2b. Labour

Question 1

Define miscarriage

Answer 1

Loss of a non-viable pregnancy

Usually occurs within 13 weeks of fertilisation

Question 2

What would be the time frame considered as term?

Answer 2

37-41 weeks of gestation

Question 3

What would be the time frame considered as preterm?

Answer 3

23-37 weeks of gestation

Often occurs due to preterm labour as we cannot easily stop labour once it has been induced

Question 4

What would be the size of a baby born in term?

Answer 4

Length of the body of the baby is the size of a human forearm and the head is the size of a human hand

Question 5

How are the baby’s structures different in preterm delivery?

Answer 5

All the structures are present but they are much smaller and may not work properly

Question 6

What does it mean to be in labour?

Answer 6

1. Fundally dominated contractions - The uterus is undergoing regular coordinated contractions - they go from the top of the uterus (fundus) and pushes downwards so the baby moves towards the cervix
2. Cervical ripening and effacement - the cervix is a thick structure that holds the baby in place. It must relax to let the baby out during labour which involves tissue change along it the contractions

Question 7

Outline the different processes that occur in labour

Answer 7

Cervical ripening and effacement (increasing)
Co-ordinated myometrial contractions (increasing)
Rupture of fetal membranes
Delivery of infant
Delivery of placenta
Contraction of uterus

Question 8

What are braxton hicks contractions? What is the function of these?

Answer 8

When the uterus contacts partly or when it contracts then relaxes again
The uterus is relaxed throughout pregnancy to allow growth of the fetus so these small contractions are a training phase which allows the uterus to get into the routine of contracting

Question 9

How long does labour last for?

Answer 9

12-48 hours

Question 10

What happens in each of the three phases of labour?

Answer 10

Phase 1 - the contractions and cervical changes start (longest part of pregnancy as the uterus has to go from relaxed to contracting)
Phase 2 - delivery of the baby
Phase 3 - delivery of the placenta

Question 11

What initiates human term labour and pre-term labour?

Answer 11

Term - could be low progesterone, oestrogen CRH or oxytocin but not sure
Pre-term - Intrauterine infection
Intrauterine bleeding
Multiple pregnancy
Stress (maternal)

Question 12

What happens in cervical ripening and effacement? What molecules are involved?

Answer 12

Change from rigid to flexible structure
Remodelling (loss) of extracellular matrix
Recruitment of leukocytes (neutrophils)
Inflammatory process
  -Prostaglandin E2, interleukin-8
  -Local (paracrine) change in IL-8

Question 13

What happens in myometrial contractions? What are the key mediators involved?

Answer 13

Fundal dominance
Increased co-ordination of contractions
Increased power of contractions
Key mediators
  -Prostaglandin F2a (E2) levels increased from fetal membranes
  -Oxytocin receptor increased
  -Contraction associated proteins

Question 14

What happens in the rupture of fetal membranes during labour?

Answer 14

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

Question 15

What is the main transcription factor involved in these inflammatory processes?

Answer 15

NF-kB

Question 16

What does NF-kB do?

Answer 16

Upregulates inflammatory molecules such as:

COX-2 (prostaglandins - PGs), IL-8, IL-1b, MMPs, Oxytocin receptor, PG receptors; contraction-associated proteins

Question 17

Why is it hard to stop labour once it has been initiated?

Answer 17

There are many different initiators of labour that increase NF-kB levels so it will be hard to turn them all off
Molecules formed due to NF-kB such as IL-1b can further increase NF-kB levels resulting in a feed forward loop

Question 18

What is one of the main causes of preterm labour?

Answer 18

Activators of inflammation (e.g. intrauterine infection)

Question 19

What are the two main molecules involved in term labour?

Answer 19

CRH and PAF (platelet activating factor)

CRH levels steeply rise in the 3 weeks before delivery

Question 20

What is the function of platelet activating factor and where is it found?

Answer 20

Part of lung surfactant which is needed to allow the baby to breathe
Surfactant proteins and complexes
Produced by maturing lung, before birth
Levels in amniotic fluid increase near term
Fetal signal of maturity - matured lungs produce a factor which allows the baby to then be born

Question 21

What do CRH and PAF produce?

Answer 21

Prostaglandins from fetal membranes

Question 22

What is the function of the increasing levels of CHR?

Answer 22

CRH is normally produced in the placenta, and the levels are low in early pregnancy. As pregnancy proceeds, levels of CRH produced increase. It goes through the umbilical cord to the baby, and works on the baby’s HPA axis (stimulates ACTH production, which in turn stimulates the foetal adrenal glands).
The adrenal gland, under stimulation, produces cortisol which causes lung maturation (and also travels back, via the umbilical cord, to the placenta).
Cortisol normally switches DOWN the production of CRH (negative feedback). In the placenta, cortisol switches UP CRH production (feed-forward loop). More CRH and more cortisol feedback loop. There is a rapid rise in CRH in the last few weeks of pregnancy

Question 23

How does CRH upegulate PAF and how does this then act?

Answer 23

The high levels of CRH will start to switch UP IL and prostaglandin production in the foetal membranes
Cortisol from the adrenal gland is acting on the foetal lung
It stimulates the foetal lungs to produce surfactant (including PAF)
Lungs are in intimate contact with amniotic fluid (baby takes amniotic fluid into lungs, and expels it)
This allows PAF to enter the amniotic fluid, and PAF upregulates the same factors in the membranes
PAF is a signal that the lungs are mature, and therefore the baby is safe to be born

Question 24

What is the function of DHEAS

Answer 24

This is a steroid produced in the adrenal glands
It can move to the placenta and can be converted to oestrogens (it is an oesrogen precursor)
Oestrogens upregulate PGs, OT and OT receptors – all required for increased myometrial contractility

Question 25

What hormone is absolutely necessary for preganancy to occur and what happens to this during labour?

Answer 25

Progesterone

Its effects are lost in normal term labour

Question 26

How does progesterone stop labour from occurring?

Answer 26

During pregnancy, there are a lot of progesterone receptors as well as progesterone present
The receptors can bind to NF-kB and stop it from activating pro-inflammatory molecules

Question 27

Why do the effects of progesterone cease at the end of pregnancy and how is labour then induced?

Answer 27

Progesterone receptor levels decrease at the end of pregnancy. This means that progesterone can’t have its effect and NF-kB will also be unbound and can exert its pro-inflammatory effects

Question 28

What is this process of reduced progesterone function called?

Answer 28

Functional progesterone withdrawal - Progesterone itself is not removed but its function is reduced

Question 29

What are the different progesterone receptors and how do the proportion of these change?

Answer 29

PR-B mediates the main effects of progesterone via gene expression
PR-A is less able to mediate these effects
Ratio of PR-A : PR-B increases at term
Loss or change in PR may lead to ‘functional progesterone withdrawal’