Labour and Parturition Flashcards
What holds pregnancy inside uterus?
cervix
What changes occur in the cervix during labour and birth?
The cervix is usually tight and closed during pregnancy and birth it needs to open to allow the expulsion of contents of the uterine cavity
During the 9 months of pregnancy the cervix acts as the stopper between the inside and outside. How is the cervix prompted to change for pregnancy?
By a phenomenon called uterine quiescence (where the muscles of the uterus remains not active or contracting it is stretching and growing)
How is uterine quiescence controlled?
by progesterone
How does progesterone function?
inhibits NFkB and COX-2 pathway which controls the myometrial contractility and reduced the inflammatory process
What is the role of progesterone during pregnancy
minimise myometrial contractions
promotes a firm and closed cervix
- helps keep pregnancy in uterus and prevents accidental expulsion
What are the factors that initiate labour?
- progesterone withdrawal
- extracellular matrix remodelling
- inflammatory mediators
- prostaglandins
- surfactant protein A
- corticotropin releasing hormone (CRH)
How does the withdrawal of progesterone help initiate labour?
progesterone helps keeps cervix long and closed during pregnancy and inhibits the myometrium from contracting in mice and rats
In humans does progesterone withdrawal help with initiating labour?
no circulating progesterone levels are unchanged during labour
Why does progesterone withdrawal not initiate labour in humans?
humans have a slightly different progesterone receptor.
Progesterone in humans can be bound to progesterone receptor A or B or a hetero-dimer whereas rats and mice only have one progesterone receptor
The targets for gene expression in the 3 human progesterone receptors are all different
Progesterone receptor expression is altered in labour in humans. What are the different levels of progesterone during different points of labour?
in preterm labour (pregnancy and not ready to go into labour)
- low expression of progesterone receptor A and B
in labour
- up-regulation of receptor A
What is the relationship between progesterone receptors and labour in humans?
the up regulation of receptor A is what plays an important role in the initiation of labour
With the increased expression of progesterone receptor A there is also an increase in what kind of gene expression?
the genes expressed by receptor A are pro-inflammatory which leads to the up-regulation of pro-inflammatory markers and cytokines
this with-drawls the effects of progesterone on reducing inflammation
*note that progesterone itself is inflammatory
With the up-regulation of progesterone receptor A there is a simultaneous withdrawal of progesterone. Why is this?
There is a down regulation of the things that enhance progesterone activity:
- cAMP response element binding protein (CBP) and steroid receptor co-activators (SRC) are significantly reduced
Why is CBP and SRC significantly reduced when there is a functional progesterone withdrawal?
these molecules enhance the activity of progesterone (helping it suppress our inflam responses)
How do we know that inflammation plays an important role in the initiation of labour?
as progesterone receptor A is up-regulated during labour it produces more inflammatory molecules and simultaneously withdrawing the effects that progesterone has on reducing inflammation (too much to keep up with).
What is the function of the cytotrophoblast in inflammation?
manage and monitor the pro-inflammatory pathways stimulated by the withdrawal of progesterone function and stimulation of progesterone receptor A response genes
Why is corticotrophin releasing hormone (CRH) known as the clock of the placenta?
it is a protein released by the placenta that seems to play a role in initiating the onset of labour
As you get closer to labour CRH levels increase significantly
- CRH binding protein (CRH BP) is high throughout pregnancy preventing CRH from being used until labour when it decreases significantly when CRH increases
CRH levels increase corresponding with labour. What occurs in CRH levels in pre-term labour
CRH levels are higher in pre-term labour than term labour
In spontaneous pre-term labour mother the CRH levels were high throughout the whole pregnancy rather than a normal term pregnancy.
- CRH levels in pre-term labour mother rise exponentially the closer they got to delivery
What are the trends seen in term and post term labours with CRH levels?
term labour
- have relatively low CRH until the 3rd trimester
post term
- lower levels of CRH than term mothers that very slowly rose as they went into the third trimester
CRH is produced by the placenta and plays a role in fetal and maternal circulation. What suppresses CRH?
progesterone and nitric oxide
The presence of CRH promotes the production of what hormone?
estrogens
and the effect of estrogen dependant hormones
The presence of CRH accumulates in the placental circulation. What is the effects of this on maternal hormone pathways?
stimulates ACTH which then increases cortisol and DHEAS
cortisol and DHEAS simultaneously promote the production for more CRH
The presence of CRH accumulates in the placental circulation. What is the effects of this on fetal hormone pathways?
fetal brain will also respond by releasing ACTH and releasing cortisol
ACTH also increases surfactant protein A (lines the lungs and allows for fetus to transition from a water envrio to air enviro)
Cortisol also promotes production of DHEAS which also produces more CRH from placenta
Levels of CRH are increased due to maternal and fetal stress hormones. Increases in CRH help the placenta with
getting ready for delivery and labour
Why is the sex steroid pathway important
most hormones in the pathway are significant in labour and birth
respond to stress environment
important for natural hormonal cycle of women
many hormones are produced from this pathway whose actions counteract each other. It is the balance of counteraction between the hormones that allow for the process to occur in a regulated fashion
Sex steroid pathway notes:
- cholesterol levels increase
- progesterone is being produced
2a. promotes production of cortisol and aldosterone - progesterone also leads to production of the estradiols
CRH is produced by the syncytiotrophoblast where it is able to cross into the maternal and fetal circulation both resulting in cortisol being released. Also the production of different inflammatory molecules that are promoted as a result of the functional withdrawal of progesterone. What doe these result in?
there is going to be a change in the production of prostaglandins
change in production of progesterone itself
this causes the balance of quiescence to swing into some kind of activity
Due to the CRH increase in fetal circulation surfactant protein A is produced. It is produced just prior to brith and allows for the lining of the lungs to prepare for gas exchange. What is known about the presence of surfactant protein and the initiation of labour?
in mice/rats
- it is know that surfactant in fetus and amniotic fluid helps initiate labour
in humans
- it is not known
How does surfactant protein A help stimulate labour in mice/rats?
- surfactant is produced as a response to stressful stimuli it can then be excreted out into the amniotic fluid
- surfactant is taken up by macrophages lining the amniotic cavity and then presented to maternal circulation via the myometrium though macrophage pathway
- as higher and higher levels of surfactant are presented to maternal circulation this help initiate labour
In humans, what is surfactant protein A’s role in labour?
higher amounts of surfactant protein A does not seem to change any of the other molecules that are involved in initiating labour
While surfactant protein A stimulates the uterine muscles to contract in mice it does not do the same in humans and role is not completely clear
Prostaglandins are important for the inflammatory process. They play an important role in the COX-2 pathway as part of their inflammatory response. What are the two main prostaglandins involved in initiation labour?
PGE2 and PGF2a
When we want to initiate labour we use the prostaglandin pathway. How does this help initiate labour?
prostaglandins play an important role for uterine contractions and the eventual separation of the placenta from the wall of the uterus
Prostaglandin production promotes cervical change and remodelling of muscles within the cervix to allow to cervix to become open
Prostaglandins promote the changes within the membranes of the amniotic that allow for it to eventually break
How can we increase prostaglandins to help initiate labour?
medically administer vaginally and onto the cervical muscles
stretching and stripping the membranes the cervical muscle helps initiate the production of natural prostaglandins
This is used to induce labour when baby needs to be delivered earlier or the body is not progressing in labour
What is NFkB and how is it regulated?
cytokine
down-regulated by the presence of progesterone
unregulated by :
- stretching of the muscles
- other inflam cytokines (interleukin 1B)
- CRH (theorised)
Having uterine activity and contractions is not enough to result in labour. Why is this?
There are sophisticated processed in place so that the pregnancy is maintained for as long as possible
Extracellular remodelling needs to occur in the cervix to do what?
to help initiate labour so that once uterine contractions happen the cervix can start to open
For the placenta, extracellular matrix remodelling needs to occur for what to happen? where the membranes that are keeping the sac of amniotic fluid contained need to break to allow expulsion of uterine cavity
The membranes that are keeping the sac of amniotic fluid contained need to break to allow expulsion of uterine cavity
How does extracellular matrix remodelling occur?
- inflammatory cytokines stimulate the production of COX-2 leading to the inhibition of progesterone and the up-regulation of prostaglandin receptor A
- other maternal hormones are up-regulated (prolactin, relaxin and urocortin) these all play a role of the upregulation of of metello matrix proteases
2b. MMP’s are proteins enzymes that break down extracellular matrix between cells, remodelling the tissues, so they can change their function in response to labour
What are the basic stages of labour
first stage
- active
- latent
- cervical remodelling is occurring and cervix itself is changing (opening, dilating and thinning)
- membranes may or may not break sometime during this stage
second stage
- passive (cervix is completely open but no active maternal or expulsive effort)
- active (maternal effort to expel fetus)
third stage
- uterine cavity is emptied
- placenta removed
- there is a bit of bleeding but the uterus is able to invert back to its non-pregnancy form
What are the factors the affect the success of labour?
- passenger
- power
- passage
What is the power factor in a successful labour?
this is about the way uterine contractions are occurring and what is stimulating those contractions
Contractions during labour are stimulated by oxytocin. What is oxytocin?
nonapeptide released from posterior pituitary, decidua, amnion and placenta
Why does the oxytocin receptor expression increase with advancing gestation?
- evolutionary survival instinct
- helps promote love for the child the women is carrying
- the desire and care for the child to ensure it is safe and looked after - Uterine activity
- within the muscles of the uterus the receptor expression increases to allow increasing efficacy of oxytocin as labour progresses
Why do women report that with each pregnancy their labour is shorter and shorter?
oxytocin receptor expression increases with each subsequent pregnancy
Is the release of oxytocin from the pituitary gland essential for labour?
no it is not
you can functional labour in. women who do not have functioning pituitary release of oxytocin
women with pituitary failure still have normal initiation and labour
How can we increase and stimulate labour in regards to oxytocin
synthetic oxytocin can be given to help increase and stimulate labour
can be used if they are in labour but not producing effective contractions to further labour or initiate labour entirely
How does the oxytocin receptor work to help continue labour?
the more oxytocin receptors are stimulated the more it regulates it own production to allow for more oxytocin receptors to be present (positive feedback loop)
How do oxytocin receptors work to create contractions?
- oxytocin binds to oxytocin receptors on myometrial cells
- stimulates a signalling cascade that results in the influx in calcium into the cytoplasm of cells via calcium channels in the cell membrane
- this also promotes the release of calcium from the endoplasmic reticulum
- the calcium influx allows for the activation of myosin by phosphorylation
- this can then interact wth actin producing actinamyosin
- this results in uterine contraction and as oxytocin up regulates itself which continues the process further
What is the passage factor affecting labour?
need to ensure that the fetus can move through the birth canal in an appropriate fashion
What is the phenomenon of cephalic pelvic disproportion
when the pelvis does not allow for the passage of the fetus as the babys head cannot fit neatly into the pelvis shape
What is the passenger factor affecting labour?
this is the baby
different ways the baby is presenting may prevent or enhance the natural process of labour
What are the different fetus positions in the uterus and how does this affect labour?
- baby neck tucked in with head down and eyes down
- presents into pelvis at about 9.5 cm
- good position for baby to appropriately pass through 10 cm pelvis - The further back the baby’s chin is tucked the larger the diameter becomes until the baby is very flexible and head flips the neck completely back
- when head is completely back the diameter is less than 10 cm allowing for good passage
mal-position and mal-representation affects a number of births. The different way the baby is presenting will affect the process of labour and may effect the expulsion of the baby during the second phase of labour.
1:500 = face presentation
1:1500 = brow representation
3% of babies are breech
1% will be in an oblique or transverse lie
vast majority of babies are going to be in the right position in order to facilitate effective childbirth but a small number of babies will be in a position where we cant effectively get the fetus through the birth canal
What is a partogram and how is it used to monitor mothers in labour?
- how dilated the cervix is
- how far babys head is descending
monitor both through latent phase
- progress in the dilation of cervix might be slow and unpredictable
AND also the active phase
- dilation of cervix should be predictable over a certain rate of time
What are action and alert lines on a partograph?
arbitrary lines that alert us to the fact that the rate of which the cervix is changing and the rate at which the fetus head is descending is not following the pattern we would normally expect
serves as an early warning marker for clinicians that things are not changing and we may need to intervene in some way
How can clinicians intervene if partograph showing alert or warning lines
- trying to position the baby differently
- moving the mother into a position where her pelvis is more open
- increasing the frequency contraction or strength of contraction
How can we monitor the fetus during labour to make sure they are not becoming distressed?
- cardiotocograph
- tracings of the babys heart rate - fetal blood sampling
- see signs of hypoxic stress
What is the difference between stress and distress in the fetus during labour?
stress naturally occurs during labour
distress is when indicators monitoring the fetus fall outside the regular stress of labour and may have a pathological cause
labour ideally occurs at 40 weeks of pregnancy when the fetus
is aqdeuately grown and internal structures and organs development allow it to survive independently outside
it occurs when fetus is well oxygenated, healthy and well nourished and doesn’t occur too far as the placenta has a use by date
What happens with birth occurs too early?
when labour is initiated too early about 1 million babies die globally
we are able to resuscitate from 23 weeks
- some exceptions at 22 weeks depending on size of baby
significant costs in health care dollars, significant heart ache for families and significant trauma for babies
being born too early leads:
increased hospitalisation throughout their life
What if labour occurs too late?
placenta only can function for about 40 weeks (varies based on ethnicity)
6 still born babies everyday in australia
