3. Pregnancy + labour Flashcards
Which trimester are spontaneous miscarriages more likely in?
First trimester
What is the absolute limit survival outside the womb, without the intensive care unit?
27 weeks
What factor defines the end of the 2nd trimester?
Absolute limit of survival outside the womb (end of 27 weeks)
What happens to maternal blood volume, blood clotting tendency and blood pressure during pregnancy?
- Blood volume - increased
- Blood clotting tendency - increased
- Blood pressure - decreased
(all in 2nd trimester)
In which trimester is matenral brain function, hormones, immune system, appetite and emotional state altered?
1st trimester
What functional homologue of LH (driving oestrogens and progesterones production) is the key hormone of human pregnancy?
Human chorionic gonadotrophin
Where does hCG stimulate progesterone production from to keep the pregnancy going?
Corpus luteum
Which somatotrophin hormone increases as the size of the placenta increases?
Placental lactogen (oestrogens and progesterones show the shame pattern)
Which organ takes over oestrogen/progesterone production from the corpus luteum a few months into pregnancy?
Placenta
In which trimester are there peak hCG levels?
1st trimester (then declines after)
What happens to LH and FSH during pregnancy?
Suppressed by steroids negative feedback on HPG
Which part of pregnancy poses the biggest threat to maternal health and life?
Delivery process
What is a conceptus?
Everything resulting from ferilised egg (baby, placenta, umbilical cord etc.)
What is the expected timing of delivery?
- 39-40 weeks
* 280 days since the beginning of the last menstrual period
When do we establish ovulation, and what do embryologists use as the point of fertilisation?
- We take first day of the last menstrual period, and work out ovulation as 2 weeks after that day
- Embryologists take the first day as the point of fertilisation
2 week difference, but not huge difference in the scheme of term dates
Which gestational ages does ‘term’ cover?
37-41 weeks gestation
Any deliveries either side of these limits are pre-term or post-term
What are agents that can harm the development of an embryo or foetus?
Teratogen (more vulnerable earlier on in pregnancy)
What are the separations in the placenta called?
Cotyledons (30-60 per placenta)
What is the primary subunit of the placenta?
Placental villus
Describe the development of the human placenta?
- Conceptus is almost completely implanted within the endometrium (day 9 post-fertilisation)
- Outer layer is multinucletated syncytiotrophoblasts, containing fluid-filled lacunae
- Underlying cytotrophoblast is proliferating into the syncytium
- Columnar structure forms (cytotrophoblast column) which undergoes branching (villous sprouts)
- Mesenchymal cells at the centre of each villus - villus vascular system develops from these cells
- Branching continues
Why are there fewer cytrotrophoblasts at term?
For closer apposition between the syncytium and placental capillaries
Explain the remodelling of arteries in the placenta?
• Cytotrophoblast cells block spiral arteries - part of remodelling them
- limited oxygen supply could keep free radicals low
• Also involves loss of endothelium and smooth muscle cells of the arteries
• End up with distended, non-vasoactive vessels - can carry more blood at low pressure
• Allows high blood supply in trimesters 2 and 3 (greatest growth)
What does the cytotrophoblast do to the conceptus for 4 week post-fertilisation?
- Forms a shell around the conceptus
- Isolates it from maternal blood
- Shell remains in place for 8 weeks, plugging the spiral arteries
- Breaks down during week 10-12 starting with those at periphery of placenta
What initally provides the nutrients to the placenta and developing baby?
Decidual glands (hypertrophy)
What can happen if the placenta isn’t fully anchored to the maternal decidua?
Increased pressure from arterial supply can detatch it => miscarriage
What percentage of pregnancies end in labour (including emergency Caesarean), or are delivered by electrive Caesarean?
- Labour - 75%
* Caesarean - 25%
What should a newborn baby look like?
- Soaking wet
- Tension in its limbs
- Air bubble at the mouth (indicates crying)
- Head and body are the size of an adult hand and forearm respectively
What is a breach?
The baby is the wrong way up
What happens to the foetal membranes during labour?
- Remodelled
* More likely to rupture
What are Braxton Hicks contractions?
- Part of the myometrium contracts briefly, then relaxes
- Occurs intermittently, but regularly
- Last 8 weeks of pregnancy
What happens in Phase I of labour?
- Can last many hours
- Fundally dominant contractions
- Cervical ripening (softening) and effacement (thinner)
- Varies from 12-48 hours
What happens in Phase II of labour?
- Can last hours
* Baby is delivered in this phase
What happens in Phase III of labour?
- Half an hour (approx.)
* Placenta is delivered in this phase
How does the length of labour change with time?
- Gets shorter
* Uterus might get better at changing
What causes labour?
- Not really known
* Could by driven by oestrogens, low progesterone or CRH (corticotrophin-releasing hormone) and oxytocin
What can cause pre-term labour?
- Intrauterine infection (or elsewhere
- Intrauterine bleeding
- Multiple pregnancy
- Maternal stress
What does cervical ripening and effacement involve?
• Loss of ECM • Recruitment of leukocytes (neutrophils) • Inflammatory, production of: - prostaglandin E2, IL-8 • Local (paracrine) change in IL-8
What mediators does the myometrium become more responsive to, to make it contract in labour?
- Prostaglandin E2 (levels increase)
- Oxytocin receptor increased
- Contraction associated proteins
What contributes to the rupture of foetal membranes in labour?
- Loss of strength due to changes in amnion basement component
- Inflammatory changes - leukocyte recruitment
- PGs, interleukins
- Increased levels and activity of matrix metalloproteinases
Which key transcription factor switches on many processes in labour?
NF-kappa-B (NFkB)
• Part of the classic pro-inflammator cascade
• Enters the nucleus to upregulate a range of protiens e.g. cytokines, chemokines, adhesion molecules and COX-2
Which cytokine is an example of why labour is so difficult to stop once it’s started?
IL-1 can uprefulate the NFkB pathway further - positive feed-forward loop
Can foetal membranes influence PGE2 production (the ones that induce labour)?
Yes
How does the CRH binding protein change in labour?
Declines => increased free CRH
How does platelet activating factor (PAF) affect the pro-inflammatory cytokines involved in labour?
Upregulates them - could be part of labour control
How does PAF affect the lungs?
- Part of lung surfactant
- Increase of PAF could be for baby surfactant, as they don’t have it in utero (all O2 from placenta)
- Surfactant proteins and complexes are produced in the last months of pregnancy (increase in amniotic fluid)
- This is a foetal sign of maturity (lungs are the last thing to develop in a baby)
Where is CRH produced in pregnancy?
Placenta
Which hormone stimulates lung development and how does it affect CRH?
- Cortisol
- Stimulates PAF (production and) to enter the amniotic fluid, which is taken up by baby into lungs
- Normally it switches down CRH production
- In the placenta, it switches up CRH production
- Causes the rapid rise of CRH in the last few weeks of pregnancy
What is DHEAS and what does it do in labour?
- Steroid produced in the adrenal glands
- Can move to the placenta and be converted to oestrogens
- Oestrogens upregulate PGs, oxytocin and oxytocin receptors
Why might multiple pregnancies cause pre-term labour?
- Multiple placentae
- More CRH
- Accelerated labour
- Also more stretch of the uterus
Which hormone is needed to sustain pregnancy?
Progesterone
progesterone antagonist can cause pregnancy loss
What happens to the effect of progesterone in labour?
- Lost
* Interaction between the progesterone receptor and NFkB
Why does NFkB not upregulate inflammatory cascades for most of pregnancy?
- Lots of progesterone receptors
* NFkB interact with them, so they cannot do their normal job
Describe the 2 sorts of progesterone receptors and how they change at term
- PR-A and PR-B
- PR-B is more active and 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
- Causes progesterone to have less of an effect - allows labour to take place
