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Biomedical subjects

R M Kliegman

Publications and source records attributed to R M Kliegman.

At least 19 recordsLinked to original sources
PubMed1995

Neonatal technology, perinatal survival, social consequences, and the perinatal paradox.

Exogenous surfactant therapy for premature infants with respiratory distress syndrome has had a significant impact on infant mortality and on some complications of prematurity. Yet the total number of low-birthweight infants has not declined, resulting in a high-risk population who would require surfactant therapy and long-term child care. Surviving low-birthweight infants (despite surfactant therapy) remain at risk for the consequences of premature birth, such as neurosensory impairment, cerebral palsy, and chronic lung disease. In addition, because of the close association between poverty and low birthweight, surviving premature infants are at increased risk for the new morbidities such as violence, homelessness, child abuse and neglect, and addictive drug use. A goal should be to reduce the risk of being born with a low birthweight, rather than having to treat the consequences of premature gestation. Despite the marvelous advances that permit us to treat respiratory distress syndrome, the continuing high low-birthweight rate places a significant strain on our health care system. The goal should be redirected to identifying large population-based efforts to reduce the number of low-birthweight infants.

Humans↗
PubMed1994

Relation of maternal cocaine use to the risks of prematurity and low birth weight.

To determine whether maternal cocaine use at the time of delivery of the infant is an independent risk factor for low birth weight or prematurity, we performed a prospective anonymous urine toxicology screening study among 425 women in a large urban university-based maternity hospital. The data were subjected to univariate analysis with the Fisher Exact Test and odds ratio determination, and to multivariate analyses by logistic regression. Of 11 variables analyzed, cocaine use near delivery, no prenatal care, marijuana and cigarette use, black race, a previous preterm infant, and staff service were significantly associated with premature birth by univariate analysis. No prenatal care (odds ratio, 9.89; 95% confidence intervals, 3.74 to 26.17) and cocaine use (odds ratio, 7.31; 95% confidence intervals, 2.87 to 18.61) demonstrated the greatest risk associated with premature birth by univariate prediction. After analysis by multivariate logistic modeling, only cocaine use detected at birth remained a significant predictor of prematurity (odds ratio, 13.4; 95% confidence intervals, 1.23 to 145.0). Staff service, black race, cocaine use near the time of delivery, marijuana and cigarette use, a previous preterm infant, and no prenatal care were significant univariate predictors of low birth weight. Cocaine use (odds ratio, 4.14; 95% confidence intervals, 1.18 to 14.56) and marijuana use (odds ratio, 4.52; 95% confidence intervals, 1.42 to 14.39) were the strongest univariate factors. After analysis by multivariate logistic modeling, cocaine use near the time of delivery demonstrated the highest odds ratio (9.90) for predicting low birth weight, but the 95% confidence intervals included 1 (0.53 to 184.0). We conclude that independent of potentially interrelated covariables, a positive result on a cocaine urine toxicology test at the time of delivery is the most dominant factor that was tested to predict prematurity and possibly low birth weight. The effect of cocaine on the duration of gestation or fetal growth may be due to its pharmacologic properties, or cocaine use during pregnancy may identify a subgroup of women whose risk is due to as-yet-unidentifiable socioeconomic or cultural characteristics.

Analysis of Variance↗
PubMed1993

Atypical extrapulmonary presentations of severe respiratory syncytial virus infection requiring intensive care.

The patterns and nature of a four-month epidemic of severe respiratory syncytial virus (RSV)-associated disease were analyzed using presenting, demographic, clinical, and therapeutic data. Of 218 infants with RSV infection admitted to Rainbow Babies and Childrens Hospital, 49 (22.4%), most born prematurely, entered the pediatric intensive care unit (PICU). Fluorescent antibody and/or enzyme-linked immunosorbent assay documented RSV infection. PICU patients underwent airway stabilization; 53.5% were intubated and evaluated for sepsis. Patients with positive bacterial cultures received antibiotics; 18% were given ribavirin. Patterns of infection included hypothermia, septic shock appearance, apnea, pneumonia, and wheezing due to bronchiolitis. The average age difference between patients with hypothermia (23.3 days) and those with pneumonia (11.2 months) was statistically significant. There were no significant differences in average age, gestational age at birth, number intubated, worst pH and PCO2, duration of intensive care, or treatment modalities between infants with bronchopulmonary dysplasia who received ribavirin and those who did not.

Age Factors↗
PubMed1993

Necrotizing enterocolitis: research agenda for a disease of unknown etiology and pathogenesis.

Necrotizing enterocolitis (NEC) is a significant neonatal public health problem that affects low-birth weight infants in neonatal intensive care units throughout the country. As the survival rate of low-birth weight infants continues to increase and as the number of low-birth weight births remains unchanged, we can anticipate that NEC will continue to be a cause of significant morbidity and mortality in the future. Despite many reports about NEC that describe demographic risk factors and short-term or long-term outcome, there is a paucity of basic science information about neonatal gastrointestinal physiology and pathophysiology in human preterm and even full-term infants. It has become increasingly evident that we need a much better understanding about the developmental aspects of gastrointestinal function in health and disease before we can achieve further advances in our understanding of and thus rational therapy for and prevention of NEC. The purpose of the National Institute of Child Health and Human Development conference "Necrotizing Enterocolitis: Basic Science Approaches to Gut Maturation and Pathogenesis" was to bring together basic science investigators, clinical epidemiologists, and clinical scientists to identify important areas of research that need to be applied to the problem of NEC. The concept of applying the "bench to bedside" type of collaborative research was emphasized and encouraged because many clinical neonatologists may have little scientific interaction with basic scientists. In addition, many basic scientists may be unaware of NEC and the implications for targeted research related to this disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Digestive System↗
PubMed1991

The relationship of neonatal alimentation practices to the occurrence of endemic necrotizing enterocolitis.

Enteric alimentation has been one of several factors implicated in the development of necrotizing enterocolitis (NEC). To examine this relationship further, the alimentation records of 19 patients who developed NEC were each compared with two matched patients controlled for birthweight and time of admission to the intensive care nursery. Parameters compared included total fluids provided, rate of enteral feed volume advancement, milk selection, and medications given. In addition, because there were no marked day-to-day differences between the mean values of most parameters and because we noted a marked fluctuation of formula intake and volume increments, we analyzed the maximum differences between the two groups. Maximum total fluids intake occurred on day 5 of life for the NEC patients and was 180.7 +/- 44 ml/kg. The control group on this same day received 149.7 +/- 35 ml/kg (p less than 0.01). Maximum enteral intake occurred on day 8 for the NEC patients at 124.3 +/- 5.7 ml/kg, whereas the control group had consumed only 83.5 +/- 60 ml/kg (p less than 0.05) on this matched day. The feed increment rate from initiation of feeds to day of maximum feeds was 27.8 +/- 16 ml/kg/day for the NEC patients and 16.8 +/- 11 for the control patients (p less than 0.0005). Furthermore, during the entire study period patients who developed NEC had the greatest 1 day increment compared with the controls (56.7 +/- 19.4 vs 44.6 +/- 26.2 ml/kg, p less than 0.05). Very rapid advancement of enteral feedings and excessive fluid volumes may predispose premature infants to the development of NEC and should be discouraged.(ABSTRACT TRUNCATED AT 250 WORDS)

Case-Control Studies↗
PubMed1991

Insulin receptor number and binding affinity in newborn dogs.

The insulin resistance in newborn mammals may be caused by a receptor or postreceptor defect. Although liver and umbilical cord blood monocytes have increased numbers of insulin receptors, there is a paucity of information about other neonatal tissues. Glucose disposal takes place primarily in the skeletal muscle; therefore, it is important to evaluate this tissue for an insulin receptor defect. To determine the role of insulin receptors in neonatal insulin resistance, neonatal and adult canine skeletal muscle, heart, and liver were compared for numbers of insulin receptors and their affinity for insulin. Partially purified receptors from four animals in each group were obtained by wheat germ lectin affinity chromatography and used in competition binding studies. Specific binding (mean +/- SE) in the absence of cold insulin was increased in newborn skeletal muscle (9.7 +/- 0.8 versus 4.8 +/- 0.5%, p less than 0.001) and heart (8.1 +/- 1.2 versus 5.5 +/- 0.6%, p less than 0.05). High-affinity insulin receptor number (mean +/- SEM) was increased in newborn skeletal muscle (183 +/- 40 versus 120 +/- 29 pM, p less than 0.002) and heart (264 +/- 94 versus 157 +/- 51 pM, p less than 0.05) as estimated from the X intercept of the Scatchard plot. Using half-maximal binding to estimate affinity, there were no differences between adults and newborns among all tissues studied. High-affinity receptor number and percentage of specific binding were similar for newborn and adult liver tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1991

Rational principles for immunoglobulin prophylaxis and therapy of neonatal infections.

Immunotherapy was a common method of treating infectious diseases in the preantibiotic era. Serotherapy was a popular approach to serious infections and employed hyperimmune globulins harvested from various large animals. Such antisera needed to be administered early in the course of the disease and unfortunately was associated with significant risks of anaphylaxis and serum sickness. Because of the allergic risks associated with animal immunoglobulin preparations, the development of methods to isolate human immunoglobulins heralded a new era in immunotherapy. This article examines the uses of immunotherapy in the treatment of neonatal infections.

Bacterial Infections↗
PubMed1990

Pathology of neonatal necrotizing enterocolitis: a ten-year experience.

We reviewed pathology specimens from 84 patients seen during a 10-year period with neonatal necrotizing enterocolitis, and these findings were correlated with clinical features. Coagulation (ischemic) necrosis, inflammation, and bacterial overgrowth were all present in the intestine of nearly all patients but with individual variability in the severity of these findings. Overall, coagulation necrosis was more severe than any other finding in most infants, indicating the importance of ischemia in the pathophysiology of necrotizing enterocolitis. Reparative tissue changes such as epithelial regeneration, granulation tissue formation, and fibrosis, found in two thirds of cases, suggested ongoing tissue injury of at least several days' duration. Birth weight, Apgar score, age, feeding status, and the presence of respiratory distress syndrome were not correlated with any particular histologic feature. The pathologic changes of necrotizing enterocolitis suggest that its cause is multifactorial, with ischemia, inflammation, bacterial overgrowth, and reparative tissue changes all playing important roles.

Apgar Score↗
PubMed1990

Pharmacokinetics, outcome of treatment, and toxic effects of amphotericin B and 5-fluorocytosine in neonates.

To determine the pharmacokinetics of amphotericin B and 5-fluorocytosine in neonates, we measured serum concentrations at first dose and after 5 days of therapy by high-performance liquid chromatography in 13 neonates (mean birth weight 1.2 +/- 0.8 kg). The dose of amphotericin B was serially increased from 0.1 to 0.5 mg/kg/day in 10 infants but was decreased from 0.8 to 1.0 to 0.5 mg/kg/day in three infants. Amphotericin B concentrations were not detectable in infants receiving 0.1 mg/kg/day. Amphotericin B cerebrospinal fluid concentrations were 40% to 90% of serum values obtained simultaneously. Serum concentrations after oral administration of 5-fluorocytosine (dose 25 to 100 mg/kg/day) were detectable in all infants. We found extreme interindividual variability for the half-life, volume of distribution, and clearance for both drugs. Four infants had minimal elimination for both drugs between doses, a finding that correlates with rises in serum creatinine (greater than 0.4 mg/dl, 40 mumol/L) and blood urea nitrogen (greater than 10 mg/dl, 3.6 mmol/L). We recommend that the dose of amphotericin B given on the first day of treatment be greater than the usual testing dose of 0.1 mg/kg/day. We also recommend an initial 24-hour dosing interval for amphotericin B and 5-fluorocytosine. Serum drug concentrations may need to be monitored in high-risk, low birth weight infants.

Amphotericin B↗
PubMed1990

Clinical pharmacology of imipenem and cilastatin in premature infants during the first week of life.

The first-dose and multidose pharmacokinetics of imipenem and cilastatin were evaluated in 41 premature infants during their first week of life. Premature infants (gestational age, less than or equal to 37 weeks) were assigned to receive 10-, 15-, 20-, or 25-mg/kg doses of imipenem-cilastatin (1:1) as a single- or multiple-dose regimen. A total of 39 infants received a single dose, whereas 18 infants received multiple doses. No differences were observed in pharmacokinetic parameter estimates for either agent relative to the dose administered or infant body weight; thus, the data were pooled. Elimination half-life, steady-state volume of distribution, and body clearance averaged 2.5 h, 0.5 liter/kg, and 2.5 ml/min per kg, respectively, for imipenem and 9.1 h, 0.4 liter/kg, and 0.5 ml/min per kg, respectively, for cilastatin. Similar values for these parameter estimates were observed after multidose administration, although substantial accumulation of cilastatin in serum was observed. A total of 21% of the imipenem and 43% of the cilastatin were excreted unchanged in the urine over a 12-h collection period. Corresponding renal clearances averaged 0.4 and 0.2 ml/min per kg for imipenem and cilastatin, respectively. Substantial differences were observed in the route by which imipenem was cleared from the body compared with data from adult volunteers. These data suggest that infants should receive an imipenem dose of 20 mg/kg administered every 12 h for the treatment of bacterial infections outside the central nervous system.

Cilastatin↗
PubMed1990

Effects of maternal obesity on fasting metabolism in newborn rats.

Maternal obesity is a risk factor for subsequent fasting hypoglycemia in human infants after birth. To investigate further this problem, we employed an animal model of obesity to study neonatal extrauterine metabolic adaptations in pups of obese and lean rats. Female Sprague-Dawley rats were fed a 'cafeteria diet' to induce obesity prior to and during pregnancy. Prior to mating, the cafeteria fed rats were significantly heavier (449 v. 345 g, P less than 0.001) than the controls. Furthermore, weight gain during pregnancy and weight at term were also significantly greater in the obese rats even though they consumed less food during pregnancy. Pup weights and the number of pups per litter were similar between the two groups. Pups born to obese mothers demonstrated hypoglycemia after being fasted for 150 and 180 min when compared with control pups. Hepatic glycogen stores were increased in the fetus of pups born to obese mothers. Glycogen content in pups born to obese mothers declined minimally after birth and remained greater than hepatic glycogen values in control pups throughout the study. In addition to increased fetal storage of glycogen, fetal hepatic triglyceride content was augmented in pups of obese rats. These triglyceride stores declined and were mobilized during fasting after birth. In contrast, hepatic triglyceride content increased after birth among control rats. These results suggest that maternal obesity results in augmented fetal hepatic tissue stores of both glycogen and triglycerides. Hypoglycemia among pups of excessively obese mothers may be due to attenuated mobilization of hepatic glycogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Use of intravenously administered immune globulin to prevent nosocomial sepsis in low birth weight infants: report of a pilot study.

To evaluate the use of intravenously administered immune globulin (IVIG) for prevention of sepsis in preterm infants, we administered IVIG in a protocol designed to maintain a therapeutic serum "target level" of 700 mg/dl. The 200 patients who were eligible for the study (600 to 2000 gm birth weight) were monitored throughout their initial hospitalization. Of these, 115 patients were randomly assigned in a double-blind, controlled trial to treatment and placebo groups. The remaining 85 infants were not randomly assigned to a group, by parental request, but were followed and analyzed separately. In one patient who received IVIG, transient tachycardia and a decrease in blood pressure developed during an infusion; resolution occurred promptly after the infusion was discontinued. No persistent hepatic or renal abnormalities were noted in either the IVIG- or the placebo-treated group. There were seven episodes of sepsis in the placebo group and nine in the group whose parents refused consent to the study. No infant who received IVIG acquired nosocomial sepsis (p less than 0.01). All patients in the placebo group in whom sepsis developed had serum IgG levels less than 400 mg/dl at the time sepsis developed. Serum IgG levels were maintained near 700 mg/dl in patients who received IVIG. These data indicate that administration of sufficient IVIG to maintain target serum IgG levels throughout hospitalization may decrease the incidence of nosocomial sepsis in preterm infants.

Cross Infection↗