Pregnancy/Labour

Question 1

How can human pregnancy be divided into?

Answer 1

3 Trimesters - defined by experience

1st trimester: 0-13 weeks - If the pregnancy gets to the end of the 1st trimester it is very likely to continue successfully.
2nd trimester: 14-26 weeks - Without a neonatal intensive care they are highly unlikely to survive.
3rd trimester: 27-40 weeks

There are maternal changes throughout the 3 trimesters - 1st trimester difficult to see they’re pregnant. 2nd and 3rd you can see they are pregnant. The placental changes are complex
See diagram

Question 2

Describe the maternal changes in pregnancy and in what trimesters?

Answer 2

Increased weight [3rd]
Increased blood volume [2nd & later]
Increased blood clotting tendency [2nd & later]
Decreased blood pressure [2nd] - Postural hypotension, fainting

Altered brain function [1st & later]
Altered hormones [1st & later]
Altered appetite (quantity and quality) [1st & later] – GI imbalance, Hyperemesis gravidarum (morning sickness)
Altered fluid balance [2nd & later]
Altered emotional state [1st & later] - postnatal depression
Altered joints [3rd] - joints become more flexible
Altered immune system [1st & later] - the foetus and placenta are rejected as foreign bodies

Question 3

Describe maternal changes in the endocrine system

Answer 3

HCG - reaches the peak around 8 weeks during gestation in the 1st trimester. Correlated to morning sickness.

Progesterone oestrogens and placental lactogen all increase gradually. This increase is due to the gradually increase in the size of the placenta. Progesterone>Oestrogens>Placental lactogen
These hormones fall when the placenta is delivered. Progesterone is required to maintain pregnancy - this is important.

All of these hormones are produced in the placenta

Question 4

Summarise the risks pregnancy has on the mother?

Answer 4

Relatively little risk in the early parts of pregnancy, the main risk to maternal health (or life) linked to delivery

Question 5

Define conceptus

Answer 5

everything resulting from the fertilised egg (baby, placenta, fetal membranes, umbilical cord)

Question 6

Define embryo

Answer 6

the baby before it is clearly human

Question 7

Define fetus

Answer 7

the baby for the rest of pregnancy. It is about 8 weeks when you start describing the embryo as a fetus.

Question 8

Define infant

Answer 8

less precise, normally applied after delivery

Question 9

Describe the development from blastocyst to fetus

Answer 9

1) Blastocyts - 9 days. consists of bilayer of epiblast and hypoblast cells. Starts off as a ball of cells.
2) Embryo - 5-6 weeks.
3) Fetus - 3 months.

The timings refer to post fertilisation. Counting from when fertilisation happens.

Question 10

When do you start counting pregnancy. How is pregnancy is normally counted.

Answer 10

1st day of the last menstrual period - this system is used because it is easier for the women to remember when their last period was. Embryology timings are different!

Question 11

How can you observe human pregnancy?

Answer 11

Measurements can be made of circulating factors or dimensions
Scans

Question 12

What determines pregnancy lengths between different species?

Answer 12

Essentially the length of pregnancy correlates to how big the baby is when its born

Question 13

What are teratogens?

Answer 13

An agent or factor which causes malformation of an embryo. Exposure of the embryo to teratogens early on can cause problems. The first 8 weeks of development is when the embryo is most vulnerable. See slide

Question 14

Describe the placenta on the fetal side

Answer 14

20 cm wide
Umbilical cord attached in the middle
Around the placenta are membranes - fetal-placental membranes which surround the baby and hold the amniotic fluid in place during pregnancy.

Question 15

Describe the placenta on the maternal side

Answer 15

Placenta is made up of sections of tissue called cotyledons - usually small at the edge and bigger in the middle. These are the functional subunits of a placenta.

Question 16

Describe the basic placental structure

Answer 16

See slide
Placental vilus:
Very highly branched structure, provides a large surface area (~11m2).
Very effective for transport of molecules between maternal and fetal circulations.
Also anchors the placenta (and hence the baby) securely for 9 months.
Intimate contact between maternal and placenta tissues – cytotrophoblast layer separates the main maternal blood supply from the placenta itself. This anchoring of the placenta must take place properly - if this cytotrophoblast layer breaks down then the high blood pressure of the mother may go in and move the placenta causing a miscarriage in the 1st trimester.

Cytotrophoblast shell limits blood (oxygen) supply to embryo during early development. The embryo requires a low oxygen environment for it to develop - oxygen holds a potential to generate free radicals.

Remodelling of spiral arteries allows high volume blood supply in trimesters 2 and 3, when infant growth is greatest. It remodels so the it is no longer vascular smooth muscle which can contract.

Question 17

What are the placental (or villous) functions?

Answer 17

Separation - separates blood supply
Exchange
Biosynthesis
Immunoregulation -  means the mother immunesystem doesn't reject the conceptus. 
Connection

Question 18

Describe placental development

Answer 18

Starts as a layer of single cells in the blastocyst (see slide 11)

These proliferate and differentiate

Form simple branched structure, expands iteratively. Chorionic villus grows and develops until it starts to fold back on itself
See diagrams

Question 19

What happens when you get placental mal-development

Answer 19

Miscarriage (late first trimester)
Miscarriage (second trimester)
Pre-eclampsia (early delivery)
Fetal growth restriction (small infant)

Question 20

Define miscarriage

Answer 20

loss of a nonviable pregnancy (<23 weeks of gestation)

Question 21

Define term

Answer 21

This is a time frame of 37-42 weeks when the baby is ready for extra uterine life.

Question 22

Define preterm

Answer 22

Is any baby delivered before 37 weeks of gestation
23-37 weeks of gestation

We can initiate early labour when the baby is in danger or if the mother is danger. E.g the mother has pre-eclampsia - high blood pressure.

Question 23

Define labour

Answer 23

Uterus is undergoing regular coordinated contraction.
The fundus is where the contractions start and go down pushing the baby towards the cervix.

Cervical ripening and effacement

Question 24

Describe the process of labour

Answer 24

Independent of gestational age:

1) Cervical ripening and effacement (increasing)
2) Co-ordinated myometrial contractions (increasing)
3) Rupture of fetal membranes - keeps the amniotic fluid in.
4) Delivery of infant
5) Delivery of placenta
6) Contraction of uterus

Question 25

Describe the labour stages

Answer 25

See diagram
Latent stage (~8 weeks) - where you get braxton hicks contractions = partial contraction of the uterus. "Uterus training"

Labour can last up to 48 hours:
Phase 1 - contractions increase in force, cervical changes. This phase take many hours
Phase 2 - baby delivered
Phase 3 - delivery placenta

Question 26

What causes the initiation of labour?

Answer 26

Term - normal labour

• Not really sure!!!
• Estrogens; low progesterone?; CRH?; oxytocin?

Preterm - early labour
 - Intrauterine infection
 - Intrauterine bleeding
 - Multiple pregnancy
 - Stress (maternal)
 - Others
Inflammatory changes are strongly linked with labour
Activators of inflammation are readily linked with preterm labour (eg intrauterine infection)

Question 27

Describe cervical ripening and effacement

Answer 27

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 28

Describe coordinated myometrial contractions

Answer 28

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 29

Describe the rupture of fetal membranes

Answer 29

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 30

Summarise the tissues and process in labour

Answer 30

Cervix
- Prostaglandin E2, interleukin-8, MMPs

Myometrium

• Prostaglandin F2a (E2) levels increased from fetal membranes
• Oxytocin receptor increased
• Contraction associated proteins

Fetal membranes

• Inflammatory process in fetal membranes
• PGs, interleukins, MMPs

Question 31

What is NF-kappaB?

Answer 31

Pro-inflammatory transcription factor - NF-kappaB upregulates inflammatory factors such as COX-2, IL8, TNF-a, oxytocin receptor, IL-1beta(this interleukin has a positive drive on NF-kappaB) etc

Many different initiators can activate NK-kappaB and drive all the process of 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

Question 32

Describe the control of term labour

Answer 32

CRH and PAF are important in controlling labour.

CRH levels increase very sharply in the 3 weeks before delivery in human pregnancy.

PAF: Platelet activating factor 
Part of lung surfactant
Surfactant proteins and complexes
Produced by maturing lung, before birth
Levels in amniotic fluid increase near term
Fetal signal of maturity

CRH and PAF stimulate prostaglandins E2 and COX2.

CRH and PAF can upregulate inflammatory pathways in fetal membranes. Initiators of term human labour.

1) Lungs mature - produce PAF which upregulates inflammatory process in the fetal membranes
2) Plancenta is the source of the CRH - increases CRH which also upregulates inflammatory processes. It goes into the baby which stimulates the anterior pituitary to release ACTH which stimulates the adrenal glands to produce cortisol. Cortisol activates lung maturing and also goes back into the placenta via the umbilical cord and stimulate more CRH production.

• 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
• The above apply to preterm labour (intrauterine infection, bleeding, twins)

Question 33

Describe the effects of progesterone in human pregnancy

Answer 33

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

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’