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Biomedical subjects

M F Epstein

Publications and source records attributed to M F Epstein.

At least 19 recordsLinked to original sources

Persistent pulmonary hypertension of the newborn and smoking and aspirin and nonsteroidal antiinflammatory drug consumption during pregnancy.

OBJECTIVE: Prenatal causation of persistent pulmonary hypertension of the newborn (PPHB) is suggested by a specific pattern of pulmonary vascular remodeling observed immediately after birth in some infants with fatal PPHN. The goal of this study was to determine whether PPHN is associated with fetal exposure to: (1) tobacco and marijuana smoking (ie, contributors to fetal hypoxemia), (2) consumption of aspirin and other nonsteroidal antiinflammatory drugs (ie, inhibitors of prostaglandin synthesis), and (3) cocaine use (ie, a contributor to vasospasm). DESIGN: Case-control interview study. SETTING: Two Harvard-affiliated newborn intensive care units. PARTICIPANTS: Mothers of case infants who had PPHN or who met criteria for the referent group. INTERVENTIONS: During July 1985 through April 1989, we interviewed mothers of 103 infants with PPHN and 298 control infants. Because of potential selection bias that might result from recruiting only inborn control infants even though two-thirds of cases were outborn, separate analyses compared the 103 total and 35 inborn infants with PPHN with the 298 inborn control infants. Multivariate analyses were used to adjust for potential confounding factors, including maternal education and Medicaid health insurance (ie, two markers of socioeconomic status), other antenatal factors found to be associated with PPHN (ie, maternal urinary tract infection and diabetes mellitus), and the infant's sex. MAIN OUTCOME MEASURES: Self-reported use or consumption of tobacco, marijuana, cocaine, aspirin, and other nonsteroidal antiinflammatory drugs during pregnancy. RESULTS: The adjusted odds ratios (and 95% confidence intervals) for maternal pregnancy exposures to the factors of principal interest among the total study population were: aspirin, 4.9 (1.6-15.3); and nonsteroidal antiinflammatory drugs, 6.2 (1.8-21.8); for the inborn group they were aspirin, 9.6 (2.4-39.0); and nonsteroidal antiinflammatory drugs, 17.5 (4.3-71.6). Although the association between tobacco smoking during pregnancy and PPHN was elevated in univariate analyses, with odds ratios (and 95% confidence intervals) of 2.0 (1.2-3.4) and 1.3 (0.6-3.3) for total and inborn populations, respectively, the relationship was not significant after adjustment for all other factors in the final logistic regression model. Acknowledged illicit drug use was too infrequent (3.2%) to evaluate. CONCLUSION: Maternal consumption of nonsteroidal antiinflammatory drugs and aspirin during pregnancy or the reasons these drugs were ingested seem to contribute to an increased risk of PPHN.

Adult

Caring for gravely ill children.

BACKGROUND: Much has been written about the care of the hopelessly ill adult, but there is little guidance for pediatric health care professionals in the management of children who are critically or terminally ill. METHODS: Through a 3-day meeting in Tarrytown, NY, attended by a group of pediatricians and others directly involved in these issues, a principled approach was developed for the treatment of, and health care decision-making for, children who are gravely ill. RESULTS: The group agreed that the needs and interests of the child must be the central focus of any treatment plan and that the child should be involved to as great extent possible, consistent with developmental maturity, in the decision-making process. Quality of future life should be viewed as being relevant in all decisions. Parents are believed to be the natural guardians of children and ought to have great latitude in making decisions for them. However, parental discretion is not absolute and professionals must maintain an independent obligation to protect the child's interests. CONCLUSIONS: Decision-making should be collaborative among patient, parents, and professionals. When conflict arises, consultation and ethics committees may assist in resolution. When cure or restoration of function is no longer possible, or reasonable, promotion of comfort becomes the primary goal of management. Optimal use of pain medication and compassionate concern for the physical, psychological, and spiritual well-being of the child and family should be the primary focus of the professionals caring for the dying child.

Adolescent

Association of intravenous lipid emulsion and coagulase-negative staphylococcal bacteremia in neonatal intensive care units.

BACKGROUND AND METHODS: Coagulase-negative staphylococci are now the chief cause of bacteremia in neonatal intensive care units. To investigate potential risk factors for this nosocomial infection, we conducted a case--control study among 882 infants treated in two neonatal intensive care units during 1982. RESULTS: The 38 case patients and 76 controls were similar with respect to 27 indicators of the severity of the underlying illness. In addition, of the 20 potential risk factors for bacteremia that we investigated, only 2 met conventional criteria for causality. Infants with coagulase-negative staphylococcal bacteremia were 5.8 times as likely as controls (95 percent confidence interval, 4.1 to 8.3) to have received intravenous lipid emulsion before the onset of bacteremia. Because the use of lipids was common, 56.6 percent of all of the cases of nosocomial bacteremia could be attributed to lipid administration. Infants with bacteremia were also 3.5 times as likely as controls (95 percent confidence interval, 1.4 to 8.3) to have had a percutaneously inserted central venous catheter (attributable risk, 14.9 percent). The induction time for bacteremia after lipid administration, usually through peripheral catheters, was often less than one day. In contrast, the average induction period for nosocomial bacteremia associated with the use of central catheters, which were rarely used for lipid administration, was at least 5.5 days. Similar analyses of data on an additional 31 neonates treated in 1988 confirmed the strong and apparently independent association of coagulase-negative staphylococcal bacteremia with the intravenous administration of lipids (adjusted odds ratio, 5.3; 95 percent confidence interval, 3.5 to 6.7). CONCLUSIONS: The risk of coagulase-negative staphylococcal bacteremia in infants in neonatal intensive care units can be attributed primarily to the intravenous administration of lipid emulsions. Since lipids are critical for the nutritional support of premature infants, further studies are needed to examine the pathogenesis and prevention of lipid-associated bacteremia.

Catheterization, Central Venous

Extra hospital stay and antibiotic usage with nosocomial coagulase-negative staphylococcal bacteremia in two neonatal intensive care unit populations.

Coagulase-negative staphylococci were the leading cause of nosocomial bacteremia in the neonatal intensive care units of the Brigham and Women's Hospital and Children's Hospital, Boston, Mass, in 1982. To determine the consequences of these nosocomial bacteremias, a cohort study was conducted in which two comparison subjects were matched with each of 38 bacteremic infants by hospital, birth weight within 100 g, and nearest date of discharge. To adjust for duration of stay in the hospital, it was also required that both comparison subjects have survived and remained in the hospital for as long as the time until bacteremia occurred in the bacteremic infant. The average day of onset of bacteremia was the 20th hospital day. Despite having similar birth weights and comparable severity of underlying illness, bacteremic infants remained in the hospital for an average of 19.8 days longer than the nonbacteremic comparison subjects (77.3 vs 57.5 days). The bacteremic patients received antibiotics for an average of 11.2 more days than the nonbacteremic infants. Vancomycin hydrochloride was given to 20 (52.6%) of the bacteremic patients but only 4 (5.3%) of the comparison patients. All of the comparison subjects and 37 of the 38 infants with bacteremia survived. Thus, nosocomial bacteremia with coagulase-negative staphylococci is a late complication of hospitalization that occurs in infants who are already relatively long-term survivors. This bacteremia appears to be associated with substantially longer hospital stay and antibiotic therapy but little, if any, excess mortality.

Cross Infection

Recent patterns of drug use in newborn intensive care.

To better understand patterns of medication use in neonatal intensive care, we examined data collected prospectively over a recent 9-year period in the newborn intensive care units of two large teaching hospitals. Among 2690 infants studied, 91% received at least one drug; 99% of infants weighing less than 1500 gm were exposed to drugs, compared with 90% of infants weighing more than 1500 gm. Among treated infants, the median number of drugs received was eight; the number of drugs administered was inversely related to birth weight and directly related to both length of hospital stay and the complexity of the infant's clinical condition. Within categories of length of hospital stay, the number of drugs received per day was greatest during the first week in the neonatal intensive care unit and fell to a relatively stable lower level during the second week. The most commonly used single drug was gentamicin (71% exposed), followed by sodium chloride (60%), potassium chloride (59%), heparin (58%), and packed erythrocytes (45%). Between 1978-1979 and 1985-1986 the prevalence of use increased substantially for some drugs (ampicillin, morphine, calcium salts, and acetates of sodium and potassium) and decreased for others (kanamycin, sodium bicarbonate, and blood products). These data document the dynamic nature of drug therapy in the neonatal intensive care unit and provide information that can guide cost-benefit assessments in this setting.

Anti-Bacterial Agents

Birth weight and length of stay as determinants of nosocomial coagulase-negative staphylococcal bacteremia in neonatal intensive care unit populations: potential for confounding.

Coagulase-negative staphylococci are the most common cause of bacteremia in the neonatal intensive care units of the Brigham and Women's Hospital and the Children's Hospital, Boston, Massachusetts. In 1982, nosocomial bacteremia with coagulase-negative staphylococci occurred in 45 of 882 (5.1%) infants admitted to these units who survived and remained in intensive care for more than 48 hours and were therefore at risk. The overall cumulative incidence (attack rate) of nosocomial bacteremia rose dramatically with decreasing birth weight. The smallest infants, those with birth weights of less than 750 g, experienced an overall risk of nosocomial bacteremia 44.5 times that of infants with birth weights of greater than 2,000 g. A large part of the excess risk for small babies was attributable to their longer hospitalizations. However, after adjustment for length of stay, the smallest infants still suffered a daily rate of bacteremia (incidence density) 5.3 times that of the largest, indicating a considerable residual effect of birth weight on the daily risk of nosocomial coagulase-negative staphylococcal bacteremia. The results were similar in the two nurseries. Thus, there is still a substantially increased intrinsic risk of nosocomial coagulase-negative staphylococcal bacteremia among infants with very low birth weights, even after adjustment for duration of hospitalization, and differences in birth weight can confound comparative studies.

Birth Weight

Hyperbilirubinemia following exposure to pancuronium bromide in newborns.

We investigated the risk of hyperbilirubinemia in relation to the administration of pancuronium bromide among newborn infants requiring mechanical ventilation. One hundred and twenty-nine infants treated with pancuronium were compared to 129 infants who were never exposed, matched on ventilatory status, hospital, birthweight, initial total serum bilirubin, and date of hospital discharge. Overall, the adjusted summary relative risk (RR) for hyperbilirubinemia among pancuronium-exposed infants compared to nonexposed infants was 1.2 (95% confidence interval 1.1-1.4). The risk was greatest among exposed infants during the 4 days following the last dose of pancuronium (RR = 1.4; 1.0-1.8). These data suggest that the use of pancuronium in sick newborns may be associated with an increased risk of clinically important hyperbilirubinemia.

Bilirubin

Pregnancy outcome after premature rupture of the membranes at or before 26 weeks' gestation.

Pregnancy outcome was examined in 59 clinically stable patients with rupture of the membranes at or before 26 weeks' gestation. The mean gestational age at rupture of the membranes was 23.2 weeks, and the mean latent period was 21.5 days. Delivery occurred within 7 days in 29 patients (49.2%), chorioamnionitis developed in 27 patients (45.8%), and operative delivery was required in 24 patients (40.7%). Sixty-three infants were delivered, with a perinatal mortality rate of 49.1%. Among survivors, 84% required newborn intensive care during the initial hospitalization, 77% were discharged with minor to moderate reversible sequelae, and 16% were discharged with sequelae that were likely to be of long-term duration. Obstetric factors present at rupture of the membranes were evaluated for their ability to predict maternal and neonatal morbid outcomes; obstetric interventions were evaluated for their ability to modify outcomes. These data suggest that outcomes in this subset of patients may not be uniformly dismal, and support clinical decision-making on an individualized basis.

Adult

Extracorporeal membrane oxygenation and conventional medical therapy in neonates with persistent pulmonary hypertension of the newborn: a prospective randomized study.

Thirty-nine newborn infants with severe persistent pulmonary hypertension and respiratory failure who met criteria for 85% likelihood of dying were enrolled in a randomized trial in which extracorporeal membrane oxygenation (ECMO) therapy was compared with conventional medical therapy (CMT). In phase I, 4 of 10 babies in the CMT group died and 9 of 9 babies in the ECMO group survived. Randomization was halted after the fourth CMT death, as planned before initiating the study, and the next 20 babies were treated with ECMO (phase II). Of the 20, 19 survived. All three treatment groups (CMT and ECMO in phase I and ECMO, phase II) were comparable in severity of illness and mechanical ventilator support. The overall survival of ECMO-treated infants was 97% (28 of 29) compared with 60% (6 of 10) in the CMT group (P less than .05).

Extracorporeal Membrane Oxygenation

Fifteen-year experience with bloodstream isolates of coagulase-negative staphylococci in neonatal intensive care.

Investigators worldwide, as well as the neonatologists and infection control team at our hospital, have reported that the incidence of coagulase-negative staphylococcal bacteremia in critically ill neonates has increased dramatically in recent years. To investigate these claims, we examined the results of all blood cultures obtained from 1970 to 1984 in our neonatal intensive care unit. Throughout this study period, coagulase-negative staphylococci were prominent blood culture isolates (crude overall incidence of 4.4 positive bacteremia workups per 100 neonates admitted; range, 2.5 to 6.7), representing 26.3 to 69.6% of all positive cultures. There was no significant increase in incidence over time by analysis of linear trend. Detailed analysis of data from 1976 and 1982 (two selected years for which complete information concerning culturing practices and patient characteristics was available) revealed that these observations were not explained by changes in the frequency of blood culturing. In both 1976 and 1982, the probability that a blood culture would grow coagulase-negative staphylococci increased steadily from 2 to 3% shortly after admission to reach a level of about 12% in week 3 of hospitalization, before declining to an intermediate level thereafter. This pattern is more consistent with nosocomial bacteremia than with contamination of blood cultures. Contrary to clinical reports, coagulase-negative staphylococci have been the principal pathogens isolated from blood cultures in our neonatal intensive care unit since at least 1970, with no measurable increase over the subsequent 14 years.

Coagulase

Bilirubin, intraventricular hemorrhage, and phenobarbital in very low birth weight babies.

The relationships among serum bilirubin concentration on days 5 and 7, birth weight, the presence of intraventricular hemorrhage, and the receipt of phenobarbital were examined in a group of 232 newborns weighing less than 1,751 g who were intubated, mechanically ventilated by 12 hours after birth, and whose parents had given permission for a randomized trial of phenobarbital prophylaxis of intraventricular hemorrhage. The ratio of serum bilirubin concentration to birth weight (the bilirubin divided by birth weight index [BBI]) was used to examine the impact of 25 variables on a clinical guideline for therapy of hyperbilirubinemia in newborn infants. A linear regression model was used; the most powerful covariate was a birth weight less than 1.0 kg. The only other variable that reduced the BBI was phenobarbital receipt. The presence of intraventricular hemorrhage and ecchymoses had a significant influence increasing the BBI.

Bilirubin

Coagulase-negative staphylococcal bacteremia in the changing neonatal intensive care unit population. Is there an epidemic?

A fivefold increase in the number of cases of nosocomial coagulase-negative staphylococcal bacteremia was investigated in a neonatal intensive care unit between 1975 and 1982. This apparent outbreak was not the result of increased isolation of coagulase-negative staphylococci from blood cultures nor an increased frequency with which blood cultures were obtained. Rather, it was attributable to a dramatic increase in the overall probability that a positive blood culture would be interpreted as "bacteremia" as opposed to a contaminant by both physicians and infection control staff. Specifically, there had been a 62.3% increase in neonatal intensive care unit bed use by very-low-birth-weight (less than 1000-g) infants between 1975 and 1982, and in both years, positive blood cultures were 3.8 times as likely to be perceived as clinically significant if obtained from such tiny infants. The growing number of very-low-birth-weight babies occupying neonatal intensive care unit beds, coupled with the observation that blood cultures positive for coagulase-negative staphylococci are almost four times as likely to be perceived as clinically significant if obtained from extremely premature infants, may account for the reported increase in nosocomial coagulase-negative staphylococcal bacteremia.

Boston

Parental and physician-related determinants of consent for neonatal autopsy.

We undertook a cross-sectional epidemiologic study of potential determinants of parental consent for neonatal autopsy at the Brigham and Women's Hospital, Boston. Data were abstracted from maternal and infant medical records in 184 cases of neonatal death occurring between January 1982 and October 1984. The overall consent rate for neonatal autopsy was 72%. Multivariate analysis by logistic regression found previous fetal loss, gestational age, and cause of death to be significantly different between the groups of consenters and nonconsenters. Parents least likely to consent to autopsy were those who had no history of previous fetal loss, who had pregnancies in which the birth weight of the infant was less than 1000 g or the gestational age was less than 28 weeks, or those who had an infant die of extreme prematurity. Factors not significantly associated with consent were maternal age, race, marital status, transfer status, type of prenatal care, the infant's sex, and the staff position of the requester. A second phase of the study surveyed physicians' attitudes regarding the importance of neonatal autopsy. The staff position and previous experience of the physician-requester, in addition to the presumed cause of the infant's death, were significantly associated with the rating assigned to the importance of the autopsy. These findings suggest that the mother's past and present obstetrical experience, the presence of extreme prematurity, and possibly the attitude and experience of the physician requesting autopsy permission may exert important influences on the likelihood of obtaining consent for a neonatal autopsy.

Adult

Elevated levels of alpha 2-macroglobulin-protease complexes in infants.

Proteases form stable complexes with alpha 2-macroglobulin (alpha 2-MG) in human plasma. We previously showed that the intestine of newborn rabbits takes up greater amounts of proteases than the intestine of weaned animals, and we suggested that the same phenomenon might occur in the human newborn. To test this possibility, alpha 2-MG complexes were sought in plasma from 3-day-old human infants and adults. In addition, the level of alpha 2-MG was measured. The concentration of alpha 2-MG complexes and of alpha 2-MG was significantly increased in the plasma of infants compared to adults. We suggest that the elevated levels of alpha 2-MG complexes in infants may reflect the enhanced uptake of proteases from the intestine. In addition, there may also be decreased clearance of complexes by the mononuclear phagocytic system in infants. The elevated levels of alpha 2-MG in the infant may reflect a response to the need for neutralizing proteases absorbed from the intestine.

Adult

Is chronic lung disease in low birth weight infants preventable? A survey of eight centers.

Chronic lung disease in prematurely born infants, defined as the need for increased inspired oxygen at 28 days of age, was thought to be more common in some institutions than in others. To test this hypothesis, we surveyed the experience in the intensive care nurseries at Columbia and Vanderbilt Universities, the Universities of Texas at Dallas, Washington at Seattle, and California at San Francisco, the Brigham and Women's Hospital in Boston, Texas Children's Hospital in Houston, and Mt Sinai Hospital in Toronto. The survey included 1,625 infants with birth weights of 700 to 1,500 g. We confirmed the relationship of risk to low birth weight, white race, and male sex. Significant differences in the incidence of chronic lung disease were found between institutions even when birth weight, race, and sex were taken into consideration through a multivariate logistic regression analysis. Columbia had one of the best outcomes for low birth weight infants and the lowest incidence of chronic lung disease.

Bronchopulmonary Dysplasia