Functional assessment of a multicenter very low-birth-weight cohort at age 5 years. Newborn Lung Project.

BACKGROUND: Very low-birth-weight newborns (birth weight < or = 1500 g) experience serious neonatal complications, but long-term outcomes are not completely known. Most studies reflect an era of neonatal care that was fundamentally different from the present. OBJECTIVES: To compare the functional level of very low-birth-weight children before and after surfactant introduction and to relate functional level to clinical and socioeconomic factors. DESIGN: Inception cohort followed up from birth to an average age of 5 years. SETTING: Six regional neonatal intensive care units in a contiguous geographic area. PARTICIPANTS: Four hundred twenty-five very low-birth-weight children, born between August 1, 1988, and June 30, 1991, of 438 located among 626 whose parents provided follow-up information before neonatal intensive care unit discharge. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Diagnosis of cerebral palsy and standardized scores for self-care, mobility, and social function from the Pediatric Evaluation of Disability Inventory. RESULTS: Cerebral palsy was present in 12.6% of the children, with no change after surfactant introduction. Intraventricular hemorrhage (odds ratio, 2.3 per grade; 95% confidence interval, 1.8-2.8) and bronchopulmonary dysplasia (odds ratio, 2.3; 95% confidence interval, 1.2-4.6) were independently predictive of cerebral palsy and of functional outcome. For self-care, mobility, and social function, 11.7%, 29.5%, and 10.7% of the children, respectively, scored at least 2 SDs below the normative means. Social function was 0.25 to 0.50 normative SDs lower after general surfactant availability than before general surfactant availability. CONCLUSIONS: While there was no increase in major disability after surfactant introduction, there may have been a decrease in social function associated with the lower neonatal mortality. Most very low-birth-weight children functioned within the normal range in everyday tasks. Several predictors of outcome were identified.

Lack of efficacy of oral bacitracin plus doxycycline for the eradication of stool colonization with vancomycin-resistant Enterococcus faecium.

In a prospective observational cohort study designed to assess the role of oral bacitracin solution plus doxycycline in the eradication of intestinal carriage of vancomycin-resistant Enterococcus faecium (VREF) in patients on a renal ward, rectal swab specimens were obtained from 15 treated and 24 control patients. Cultures of the rectal swabs were negative for 15 (100%) of the antibiotic-treated vs. eight (33.3%) of the untreated patients (P < .001) on day 14. However, follow-up for a mean of 127 and 130 days revealed 9 of 15 (60%) and 15 of 24 (62.5%) in the treated and untreated cohorts (P = .86), respectively, carried VREF intermittently or persistently. Quantitative VREF stool cultures in the treated cohort revealed an initial 3.1-log10/g decrease, but there was an increase to pretreatment levels at 2-4 and 5-7 weeks post-treatment (7.8 and 7.4 log10/g). Oral bacitracin and doxycycline were not efficacious in reducing the carriage of VREF beyond the 2-week interval during which they were given.

Associations between family history of asthma, bronchopulmonary dysplasia, and childhood asthma in very low birth weight children.

Very low birth weight (VLBW) infants are at risk for childhood wheezing and asthma, as are children with a family history of asthma. Family history of asthma may also be associated with premature labor and, among VLBW infants, with bronchopulmonary dysplasia (BPD) and chronic lung disease (CLD) of prematurity. This study targeted all neonates with birth weight <1,501 g who were admitted to seven perinatal centers in Wisconsin and Iowa between August 1, 1988 and June 30, 1991. Comprehensive information was collected for 723 of the 1,007 30-day survivors, and for 106 full-term controls. A representative subgroup of 257 VLBW children was contacted at age 5 years to ascertain bronchodilator and/or steroid use and diagnosis of asthma. Some evidence of an association between family history of asthma and premature birth was found, but it was not associated with neonatal BPD/CLD or BPD/CLD severity. Among BPD/CLD indicators, radiographic evidence of BPD at age 25-35 days was most strongly associated with bronchodilator use up to age 2 years (odds ratio (OR) = 10.1, 95% confidence interval (CI) 4.07-25.2) and with asthma between ages 2 years and 5 years (OR = 4.83, 95% CI 2.18-10.7). Among children without radiographic evidence of BPD, family history of asthma was associated with childhood asthma and bronchodilator use.

Evaluation of criteria for chronic lung disease in surviving very low birth weight infants. Newborn Lung Project.

Criteria in common use for the diagnosis of chronic lung disease of prematurity or bronchopulmonary dysplasia in the neonatal period have not been sufficiently compared and validated against indicators of later respiratory complications. In this study of all 680 infants < or = 1500 gm birth weight admitted to six perinatal centers August 1, 1988, to July 31, 1990, 524 were alive and had no major congenital anomalies at 5 years old. Of 419 who had given permission to release their names and addresses, 272 were located and participated in a follow-up study. The following diagnostic criteria for bronchopulmonary dysplasia and chronic lung disease of prematurity were used during the initial hospitalization: (1) use of supplemental oxygen on day 30 of life, (2) a comprehensive bronchopulmonary dysplasia severity score applied at 25 to 35 days of life developed by a clinician panel to adjust for practice variation in ventilatory support and blood gases, (3) use of supplemental oxygen on day 30 of life with radiographic evidence consistent with bronchopulmonary dysplasia between days 25 and 35 of life, (4) radiographic evidence consistent with bronchopulmonary dysplasia alone, and (5) use of supplemental oxygen at 36 weeks' postconceptional age. These criteria were assessed against use of bronchodilators or steroids during the first 2 years of life, diagnosis of asthma, and hospitalizations for respiratory causes up to age 5. Although all criteria were significantly associated with all the outcomes, radiographic evidence was most predictive. These results indicate that, during a period when 21% of neonates were exposed to antenatal steroids, 24% received surfactant and 9% received postnatal corticosteroids, radiographic evidence was more predictive of long-term respiratory outcome than other commonly used criteria.

Invasive infections due to a fish pathogen, Streptococcus iniae. S. iniae Study Group.

BACKGROUND: Streptococcus iniae is a pathogen in fish, capable of causing invasive disease and outbreaks in aquaculture farms. During the winter of 1995-1996 in the greater Toronto area there was a cluster of four cases of invasive S. iniae infection in people who had recently handled fresh, whole fish from such farms. METHODS: We conducted a prospective and retrospective community-based surveillance for cases of S. iniae infection in humans. To obtain a large sample of isolates, we studied cultures obtained from the surface of fish from aquaculture farms. Additional isolates were obtained from the brains of infected tilapia (oreochromis species). All the isolates were characterized by pulsed-field gel electrophoresis (PFGE). RESULTS: During one year, our surveillance identified a total of nine patients with invasive S. iniae infection (cellulitis of the hand in eight and endocarditis in one). All the patients had handled live or freshly killed fish, and eight had percutaneous injuries. Six of the nine fish were tilapia, which are commonly used in Asian cooking. Thirteen additional S. iniae isolates (2 from humans and 11 from infected tilapia) were obtained from normally sterile sites. The isolates from the nine patients were indistinguishable by PFGE and were highly related to the other clinical isolates. There was substantial genetic diversity among the 42 surveillance isolates from the surface of fish, but in 10 isolates the PFGE patterns were identical to those from the patients with S. iniae infection. CONCLUSIONS: S. iniae can produce invasive infection after skin injuries during the handling of fresh fish grown by aquaculture. We identified a clone of S. iniae that causes invasive disease in both humans and fish.

Short course monotherapy with clarithromycin for localized Mycobacterium marinum skin infection.

In vitro studies have shown that Mycobacterium marinum is usually susceptible to clarithromycin. However, there are limited published data on the clinical use of clarithromycin for the treatment of M marinum infections. This report describes a previously healthy 58-year-old man who developed a chronic soft tissue infection of his right hand caused by M marinum. He responded to four weeks' therapy with clarithromycin. Follow-up at six months showed no relapse. Our experience and review of the literature suggest that short course monotherapy with clarithromycin may be quite effective for uncomplicated soft issue infections caused by M marinum.

The relation of maternal complications to outcomes in very low birthweight infants in an era of changing neonatal care.

We examine the relation of key neonatal outcomes to pregnancy complications and to the use of antenatal steroids and investigate whether there is evidence of recent change in this relation. Complete information on pregnancy and neonatal course was available for 749 out of 949 singleton births without major congenital anomalies below 1501 g admitted to seven regional neonatal intensive care units between August 1, 1988 and June 30, 1991. Mortality was highest in infants born after labor with spontaneous rupture of fetal membranes of less than 24 hours duration (odds ratio [OR] = 1.6, 95% confidence interval [1.0, 2.6]). Spontaneous rupture of membranes of over 24 hours duration was associated with decreased risk of respiratory distress syndrome (OR = 0.42, [0.28, 0.64]) and decreased risk of patent ductus arteriosus (OR = 43, [0.28, 0.66]). Pregnancy induced hypertension was associated with increased risk of respiratory distress syndrome in those born at less than 20 weeks' gestation (OR = 6.0, [2.0, 17]). Labor with or without rupture of membranes of short duration was associated with increased risk of intraventricular hemorrhage (OR = 1.9, [1.2, 2.5]). These associations were not different in early versus late time periods of the study. Antenatal steroids were associated with dramatically reduced risk of mortality (OR = 0.20, [0.09, 0.50] ), respiratory distress syndrome (OR = 0.52, [0.32, 0.85]), and intraventricular hemorrhage (OR = 0.37, [0.21-0.65]).

A population study. Mortality and morbidity after availability of surfactant therapy. Newborn Lung Project.

OBJECTIVE: To assess the impact of recent changes in neonatal intensive care on the mortality and morbidity of very-low-birth-weight neonates (< 1501 g). DESIGN: Prospective cohort study. SETTING: Six neonatal intensive care units in Wisconsin and Iowa. PARTICIPANTS: All very-low-birth-weight neonates who were admitted to the neonatal intensive care units the year before the availability of exogenous surfactant (n = 333), during the investigational new drug protocol for synthetic surfactant (Exosurf) (n = 347), and after the release of synthetic surfactant (n = 356) (designated as periods 1, 2, and 3, respectively). INTERVENTIONS: None. MAIN RESULTS: The percentage of neonates receiving exogenous surfactant in the three periods was 3%, 37%, and 56%, and the percentage receiving antenatal steroids was 12%, 17%, and 27% (P = .0001 for increase in both modalities). The percentage of neonates dying in the three periods was 23%, 14%, and 19% (P = .05 for downward trend). The percentage of neonates with intraventricular hemorrhage decreased in the subgroup weighing between 700 and 1350 g (35%, 28%, and 24%) (P = .04) and increased in the subgroup weighing below 700 g (8%, 41%, and 45%) (P = .03). The percentage of neonates with bronchopulmonary dysplasia increased from 21% to 36% between periods 1 and 2 (P = .003) and decreased to 27% (P = .04) in period 3. Antenatal steroid use was strongly associated with the decrease in intraventricular hemorrhage (odds ratio, 0.35) and mortality risk (odds ratio, 0.20). CONCLUSIONS: Several developments in care have contributed to changes in mortality risk, incidence of intraventricular hemorrhage, and the severity of respiratory disease in very-low-birth-weight infants.

A new radiographic scoring system for bronchopulmonary dysplasia. Newborn Lung Project.

OBJECTIVES: To develop a simple, clinically meaningful radiographic score for bronchopulmonary dysplasia (BPD). To investigate its reliability, validity, and usefulness and to compare it to the Edwards score. WORKING HYPOTHESIS: Our radiographic scoring of BPD is reliable, correlates with respiratory support, and provides a necessary standardization in comparing severity of respiratory disease between hospitals. STUDY DESIGN: Prospective cohort study. PATIENT SELECTION: The study included all neonates (n = 366) with birth weight below 1501 g admitted to 7 neonatal intensive care units, who had chest radiographs taken at age 25-35 days. METHODOLOGY: A simple radiographic scoring system was developed. Scores ranging from 0 to 6 were assigned based on standard radiographs and descriptors of degree of abnormality. All radiographs taken between days 25 and 35 of age (n = 1087) were graded by a radiologist and a neonatologist. Radiographs from a stratified random sample of 37 neonates (10%) were also scored by the method of Edwards (n = 128 radiographs). A respiratory support index was constructed for days 25-35 and correlated with the radiographic score. RESULTS: Between-reader correlation was r = 0.87 for our score and r = 0.88 for the Edwards score. The two scores correlated with each other at r = 0.94. The respiratory support index correlated with our radiographic score at r = 0.75 overall, and r = 0.56 to 0.88 within hospitals. Higher postnatal corticosteroid use was found at the hospitals with the lower correlations. CONCLUSIONS: Our radiographic scoring is reliable, valid, and gives results similar to the Edwards score. Radiographs play a standardizing role in assessing severity of BPD between hospitals.

Multivariate assessment of traditional risk factors for chronic lung disease in very low birth weight neonates. The Newborn Lung Project.

All neonates (n = 581) with birth weights less than 1501 gm admitted to seven neonatal intensive care units in Wisconsin and Iowa were candidates for a study aimed at the multivariate assessment of risk factors for chronic lung disease while controlling for baseline severity of respiratory disease. Data from 361 neonates were analyzed for all risk factors except fluids; only neonates weighing less than 1200 gm were included (n = 220). Information on traditional risk factors for chronic lung disease was abstracted. A total of 110 (30%) of the analyzed neonates were oxygen dependent on day 30 of life. The following baseline factors were associated with increased risk of oxygen dependence in a joint multivariate model: lower birth weight (odds ratio 1.4/100 gm), higher baseline severity score (odds ratio 2.7/doubling at 32 weeks gestational age), lower gestational age (odds ratio 2.4/week at severity 0), Apgar score at 1 minute (odds ratio 1.6/2 points), male gender (odds ratio 1.9), and nonblack race (odds ratio 2.2). After adjustment for all baseline factors, patent ductus arteriosus, ventilator pressure at 96 hours, oxygen at 96 hours, and fluid intake were associated with oxygen dependence. Neonates with a low baseline severity score who remained oxygen dependent had a higher intake of fluid relative to output, whereas neonates with a higher baseline severity score had higher fluid intake and output. Lack of weight loss was associated with increased severity but not with oxygen dependence. The results of this study generally confirm the significance of previously reported risk factors for chronic lung disease in a multivariate setting but show that risk factors may not have the same impact in neonates with different baseline severity.

The effects of formula change on triglycerides and free fatty acids in preterm infants.

We measured preprandial and 2-h postprandial plasma triglycerides (TG) and free fatty acids (FFA) in 13 preterm infants weekly for 3 consecutive weeks to examine the effects of a premature, medium-chain triglyceride (MCT)-containing formula advancing to a term, long-chain triglyceride (LCT)-containing formula. The infants were on premature formula for the first 2 weeks of the study and were switched to term formula 4-5 days before the last sampling. Significant increases were seen in preprandial and 2-h postprandial TG when the infants were advanced from the premature to the term formula. It was speculated that this increase was due to the predominance of LCT in term formula, which differed in its absorption and metabolism from MCT. Whether these increases persist and if their clinical significance requires further investigation. No consistent change was observed in the preprandial or postprandial FFA.

Transient focal abnormalities of neuroimaging studies during focal status epilepticus.

We report transient changes in computed tomography (CT) and magnetic resonance imaging (MRI) scans in a patient with focal status epilepticus, referred to us with a tentative diagnosis of neoplasm based on CT and angiographic findings. EEG seizures originated independently from each temporal-occipital area, predominantly from the right. Previous EEGs had shown almost exclusively right temporo-occipital epileptogenic activity. MRI showed increased signal intensity, and CT showed decreased right hemisphere attenuation without enhancement. One month later, there was resolution of the radiological and clinical abnormalities. The transient CT and MRI changes probably represented focal cerebral edema, developing during focal status epilepticus. Lack of change in the left hemisphere probably reflected the quantitative difference in epileptic activity. Clues to the diagnosis of focal edema due to status include: (1) changes on electrical and imaging studies that correlate anatomically with the clinical status, and (2) resolution of abnormalities with appropriate seizure control. In patients with suspected seizure disorders, electrical and clinical data should be correlated before interpretation is made of focal lesions seen by neuroimaging techniques.

Intravenous energy and amino acids in the preterm newborn infant: effects on metabolic rate and potential mechanisms of action.

The effects of intravenously administered amino acids and of varying amounts of energy on metabolic rate were studied and potential mechanisms examined in 19 healthy 4- to 6-day-old preterm (30 to 32 weeks gestation) infants. The infants were randomized to three groups. Group 1 (n = 6) received nonprotein energy 38 kcal/kg/d; group 2 (n = 5), 64 kcal/kg/d; and group 3 (n = 8), 64 kcal/kg/d plus 1 to 2 g/kg/d crystalline amino acids. Thirty-six hours after beginning the infusion, oxygen consumption (VO2) was measured by indirect calorimetry for 5 to 6 hours. Simultaneously, urine was collected for urinary norepinephrine excretion, which was determined using liquid chromatography with electrochemical detection. Serum thyroxine (T4) and triiodothyronine (T3) concentrations were determined by radioimmunoassay. Group 1 had lower VO2 and urinary norepinephrine excretion than did groups 2 and 3, which did not differ. T4 and T3 were not different among the three groups. The demonstrated simultaneous changes in VO2 and norepinephrine excretion with varying energy intakes independent of age supports energy intake as a modulator of the sympathetic nervous system, which in turn controls metabolic rate. Moderate amounts of intravenously administered amino acids do not appear to play an active role in this process; nor do they alter T3 and T4 valves. When VO2 increased with increasing energy intake, T3 and T4 were unaffected, supporting a passive role for thyroid hormones in diet-induced thermogenesis.

Energy intake, norepinephrine excretion, and oxygen consumption in low birthweight infants.

Eleven healthy, appropriately grown low birthweight infants, ages 3-15 days and 28-33 weeks gestation, were the subjects of this study. Energy intake, urinary norepinephrine excretion, and metabolic rate as reflected in VO2 were examined concurrently. Energy intakes were recorded. Simultaneous collection of a timed urine for norepinephrine excretion and measurement of VO2 using indirect calorimetry were performed. A servo control device was used to maintain an abdominal skin temperature of 36.5 degrees C. The results demonstrated increases in energy intake, urinary norepinephrine, and VO2 with advancing postnatal age. Simple linear regression analysis revealed significant positive correlations between energy intake and VO2 (p less than 0.003), norepinephrine excretion and VO2 (p less than 0.003), postnatal age and VO2 (p less than 0.01), and postnatal age and energy intake (p less than 0.001). Multiple regression analysis revealed a strong positive correlation between urinary norepinephrine excretion and VO2, and energy intake and VO2. When postnatal age was added to the multiple linear regression analysis as a variable, energy intake was no longer strongly correlated with VO2. This implies postnatal age and energy intake are closely linked in this study, and further studies are needed to better define these relationships.

Effects of intravenously administered safflower oil emulsion on respiratory gas exchange of low-birth-weight infants.

Safflower oil emulsion (Liposyn 10%) was infused intravenously to supplement energy intake in five low-birth-weight infants. Respiratory gas exchange was measured before and after the addition of fat emulsion in doses of 1-2 g of fat/kg/day to an intravenous feeding regimen of dextrose and amino acids. The oxygen consumption and carbon dioxide production rates were greater during fat infusion in all infants, but the mean respiratory quotient was not different. The increase in energy intake provided by the fat emulsion exceeded the increase in energy expenditure, allowing more energy to be stored for growth.

The effects of thermal environment on heat balance and insensible water loss in low-birth-weight infants.

To define the neutral environmental temperature and assess the effects of deviation from that temperature on insensible water loss and heat balance, 12 premature infants were studied in a conventional incubator at four different predetermined ambient temperatures. Our method combines insensible water loss measured by a continuous read-out electronic scale with heat production as determined by open circuit measurement of oxygen consumption. An increase of 1 to 2 degrees C, to an ambient temperature above or near the top of the neutral zone, produced a significant rise in insensible water loss, from 1.90 +/- 0.76 to 3.08 +/- 1.19 ml/kg/hour (mean +/- SD), a corresponding rise in evaporative heat loss, and a fall in nonevaporative heat loss. A decrease of 1 to 2 degrees C, to a slightly subneutral ambient temperature, resulted in an increase in oxygen consumption from 5.82 +/- 0.92 to 7.45 +/- 1.50 ml/kg/minute, and an increase in total heat loss, but no change in insensible water loss and evaporative heat loss. The increased total heat loss was judged to be due entirely to a greater nonevaporative heat loss, both by convection and by radiation. The data confirm that ambient temperature is an important determinant of the magnitude and the partition of heat loss in low-birth-weight infants.

Heat balance in premature infants: comparative effects of convectively heated incubator and radiant warmer, with without plastic heat shield.

Insensible water loss, oxygen consumption, and carbon dioxide production were measured in eight premature infants under four different conditions: in conventional single-walled incubator with and without plastic heat shield, and under radiant warmer with and without heat shield. IWL was greater under the radiant warmer (3.40 +/- 1.50 ml/kg/hour, mean +/- SD) than in the incubator (2.37 +/- 1.15 ml/kg/hour) when both were compared without heat shield. Addition of the heat shield reduced IWL in the incubator (2.13 +/- 0.76 ml/kg/hour) but not under the radiant warmer (3.37 +/- 0.94 ml/kg/hour). There were no significant differences in VO2 or respiratory quotient between any two of the four study conditions.