Pregnancy (21.02.2020) Flashcards
1
Q
Which trimester is the most risky?
A
- 1st
- miscarriage is most likely then
2
Q
Which 3 component do changes occur to in pregnancy?
A
- mother
- embryo/foetus/baby
- placenta
3
Q
Maternal changes in pregnancy
A
- Increased weight [3rd]
- Increased blood volume [2nd & later]
- Increased blood clotting tendency [2nd & later]
- Decreased blood pressure [2nd]
- Altered brain function [1st & later]
- Altered hormones [1st & later]
- Altered appetite (quantity and quality) [1st & later] – GI imbalance (‘‘morning sickness’’ can be a big problem)
- Altered fluid balance [2nd & later] - drink more, pee more
- Altered emotional state [1st & later] - e.g. some women are very happy in this time, others aren’t, some women suffer from postpartum depression.
- Altered joints [3rd] (some athletes have better performance after having a baby) also a change in pelvis shape after having a baby.
- Altered immune system [1st & later]
4
Q
Draw a graph of how hormones change throughout pregnancy
A
- 100x more progesterone in pregnancy than before
- hcg peaks in the 1st trimester
- this change starts very quickly after fertilisation and implantation.
5
Q
How long does each trimester last?
A
1st: 0-13
2nd: 14-26
3rd: 27-39
6
Q
Morning sickness
A
- HCG may be the hormone causing morning sickness because it is the highest in the 1st trimester
- can be very debilitating
- does not have to be in the morning, can also be at night.
7
Q
Risks to mothers health in pregnancy
A
- Relatively little risk in the early parts of pregnancy
- Main risk to maternal health (or life) linked to delivery
Generally pregnancy is safe for the mother, except the delivery process.
8
Q
Conceptus definition
A
everything resulting from the fertilised egg (baby, placenta, fetal membranes, umbilical cord)
-> anything you might find in the uterus in pregnancy that is usually not there.
9
Q
Embryo vs. foetus
A
Embryo – the baby before it is clearly human (i.e. a cell can be anything when you look at it)
Fetus – the baby for the rest of pregnancy
10
Q
Infant definition
A
less precise, normally applied after delivery
11
Q
How does the term for the developing baby change in time?
A
Blastocyst -> embryo -> foetus -> infant
12
Q
How are pregnancies dated by obstetricians?
A
- first day of last menstrual period
- other term used is post fertilisation (after)
- there is a 2 week time difference
13
Q
Blastocyst
A
- disk in the middle
- 2 layers of cells
14
Q
Carnegie stages of human development
A
- standardized system of 23 stages used to provide a unified developmental chronology of the vertebrate embryo.
15
Q
Timing issues in pregnancy
A
How is pregnancy normally ‘counted’? - first day of last menstrual period
Why is this system used? easy
Embryology timings are different! post fertilisation
Implications of this
16
Q
How is embryological research done?
A
- Fish, chick, mouse used as model genetic systems to study human diseases – as gene families involved in development are similar
- not done in humans because of ethical concerns
- comparative studies (From such investigations, some careful conclusions can be drawn; It is necessary to be cautious - misinterpretations are likely)
17
Q
Pregnancy lengths in different species (don’t have to know this!!!!!)
A
Mouse: 21 days Zebrafish: 4 days hatching, maturity 3 months Chicken: 21 days Human: 9 months (3.5kg) Dog: 9 weeks Hedgehog: 5-8 weeks Alligator: 9 weeks Deer: 200-260 days (29-37 weeks). Elephant: 18-22 months (100kg+) Whale: 11 months (blue, 2 tonnes or more) – 18 months (killer)
18
Q
Teratogen
A
any factor that deranges development
19
Q
Development and teratogens
A
When is the embryo most vulnerable?
- the more rapidly dividing the more vulnerable
- mainly tissues are vulnerable in the 1st trimester
- CNS incl. brain also in the second trimester
- some tissues also vulnerable in the3rd trimester.
20
Q
Mal-development
A
Helps to identify when the conceptus is most vulnerable
Generally during embryology, but there are exceptions
21
Q
Placenta
A
- communication system between mom and baby (via umbilcal cord)
- 2 cm across
- disk shaped
- foetal membranes?????
- there is a side that is in contact with the foetus and the other side is in contact with the mother (cotyledons are the components of it -> bigger in center, smaller on the outside)
22
Q
What is inside a placental cotyledon?
A
- placental villous tree with a central stem through which vessles pass
- there are 2 blood systems!!
- maternal oxygenated blood is transferred through the placenta to the foetus
- deoxygenated blood from the foetus comes back to the placenta and goes back to the mother
23
Q
umbilical cord vessles
A
- arteries are blue, carry deoxygenated blood to the mothers circulation
- umbilical vein carries oxygenated blood to the foetus
24
Q
Keyfeatures of the placenta
A
- 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 – interesting immunology!
25
What are the placental (villous) functions?
- Separation (of blood systems0
- Exchange (waste, nutrients)
- Biosynthesis (many hormones made by placenta e.g. hpl, hcg, progesterone...)
- Immunoregulation (regulates the maternal immune system, also there is AB exchange from mother to baby)
- Connection
26
Placental development
- Starts as a layer of single cells in the blastocyst (see slide 11)
- These proliferate and differentiate (proliferation and branching)
- Form simple branched structure, expands iteratively
27
Placental mal-development
- Miscarriage (late first trimester) - e.g. if the placenta does not anchor properly
- Miscarriage (second trimester) - rare but still happens
- Pre-eclampsia (early delivery)
- Fetal growth restriction (small infant)
28
Define 'term' delivery
- Term (39-40 weeks) is the expected timing of delivery.
- While this is normally stated as 280 days since the beginning of the last menstrual period (40 weeks), as a medical terminology, ‘term’ covers gestational ages from 37 – 41 weeks of gestation, with deliveries either side of these limits being ‘preterm’ or ‘post-term’ respectively.
29
What fraction of conceptions do not complete the 1st trimester?
estimated that 1/3 of all conceptions do not complete the first trimester.
30
When is the different timing of pregnancy by obs-gynaes and embryologists a problem?
- in pre-term babies
- in term babies there isn't really a problem but if the baby is born early those weeks/the week could have a major impact.
- there will be a difference of 2 – 2 1/2 weeks between Gestational Age (GA, derived from the LMP) and the Gestational Age in an IVF pregnancy.
31
Increased weight in pregnancy
- The overall weight gain in pregnancy is variable, but on average will be in the range of 10-15 kg.
- This will include the weight of the fetus, amniotic fluid and placenta; increased fluid retention; increased nutritional stores (to feed the baby after delivery).
- These changes are concentrated into the second and particularly the third trimester.
32
What is the final phase of pregnancy?
birth
33
Draw a diagram showing how hormones change throughout pregnnacy
- see notes!!
- hcg
- progesterone
- oestrogen (mainly oestriol)
- placental lactogen
- hCG shows peak levels in maternal plasma in the first trimester, and declines thereafter
- while the other main hormones (or hormone families) increase as pregnancy progresses.
- The increases in progesterone, oestrogens and human placental lactogen parallel the increased size of the placenta, and a range of studies underline the importance of the placenta in producing these hormones.
- It must be emphasised that hCG is also produced by the placenta, but regulation of its production is obviously very different, as the peak production is in the first trimester.
34
How high are hormone levels in pregnancy?
- Levels of progesterone (up to 1µM) and estrogens (up to 20nM) greatly exceed the levels seen during the normal menstrual cycle, so they may have potent effects on the maternal system in pregnancy.
- The very high levels of progesterone are of particular importance, as progesterone is the key hormone in allowing the pregnancy to continue.
- Low progesterone levels, or administration of a progesterone antagonist, will lead to loss of the pregnancy at all gestational ages.
35
What happens to ovarian and uterine functions in pregnancy?
The maternal endocrine system is modified substantially during pregnancy, with the high levels of steroids suppressing the HPG, leading to very low levels of LH and FSH throughout pregnancy, and hence no cyclic ovarian or uterine functions.
36
Luteo placental shift
- fertilisation -> 8w: corpus luteum is the main source of progesterone
- The placenta can also produce progesterone, but in the earliest weeks of pregnancy, the small size of the placenta means that its net contribution to maternal progesterone levels is limited.
- Increasing placental size means that it contributes increasingly to the levels of progesterone in the maternal circulation, and by 10 weeks of gestation the placenta is the source of all progesterone.
- From about 6 w of GA, the corpus luteum gradually produces less progesterone (despite the very high hCG levels), and by about 9w it has ceased to make steroids.
- This change in the source of progesterone to sustain pregnancy is the ‘luteo-placental shift’. The placenta produces progesterone constitutively at increasing levels for the rest of pregnancy.
37
Sources of oestrogen during pregnancy
- early weeks of pregnancy, the corpus luteum also produces the oestrogens needed for pregnancy (mainly 17beta-oestradiol).
- Once the luteo-placental shift has completed, the production of oestrogens in human pregnancy changes, involving a complex interaction between the placenta and the fetal adrenal glands.
- The human placenta does not express the enzyme (Cytochrome P450 17A1, or CYP 17, or Cytochrome P450 17,20-lyase) that converts pregnenolone to androgens, so this part of biosynthesis takes place in the fetal adrenals (which are large and well-developed even in the first trimester).
- The weak androgen produced (dehydroepiandrosterone, DHEA) is sulphated as well to give DHEA-S, which is inactive.
- Hence a female fetus is not exposed to an androgen during development.
- The DHEA-S circulates to the placenta, where it is converted to 17beta-oestradiol as shown.
- In human pregnancy, very high levels of oestriol are found, which are produced by a parallel mechanism (Figure 3.5), which includes hydroxylation of DHEA-S in the fetal liver to produce the precursor 16OH-DHEA-S.
38
BP in pregnancy
Decreased blood pressure
We are very used to the concept that increased blood clotting and increased blood pressure are parallel changes, as it is well established that hypertension is strongly linked to an increase in stroke and heart attacks.
Human pregnancy shows one of its atypical features, in that these two parameters change in opposite directions. Maternal blood pressure is lowest during the second trimester, and increases the risk of maternal fainting – so pregnant women should not stand for prolonged periods of time! Blood pressure tends to increase during the third trimester, but should still remain below a level that would be considered as hypertension; 120/70 mmHg would be considered normal.
39
Morning sickness in pregnancy
‘Morning sickness’ is not really an accurate name, as nausea and vomiting can occur at any time of day! It is however a relatively common problem, affecting up to 80% of pregnancies in some studies. The severity varies from relatively minor to so severe that it can cause weight loss – the most severe version is ‘hyperemesis gravidarum’, but affects 1-2% of pregnancies.
The causes are not known, but the highest incidence is during the first trimester, and co-incides with the highest levels of hCG in the maternal circulation. It is therefore considered likely that there is a causative link between very high hCG and ‘morning sickness’, but the mechanism is not known.
In most pregnant women the problems decline substantially during the second trimester, again in parallel with declining hCG levels.
40
altered brain function in pregnancy
- There is considerable ancedotal evidence of altered function in the maternal brain during pregnancy, often referred to as ‘baby brain’.
- The high levels of steroids, particularly progesterone, are thought to influence brain function during pregnancy, but due to the difficulties of doing detailed studies during pregnancy a precise understanding is lacking.
- It is well established that many steroids affect brain function in humans generally, so an effect of the very high hormone levels of pregnancy is consistent with this.
- Note that the size of the brain decreases very slightly, but this may not be of functional significance.
41
altered fluid balance and urination frequency in pregnancy
Kidney function changes in the mother as pregnancy proceeds leading to increased fluid retention and a higher plasma volume. By the end of pregnancy, maternal blood volume is ~50% higher than before pregnancy.
Urinary frequency increases during the first trimester of pregnancy, generally normalises during the second trimester, and increases again in the third trimester. The changes in the first trimester are generally thought to be due to changes in the maternal hormones, regulating altered kidney function. By the third trimester, the greatly enlarged uterus will be exerting pressure on the bladder, decreasing the maximum size and volume of urine it can contain, so the mother will pass smaller volumes of urine more frequently.
42
altered joints in pregnancy
Changes to the maternal pelvis, making the connections between the bones more flexible are necessary to permit the delivery of a normally-grown human infant.
Parallel changes are observed in other maternal joints, and these generally persist after pregnancy, causing permanent modifications to joint structure and (modestly) function.
43
altered emotional state in pregnancy
Changes in the emotional state of the mother are thought mostly to be due to changes in hormone levels within the maternal system. The nature and extent of such changes are extremely variable, and will differ between women, and also between sequential pregnancies in a woman. As outlined below, emotional changes linked to pregnancy can be very variable.
In some cases women are said to ‘glow’ with their pregnancy and with happiness – they are delighted to be pregnant, and the world is wonderful.
Alternatively, women may be equally happy to be pregnant, but may be emotionally very labile, crying with little or no obvious cause; or they may become clinically depressed during pregnancy, which may continue into post-natal depression. Or the pregnancy may be a very positive experience, and after delivery the mother develops post-natal depression.
44
altered immune system in pregnancy
- decrease Th1 response, increased Th2 response
- placenta expresses HLA-G which is almost invariant and shows that the tissue is human - but little or no information about which human it is from
45
Chromosome loss
- the only viable one is turners syndrome (monosomy X, 45X0)
| - if autosomes are lost this leads to non-viability (and so does 45Y0)
46
Chromosome gain
Extra sex chromosomes (XXX, XYY, XXY (Kleinfelter’s syndrome)) have modest effects, and the only viable autosome trisomy is Down’s syndrome (chromosome 21 trisomy).
47
What size is a 26 w foetus?
about the size of a human hand
48
What are the 4 main organ systems that still develop quite late in pregnancy?
- lungs
- digestive system
- immune system
- brain
The fetus has limited need of them in utero, whereas they become much more important after birth, so their late development is logical. However, this means that in a preterm infant, they may not function correctly, and thereby cause illness or death to the infant.
49
Risks in the 1st trimester
- Early development of the human embryo is vulnerable to teratogens – factors that can affect the details of development, although the primary structures will be present.
- Other complications of human development, including spina bifida and cleft palate, also occur in this early stage of development.
- aneuploidies can lead to non-viability
The main risks for the foetus are in the 1st trimester.
50
Risks in the 2nd trimester
There are few known risks to the fetus specifically in the second trimester.
51
risks in the 3rd trimester
mainly concerned with brith
52
Embryology
- most dynamic part of human development
- This is the process through which a single cell (fertilised human oocyte) develops into a recognisable human being over a period of about 8 weeks.
53
What are the different terms used to describe the 'baby' during development?
Conceptus – everything resulting from the fertilised egg
Embryo – the baby up to week 8 of development
Fetus – the baby for the rest of pregnancy
Infant – less precise, normally applied after delivery.
54
How does the terminology for the cells change from ovum to after implantation?
```
oocyte
fertilised egg (ZYGOTE)
2-cell stage (day 2)
4-cell stage (day 3-4)
8-cell uncompacted morula (DAY 4)
8-cell compacted morula (day 4)
early blastocyst (day 5)
late blastocyst (day 6-7)
implanted blstocyst (day 8-9)
```
55
Summary of embryo development
- 2nd week: Development of bilaminar dsic
- 3rd week: Formation of trilaminar disc (mesoderm), CNS & somites. Blood vessel initiation. Formation of placental villi. (3mm).
- 4th week: Closure of neural tube. Heart, Face, arm initiated. Umbilical cord. Elaboration of placental villi. (4mm)
- 5th week: Face & limbs continue. (5-8mm)
- 6th week: Face, ears, hands, feet, liver, bladder, gut, pancreas. (10-14mm)
- 7th wee: Face, ears, fingers, toes. (17-22mm)
- 8th week: Lungs, liver, kidneys, (28-30mm)
All of this takes place in a low oxygen environment (~3%)
Week 8 of embryonic development = Week 10 of gestation
56
What are the functions of the placenta?
SEBIC
- Separation: Despite the close contact between the tissues, the fetal and maternal vascular systems must remain separated. The structure of the placenta must be maintained to ensure that this happens.
- Exchange of nutrients (maternal to fetal) and waste products (fetal to maternal): Between the vascular systems of the mother and embryo or fetus.
- Biosynthesis: The placenta is synthetically very active, and some workers have suggested it is second only to the liver in terms of the range of functions that it performs.
- Immunoregulation: It is interactions between the placenta and maternal tissues that ensures that there is no rejection of the conceptus during pregnancy. We can be confident that the placenta (rather than the uterus) is the key tissue, as ectopic pregnancy (implantation other than in the uterus), and the occasional survival of such pregnancies until delivery, demonstrates that the uterine lining is not completely essential for pregnancy. It may still be the optimum maternal tissue for pregnancy, though.
- Connection (or anchorage): The placenta must make sufficiently strong connections with the underlying maternal decidua to last for the 9 months of pregnancy. The placenta is in contact with maternal arterial blood (see point 1), so anchorage is essential.
57
What is the point of viability?
- The limit of viability is the gestational age at which a prematurely born fetus/infant has a 50% chance of long-term survival outside its mother's womb.
- currently: 24w
58
Structural features of the human placenta
- The primary subunit is the placental villus, which have the complex branched structure shown. This provides a very large surface area (estimated to be 11 square metres) for exchange between the maternal and fetal vascular systems, thus meeting a primary requirement for exchange functions
- Anchorage to the maternal decidualised endometrium. Within each villus there is a complex blood supply, including arterial and venous vessels, connected to smaller capillaries in the terminal portions of each villus. Note that the arterial system contains de-oxygenated blood, and the venous blood is oxygenated – because the placenta has a parallel function to the lungs for the fetus during pregnancy.
- The maternal surface of a placenta is sub-divided into cotyledons (30-60 per placenta). Each cotyledon contains one or more villi, with larger cotyledons containing more villi. The variability in the shape and size of cotyledons does not affect placenta function.
59
maternal and foetal blood supply
Maternal and foetal blood supplies are separated!! despite being in close proximity
60
Cotyledon of placenta
- The maternal surface of a placenta is sub-divided into cotyledons (30-60 per placenta).
- Each cotyledon contains one or more villi, with larger cotyledons containing more villi.
- The variability in the shape and size of cotyledons does not affect placenta function.
61
When is the conceptus implanted?
approximately 9d after fertilisation the coneceptus is almost completely implanted within the maternal decimalising endometrium
- At this stage of development, the outer layer of the conceptus are multinucleated syncytiotrophoblast, which contain fluid-filled lacunae.
- The underlying layer of cytotrophoblast is proliferating adjacent to the embryo: this is where the placenta will develop.
62
Development of the human placenta
- Following implantation, the cytotrophoblast proliferate into the syncytium;
- first a columnar structure is formed (cytotrophoblast column), which then undergoes branching (villous sprouts). - At the centre of each villus are mesenchymal (extra-embryonic mesoderm) cells, from which the villus vascular system develops.
- The branching process continues through out pregnancy, giving rise to the complex branched villi
- The overall structure of a placental villus does not change throughout pregnancy but there are modifications. - In brief, there are fewer cytotrophoblast present at term, so that there can be a closer apposition between the syncytium and the placental capillaries.
- This will maximise the efficacy of nutrient transfer into the fetal blood, and enhance fetal growth in later pregnancy.
63
What does an early conceptus consist of?
- inner cells mass (-> foetus)
| - trophoblasts (-> extra embryonic tissue and ultimately the placenta)
64
Steps in implantation
Attachment phase
- trophoblast cells attach to the endometrial surface
- before this can happen, the zona pellucida is removed by digestive enzymes secreted by the trophoblast cells and/or endometrial glands.
- particular endocrine environment is required (oestrogens superimposed on a dominant progesterone background) for attachment and subsequent implantation
- LIF (leukemia inhibitory factor) is a ket molecule in bringing about the apposition of the outer trophoblast cells and the epithelial lining cells of the uterus.
- LIF provides general receptivity of the endo,etrial lining to the approaching blastocyst and without it implantation does not occur.
- the more localised attachment process is brought about by various molecules including the oestrogen stimulated release of heparin bound epidermal GF (HB-EGF), IL-11 and leptin.
- within hours of the outer trophoblast cells touching the endometrial lining, they begin to infiltrate the epithelial cells and penetrate the storm
- the stromal cells in the late part of the luteal phase are transformed into decimal cells and these cells are phagocytksed by the invading trophoblast cells which lose their membranes and interconnect, forming a syncytiotrophoblast.
- the decider becomes the source of nutrients for the implanting blastocyst (in a process called decidualisation).
- epithelial layer gradually re-forms over the implanting blastocyst as it invades the endometrium.
- IL-11 plays a role in the decidualisation process.
- subsequent growth of the decimalised tissue and the development of maternal arteries and arterioles provide the base for the formation of the placental interface between mother and foetus.
65
syncytiotrophoblast
Outer multinucleate layer of the trophoblast that serves to invade the endometrium of the uterus.
- at about 8d PF the blastocyst is partially embedded in the endometrial storm
- there are two layers:
- inner layer of mononucelated cells (cytotrophoblaast)
- outer, multiucleated zone without distinct cell boundaries (syncytiotrophoblast)
Mitotic figures are found in cells in the cytotrophoblast but not in the syncytiotrophoblast. Cells in the cytotrophoblast divide and migrate into the syncytiotrophoblast where they fuse and lose their individual cell membranes.
66
amnioblasts
epiblasts cells that are adjacent to the amniotic cavity
67
How is uteroplacental circulation established?
- vacuoles appear in the syncytiotrophoblast layer and form lacunae (day 9) -> lacunar stage
- intercommunicating network of lacunae forms (day 12); this is more prominent at the embryonic pole and not at the abembryonic pole)
- syncytiotrophoblast cells penetrate deeper into the endothelial lining of maternal capillaries; these capillaries are congested and dilated and are known as sinusoids.
- maternal blood then enters the lacunar system
- begins to flow through the trophoblastic system.
=> UTEROPLACENTAL CIRCULATION
68
When is the blastocyst fully embedded?
After 2w PF the blastocyst is fully embedded and the surface defect in the mucosa has healed.
69
Why is the second week of development known as the week of 2s?
1. the trophoblast differentiates into two layers: cytotrophoblast and syncytiothrophoblast
2. the embryoblast forms 2 layers: the epiblast and the hypoblast
3. the extraembryonic mesoderm splits into two layers: somatic and splanchnic layers
4: two cavities form: the amniotic cavity and the yolk sac
70
Development of placental villi
1. Primary villi: cytotrophoblast forms cellular columns penetrating into and surrounded by syncytium (by the beginning of week 3)
2. secondary villi: has a mesoderm core; by the end of the 3rd week these mesodermal cells begin to differentiate into blood cells and small blood vessles.
3. tertiary / definitive placental villus: with a villous capillary system; make contact with capillaries developing in the mesoderm of the chorionic plate and in the connecting stalk. These vessles in turn establish contact with the intraembryonic circulatory system, connecting the placenta and the embryo with proper essential nutrients and oxygen when the heart begins to beat in the 4th w of development
Meanwhile cytotrophoblastic cells in the cilli penetrate progressively into the overlying syncytium until they reach the maternal endometrium.
Here they establish contact with similar extensions of neighbouring villous stems forming a thin outer cytotrophoblast shell. The shell gradually surrounds the trophoblast entirely and attaches the chorionic sac firmly to the maternal endometrium.
71
What develops into the umbilical cord?
The connecting stalk
72
What are stem or anchoring villi?
What are free (terminal) villi?
Stem: villi that extend form the chorionic plate to the decider balls (decimal plate; the part of the endometrium where the placenta will form.
Terminal villi: those the branch from the sides of stem villi, through which exchange of nutrients and other factors wil occur.
73
How does the contact of the conceptus with maternal tissues change in early pregnancy?
- At the earliest stages of pregnancy, the conceptus is in contact with maternal endometrial cells.
- As it grows, it makes transient contact with the maternal capillaries, but the rapidly proliferating cytotrophoblast cells form a shell around the conceptus , isolating it from maternal blood by about 4w PF.
74
What is the decidua?
The decidua is the modified mucosal lining of the uterus (that is, modified endometrium) that forms in preparation for pregnancy.
The decidual glands hypertrophy during the first trimester of human pregnancy (Figure 3.17), and these provide the nutrients for the placenta and developing baby. It must be emphasised that the placenta functions normally (see p60) at this time, it is the source of the nutrients
75
Regulation of placental growth and development
- In general terms, the placenta regulates its own growth and development through autocrine mechanisms.
- We know that it can produce a range of different growth factors and other proteins, but their roles are not understood in detail.
- This is mainly due to the difficulties of studying human tissues during pregnancy.
- The maternal decidua mainly seems to modulate (restrain) placental growth and development, so that the placenta is optimal for both the mother and the fetus.
- Again, the details of the regulation are not well understood.
76
Placenta development around 10w GA
- the cytotrophoblast shell remains in place until about 8w PF, which is 10 weeks GA. The spiral arteries are blocked by cytotrophoblast plugs.
- During w 10-12 (GA), the cytotrophoblast plugs gradually break down, beginning with those at the periphery of the placenta, and ending with those near the centre.
- The result is spiral arteries providing maternal blood to the placenta, and hence forming the main supply of nutrients to the developing placenta and fetus.
- Note that this is one of the risky time-frames of pregnancy; if the placenta is not fully anchored to maternal decidua, the increase in pressure as it is exposed to the maternal arterial supply can detach the placenta and lead to miscarriage (late first trimester).
77
How does the placenta change in size during pregnancy?
The placenta is about 5cm in diameter at the stage of pregnancy; during the second and third trimesters it grows to ~20cm in diameter, but the key structural components do not change. Most of the growth is due to increased size and branching of the villi.
78
Remodelling of spinal arteries
- remodelling of the spiral arteries by cytotrophoblast cells, during which the vascular endothelium, and underlying smooth muscle cells are lost, and replaced by cytotrophoblast.
- This remodelling process begins during the first trimester, and continues until weeks 16-18 of gestation.
- This remodelling is critical for later growth of the fetus, as it converts the narrow, vasoactive spiral arteries to wide-bore vessels that can transport very large volumes of maternal blood to the placenta, and hence provide the quantities of nutrients needed.
- The lack of smooth muscle cells in these remodelled vessels is important, as this means that the blood flow remains high as these arteries cannot respond to vasoconstrictors.
79
Does the placenta have nervous supply?
- The placenta has no nervous system, so it is not regulated by such systems at any stage of pregnancy.
- This means that it can feel no pain during delivery, and the umbilical cord can be cut after delivery without any impact on the infant.
80
What is the conception rate in a normal menstrual cycle?
estimated to be 10-20%
81
Maternal risks in pregnancy
- relatively few risks to the mother in normal human pregnancy, at all gestational ages.
- the process of labour and delivery poses the dominant risk and is the commonest cause of maternal death linked to pregnancy.
- The remodelling of the uterine spiral arteries means that these vessels can lose relatively large volumes of blood after delivery. This should be limited by contraction of the uterus after the placenta has been delivered, which diminishes the blood loss very strongly. Sometimes it is necessary for drugs to be given to ensure this happens correctly.
- More important that this, the placenta must be carefully checked to ensure that no pieces are missing after delivery.
- Placental tissue is relatively inflexible, and any left within the uterus will prevent the contraction of uterine tissue, and permit continued blood flow through the spiral arteries into the uterine lumen. Surgery may be required to remove any retained placenta, as it is vital that no placental tissue remains in the uterus.
- In previous centuries, maternal death rates were up to 5% per pregnancy; in conjunction with an absence of contraceptives, and multiple sequential pregnancies, the risks of pregnancy can well be understood.
82
Pregnancy risks to the infant
- most severe risks to the infant are caused by defects in the production of gametes, so that they contain too few or too many chromosomes.
- Loss of any autosome is not compatible with life, and any pregnancies with a 43 XX or 43 XY chromosome number will miscarry early.
- The only trisomy (extra autosome) with long term viability is Down’s Syndrome (Chromosome 21 trisomy), and this trisomy shows very variable phenotypes.
- Changes in sex chromosomes are generally less severe, as an extra chromosome (44 XXX, 44 XXY and 44 XYY) are normally viable but may show some phenotype and have variable fertility. Loss of a sex chromosome is more serious; 44 XO (Turner’s syndrome) is normally infertile with clear phenotypic changes, and 44 YO is not viable.
- Partial chromosome loss, exchange of sequences between chromosomes, chimeras and mosaics, all show very variable effects on phenotype, ranging from the mild to the lifethreatening.
83
Pregnancy risks to the foetus via placenta
- most serious placental problem is the incomplete anchorage of the placenta can lead to loss of the pregnancy (miscarriage if a non-viable infant, or early delivery).
- These are most common in the first trimester.
- Some will be due to developmental problems affecting the embryo/fetus or placenta, others will result from detachment of the placenta in late first trimester.
- It has been estimated that 30% or more of conceptuses are lost during the first trimester; data from IVF pregnancies has been the most useful source of this information.
- Once the pregnancy passes the limits of viability (23 weeks of gestational age), early delivery of the infant is the key problem.
- About 10% of infants are delivered early; half of these result from the process of labour starting before term (see Session 4 for more information on labour).
- The other half are from pregnancies with deteriorating maternal or fetal health, to the extent that delivery is the best option to save the life of the mother, or the fetus, or both of them.
- This latter group include the Growth Restricted infants, and Pre-eclamptic pregnancies.
- Infants born before 32 weeks of Gestational Age are at greatest risk, due to incomplete development of their lungs, digestive system, brain and immune system, and these account for ~1% of all deliveries, and are often referred to as Very Preterm deliveries to differentiate them from the Moderately Preterm infants (32-37 weeks of gestation) who are at much less risk of severe complications.
- The process of labour has risks for the infant, but these can be minimised by monitoring of fetal health and delivery by Cesarean section if this is indicated.
84
Very-preterm and preterm deliveries
- Infants born before 32 weeks of Gestational Age are at greatest risk, due to incomplete development of their lungs, digestive system, brain and immune system, and these account for ~1% of all deliveries, and are often referred to as Very Preterm deliveries
- Moderately Preterm infants (32-37 weeks of gestation) who are at much less risk of severe complications.
85
Define ''stillbirth''
Stillbirth refers to the death of an infant within the uterus, so that it is delivered without any signs of life. Precise definitions vary, and may include gestational age or fetal weight limits.
One option is to use the viability limit (23 weeks), so deliveries before this gestational ages are defined as miscarriages (nonviable infants), and those after it (potentially viable infants) as stillbirths. Given that the viability of an infant born at less than 28 weeks gestational age is so variable, it is hard to provide a completely rigorous time definition, so ‘delivered without any signs of life’ may be the best option.
86
What is the difference between miscarriage and stillbirth?
Miscarriage: If a pregnancy ends before 24 weeks, it is known as a miscarriage.
Stillbirth: Stillbirth is when a pregnancy has lasted for at least 24 weeks and the baby is dead when it is born.
87
Detection of stillbirth
- The detection of stillbirth depends on monitoring of fetal wellbeing;
- a decrease in, or lack of, fetal movements may indicate an increased risk.
- The preferred method is ultrasound assessment of the infant, perhaps coupled with assessment of the fetal blood flow (doppler ultrasound).
- The variation in stillbirth rates listed above is thought to be due to the availability of monitoring equipment, coupled with access to facilities for an emergency C-section if complications in the infant are detected.
- If fetal compromise is detected, then C-section as soon as possible is needed.
88
Causes of stillbirth
- the causes of stillbirth are not well understood;
- about 50% of cases are thought to occur during the process of labour, which emphasises the importance of monitoring fetal wellbeing during pregnancy.
- Emergency Cesarean section would often be required in such cases.
- Many causes other than labour have been suggested, but detailed investigations may not reveal an obvious cause in up to 60% of cases.
- Some studies have suggested that the risk of stillbirth is increased in a subsequent pregnancy, but it is not clear if this is universally applicable, or what the mechanism might be.
89
Rates of stillbirth
- vary greatly between countries, and within countries.
- In general terms, the lowest rates of stillbirth (0.2% – 0.5% of deliveries) are found in Europe and North America
- higher rates (up to 4.5% of deliveries) in Africa, and South and Southeast Asia.
- Globally it is thought that ~2.5 million stillbirths occur per year (~1.9% of deliveries), which is similar to the numbers thought to suffer from pre-eclampsia.
- In the UK the stillbirth rate (2009 figures) was 0.35%, or 2,600 infants per year, so a large hospital with 4,000 deliveries per year is likely to have 10-15 cases per year.
90
When can stillbirth occur?
- important: stillbirth can occur at any gestational age, including term;
- the shock of stillbirth to the parents, particularly the mother, must not be underestimated, as an apparently normal pregnancy, with labour at term, can end with the delivery of a dead infant.
- While stillbirth has been linked to labour (see later point in this section), many cases occur before delivery, so this is included here as it is a complication of pregnancy (as well as of labour).
