Probable causes of preterm labour
The role of genetics in the pathogenesis of preterm labour has been duly
recognised and well documented. Emerging evidence indicates that preterm
birth appears to be transmitted primarily in a matrilineal manner across
generations and is greatly influenced by mutual environmental factors.
Thus, the risk of a woman having a preterm delivery is heightened if her
maternal biological relations had preterm deliveries but appears not to
follow paternal lines(20,21). In human genomic studies, changes in
single gene sequence were found to be associated with disorders such as
polyhydraminos, myotonic dystrophy, cervical incompetence(10,21,22) and
twin gestation which increase the risk of preterm labour and may be
transmitted from one generation to the next(23,24). These observed
single nucleotide polymorphisms in the gene can respond to inflammatory
stimuli such as infection resulting in the production of
pro-inflammatory mediators and breakdown of extracellular matrix by
matrix metalloproteinases leading to preterm labour (figure 1) (23).
Also because of the genotypic variations among different individuals,
exposure to environmental pollutants put them at increased risk of
preterm labour(10,22).
Evidence has shown that maternal psychological stress, anxiety,
financial difficulties and other life events increase endogenous
catecholamines and cortisol release which stimulate premature production
of placental corticotrophin-releasing hormone (CRH) thereby activating
the biological cascade leading to the onset of preterm labour(24).
Psychological stress also increases maternal vulnerability to infection
and inflammation due to weakened immune system (figure 1) (24).
Behavioural factors such as smoking and alcohol use are associated with
increased risk of preterm labour. Given that smoking and alcohol have
teratogenic effects and habitual engagement in these agents during
pregnancy puts them at high risk of sudden infant death syndrome (SIDS)
due to variability in autonomic nervous system function(25–27). The
Nicotine and carbon monoxide contained in smoke cause foetal hypoxia due
to carboxyhaemoglobin and vasoconstriction(27). They increase the risk
of low birth weight, foetal defects and placental complications and
compromise immune response to inflammation leading to preterm premature
rupture of membranes and preterm labour (figure 1) (24,25,27).
Consumption of alcohol during pregnancy has also proven to have
detrimental effect on foetal growth and development leading to
intrauterine growth restriction (IUGR) which poses a potential risk for
preterm labour (figure 1) (24,28).
Furthermore, pervasive indulgence in illegal drugs such as marijuana and
cocaine as well as the use of herbal medications in pregnancy have
severe embryotoxic and teratogenic effects increasing the risk of
small-for gestational age and foetal defects(29,30). Marijuana smoking
also increases the risk of carboxyhaemoglobin leading to foetal hypoxia.
On the other hand, cocaine causes elevated blood pressure due to
vasoconstriction since these psychoactive agents appear to interfere
with the reuptake of serotonin and catecholamines leading to compromised
immune response to inflammation (figure 1) (24,29).
Nutritional deficiencies (e.g. deficiencies in iron, folate or zinc, low
pre-pregnancy weight) have been implicated in preterm labour. For
instance, deficiency in iron causes iron deficiency anaemia which
increases the synthesis and hypersensitivity to endogenous
catecholamines leading to maternal and foetal hypoxia which in-turn
stimulates synthesis of foetal CRH and cortisol. The increased cortisol
production may activate the biological cascade leading to preterm
premature rupture of membranes, gestational hypertension, eclampsia IUGR
and preterm labour (24,31,32). In another pathway, iron deficiency
anaemia increases risk of infection and inflammation leading to preterm
birth (figure 1) (31,32). Physiologically, vitamin C stimulates the
synthesis of collagen fibres of connective tissue extracellular matrix
of the amnionchorion and deficiency in vitamin C depletes collagens
leading to preterm premature rupture of membranes and preterm
labour(figure 1) (24,33,34). Similarly, folate, zinc and pre-pregnancy
weight deficiencies increase the risk of restricted foetal growth and
birth defects(figure 1) (24,35). To buttress the importance of specific
nutrients, adequate maternal levels of fat-soluble nutrients provide
antioxidative, anti-inflammatory, and immunomodulatory health benefits
which are vital in preterm birth prevention. For instance, omega-3 fatty
acids facilitate increased production of specialized anti-inflammatory
mediators with resultant reduction in preterm birth risk (figure 1).
Combined effects of these nutrients support appropriate placental
organogenesis and function(36).