Preterm birth is a significant perinatal problem contributing to perinatal morbidity and mortality. Heavy vaginal ureaplasma colonisation is suspected of playing a role in preterm birth and preterm rupture of the membranes. Antibiotics are used to treat infections and have been used to treat pregnant women with preterm prelabour rupture of the membranes, resulting in some short‐term improvements. However, the benefit of using antibiotics in early pregnancy to treat heavy vaginal colonisation is unclear.
To assess whether antibiotic treatment of pregnant women with heavy vaginal ureaplasma colonisation reduces the incidence of preterm birth and other adverse pregnancy outcomes.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2011).
Randomised controlled trials comparing any antibiotic regimen with placebo or no treatment in pregnant women with ureaplasma detected in the vagina.
Three review authors independently assessed eligibility and trial quality and extracted data.
We included one trial, involving 1071 women. Of these, 644 women between 22 weeks and 32 weeks' gestation were randomly assigned to one of three groups of antibiotic treatment (n = 174 erythromycin estolate, n = 224 erythromycin stearate, and n = 246 clindamycin hydrochloride) or a placebo (n = 427). Preterm birth data was not reported in this trial. Incidence of low birthweight less than 2500 grams was only evaluated for erythromycin (combined, n = 398) compared to placebo (n = 427) and there was no statistically significant difference between the two groups (risk ratio (RR) 0.70, 95% confidence interval (CI) 0.46 to 1.07). There were no statistically significant differences in side effects sufficient to stop treatment between either group (RR 1.25, 95% CI 0.85 to 1.85).
There is insufficient evidence to assess whether pregnant women who have vaginal colonisation with ureaplasma should be treated with antibiotics to prevent preterm birth.
Preterm birth is a significant perinatal problem. Upper genital tract infections, including ureaplasmas, are suspected of playing a role in preterm birth and preterm rupture of the membranes. Antibiotics are used to treat women with preterm prelabour rupture of the membranes; this may result in prolongation of pregnancy and lowers the risks of maternal and neonatal infection. However, antibiotics may be beneficial earlier in pregnancy to eradicate potentially causative agents.
Antibiotics for ureaplasma in the vagina in pregnancy
Ureaplasmas are normal flora in the vagina of many women. In some women high levels of ureaplasma in the vagina, which probably reflect the presence of infection in the uterus, may have a role in pregnancy complications, or may contribute to babies being born before full term (preterm birth), or both. These babies can have serious health problems. Some antibiotics can be safely used during pregnancy and are also active against ureaplasma. The authors identified only one trial (involving 1071 women) that was eligible for inclusion in this review. Therefore, there is insufficient data to assess whether giving antibiotics to women with ureaplasma in the vagina reduces the risk of preterm birth.
Preterm birth (less than 38 weeks' gestation) is a leading cause of mortality and morbidity (Gravatt 2010; Kramer 2000; Lawn 2010; Roberts 2000; Wood 2000). Globally, preterm birth occurs for approximately 13 million babies annually (Lawn 2010). Rates vary by many factors, including country of birth (Hall 1997), sociodemographic variables, race and ethnic groups. The causes of most spontaneous preterm birth are unknown and are most likely a complex relationship of causality (Lawn 2010). Known causal pathways tend to vary by gestation. Between the 22nd and 32nd week, inflammation caused by infection occurs commonly (Gravatt 2010). There is some evidence suggesting that genital colonisation, infections, or both, including with ureaplasmas, contribute to preterm labour and preterm rupture of membranes (Gilbert 1995; Goldenberg 2000).
Genital colonisation with ureaplasmas is common, and are normal flora carried by up to 80% of healthy women (McDonald 1997). They are usually harmless, presumably because the organisms stimulate a mucosal antibody response which controls their numbers and prevents local tissue invasion. In a small proportion of colonised women, ureaplasmas are found in the vaginal fluid in relatively high concentrations, presumably because they are poorly controlled by the host immune response. This may lead to ascending infection and subacute or chronic endometritis and contribute to infertility; and during pregnancy to complications such as spontaneous abortion or chorioamnionitis; and preterm birth may occur (Gilbert 1995). Whatever the mechanism, there is an association between preterm birth and ureaplasma colonisation or infection of the amniotic fluid, membranes, placenta and the infant (Gilbert 1995).
Ureaplasmas are the commonest isolates, often in pure culture, from the amniotic fluid and placentas of women who deliver prematurely and their presence is strongly associated with histological evidence of chorioamnionitis (Cassell 1993a; Hillier 1988). They are more commonly isolated from the respiratory tract of extremely preterm than from term infants, and their presence often is associated with congenital pneumonia and chronic neonatal lung disease (Cassell 1988; Hannaford 1999). Despite these associations, prospective studies have not shown a consistent association between lower vaginal colonisation and preterm birth (Cassell 1993b; McDonald 1992). Moreover, treatment during pregnancy has not consistently reduced the incidence of preterm birth (Eschenbach 1991; McGregor 1990). A 1995 review of two trials concluded that "there is no evidence currently to support the routine treatment at any stage of pregnancy of women found to be positive for Ureaplasma urealyticum to prevent prematurity" (Smaill 1995). The most likely explanation for the apparently contradictory findings is that the causes of preterm birth are multifactorial. There is evidence that other types of infection, including bacterial vaginosis, chlamydia and group B streptococcal infection, may predispose to preterm birth (Goldenberg 2000; McGregor 1990) and only a subset of women colonised with ureaplasmas is at risk of complications. Vaginal colonisation per se is a poor predictor of risk, but a cohort study showed that high‐density vaginal ureaplasma colonisation (more than 1000 colony forming units/ml) was a risk factor for chorioamnionitis and preterm birth (Abele‐Horn 2000).
Macrolide antibiotics, such as erythromycin, are one of the few agents active against ureaplasmas and can be safely used in pregnancy. Tetracyclines and fluoroquinolones are active against ureaplasmas but not used in pregnancy. For women with spontaneous preterm labour and intact membranes, treatment with antibiotics confers no clear benefit (Kenyon 2001; King 2002). However, for women with preterm prelabour rupture of the membranes treatment with antibiotics results in prolongation of pregnancy and lower risks of neonatal infection although the longer term health benefits are unclear (Kenyon 2010).
It may be possible to prevent the inflammatory cascade which is believed to lead to spontaneous preterm labour, preterm prelabour rupture of the membranes and preterm birth; however, we first need to identify women with abnormal genital colonisation who are at increased risk of infection and identify an appropriate treatment schedule suitable for use in early in pregnancy to eradicate their infection. The effectiveness of such treatment is likely to be affected by the type of antibiotic, the timing in pregnancy, dosage, duration of treatment and the route of administration. The purpose of this review is to assess whether antibiotic treatment of pregnant women with ureaplasma in the vagina reduces the incidence of preterm birth and other adverse pregnancy outcomes.
This review is separate to the 'Antibiotics for treating bacterial vaginosis in pregnancy ' Cochrane Review ‐ please seeMcDonald 2007.
To assess the effectiveness of antibiotics in reducing preterm birth among pregnant women with ureaplasma in the vagina.