Elsevier

Journal of Reproductive Immunology

Volume 57, Issues 1–2, October–November 2002, Pages 169-183
Journal of Reproductive Immunology

Mechanisms, organisms and markers of infection in pregnancy

https://doi.org/10.1016/S0165-0378(02)00018-9Get rights and content

Abstract

Premature delivery is still a significant problem in Obstetrics. It has multiple causes, with around 50% thought due to infection. Of note infection as a pathogenesis is more likely in those pre-term births occurring <30 weeks gestation and is largely sub-clinical. Potential pathogens largely arise from the ascending route and from the endogenous vaginal flora, causing chorioamnionitis. Resultant morbidity from the release of endo+/exotoxins from such pathogens, the stimulation and production of inflammatory cytokine pathways, prostaglandins, metalloproteinases includes maternal sepsis (chorioamnionitis, septicaemia, post-partum endometritis), pre-term delivery (infant pre-maturity and its consequences, increased susceptibility to cerebral palsy and neonatal sepsis). As well, infection increases mortality due to fetal loss (extreme pre-maturity) as well as severe neonatal sepsis.

Introduction

Pre-term delivery is a significant problem in obstetrics, accounting for 70% of perinatal mortality (Hack et al., 1993, McCormick, 1985). Despite advances in obstetric care in the past few decades, the rate of pre-term births has not decreased, although the survival of pre-term infants has increased (McCormick, 1985, Doyle et al., 2000). Approximately, 6–10% of all births are pre-term, although significant morbidity and mortality are concentrated to the very low birth-weight (<1500 g) infant (McCormick, 1985, Doyle et al., 2000). Risk factors for pre-term delivery include previous spontaneous pre-term delivery (particularly if mid-trimester (Goldenberg et al., 1993)) and African American race (Fiscella, 1995).

Section snippets

Epidemiology

Whilst the causes of pre-term birth are multiple (e.g. multiple births, antepartum haemorrhage), infection, (particularly unrecognised/subclinical infection in utero) is considered an aetiological factor in around 50% (Hillier et al., 1993). Of interest (and largely unexplained) is that infection is more likely to be associated with deliveries that occur <30 weeks, whereas it is uncommon in late (34–36 weeks’ gestation) pre-term deliveries (Hauth et al., 1998). Furthermore, there is evidence

Micro-organism–host interaction

All bacterial, viral or parasitic infections are the outcome of a dynamic interaction between the host's immune system and the virulence determinants of the infecting organism. Hosts have developed specific and non-specific factors to protect themselves from invading pathogens, while pathogens have evolved mechanisms to subvert these defenses and cause disease. Infectious agents display a wide spectrum of virulence: some may cause disease in otherwise healthy individuals, whilst others can only

Routes of transmission

Micro-organisms may enter and infect the uterus and developing fetus via haematogenous spread through the placenta, or ascending from the vaginal flora, or (rarely) iatrogenically, via needle contamination from abdominal skin flora, for example, during amniocentesis, or from the vaginal microbial flora during chorionic villous sampling (see Table 1 for specific examples). The mechanism for ascending infection by endogenous vaginal organisms is thought first to involve the choriodecidual space;

Specific organisms

Women with spontaneous pre-term labour with intact membranes most commonly have endogenous vaginal isolates of low virulence isolated from membranes/amniotic fluid—e.g. the genital mycoplasmas Ureaplasma urealyticum (U urealyticum) Mycoplasma hominis and other species commonly seen in bacterial vaginosis, such as peptostreptococci and Bacteriodes spp. Ureaplasmas may also colonise the premature infant's lower respiratory tract and this has been associated with adverse respiratory outcome (

Mechanisms of pre-term delivery due to infection

During pregnancy and parturition the extracellular matrix (ECM) of the decidua, the cervix and the fetal membranes are subject to extensive remodelling which in turn leads to cervical ripening, fetal membrane rupture and placental and membrane separation from maternal tissues (Keelan et al., 1997). This process of remodelling is activated prematurely in pre-term birth. Further, there is evidence of infection in most cases of spontaneous birth that occur prior to 30 weeks’ gestation (Goldenberg

Markers of infection

Potential markers of infection have been studied in amniotic fluid, maternal serum and cervicovaginal fluid, but the clinical utility of measuring the concentration of inflammatory cytokines in amniotic fluid is limited in clinical practice, because of a reluctance to perform amniocentesis in women in pre-term labour.

IL-1 concentrations in amniotic fluid are elevated in women in pre-term labour when there is microbial invasion of the amniotic cavity (Romero et al., 1992). However, data on the

Cerebral palsy

Apart from premature delivery, chorioamnionitis has been implicated in the pathogenesis of cerebral palsy. In a recent meta-analysis, clinical chorioamnionitis was found to be associated with cerebral palsy in both term and pre-term infants. In addition, histological chorioamnionitis was associated with cystic periventricular leukomalacia (presumed precursor of cerebral palsy) in pre-term infants (Wu and Colford, 2000).

Treatment of infection to prevent pre-term delivery

In general, for symptomatic and asymptomatic women with intact membranes in pre-term labour, antibiotic treatment does not delay delivery, improve the neonatal outcome, or reduce the risk of early birth (Gibbs and Eschenbach, 1997, Goldenberg et al., 2000). For those with pre-term rupture of membranes, antibiotic treatment increases the time to delivery and reduces the incidence of chorioamnionitis and neonatal infectious morbidity, but it does not improve neonatal mortality and morbidity in

Conclusions

The cost associated with pre-term birth is substantial in economic, social and emotional terms (Rogowski, 1998). Upper genital tract infection is important in the mechanism of pre-term birth, although it is usually asymptomatic. A more comprehensive understanding of the mechanisms of infection and spontaneous labour is needed to permit clinical intervention and reduce early birth and its associated long-term morbidity and mortality. Furthermore, because up to 80% of threatened pre-term labour

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