Introduction
Preterm labour is defined as the spontaneous onset of regular and painful uterine contractions resulting in the dilatation of the cervix or cervical effacement prior to 37 weeks of gestation(1,2). Preterm labour may result in preterm birth which is generally classified based on the gestational age at birth as: extremely preterm (before 28 weeks), very preterm (between 28 and 32 weeks) and moderately preterm (after 32 weeks and before 37 weeks)(3,4). The moderate preterm birth can further be described as late preterm if the onset of it occurs between 34 and 37 weeks of gestation(3,4). Etiologically, preterm birth can either be spontaneous (natural onset of labour or preterm premature rupture of membranes) or provider-initiated (medically induced labour or caesarean delivery) depending on the clinical presentation(5–7).
The global incidence of preterm birth is 12% which is equivalent to approximately 15 million babies born preterm each year(8,9). The incidence ranges from 5% among the European countries to nearly 20% in some African countries(9–11). As the principal cause of increased morbidities and mortalities among children less than five years old, prematurity has become a major public health concern(9,12) and compromises the emotional and psychological states of many families with preterm infants born to them. This is attributable to the accelerated economic burdens exerted due to increased cost of health care and learning demands(5,10,11,13). Evidence has shown that infants who are born at the extremes of gestational age are at increased risk of severe longstanding health complications (11,13–15). The consequences of preterm birth are common during the neonatal period and may persist into adulthood. Studies have also shown that male infants born preterm have poorer prognosis and are at increased risk of health complications compared to their female counterparts(11,16,17).
The actual aetiology of preterm labour is not known, although multiple mechanisms have been propounded in the pathogenesis of preterm labour. For instance, intrauterine infections, inflammation, mechanical stress or over distension of the uterus, intrauterine growth restriction (IUGR) and uteroplacental hypoxia or haemorrhage are said to trigger the onset of preterm labour (5,11,15,18). Additionally, maternal race (black women, African-American or Afro-Caribbean) or ethnicity, younger maternal age, advanced maternal age (>35 years), cigarette smoking, low maternal weight, obesity, multiple pregnancy, use of assisted reproductive techniques, maternal history of preterm birth and the marginalised may also contribute to the onset of preterm labour(11,19). Regardless of the predisposition, maternal pro-inflammatory mediators play a central role in the initiation of preterm labour.
Clinical management of preterm labour is extremely challenging with poor outcomes especially when uterine contractions are established with progressive cervical changes. The well-known unpredictability of the clinical course of preterm labour results from the unresolved pathophysiology of the condition. The major hypothesized pathophysiological mechanisms of preterm labour include inflammation resulting from multiple aetiological pathways. Improved understanding of the mechanistic role of pro-inflammatory mediators in preterm labour is critical in evidence-based clinical management especially inflammation associated with chorioamnionitis and urinary tract infections(8). The aim of this review was to appraise the pathophysiological mechanism of pro-inflammatory mediators in spontaneous preterm labour and their associations with multi-factorial etiological pathways. The paper also recognises the discusses the pathophysiology of uterine contractions and the phases of uterine smooth muscle activity in the non-pregnant state, during pregnancy and parturition. In this paper, essential physiological pathways and the biological basis of available therapeutic agents for preterm labour are explored.