Abstract
Preterm labour is defined as the delivery of the fetus when birth occurs between 20 and 37 completed weeks.
Preterm labour is one of the major causes of neonatal mortality (1–5 per cent) and morbidity (necrotising enterocolitis; retinopathy of prematurity, intraventricular haemorrhage; chronic lung disease; cerebral palsy, blindness and learning difficulties; and developmental delay).
It is estimated that 40 per cent of preterm labours are due to infections that can be prevented if detected and treated early. The earlier the preterm birth, the more it is due to infection. Preterm birth is the most frequent cause of infant death in the United States, accounting for at least one-third of infant deaths in 2002.
In many cases, the reasons for preterm labour are largely unknown. In other instances, preterm labour can have a variety of different causes, e.g. infection, an ‘incompetent’ or weak cervix, multiple pregnancy, history of certain types of surgery on the uterus or cervix, lifestyle factors such as low pre-pregnancy weight, obesity, smoking during pregnancy and substance abuse.
This chapter will focus on inflammatory and infectious conditions.
Introduction
Preterm labour is defined as the delivery of the fetus when birth occurs between 20 and 37 completed weeks.
Preterm labour is one of the major causes of neonatal mortality (1–5 per cent) and morbidity (necrotising enterocolitis; retinopathy of prematurity, intraventricular haemorrhage; chronic lung disease; cerebral palsy, blindness and learning difficulties; and developmental delay).
It is estimated that 40 per cent of preterm labours are due to infections that can be prevented if detected and treated early. The earlier the preterm birth, the more it is due to infection. Preterm birth is the most frequent cause of infant death in the United States, accounting for at least one-third of infant deaths in 2002.1
In many cases, the reasons for preterm labour are largely unknown. In other instances, preterm labour can have a variety of different causes, e.g. infection, an ‘incompetent’ or weak cervix, multiple pregnancy, history of certain types of surgery on the uterus or cervix, lifestyle factors such as low pre-pregnancy weight, obesity, smoking during pregnancy and substance abuse.2
This chapter will focus on inflammatory and infectious conditions.
Pathophysiology
1 Inflammatory Conditions
Inflammation is a localised reaction that produces redness, warmth, swelling and pain as a result of irritation, injury, infection or disease that are not primarily infective (e.g. asthma, rheumatoid arthritis).
Inflammation promotes the secretion of pro-inflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukin (IL) 1β from the cells composing the uteroplacental unit. Initial pro-inflammatory stimuli by TNF-α and IL-1β trigger production of IL-8 and prostaglandins (PGE2 and PGF2α) in the decidua and the placenta, impairing the tissue integrity of fetal membranes, and leading to prostaglandin release. This causes ripening of the cervix, membrane injury and preterm labour.3
2 Infections
Intrauterine or extrauterine infections produce inflammatory reaction in the form of Toll-like receptors (TLRs). TLRs initiate immune response, inducing pro-inflammatory factors involving cytokines, chemokines, prostaglandins and other effector molecules that result in complications of labour, e.g. rupture of fetal membranes.4
There is an abundance of evidence on the relation between infection and preterm labour:
The amniotic fluid in preterm labour has higher rates of microbial colonisation and levels of inflammatory cytokines than that of preterm patients not in labour.
Extrauterine maternal infections (pyelonephritis, pneumonia and periodontal disease) or subclinical intrauterine infections have been implicated in preterm labour.
Infections and Preterm Labour
Infectious causes of preterm labour can be either:
A) Bacterial
B) Viral
C) Bacterial vaginosis
D) Chlamydia trachomatis
These four infectious conditions precipitate chorioamniotitis which in turn initiates preterm labour (as explained in the Pathophysiology section above).
A) Bacterial Infections
Intrauterine infections caused by bacteria are the leading cause of infection-associated preterm labour. Forty per cent of preterm labours are associated with intrauterine infections.
Ascending cervical and vaginal flora through the cervical canal is the most common pathway to infection of the membranes and chorion (chorioamnionitis).
Uncommonly, chorioamnionitis may occur via haematogenous spread as a result of maternal bacteraemia (e.g. Listeria monocytogenes), or via contamination of the amniotic cavity as a result of an invasive procedure (e.g. amniocentesis, fetoscopy).5
B) Viral Infections
Viruses are not a common cause, although adenovirus, cytomegalovirus and enterovirus DNA have been isolated from the amniotic fluid of some low-risk patients that had preterm delivery.
Evidence suggests that viral entry into trophoblast cells induces apoptosis inflammatory reaction, with preterm birth.6
C) Bacterial Vaginosis
There are strong associations between bacterial vaginosis and both histologic and clinical chorioamnionitis infection. Ureaplasma urealyticum and Gardnerella vaginalis are the micro-organisms most frequently identified by cultivation.
Bacterial vaginosis is associated with increased concentrations of bacterial endotoxins, proteases, mucinases and sialidases.
In two epidemiologic studies (one in a high-risk group of women in labour and another in a lower-risk group of antepartum women), the presence of bacterial vaginosis has been associated with the development of chorioamnionitis. Multiple logistic regression analysis has shown a relationship between isolation of organisms from the chorioamnion and bacterial vaginosis.7
D) Chlamydia trachomatis
Chlamydia trachomatis is the most common sexually transmitted infection worldwide. Starting as cervicitis, chlamydial infection may ascend and infect the placenta or amniotic fluid, which may subsequently lead to preterm delivery.
In a prospective, observational and non-interventional study on 320 pregnant women, histological evidence of placental inflammation was present in 40 per cent of women who had early preterm delivery.8
In a population-based prospective cohort study by Rours G.I.J.G. et al. involving 4055 women, C. trachomatis infection contributed significantly to early premature delivery.9
Chorioamnionitis
Chorioamnionitis or intra-amniotic infection is an acute infection of the membranes and chorion of the placenta, usually due to ascending bacterial infection which is commonly associated with rupture of membranes.
Chorioamnionitis is associated with as many as 40–70 per cent of preterm births with premature membrane rupture.
Preterm labour may result from a fetal and/or maternal response to chorioamnionitis.
Clinical chorioamnionitis, ruptured membranes
Among women with preterm premature rupture of membranes (PPROM), the rate of positive amniotic fluid cultures at admission is 32.4 per cent. However by the time labour begins, as many as 75 per cent will have microbial infection of the amniotic cavity, which is enhanced by removal of the physical barrier of the membranes after they rupture.10
or
Microbiological histopathologic chorioamnionitis with intact membranes
The amniotic cavity is normally sterile. The isolation of bacteria in the amniotic fluid with intact membranes is a pathologic finding, known as microbial invasion of the amniotic cavity and/or the chorioamnion. Most cases are subclinical and are undetectable without amniotic fluid culture. In patients with preterm labour with intact membranes, the rate of positive amniotic fluid cultures is 12.8 per cent.
Diagnosis of Chorioamnionitis
Ideally, an early diagnosis of intra-amniotic infection (IAI) is important for timely treatment and intervention. Usually, early diagnosis is difficult because the clinical signs and symptoms of IAI occur late and are neither sensitive nor specific. To avoid a delay in diagnosis, a high index of clinical suspicion with appropriate laboratory tests may speed diagnosis.
1 Clinical Diagnosis
1. Maternal tachycardia (>100 bpm).
2. Fever (> 38°C) is the first sign of suspected chorioamnionitis. It is mediated by the effect of pyrogenic cytokines, interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α).
3. Uterine tenderness.
4. Foul-smelling amniotic fluid if there is rupture of membranes.
5. Fetal tachycardia (>160 bpm).
6. Other cardiotocography changes (diminished or absent variability, tachycardia or sinusoidal pattern) suggesting fetal distress.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
