Chapter Thirty-Six. The onset of labour
Introduction
A great number of textbooks devoted to the social meaning of pregnancy and labour are worth reading for anyone considering how the management of childbearing is influenced by major changes and beliefs of society. The purpose of this chapter is to examine the physiological concepts associated with normal uncomplicated labour so that the reader can make informed decisions on the management of labour based on current concepts and theories.
Timing of the onset of labour
Normal labour occurs between 37 and 42 weeks gestation (Johnson 2007). However, in humans the timing of the onset of labour is less precise than in many other species, with the mean timing being 39.6 weeks with a range of 3 weeks on either side of the mean. The timing may be related to fetal brain activity via adrenocorticotrophic hormone (ACTH) and the pituitary–adrenal axis. Progesterone is then metabolised to oestrogen, which gradually increases the sensitivity of the uterus to prostaglandins and oxytocin produced by both the fetoplacental unit and maternal tissues. Large numbers of research projects into the onset of labour in cattle, sheep and humans have found that, when there is an abnormality of the fetal hypothalamus and pituitary area of the brain, extreme prolongation of pregnancy may occur (Johnson 2007, Steer & Johnson 1998).
Two major physiological changes are necessary for the expulsion of the fetus to proceed smoothly. First, the cervix must go through a structural change called softening or ripening which changes its role from support to birth canal. Secondly, myometrial tone must change to allow coordinated contractions of the body of the myometrium (assisted later in labour by contractions of striated muscles in the abdominal wall) to increase uterine pressure (Johnson 2007).
The aetiology of labour is complex and at present is not fully understood and therefore there are numerous hypotheses and theories. Consequently, an outline only of key areas of discussion is given. If the sequence of events leading to the onset of labour were fully understood it might be easier to prevent the onset of preterm labour and the devastating fetal loss and morbidity resulting from extreme immaturity. There is good evidence for a central role for prostaglandins in the initiation of labour (Karim 1966) but the composition and biosynthesis of prostaglandins by the various tissues remains unclear (see below).
The role of the fetal endocrine system
There is evidence to support the concept that the fetus is largely responsible for triggering the onset of labour. However, there is still uncertainty about the role of the fetal hypothalamus–pituitary–adrenal axis in the initiation of labour in humans. It has become apparent that the extrapolation of experimental findings from one species to another is not reliable, as events may differ between species. In sheep, parturition is initiated by a surge of cortisol secreted by the fetal adrenal cortex. This acts on placental enzymes to convert progesterone to oestrogen (Coad & Dunstall 2005). The rapid change in steroid balance stimulates the release of prostaglandins from both the placenta and the myometrium. There is increased sensitivity of the myometrium to form oxytocin receptors which are sensitive to the hormone oxytocin, and there is a reduction of the hormone progesterone, which has maintained uterine quiescence, therefore uterine contractions are produced which are powerful enough to expel the fetus (Marieb 2009).
The adrenal cortex
Johnson (2007) has summarised the research findings and suggests it is unlikely that increased production of cortisol plays a major part, as labour begins in the congenital absence of the fetal adrenals. Cortisol levels measured in the umbilical cord blood after delivery are difficult to assess, as they may increase because of the stress of labour rather than be responsible for initiating labour. Scalp blood cortisol measurements made in early labour showed no difference in spontaneous or induced labour, although there was a rise in fetal plasma cortisol as labour progressed. There is no dramatic rise in total cortisol level in fetal circulation prior to the onset of labour.
The administration of corticosteroids such as betamethasone to women in late pregnancy results in a fall in maternal circulating oestrogen levels but there is little effect on the placental progesterone synthesis or the duration of pregnancy. In the human placenta, although glucocorticoids do not induce the fall in progesterone and rise in oestrogen leading to labour, they are involved in the maturation of the fetus, in particular the fetal lung, allowing survival of a fetus born 6 weeks early. In sheep, cortisol produces both organ maturity and the onset of labour and a lamb born even 1 week or 2 weeks early may be too immature to survive.
One hormone that may be implicated in fetal control of the onset of labour is dehydroepiandrosterone sulphate (DHAS), which is the major precursor of placental estradiol and estrone synthesis. The human fetal adrenal gland is relatively large at birth with a fetal zone occupying 80% of the cortex and being responsible for the size. The function of the adrenal cortex is different in the fetus from the adult and the fetal zone atrophies after birth. It has been found that human chorionic gonadotrophin (hCG) is a major stimulator of the fetal zone during pregnancy and ACTH can also stimulate the production of DHAS.
The fetal posterior pituitary gland
Higher concentrations of the posterior pituitary hormones vasopressin and oxytocin have been found in the umbilical circulation than in the maternal circulation. Although the source of this fetal oxytocin is not clear, the levels are higher in fetal arterial blood than venous blood, which suggests fetal origin. It is possible that as much as 1–3 mU/min of oxytocin is transferred from fetus to mother, which is enough to promote uterine activity at term. An argument against the fetal role is that labour almost always follows fetal death in utero, depending on the gestational age of the fetus. Possibly the release of prostaglandins is more important and the mechanism of release differs when the fetus is dead, being provoked by the massive fall in progesterone level that accompanies fetal death.
The role of the placenta
Progesterone
It is now over 35 years since Csapo put forward a hypothesis that labour is initiated by the withdrawal of the progesterone block on myometrial activity. It has been difficult to prove or disprove this hypothesis (Steer & Johnson 1998). All attempts to use progesterone to prolong labour, postpone preterm labour or to prevent early abortion have been unsuccessful. Measurement of progesterone levels in the peripheral blood of women has not shown any withdrawal of progesterone at the end of pregnancy. However, this may not be significant if the progesterone acts locally and it may be an alteration in the binding of progesterone that is important rather than the level.
Oestrogens
Placental production of oestrogens rises as pregnancy progresses and DHAS of both maternal and fetal origin contributes to the placental production of oestrogens, most importantly of estradiol. However, women do go into labour without a rise in the concentration of estradiol and there is no dramatic rise in the levels of estradiol just prior to the onset of labour. It is probable that estradiol facilitates rather than causes the onset of labour. As yet, there is no clear evidence that changing concentrations of oestrogens and progesterone alter at the onset of labour. However, these changes in balance between the two steroid hormones facilitate increasing myometrial activity.
Fetal membranes
Steroid hormones
The fetal membranes are known to have a relatively high concentration of progesterone. Both the chorion laeve and the amnion have been shown to contain enzymes that can reduce the level of progesterone and also both chorion and amnion contain a protein which increases towards the end of pregnancy and that can bind progesterone. These two mechanisms would produce a local progesterone withdrawal effect. However, the membranes are avascular and any substance produced by them must travel by diffusion.
Prostaglandins
The amnion and chorion are both involved in the production of prostaglandins. Karim (1966) first suggested that prostaglandins play a role in the initiation of labour. It is still unclear whether prostaglandins initiate labour or maintain it. Findings from earlier studies have been unusable because of prostaglandin production by tissue trauma during sample collection. Making measurements of prostaglandins is extremely difficult as storage or temperature can affect the findings. Drugs such as aspirin act as prostaglandin inhibitors, preventing the first step in the metabolism of arachidonic acid. The fetal membranes contain significant amounts of arachidonic acid and research indicates that the membranes are significantly involved in the synthesis of prostaglandins, but once again there seems to be no significant change at the onset of labour.
Maternal influences
The decidua
The decidua within the endometrium is also implicated in the production of prostaglandins. Evidence suggests that the decidua is a major source of prostaglandins during labour. In the 1970s Gustavii studied the role of the decidua in controlling the onset of labour (Steer & Johnson 1998). Gustavii (1977) proposed that the decidual cells have lysosomes which contain phospholipase A 2, an enzyme necessary for the synthesis of prostaglandins. These lysosomes are fragile and degenerate under the influence of oestrogen in late pregnancy when progesterone levels fall and oestrogen levels rise. Steer & Johnson (1998) find this hypothesis useful in the explanation of the onset of labour at term.
Work carried out by Keirse and his colleagues in the 1970s showed that the primary prostaglandins present were PGE 2 and PGF 2α. The precursor of the two prostaglandins is an essential fatty acid called arachidonic acid which is derived from glycerophospholipids and involves several stages of conversion by enzymes. Both these prostaglandins and other PGEs are known to stimulate myometrial contractions (Johnson 2007). Production rates of prostaglandins in decidual cells may be 30 times greater in labour than at elective caesarean section.
The endocrine system
The ovaries are not necessary for the initiation of labour and it seems that maternal oxytocin from the pituitary gland plays little part in the initiation of labour. The maternal adrenal glands do not seem to play any part in labour.
Neurohormonal control
James Ferguson, a Canadian physiologist, discovered that if the cervix is stretched it increases the production of oxytocin and subsequently increased uterine activity (Banting Research Foundation 2003). The Ferguson reflex, as it is termed today, is a neurohormonal reflex (Fig. 36.1) arising from the genital tract, which may be involved in the release of both oxytocin and prostaglandin in labour (Johnson 2007
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