What is term delivery?
37-41 weeks gestational age (since LMP)
What is birth?
The final phase of pregnancy
What is pre-term delivery? What are the 4 organ system affected by preterm birth?
22-37 weeks gestational age (since LMP)
- lungs, the digestive system, the immune system and the brain develop late in pregnancy so are affected
What is very pre-term delivery?
28-32 weeks gestational age (since LMP)
Outline the stages of pregnancy up to labour.
Not in labour (~39 weeks)
Latent stage (~8 weeks)
Labour (12-48 hours)
What are the key tissues involved in labour?
- Cervix
- Myometrium
- Foetal membranes
Summarise the main biochemical processes of labour (endocrine, inflamm)
KEY REGULATOR = NFkB
Foetal membranes - Waters breaking
- Inflammatory process
- PGs, ILs, MMPs
Cervix dilation - effacement, ripening
- Prostaglandin E2, interleukin-8, MMPs
Myometrium
- Increased contraction associated proteins
- Increased oxytocin receptors
- PGF2a (E2) levels increased from foetal membranes
How is the cervix assessed before the onset of labour?
Summarise how examination of the cervix is used to assess the progress of labour.
Bishop’s score
- Pre-labour scoring system to assist in predicting whether induction of labour will be required
- Also used to assess likelihood of spontaneous preterm delivery
Total score calculated by assessing 5 components on manual vaginal examination:
- Cervical dilation in cm
- Cervical effacement as %
- Cervical consistency
- Cervical position
- Foetal station - position of foetal head in relation to pelvic bones
Call PEDS For Parturition! = Cervical Position, Effacement, Dilation, Softness; Foetal Station
What are the 3 stages of labour?
Phase 1 - longest stage (10-15 hrs) - onset of (1) coordinated myometrial contractions (2) cervical ripening, effacement and until full dilation (10cm)
Phase 2 - 1-2 hrs - (1) full cervical dilation (2) rupture of foetal membranes (water breaking) and (3) delivery of infant
Phase 3 - very fast (10-30 mins) - delivery of placenta and membranes via uterine contraction
Describe the mechanism of uterine contractions in labour.
- start at top and squeeze at bottom (fundal dominance)
- as labour progresses, contractions increase in coordination and power
- key mediators
- increased prostaglandin F2alpha and E2 (from foetal membranes) – caused by contractions – effects = more contractions and soften cervix (+ve feedback)
- increased oxytocin receptor (NOTE: oxytocin X rise only receptor no. rises)
- increased contraction associated proteins
What is cervical effacement (and dilation)? Describe the mechanism that causes effacement and dilation.
Effacement = shortening and thinning of cervical walls
- Cervix becomes + more flexible
- Cervix changes from rigid to more flexible + softer structure
- Remodelling (loss) of ECM
- Recruitment of leukocytes (neutrophils)
- Inflammatory process - PGE2, IL-8
- Paracrine (local) change in IL-8
What causes the rupture of foetal membranes?
- Loss of strength due to changes in amnion basement component
- Inflammatory changes, leukocyte recruitment
- Modest in normal labour, exacerbated in preterm labour
- Increased levels and activity of MMPs
- Inflammatory process in fetal membranes
What is the key regulator of labour? Describe its importance.
NFkB
- Proinflammatory transcription factor (many initiators > NFkB > pretty much every mediator in labour)
- Evidence of it being central in labour
- Almost all pro-labour genes have NFkB binding domains in their promoters
- Modification of NFkB sites in promoter sequences leads to loss of expression in cells or in expression vectors
What are some initiators of term delivery?
CRH and PAF rise before labour and up-regulate inflammatory pathways in fetal membranes, causing rise in PGE2, COX2 and Interleukin-1beta
NOTE: Platelet activating factor
- Fetal signal of maturity
- Part of lung surfactant
- Produced by maturing lung, before birth > Levels in amniotic fluid increase near term
What are the general rules of initating labour?
- Anything that increases CRH may predispose to labour (stress, multiple infants)
- Anything that increases muscle contraction may predispose to labour (excess stretch of uterus)
- Anything that activates inflammatory cascades may predispose to labour
- All these apply to preterm labour (intrauterine infection, bleeding, twins)
- Interuterine infection (through stimulation of TLR 2/4 receptors) can upregulate NFkB production and hence downstream inflammatory cascade > preterm labour
What is the significance of progesterone in pregnancy?
- Progesterone is NEEDED to sustain pregnancy
- Progesterone receptor blockade: pregnancy loss
- Progesterone levels remain very high until after delivery of the placenta (unlike sheep)
- Effect of progesterone lost in normal term labour
What are the 2 progesterone receptors and how are they changed at term to cause delivery?
There are 2 progesterone receptors: PRA and B
PRB mediates the effects of progesterone in pregnancy via gene expression and PRA inhibits the action of PRB
At term, there is ‘functional progesterone withdrawal’
- ratio of PR-A : PR-B increases
- Reducing the effects of PRB in relation to PRA reduces the effects of progesteron
Describe the events afterbirth.
Uterus continues to contract after baby delivered
- Causes placenta to detach from walls of uterus and eject out of vagina
- Help uterus to return to pre-gestation size = involution
- Allows abdominal organs to return to original positions
Hemostatic changes
- E.g. INcreased clotting
- To prevent maternal hemorrhage
- uterine contractions also help squeeze off maternal blood supply
