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.