We have had a wonderful match for our pediatrics and medicine/pediatrics training programs and look forward to an exciting group of new first-year residents.
Also, we are pleased to announce the addition of the following new faculty effective July 1, 2001:
Sincerely,
Professor and Chair
Parturition, the formal name for the process of labor and delivery, is the final outcome of a successful pregnancy. During pregnancy, the uterus must accommodate rapid growth of the fetus and extensive stretching of the uterine myometrium. This stretching could lead to increased uterine contractions and premature expulsion of the fetus. Fortunately, this rarely occurs. Fetal maturation is closely synchronized with uterine quiescence to prevent birth before the time of viability. Many factors have been identified that contribute to uterine quiescence vs. contractility, yet premature birth remains a perplexing health problem.
In humans, the impact of premature birth is devastating. It is estimated that approximately 10% of all pregnancies result in preterm delivery, defined as occurring before 37 weeks of gestation. Yet, these preterm births account for over 75% of perinatal mortality. Although only 2% of infants are delivered at less than 32 weeks, they constitute more than half of all neonatal deaths. Advances in the management of premature infants have significantly improved their chances for survival, but the prevalence of neurologic impairment remains alarmingly high. Despite the efforts to identify and treat the underlying factors that predispose to premature labor, the incidence of premature birth appears to be increasing. Unfortunately, the diagnosis and treatment of preterm labor is hindered by our incomplete knowledge of the mechanisms for normal parturition.
Neonatologists at the University at Kansas Medical Center always strive to provide state-of-the-art care for the wide range of problems confronting preterm infants. However, it is clear that preventing preterm birth is preferable to managing the life-threatening complications of prematurity. Thus, one aspect of our research is to define the molecular mechanisms that underlie term and preterm labor. In this regard we have continued to study the role of prostaglandins in fetal development and parturition.
Prostaglandins (PGs) are vasoactive, inflammatory, and growth-promoting molecules. They are produced by cyclooxygenase (COX)-1 and -2, which convert arachidonic acid into prostanoids and thromboxanes. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) inhibit PG synthesis by competing with arachidonic acid at the active site of the COX enzymes. Inhibition of PG synthesis provides analgesic, anti-pyretic, anti-inflammatory, and anti-thrombogenic effects. The discovery that COX exists as two distinct isoforms recently led to the development of selective COX-2 inhibitors (Celebrex, Vioxx). These "super-aspirins" reduce the symptoms of inflammation that are associated with COX-2 upregulation, without suppression of COX-1-derived PGs that are necessary for gastric cytoprotection and renal function.
Our interest focuses on the role of PGs and the COX isoforms in parturition. Known effects of PGs include increased uterine contractility and maturation of the cervix. For example, PG levels are elevated in the amniotic fluid of women with infection or preterm labor, and are increased in circulation at the time of labor. Because of this, NSAIDs like indomethacin are given as short-term tocolytics for women in preterm labor. Unfortunately, the specificity and mechanism of action of PGs and their receptors during parturition is unresolved.
We used normal and COX-deficient mice to examine the roles of PGs in labor and fetal well-being (Reese et al., PNAS 2000). These studies demonstrated that COX-1 is the enzyme responsible for most PG production during labor in the mouse. The localization of COX-1 in the mouse is similar to that of COX-2 in humans, which is the primary source of PGs for human labor. COX-1-deficient mice cannot initiate labor and ultimately deliver sick or stillborn pups. However, replacement doses of individual PGs rescued their parturition failure and neonatal mortality. Embryo transfer experiments showed that COX-1-deficient mice carrying a litter of normal pups can also deliver on time. This suggests, for the first time, that fetal PGs make a significant contribution to the onset of labor. This is also the first report that the fetal ductus arteriosus (of the mouse) does not have the capacity for PG synthesis, but must instead rely on circulating PGs to maintain its patency in-utero.
These results have profound implications for various trials of selective COX-2 inhibitors for the management of preterm labor, and the impact these compounds may have on the fetal circulatory system. We have currently identified a subset of PG receptors that are important for labor and ductal patency. In the future, the use of selective agonists and antagonists for these receptors may provide optimal control of premature labor without adverse effects on the developing child.
Assistant Professor, Division of Neonatology.
[Dr. Reese's work is supported by grants from the Philip Astrowe Trust, the NIH, and the American Heart Association.]
Anemia is one of the most common problems seen in low-birth-weight infants. As many as 80% of infants with birth weight less than 1,200 grams receive one or more red cell transfusions during their stay in the Neonatal Intensive Care Unit (NICU). Many are still anemic at the time of discharge and require ongoing monitoring.
Healthy, full-term infants demonstrate a decline in hemoglobin, often called "physiologic anemia," over the first eight to ten weeks of life. Premature infants also follow this pattern, but generally start with a lower hemoglobin level at birth than term infants, and have a steeper fall in hemoglobin over the next several weeks. Infants in the NICU also undergo numerous blood tests, with phlebotomy losses totaling as much as 11-22 cc/kg/week. It is common for 5% of a small infant's blood volume to be withdrawn for laboratory tests during the first 24 hours in the NICU. These iatrogenic losses are the largest contributor to anemia of prematurity.
Much of the effort aimed at preventing anemia of prematurity is directed toward limiting phlebotomy losses. Use of pulse oximetry and other non-invasive monitoring techniques reduces the need for blood gas sampling. Targeted ordering of laboratory tests, rather than use of routine protocols for testing, reduces blood loss. Laboratories are making great improvements in microsampling methods that minimize the blood volume required for testing. Point-of-care devices, such as the I-Stat or Irma, are employed at the bedside in NICUs, allowing for smaller blood volumes as well as faster turn-around for blood gases and other common lab tests. For example, the Irma device that is used in the NICU at the University of Kansas Medical Center analyses blood gases, electrolytes, and ionized calcium with only 0.2 cc of blood. In comparison, the more traditional laboratory testing would require 0.8 cc of blood for the same group of tests. Several ex vivo and in vivo arterial gas monitoring devices are currently in development and testing. In the near future, these will allow close tracking of this critical information with minimal blood loss.
For infants with symptomatic anemia, red cell transfusion remains the primary mode of treatment. Parents facing transfusion of their infants are concerned about transfusion safety. The risk of transfusion-associated viral infection is low. The risk of acquiring Hepatitis A, Hepatitis C, or HIV currently is estimated to be 1:1,000,000 per unit of blood. The risk of acquiring Hepatitis B is 1:30,000 to 1:250,000 per unit of blood. Using CMV-negative blood or leukocyte filters further reduces the risk. The use of dedicated blood collected into quad packs or nine packs further limits exposure to different donors and increases safety. Clinicians still must determine the circumstances under which transfusion is necessary. This can be quite difficult. There is no single laboratory or clinical parameter that can be the basis for this decision. Rather, multiple factors must be considered. A simplified approach to transfusion is presented in Table 1. Please note that many factors not included in the table should be considered also, including postnatal age, intercurrent illness, apnea, and surgery.
TABLE 1 Transfusion GuidelinesTransfusion should be considered when:
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Although anemia of prematurity continues to be a problem for many infants following discharge from the NICU, it generally resolves during the first several weeks at home. Rarely, an infant may need to be readmitted for transfusion. Physicians who provide longitudinal follow-up care for premature infants need to watch for signs and symptoms of anemia and might need to check hematocrits in premature infants. Adequate control of anemia is necessary to optimize the growth and development of these high-risk infants.
Associate Professor, Division of Neonatology.
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The University of Kansas Medical Center