145: Ureaplasma Infection

Ureaplasma belongs to the Mycoplasmataceae family. These are small pleomorphic bacteria that characteristically lack a cell wall. The genus Ureaplasma contains 2 species capable of causing human infection, U. urealyticum and U. parvum.

Ureaplasma species are frequently present in the lower genital tract of sexually active women with a colonization rate ranging between 40 and 80%. Vertical transmission to the newborn is high, especially in premature infants <1000 g birthweight where transmission rate approaches 90%.

U. urealyticum has been implicated in a variety of obstetric and neonatal diseases including preterm labor, preterm premature rupture of membranes (PPROM), chorioamnionitis, postpartum fever and endometritis, congenital pneumonia, bacteremia, meningitis, and bronchopulmonary dysplasia/chronic lung disease (BPD/CLD). The presumed mechanisms of infection include fetal exposure to ascending intrauterine infection, passage through an infected birth canal, and hematogenous dissemination through the placenta into umbilical vessels. This exposure leads to colonization of the skin, mucosal membranes, and respiratory tract, and sometimes leads to dissemination into the bloodstream and central nervous system (CNS). Phospholipases and cytokines produced through the inflammatory response can trigger uterine contractions and premature birth. Ureaplasmal infection of the respiratory tract in the newborn promotes a proinflammatory cytokine cascade with increase in tumor necrosis factor α, interleukin (IL)-1β, and IL-8. These cytokines recruit neutrophils to the lungs and intensify the inflammatory cascade, which damages the premature lung and impairs future alveolar development.

Ureaplasma colonization is associated with preterm labor, chorioamnionitis, birthweight <1000 g, and gestational age <30 weeks.

1. Preterm labor, PPROM, and chorioamnionitis. Ureaplasmas can invade the amniotic fluid early in pregnancy and are the single most common organisms that can be isolated from inflamed placentas. Ureaplasmas can persist in the amniotic fluid subclinically for several weeks. Detection of Ureaplasma in second-trimester amniotic fluid by polymerase chain reaction (PCR) correlates with subsequent preterm labor and delivery (58.6% for those with positive PCR vs 4.4% for those with negative results). In addition, Ureaplasma cord blood infections (identified by cultures) are far more common in spontaneous than indicated preterm deliveries and are strongly associated with markers of acute placental inflammation. Positive cord cultures are also associated with neonatal systemic inflammatory response syndrome.

2. Congenital pneumonia. Evidence that suggests Ureaplasma as a cause of congenital pneumonia includes isolation of the organism in pure culture from amniotic fluid and tracheal aspirate of neonates <24 hours after birth with specific immunoglobulin M (IgM) response in the midst of an acute inflammatory reaction and radiographic changes. These infants develop early interstitial pulmonary infiltrates with cystic/dysplastic changes as early as 10–14 days of age.

3. Meningitis. Multiple studies have shown Ureaplasma to be isolated from cerebrospinal fluid (CSF) of premature infants with meningitis, intraventricular hemorrhage, and hydrocephalus. The contribution of Ureaplasma to the outcome of these newborns is uncertain.

4. Predisposition to chronic lung disease. Multiple cohort studies have linked the development of BPD/CLD with colonization of the airways with Ureaplasma.

1. Laboratory studies

   1. Culture. Specimens for culture require specific transport media with refrigeration at 4°C. Dacron or calcium alginate swabs should be used instead of cotton swabs.

   2. Other tests. Several sensitive PCR assays have been developed, but they are not available routinely. Serologic assays are of limited value.

Isolation precautions for all infectious diseases, including maternal and neonatal precautions, breast-feeding, and visiting issues, can be found in Appendix F.

1. Treatment of the colonized pregnant mother. Treatment of pregnant women who present with PPROM with a 10-day course of erythromycin has been shown in a large randomized study to prolong pregnancy, reduce neonatal treatment with surfactant, decrease infant oxygen dependency at ≥28 days of age, and result in fewer major cerebral abnormalities on ultrasonography before discharge. Those same benefits were not accrued if the mother presented with preterm labor but with intact membranes.

2. Treatment of the colonized newborn infant is controversial. Limited current evidence does not demonstrate a reduction in BPD/CLD or other long-term neonatal morbidities when Ureaplasma-colonized and intubated preterm infants are treated with erythromycin. For infants with congenital pneumonia, some experts recommend treatment with erythromycin if there is radiographic evidence of early interstitial pneumonitis and when Ureaplasma is the only microorganism isolated from the respiratory tract. Antimicrobial treatment may also be considered when Ureaplasma is isolated from a normally sterile site such as the bloodstream or CSF. The macrolide azithromycin is being considered to treat colonized infants at risk for BPD/CLD as it has both anti-inflammatory and anti-infective properties.

In utero exposure to Ureaplasma is associated with increased rate of intraventricular hemorrhage and BPD/CLD in preterm infants. It is also associated with adverse neuromotor outcome at 1 and 2 years adjusted age in these infants.