Labour Flashcards
when does miscarriage most often occur by definition?
before week 22 (late)
also in first trimester (13 weeks)
in what weeks is term?
37-41 weeks gestation
by labour or caesarean
in what weeks is preterm (extremely to late) ?
23-37 weeks gestation
by pre-term labour or emergency caesarean
what is the definition of labour?
increasing fundally dominated contractions combined with increasing cervical ripening and effacement.
what can contribute to miscarriage?
the suddenly change in blood supply to the foetus
what processes are involved in labour (independent of the gestational age)?
o Cervical ripening and effacement – INCREASING.
o Co-ordinated myometrial contractions – INCREASING.
o Rupture of foetal membranes.
o Delivery of infant then delivery of placenta.
o Contraction of uterus.
in what stages of pregnancy is labour experienced?
- she may not experience labour for all 39 weeks till term
- she may experience labour in the “latent stage” –> 8 weeks leading up to term
- she will eventually experience labour in term (12-48 hours)
how is labour split?
- phase 1- many hours
- phase 2- hours
contractions and cervical changes -> baby delivered - phase 3- 30 minutes
placenta delivered
phases get shorter
labour is quicker in the second pregnancy
time frames for term terms:
Term
Post-term
Pre-term
Extremely preterm
Very preterm
Moderate to late preterm
Miscarriage
Early miscarriage
Late miscarriage
Term= 37-41 weeks Post-term= 42 weeks or more Pre-term= 22-37 weeks
Preterm:
- Moderate to late preterm= 32-36 weeks
- Very preterm= 28-32 weeks
- Extremely preterm= 22-28 weeks
Miscarriage= Less than 22 weeks (non viable infant delivered).
Early miscarriage= First trimester
Late miscarriage= Second trimester less than 22 weeks.
how is labour initiated during term?
mechanism is not understood as studies are not doable
may be oestrogen: progesterone high ratio, CRH or oxytocin
how is labour initiated during preterm? i.e. causes
intrauterine infection bleeding
multiple pregnancy
stress (maternal)
these all cause CRH, inflammation to increase or uterine contractions to increase, leading to labour
what are the cervical changes in labour?
Change from rigid –> flexible structure.
Remodelling
– loss of ECM.
Recruitment
– of leucocytes such as neutrophils.
Inflammation
– Prostaglandin E2, IL-8.
what are the 3 main processes in labour?
o Cervical ripening and effacement
o Co-ordinated myometrial contractions
o Rupture of foetal membranes
how is co-ordinated myometrial contraction mediated?
A fundal dominance with increased power and coordination.
Mediators:
- prostaglandin F2 alpha (E2) increased
- oxytocin receptors increased
- contraction associated proteins
why do the foetal membranes rupture? what is this mediated by?
loss of strength due to changes in amnion basement membrane (remodelled)
Inflammation and leucocyte recruitment
(exacerbated in preterm), increased MMPs
mediators of cervical ripening and effacement?
Prostaglandin E2
IL-8
MMPs.
mediators of myometrium contraction?
- Prostaglandin F2alpha (E2)
- oxytocin receptor upregulation
- contraction associated proteins.
mediators of foetal membrane rupture?
Prostaglandins
ILs
MMPs
inflammatory processes.
what is NFkappaB?
pro-inflammatory transcription molecule
how does NFkappaB have its inflammatory effects?
via: COX-2-->PGs IL-8 IL-1beta MMPs oxytocin receptors PG receptors contraction-associated proteins.
increase cytokines which then go into a +ve FB loop
what is the evidence for the role of NFkappaB in labour?
Pro-labour genes have NFKB binding domains in promotor regions.
Modification of NFKB sites in the domains lead to loss of expression of the cells.
what is NFkappaB closely related to?
IL-1beta , IL-6, COX2, cPLA2, IL-8
what candidate initiators of NFkappaB are involved in the regulation of labour?
1) CRH
- Corticotrophin Releasing Hormone.
2) PAF
- Platelet Activating Factor
what are the main molecules that control labour?
CRH and PAF which activate other molecules and eventually up regulate MMPs, PGE2, COX-2 and oxytocin receptors and IL-1beta
PGE2 is constitutively expressed before any changes can be witnessed that are conducive to labour
what examples of pathways for mediators to initiate the processes of labour?
e. g. COX-2–> PGE2–> cervical ripening
e. g. oxytocin receptor–> myometrium
e. g. IL-8–>neutrophils–> MMPs–> cervical ripening
all regulated by CRH and PAF
where can CRH be produced?
pituitary gland AND human placenta
how do CRH levels change during pregnancy and labour?
Levels rise at the end of pregnancy before labour whilst CRH-binding-proteins drop towards end of pregnancy (so there is more active CRH)
High CRH also correlates with high COX2 molecule expression.
what produces PAF?
part of lung surfactant that is produced by maturing lungs before birth
what happens to amniotic fluid near term?
rises
what is the level of PAF indicative of?
level of foetal maturity (may stimulate labour)
where is PAF produced? what is the effect of PAF?
directly made by the lungs which acts to create ILs which stimulate PG production.
what is the effect of CRH produced in the placenta on the baby?
Parturition hypothesis:
- stimulates the baby hypothalamus via the umbilical cord so ACTH can be released from the pituitary that go to the foetal adrenals to produce cortisol (a STRESS hormone)
- cortisol will have a +ve FB effect on CRH production in the placenta
- foetal adrenals also produce mediators for myometrial contractions
what does the parturition hypothesis describe via the CRH mechanism?
o Anything that increases CRH may lead to labour (stress, multiple infants).
o Anything that increases muscle contraction may lead labour
(excess stretch of uterus).
o Anything that activates inflammatory cascades may lead labour.
this also applied preterm e.g. stress due to IU bleeding
what is needed to sustain pregnancy?
progesterone
when does progesterone level drop after being high during pregnancy?
after the delivery of the placenta
how does progesterone have non-labour promoting effects?
binds to NFkappaB leading to its inhibition
what is the effect of high NFkappaB?
has labour promoting effects:
it binds to progesterone receptors so progesterone can not sustain pregnancy so labour can begin
hence high levels of NFkappaB towards the end of term
which progesterone receptor mediates the main effects of progesterone?
PR-B (more than PR-A)
found throughout pregnancy to maintain progesterone effects
what are the changes in number of PR-B and PR-A towards term?
more PR-A: PR-B so progesterone can have less pregnancy sustaining effects so labour can be initiated
i.e. progesterone binds best to PR-B to have pregnancy maintaining effects
what does labour resemble overall?
inflammation resposes to foetal membranes and cervix
what are the main tissues active during labour?
myometrium and cervix
what is the key regulator of labour?
NFkappaB
how does preterm and term labour differ?
the initiator factors involved
what is the role of labour in context of progesterone?
labour tries to disrupt the effects of progesterone by disrupting receptors
what is functional progesterone withdrawal?
loss or change in progesterone level at the end of term
[maternal progesterone remains high during labour until placental delivery]
what 3 main factors trigger labour?
1) increased CRH and PAF (e.g. twins,stress)
2) increased myometrial contraction (e.g. twins)
3) increased inflammation (e.g. IU infection,bleeding)
