). DESIGN: Large, multicenter, prospective cohort study. METHODS: Growth was prospectively assessed for 1660 infants with birth weights between 501 to 1500 g admitted by 24 hours of age to 1 of the 12 National Institute of Child Health and Human Development Neonatal Research Network centers between August 31, 1994 and August 9, 1995. Infants were included if they survived >7 days (168 hours) and were free of major congenital anomalies. Anthropometric measures (body weight, length, head circumference, and midarm circumference) were performed from birth until discharge, transfer, death, age 120 days, or a body weight of 2000 g. To obtain representative data, nutritional practices were not altered by the study protocol. RESULTS: Postnatal growth curves suitable for clinical and research use were constructed for body weight, length, head circumference, and midarm circumference. Once birth weight was regained, weight gain (14.4-16.1 g/kg/d) approximated intrauterine rates. However, at hospital discharge, most infants born between 24 and 29 weeks of gestation had not achieved the median birth weight of the reference fetus at the same postmenstrual age. Gestational age, race, and gender had no effect on growth within 100-g birth weight strata. Appropriate-for-gestational age infants who survived to hospital discharge without developing chronic lung disease, severe intraventricular hemorrhage, necrotizing enterocolitis, or late onset-sepsis gained weight faster than comparable infants with those morbidities. More rapid weight gain was also associated with a shorter duration of parenteral nutrition providing at least 75% of the total daily fluid volume, an earlier age at the initiation of enteral feedings, and an earlier age at achievement of full enteral feedings. CONCLUSIONS: These growth curves may be used to better understand postnatal growth, to help identify infants developing illnesses affecting growth, and to aid in the design of future research. They should not be taken as optimal. Randomized clinical trials should be performed to evaluate whether different nutritional management practices will permit birth weight to be regained earlier and result in more rapid growth, more appropriate body composition, and improved short- and long-term outcomes.

Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes.

OBJECTIVES: In the era before widespread use of inhaled nitric oxide, to determine the prevalence of persistent pulmonary hypertension (PPHN) in a multicenter cohort, demographic descriptors of the population, treatments used, the outcomes of those treatments, and variation in practice among centers. STUDY DESIGN: A total of 385 neonates who received >/=50% inspired oxygen and/or mechanical ventilation and had documented evidence of PPHN (2D echocardiogram or preductal or postductal oxygen difference) were tracked from admission at 12 Level III neonatal intensive care units. Demographics, treatments, and outcomes were documented. RESULTS: The prevalence of PPHN was 1.9 per 1000 live births (based on 71 558 inborns) with a wide variation observed among centers (.43-6.82 per 1000 live births). Neonates with PPHN were admitted to the Level III neonatal intensive care units at a mean of 12 hours of age (standard deviation: 19 hours). Wide variations in the use of all treatments studied were found at the centers. Hyperventilation was used in 65% overall but centers ranged from 33% to 92%, and continuous infusion of alkali was used in 75% overall, with a range of 27% to 93% of neonates. Other frequently used treatments included sedation (94%; range: 77%-100%), paralysis (73%; range: 33%-98%), and inotrope administration (84%; range: 46%-100%). Vasodilator drugs, primarily tolazoline, were used in 39% (range: 13%-81%) of neonates. Despite the wide variation in practice, there was no significant difference in mortality among centers. Mortality was 11% (range: 4%-33%). No specific therapy was clearly associated with a reduction in mortality. To determine whether the therapies were equivalent, neonates treated with hyperventilation were compared with those treated with alkali infusion. Hyperventilation reduced the risk of extracorporeal membrane oxygenation without increasing the use of oxygen at 28 days of age. In contrast, the use of alkali infusion was associated with increased use of extracorporeal membrane oxygenation (odds ratio: 5.03, compared with those treated with hyperventilation) and an increased use of oxygen at 28 days of age. CONCLUSIONS: Hyperventilation and alkali infusion are not equivalent in their outcomes in neonates with PPHN. Randomized trials are needed to evaluate the role of these common therapies.

Incidence, presenting features, risk factors and significance of late onset septicemia in very low birth weight infants. The National Institute of Child Health and Human Development Neonatal Research Network.

BACKGROUND: Septicemia is a major antecedent of morbidity and mortality in very low birth weight (501- to 1500-g) infants. Our purpose was to determine prospectively the incidence, clinical presentation, laboratory features, risk factors, morbidity and mortality associated with late onset septicemia in infants 501 to 1500 g. METHODS: Clinical data were prospectively collected for 2416 infants enrolled in a multicenter trial to determine the efficacy of intravenous immunoglobulin in preventing nosocomial infections. Septicemia was confirmed by positive blood culture in 395 symptomatic infants. Multivariate analyses of factors associated with septicemia were performed. RESULTS: Sixteen percent of VLBW infants developed septicemia at a median age of 17 days. Factors associated with septicemia by logistic regression included male gender, lower gestational age and birth weight and decreased baseline serum IgG concentrations. Increasing apnea (55%), feeding intolerance, abdominal distension or guaiac-positive stools (43%), increased respiratory support (29%), lethargy and hypotonia (23%) were the dominant presenting features of septicemia. An abnormal white blood cell count (46%), unexplained metabolic acidosis (11%) and hyperglycemia (10%) were the most common laboratory indicators. Septicemic infants, compared with nonsepticemic infants, had significantly increased mortality (21% vs. 9%), longer hospital stay (98 vs. 58 days) and more serious morbidity, including severe intraventricular hemorrhage, bronchopulmonary dysplasia and increased ventilator days (P < 0.001). CONCLUSIONS: Late onset septicemia is common in very low birth weight infants, and the rate is inversely proportional to gestational age and birth weight. Septicemia is more common in males and those with low initial serum IgG values. A set of clinical signs (apnea, bradycardia, etc.) and laboratory values (leukocytosis, immature white blood cells and neutropenia) increase the probability of late onset sepsis, but they have poor positive predictive value.

Early and late intraventricular hemorrhage: the role of obstetric factors.

OBJECTIVE: To evaluate the influence of active phase labor and other obstetric factors on the development of periventricular-intraventricular hemorrhage in the neonate. METHODS: A total of 230 infants were studied. Antenatal enrollment was carried out when estimated fetal weight was 1750 g or less. Serial head ultrasound scans were performed to screen for periventricular-intraventricular hemorrhage, with the initial scan performed within minutes of birth. Scan findings and obstetric and neonatal variables collected prospectively at scheduled intervals were analyzed to determine the significant factors that predispose to intraventricular hemorrhage. RESULTS: In 47 infants (20%), intraventricular hemorrhage was detected within 1 hour of birth (early) and in another 49 (21%) at a later age (late). The overall incidence of hemorrhage was similar between vaginal and cesarean deliveries (41 and 44%, respectively). Early hemorrhage was more frequent in vaginal (28%) than cesarean deliveries (11%), whereas late hemorrhage was more frequent in cesarean deliveries. When the role of delivery mode and labor was analyzed by stepwise logistic regression, the odds ratios for development of early intraventricular hemorrhage increased in the following order: cesarean delivery with no labor, cesarean delivery with latent phase labor, vaginal delivery with forceps use, cesarean delivery with active phase labor, and vaginal delivery without forceps use. For late hemorrhage, the odds ratios increased in the following order: vaginal delivery with forceps, vaginal delivery without forceps, cesarean delivery with no labor, cesarean delivery with latent phase labor, and cesarean delivery with active phase labor. CONCLUSIONS: Active phase labor may predispose to early periventricular-intraventricular hemorrhage, but its influence may be attenuated by use of forceps or by abdominal delivery. The protective effect of forceps remains for late periventricular-intraventricular hemorrhage, but abdominal delivery does not seem to protect against late hemorrhage.

Sex differences in outcomes of very low birthweight infants: the newborn male disadvantage.

OBJECTIVE: To determine the differences in short term outcome of very low birthweight infants attributable to sex. METHODS: Boys and girls weighing 501-1500 g admitted to the 12 centres of the National Institute of Child Health and Human Development Neonatal Research Network were compared. Maternal information and perinatal data were collected from hospital records. Infant outcome was recorded at discharge, at 120 days of age if the infant was still in hospital, or at death. Best obstetric estimate based on the last menstrual period, standard obstetric factors, and ultrasound were used to assign gestational age in completed weeks. Data were collected on a cohort that included 3356 boys and 3382 girls, representing all inborn births from 1 May 1991 to 31 December 1993. RESULTS: Mortality for boys was 22% and that for girls 15%. The prenatal and perinatal data indicate few differences between the sex groups, except that boys were less likely to have been exposed to antenatal steroids (odds ratio (OR) = 0.80) and were less stable after birth, as reflected in a higher percentage with lower Apgar scores at one and five minutes and the need for physical and pharmacological assistance. In particular, boys were more likely to have been intubated (OR = 1.16) and to have received resuscitation medication (OR = 1.40). Boys had a higher risk (OR > 1.00) for most adverse neonatal outcomes. Although pulmonary morbidity predominated, intracranial haemorrhage and urinary tract infection were also more common. CONCLUSIONS: Relative differences in short term morbidity and mortality persist between the sexes.

Partial plasma exchange transfusion improves cerebral hemodynamics in symptomatic neonatal polycythemia.

Cerebral arterial pulsatile flow changes and the effect of partial plasma exchange transfusion on these pulsatile flow patterns were studied in neonatal polycythemia/hyperviscosity syndrome by transcutaneous Doppler technique. Twenty-two infants with cord blood hematocrit greater than 58% (greater than 2 SD above the mean) were studied from a total of 2,400 infants who were screened for cord hematocrit over a 6-month period. Each of 22 infants had the following initial studies: radial artery hematocrit, viscosity, intracranial pressure measurement, and anterior cerebral arterial Doppler study to determine pulsatility index, mean systolic, mean end diastolic, and mean flow velocities, and area underneath the curve of the velocity tracings/min. Twelve of 22 infants had radial artery hematocrit less than 63%, were normoviscous (less than 13.5 cps, 11.25 sec-1) and were designated as control infants. Ten (study infants) were polycythemic (hematocrit greater than or equal to 63%) and hyperviscous (greater than or equal to 13.5 cps, 11.25 sec-1). All study patients were treated by partial plasma exchange transfusion. Initial studies were repeated after exchange transfusion. Control infants were not treated. Prior to exchange procedure, the polycythemic hyperviscous infants had significantly higher hematocrit, viscosity, and pulsatility index; the other Doppler measurements and heart rate were lower than those of control babies. The exchange procedure resulted in significantly decreased hematocrit, viscosity, and pulsatility index and increase in the other Doppler measurements, heart rate, and intracranial pressure. All postexchange measurements of study infants were not statistically different from the control infants. These data suggest that neonatal polycythemia/hyperviscosity syndrome may be associated with abnormal cerebral hemodynamics that could improve with partial plasma exchange transfusion.

Cerebral blood flow velocity changes after bovine natural surfactant instillation.

OBJECTIVE: To determine the effects of bovine natural surfactant (beractant) instillation on cerebral hemodynamics in preterm infants with respiratory distress syndrome (RDS). STUDY DESIGN: Preterm infants who required surfactant for RDS were enrolled. Cerebral blood flow velocity (CBFV) waveforms from the pericallosal artery were analyzed by pulsed Doppler ultrasonography with the anterior fontanel serving as an acoustic window. CBFV was measured before and at 5, 10, 20, and 30 minutes after the first dose of a bolus instillation of surfactant in four aliquots. Simultaneously with CBFV measurements, mean blood pressure (MBP), heart rate, and ventilator settings were recorded. pH, PACO2, and PAO2 before and at 30 minutes after surfactant administration were also determined. RESULTS: The 30 enrolled preterm infants had a mean birth weight of 973 gm (513 to 1996 gm) and a mean gestational age of 27 weeks (23 to 33 weeks). Mean postnatal age at surfactant administration was 4.7 +/- 2.7 hours. There were no significant changes in pH and PACO2 before and at 30 minutes after surfactant (before surfactant: mean pH of 7.29 +/- 0.07 and mean PACO2 of 44.4 +/- 7.1 torr; after surfactant: mean pH of 7.31 +/- 0.07 and mean PACO2 of 42.7 +/- 8.3 torr). PAO2 increased significantly from a pre-surfactant mean of 83 torr to 130 torr at 30 minutes after surfactant (p < 0.05), with no significant changes in mean airway pressure. There were no significant changes in MBP, heart rate, mean CBFV, peak systolic flow velocity, and diastolic flow velocity before and after surfactant instillation regardless of gestational age. Individual changes in mean CBFV were related to MBP changes (p < 0.001, linear mixed models with random effects). CONCLUSION: In low birth weight infants with RDS, bovine surfactant instillation is not associated with a significant alteration in cerebral hemodynamics. However, the direct relationship between CBFV and MBP is consistent with the reported pressure-passive cerebral circulation in sick preterm infants.

Effect of antenatal dexamethasone on neonatal leukocyte count.

The leukocyte count and differential white blood cell count during the first hour of life was determined in 164 neonates born of mothers receiving antenatal steroids and compared to 171 neonates of mothers randomly assigned to a placebo group. A leukemoid reaction (greater than 40,000 WBC/mm3) was seen only once each in the neonates born of placebo or steroid treated mothers. In addition, maternal steroid treatment had no general effect, except in a small subgroup of neonates born 3 to 7 days after the mother had been treated with 20 mg dexamethasone, where the total leukocyte and the absolute neutrophil counts were higher than the placebo group and other subgroups.

Acute phase reactants in neonatal bacterial infection.

The C-reactive protein (CRP) level was evaluated in 142 infants requiring investigation for suspected infection. After excluding two neonates because of incomplete data, there remained 140 neonates, of whom 16 had septicemia. Fifteen of 16 had increased CRP levels. The CRP value was not elevated in any baby (n = 5) who had positive blood cultures for Staphylococcus epidermidis, all of whom had an uneventful clinical course. The CRP level was elevated in all six babies with meconium-aspiration syndrome, but was normal in five infants whose viral cultures were positive. Ninety-nine percent of uninfected babies had normal CRP values. Overall, CRP was a valuable test for diagnostic confirmation of bacterial infection. Elevated CRP level was always accompanied by at least one abnormality in the other tests performed. Although the study was not intended to predict clinical onset of bacterial disease, our results suggest that the CRP level, because of a high negative predictive value, may be useful in ruling out bacterial infection.

Pancuronium attenuates associated hemodynamic and transcutaneous oxygen tension changes during nursery procedures.

Intermittent increases in blood pressure (BP) associated with motor activity have been implicated in the pathogenesis of intraventricular hemorrhage in premature infants. Inhibition of motor activity by pancuronium administration has also been shown to stabilize cerebral blood flow velocity (CBFV) and BP patterns. The purpose of this study was to determine whether administration of pancuronium to ill premature infants would attenuate changes in BP and transcutaneous oxygen tension (TcPO2) and the variability of CBFV pattern associated with common nursery procedures. Fourteen premature infants in the study were given a single dose of pancuronium bromide at a dose of 0.1 mg/kg intravenously. BP and TcPO2 changes were monitored during nursery procedures, that is, during radial artery blood gas sampling and a head ultrasonographic/Doppler procedure, before and during pancuronium therapy. During arterial blood gas sampling, mean percent increase in BP was significantly greater (32% +/- 21%) before pancuronium administration compared with 21% +/- 13% during pancuronium use (p < 0.05). Mean percent changes in TcPO2 were -30% +/- 21% and 5.8% +/- 7.2% before and during pancuronium use, respectively (p < 0.05). Similar significant changes in BP and TcPO2 were observed with a head ultrasonographic/Doppler procedure. Coefficients of variation of systolic and mean CBFV also decreased significantly during pancuronium therapy. We observed short-term benefits with pancuronium use on vascular dynamics and oxygenation during nursery procedures. Further studies are needed to evaluate the use of pancuronium in preterm babies supported by mechanical ventilation during the first few days of life for possible prevention of intraventricular hemorrhage, the pathophysiologic mechanism of which may be related to hemodynamic and biochemical derangement.

Uncommon virus infections of the mother, fetus, and newborn: influenza, mumps and measles.

The literature contains reports of epidemics of varying sizes, which in the aggregate suggest that congenital malformations are not attributable to maternal measles infection during pregnancy, that the incidence of prematurity may be somewhat higher among infected mothers, and that the incidence of abortion also may be somewhat higher. Before the introduction of measles vaccine in this country, the universality of childhood experience rendered adult infection a rare event. Gestational measles was thus uncommon. With the introduction of measles vaccine, these numbers can be expected to have decreased substantially.

Evolution of nursery design and function. The Memphis story.

The total design of a neonatal special care unit is fundamentally determined by patient load, essential staff, fiscal wherewithal, and available space. Given a commitment to this type of care, the least controllable of these factors are patient load and essential personnel. Suggestions for the design of these units can be made only in terms of effective function of personnel and optimal care of infants. The encapsulated account of our evolution is intended to present the rationale of our decisions. A straight-forward unembelished description of these physical facilities would not be meaningful without continuous reference to the staff and the infants that bring a facility to life.