The role of infection in preterm labour and delivery

Abstract

A strong body of evidence suggests that infection plays a role in the pathogenesis of preterm labour and delivery. Moreover, recent evidence indicates that intrauterine infection may also be involved in the genesis of significant neonatal and infant complications such as periventricular leukomalacia, bronchopulmonary dysplasia and cerebral palsy. This article reviews the evidence linking infection with pre-term delivery. Three lines of evidence support a role for infection in the onset of preterm labour: • administration of bacteria or bacterial products to animals results in either abortion or labour; • systemic maternal infections such as pyelonephritis, pneumonia, malaria, and typhoid fever are associated with the onset of labour; • intrauterine infection is associated with preterm labour and delivery. Infection-induced preterm labour and delivery in animals. Considerable evidence derived from animal experimentation indicates that administration of micro-organisms or microbial products (e.g. endotoxin) to pregnant animals can induce preterm labour and delivery.1–4 In 1943, Zahl and Bjerknes5 demonstrated that injection of Shigella and Salmonella endotoxin into mice and rabbits was capable of inducing abortion. Takeda and Tsuchiya6 confirmed this observation by administering Escherichia coli endotoxin to pregnant mice and rabbits. Furthermore, immunisation of animals with an anti-endotoxin antibody ameliorates the biological effect of endotoxin.7 Animal models of ascending intrauterine infection have been developed by placing bacteria through a hysteroscope into the uterine cavity of rabbits.8 Using this model, Dombroski et al.8 and Romero et al.9 have been able to induce preterm labour and delivery. Gravett et al.10 have also developed an animal model of infection-induced preterm labour in rhesus monkeys by administering bacteria directly into the amniotic cavity or into the decidua. Extrauterine infection and preterm labour and delivery. Systemic maternal infections such as pneumonia, pyelonephritis, malaria, and typhoid fever have been associated with preterm labour and delivery.11–22 The rate of preterm delivery associated with maternal pneumonia ranges from 15% to 48%.11–14 Although the advent of antibiotic treatment has dramatically reduced maternal mortality from this condition, it has not affected the preterm delivery rate.13,14 In the pre-antibiotic era, pyelonephritis was associated with preterm delivery. Currently, pyelonephritis is associated with preterm labour but not preterm delivery,16 probably as a result of early treatment. Similarly, typhoid fever in the pre-antibiotic era carried a 60% to 80% risk of abortion and preterm labour, but this risk decreased after the introduction of antibiotic therapy.18–20 Malaria has also been associated with a 50% rate of preterm delivery. However, chemoprophylaxis seems to protect patients from preterm delivery.21,22 Recently, periodontal infection has been reported to be a risk factor for preterm delivery (Odds ratio [OR]: 7.9; attributable risk 18.2%).23 Collectively, these data support the concept that untreated systemic maternal infection is associated with preterm labour and delivery and that treatment may decrease the rate of preterm delivery in some cases (e.g. pyelonephritis, typhoid fever) but not in others (e.g. pneumonia). Intrauterine infection and preterm labour and delivery. Although untreated systemic maternal infections confer a high relative risk (RR) of preterm labour and delivery, these conditions are rare during pregnancy; modern treatment is effective and thus their attributable risk for preterm delivery is low. On the other hand, intrauterine infection has recently been recognised as a major factor associated with preterm labour. We will review the definition, microbiology, and clinical significance of intrauterine infection. The gold standard for the diagnosis of an intrauterine infection is a positive microbiological culture for micro-organisms. Intrauterine infection can be classified according to the location of the micro-organisms into two broad categories: intra-amniotic and extra-amniotic infections. It is possible to obtain biological material for microbiological culture from the amniotic cavity (i.e. fluid) and the chorioamniotic space.24,25 It is not easy to culture material derived from human decidua. Therefore, in practice, most studies in patients with preterm labour and delivery have focused on microbial invasion of the amniotic cavity (defined as a positive amniotic fluid culture for micro-organisms when the fluid is retrieved by transabdominal amniocentesis). The amniotic cavity is normally sterile and therefore the isolation of any micro-organism from the amniotic fluid constitutes evidence of microbial invasion. This condition often exists in the absence of clinical signs and symptoms of infection.26 The method of amniotic fluid collection for microbiological studies is critical. The two techniques that have been