Jerold F. Lucey

Incidence, presenting features, risk factors and significance of late onset septicemia in very low birth weight infants

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.

A controlled trial of intravenous immune globulin to reduce nosocomial infections in very-low-birth-weight infants

BACKGROUND Nosocomial infections are a major cause of morbidity and mortality in premature infants. As a rule, their low serum gamma globulin levels at birth subsequently decline to hypogammaglobulinemic values; hence, prophylactic administration of intravenous immune globulin may reduce the rate of hospital-acquired infections. METHODS In this prospective, multicenter, two-phase controlled trial, 2416 infants were stratified according to birth weight (501 to 1000 g and 1001 to 1500 g) and randomly assigned to an intravenous immune globulin group (n = 1204) or a control group (n = 1212). Control infants were given placebo infusions during phase 1 of the study (n = 623) but were not given any infusions during phase 2 (n = 589). Infants weighing 501 to 1000 g at birth were given 900 mg of immune globulin per kilogram of body weight, and infants weighing 1001 to 1500 g at birth were given a dose of 700 mg per kilogram. The immune globulin infusions were repeated every 14 days until the infants weighed 1800 g, were transferred to another center, died, or were sent home from the hospital. RESULTS Nosocomial infections of the blood, meninges, or urinary tract occurred in 439 of the 2416 infants (18.2 percent): 208 (17.3 percent) in the immune globulin group and 231 (19.1 percent) in the control group (relative risk, 0.91; 95 percent confidence interval, 0.77 to 1.08). Septicemia occurred in 15.5 percent of the immune globulin recipients and 17.2 percent of the controls. During phase 1 the rate of nosocomial infections was 13.4 percent in the immune globulin group and 17.8 percent in the control group; the respective rates during phase 2 were 21.0 percent and 20.4 percent. The predominant organisms included gram-positive cocci (53.0 percent), gram-negative bacilli (22.4 percent), and candida species (16.0 percent). Adverse reactions were rarely observed during the infusions. Immune globulin therapy had no effect on respiratory distress syndrome, bronchopulmonary dysplasia, intracranial hemorrhage, the duration of hospitalization, or mortality. The incidence of necrotizing enterocolitis was 12.0 percent in the immune globulin group and 9.5 percent in the control group. CONCLUSIONS Prophylactic use of intravenous immune globulin failed to reduce the incidence of hospital-acquired infections in very-low-birth-weight infants.

Neonatal Jaundice and Phototherapy

The ready availability and simplicity of phototherapy make it an attractive means of effectively lowering serum bilirubin concentrations or preventing them from rising. Its simplicity has, however, led to a casual approach to its use, which should not be encouraged. The problems and questions that arise relative to phototherapy are discussed, and present indications for its use are presented.

Clinical Limitations and Advantages of Transcutaneous Oxygen Electrodes

We investigated the clinical use and limitations of the transcutaneous oxygen electrode described by Huch, Lübbers and Huch in 30 sick infants. One hundred and fifty‐nine measurements of arterial oxygen tension (Pao2) and transcutaneous oxygen tension (tcPo2) were made. During the comparisons, arterial blood pressures, heart rate and thoracic impedance were continuously recorded, skin axillary and environmental temperatures, haematocrit and skin thickness were measured and the degree of peripheral perfusion noted. Despite a wide range of these variables, values of tcPo2 and Pao2 were similar (slope 0.963). Two groups of infants were identified in whom tcPo2 was lower than Pao2. These were infants receiving an intravascular infusion of tolazoline and infants with mean arterial blood pressures more than 2.5 s.d. below the predicted average value. Both of these situations represent extreme alterations in peripheral blood flow and give important information regarding the limitations of the method. Less extreme alterations in flow caused by mild hypotension, hypothermia, anaemia, radiant warmers, and bilirubin lights did not adversely affect the transcutaneous Po2‐arterial Po2 correlation. Advantages of transcutaneous oxygen monitoring over more conventional monitoring methods were assessed. We conclude that the transcutaneous oxygen electrode is safe, is easy to use, has few limitations and provides data which can help improve the management of most sick infants.

Evaluation of neonatal intensive care technologies.

The development and dissemination of neonatal intensive care technology has been associated with improved survival for critically ill newborn infants, particularly those with birth weights of less than 1,500 grams (3 pounds, 5 ounces). Despite these advances, there are concerns about the long-term health status of surviving infants and the costs of their initial and subsequent care. In this article, the authors review current evidence for the effectiveness of neonatal intensive care and discuss several approaches to evaluating neonatal intensive care technology. They discuss a four-step process originally proposed by Roper for assessing and improving neonatal intensive care practices which includes (1) monitoring of practices, outcomes, and costs; (2) analysis of variation in practices, outcomes, and costs; (3) assessment of the efficacy of individual interventions, and (4) feedback and education to alter clinical behavior. The authors conclude that organized networks of neonatal intensive care units can play a crucial role in this process.

Thalidomide: Effect upon Pregnancy in the Rhesus Monkey

Thalidomide was administered to 44 female rhesus monkeys immediately after they had mated. There were no live births from these animals, whereas there were 11 live births in 57 untreated monkeys. The results are statistically significant. The hypothesis is advanced that thalidomide killed the embryo prior to implantation.

Comments on a sudden infant death article in another journal.

I have been an avid reader and admirer of the New England Journal of Medicine since I was a medical student many years ago. As an editor, I confess I envy the journal its large circulation and the many fine articles it publishes. Recently, however, the journal published an article by Schwartz et al entitled “Prolongation of the QT Interval and the Sudden Infant Death Syndrome,” (N Engl J Med. 1998;338: 1709–1714), and an editorial by Friedman and Towbin complimenting the study. The commentary cited the study as offering “compelling evidence” of a link between the sudden infant death syndrome (SIDS) and prolonged QT interval, and suggested that “the development of a more useful tool that can be used in the physician’s office to measure QT would be welcome.” Did they read the same article that I read? Even more alarming was the suggestion implying “some patients should receive b-blockers.” I was dismayed. The SIDS field of research is still bogged down by apnea monitors, which have proven of little value. Hundreds of millions of dollars have been wasted over the last 25 years. Worse still, the device continues to be used! The apnea monitoring business has become a religion. More people are living off of SIDS than dying from it. I was worried that a similar, well-intentioned, stampede would occur or that somebody would suggest a large controlled trial be done to confirm the study of Schwartz et al. I don’t believe this hypothesis is worth a multimillion-dollar study. The single major advance in this field in the last 20 years has been the introduction of the Back to Sleep Program. The incidence of SIDS in the United States has decreased to below one case per thousand live births (1997). As compliance with the program improves, this decrease could continue. Highly specialized pathologists are finding defects in the brain and conduction system of the heart in so-called SIDS cases. Rare metabolic diseases and infanticide are also being detected more often. SIDS is a diagnosis of exclusion, so the more we know, the less likely SIDS will remain useful as a diagnosis. At first glance, the study is impressive, 34 442 infants over an 18-year period with a 1-year follow-up on 33 034 infants! Close examination of the data, however, reveals many serious, if not fatal, flaws. A long, detailed letter to the editor, raising questions is the traditional response. I decided that the article warranted a more forceful critique, lest it ignite yet another misadventure in this frustrating field. I wanted to see what would happen if I asked some of our expert reviewers in the SIDS field for their opinion of the article. I recommend that you read the views of these experts, which appear in this section of special commentaries. They raise important points of concern. Developing a new gadget for use in the office or experimenting with an unproven drug therapy is not the way to go.

Pediatrics electronic pages: Looking Back and Looking Ahead

* Abbreviations: URLs = : Uniform Resource Locators • AAP = : American Academy of Pediatrics To say that the rapidity of change on the World Wide Web has been extraordinary is an understatement. In less than 5 years, the Internet and the Web have gone from marginal technologies that were often derided to increasingly central information access points for millions of scientists, physicians, teachers, students, businesses, and others. Intellectual endeavors and economic life have likely only felt the first tremors of change. Uniform Resource Locators (URLs), those sometimes cryptic combinations of letters and dots (eg, http://www.whitehouse.gov for the White House), have become common elements in all forms of advertising and most publications. Large corporate interests are investing billions of dollars in this new medium. Dozens of innovative enterprises have been launched, employing thousands of highly skilled workers devoted to furthering Web technologies. Millions of dollars in stock transactions and consumer purchases are conducted over the Web each week, often more efficiently than by traditional means. Undoubtedly, the children of tomorrow will be profoundly affected by changes to pedagogy being wrought by new levels of information accessibility and interrelation. In February 1998, the National Academy of Sciences, National Academy of Engineering, and Institute of Medicine issued a recommendation for the “retooling of education at all levels, with the World Wide Web as the centerpiece.”1 It has gone beyond fad, and done so at a dizzying pace. In short, the Internet has turned out to be the best product the “computer nerds” have yet produced. Of all its possible uses, the Web has arguably done its most important work to date in the collection and dissemination of medical information. Vast databases of medical literature and genomic, chemical, physiological, and biological research are now available to practitioners and researchers around the world. Cryosections of human cadavers can be viewed and downloaded over the Web, as can magnetic … Address correspondence to: Mr Kent Anderson, American Academy of Pediatrics, 141 Northwest Point Blvd, Box 927, Elk Grove Village, IL 60009-0927.

DISORGANIZED BREATHING“ - AN IMPORTANT FORM OF APNEA AND CAUSE OF HYPOXIA

During studies of apnea in premature infants, we nave observed an interesting phenomenon. In 21 infants (550-1870 gms) we monitored transcutaneous oxygen tension (tcPO2), thoracic impedance (ATI), and heart rate, for 145 hours. During periods of apnea detected by thoracic impedance, tcPO2 dropped as anticipated. An unexpected and frequent finding was a “disorganized” pattern of breathing, (DB), associated with a more rapid drop in tcPO2. Using a thermistor at the nose we monitored 6 infants. In each of 65 episodes of DB with a fall in tcPO2, we found either complete or intermittent absence of air flow by nasal thermistor, (An) (Fig. 1). DB without air flow at the nares was found to occur most often in sleep and to result in hypoxia more frequently than ATI. We conclude that DB is an important form of apnea and cause of hypoxia not detectable by conventional monitoring.

Physiologic observations during induced anemia in utero in the rhesus monkey

infants who experience this accident who go unrecognized because they are so depressed at birth they cannot be successfully resuscitated or they are stillborn. Dr. Sambhus, department of anesthesiology, at our institution is presently studying maternal and cord blood concentrations of local anesthetics following conduction anesthesia of the mother during labor. Dr. Sahla Daniel, who is helping to collect this data which will be published shortly, permits me to mention that the maternal levels have averaged about 2 #g per milliliter of whole blood. This should be compared with a level of 8 t~g per milliliter of whole blood which appears to be the threshold of toxicity in infusion experiments in adults. The cord blood levels have also been about 2 /tg per milliliter of whole blood, although the ratio between the maternal and fetal levels depends partly on the interval from drug injection to birth.