Pregnancy Flashcards
What are the different terms of pregnancy based on
There are 3 trimesters of pregnancy
They were not defined by science, but are based on experience
Describe the features of term 1 in pregnancy
If a pregnancy completes the first trimester (13 weeks), it is very likely to last until close to the expected delivery time (term, 39-40 weeks). The other way of expressing this is that spontaneous loss of the pregnancy during the first trimester is relatively common (see Table 3.1), and is estimated that one third of all conceptions do not complete the first trimester.
What is meant by the viability point that occurs at the end of the second trimester
The end of the second trimester (26-27 weeks) is the absolute limit of infant survival, in the absence of modern neonatal intensive care. Older literature includes references to ‘7 month’ babies, which would be ~30 weeks gestational age, and sometimes survived but generally were unlikely to do so. So this matches relatively closely with the end of the second trimester. With modern neonatal intensive care, the absolute limit is about 22 weeks of pregnancy, and 50% survival at about 25 weeks.
Viability: limit of viability at 24 weeks due to lung surfactant
Summarise the third term of pregnancy
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.
What are the main risks in the third term of pregnancy
Third trimester: 27-39 weeks
Features: maturation of brain, immune system, lungs and GI - therefore if premature then problems with these systems
Risks: largely to mother - labour and haemorrhage
What are the risks in the second trimester
Risks: survival of preterm birth associated with morbidity (even later in life)
Summarise the placental and maternal changes throughout the pregnancy
Placental- changes are complex and mostly occur in the first half of the pregnancy
Maternal- changes occur throughout
Summarise the fetal changes throughout the pregnancy
O-13 weeks : embryo - fetus
13- 26 weeks-: fetus -viability
26-39 weeks - viability - term
Outline the maternal changes that take place during the pregnancy
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
Altered fluid balance [2nd & later]
Altered emotional state [1st & later]
Altered joints [3rd]- why women are better at sports after pregnancy- joints become more flexible
Altered immune system [1st & later]
Summarise the key maternal changes that occur during the pregnancy
Increased weight Increased hormone levels / altered endocrine system Increased blood clotting tendency Decreased blood pressure Increased basal body temperature Increased breast size Increased vaginal mucus production Increased nausea and vomiting (‘morning sickness’) Altered brain function Altered appetite Altered fluid balance and urination frequency Altered emotional state Altered joints Altered immune system
Explain the anatomical and phsyiological changes that occur throughout the pregnancy
First trimester:
Altered immune system
Altered emotional state - changing hormones
Altered appetite - enlarging uterus compresses GI and stomach, so less distensible
Altered hormones
Altered brain function - steroids influence brain function
Increased breast size - depends on HPL and prolactin; needed for milk production
Second trimester:
Decreased blood pressure
Altered fluid balance - change in hormones changes kidney function initially increasing frequency, but enlarging uterus then compresses bladder to same effect
Increased blood volume
Increased blood clotting tendency - protective against PP haemorrhage
Third trimester:
Altered joints - changes to pelvis to increase flexibility to permit delivery
Increased weight
Summarise how we count the start of pregnancy
§ Pregnancy is counted from the first day of the last menstrual period (LMP), with other events dated from this time.
o This is important as an embryologist and an obstetrician would use different time-scales.
§ IVF pregnancy timing – fertilisation occurs 2-3 days before:
o There will be a difference in time of 2-2.5w from the gestational age (GA, derived from LMP) and the GA in an IVF pregnancy – this can make a large difference when determining viability (22 vs 24 weeks for example).
Explain the consequences of the different methods of measuring gestational age
An embryologist would start the count from fertilisation – and whether that embryologist is studying development, or working in an IVF unit, does not make any difference. The corollary of this is that the different time-frames matter; discussions about the earliest weeks of pregnancy and development need to stipulate very careful which time-scale is being used, as the difference can be very important. It also matters precisely how an IVF pregnancy timing is identified. Does the clock start to run from the addition of sperm to the oocyte (fertilisation), or from the insertion of the fertilised oocyte into the mother (probably day 3 or day 5 after fertilisation, embryo transfer). So 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.
At term, this is unlikely to matter (term has a range of 37-41 weeks), but for very preterm infants, the situation is very different. Two of the most premature infants to survive are stated to have ages of just under 22 weeks – and then it is stated that both were IVF pregnancies.
Very precise dates are given for the pregnancies (eg 21 weeks and 5 days), suggesting that the ‘count’ started with one of the IVF procedures above – and therefore the GA comparison timings differ by the 2 weeks or so stated. So the corrected GA for these pregnancies will be close to 24 weeks (21 weeks and 5 days, plus 2 weeks and 3 days would be 24 weeks and 1 day).
This could make a great difference, as (a) the most likely outcomes would be very different, and what the parents would be told would therefore differ greatly and (b) in the UK (in 2017) a baby with GA of 24 weeks or more would always be revived and treated a very positively; a baby of lower gestation (eg 22 weeks) would be considered borderline for survival, and a clinical decision whether to treat or not would be taken.
Explain the increase in maternal weight during pregnancy
This has been considered already briefly (see Figure 3.2). 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.
Describe the levels of hCG and human placental lactose throughout the pregnancy
Human Chorionic Gonadotrophin (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.
Describe the scale of the increase of the progesterone and oestrogens seen from the menstrual cycle to 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.
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.
What is the source of progesterone during the pregnancy
From the time of fertilisation to about 8 weeks gestation, the corpus luteum is the main source of progesterone, and this production is sustained by the rapidly increasing levels of hCG (Figure 3.4).
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.
What is meant by the luteo-placental shift
From about 6 weeks of gestational age, the corpus luteum gradually produces less progesterone (despite the very high hCG levels), and by about 9 weeks 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.
Describe the inter-dependence between the mother, fetus and placenta in steroidogenesis
Steroidogenesis: all of mother, foetus and placenta produce steroids
Maternal adrenals: use cholesterol to produce DHEA-S, cortisol and aldosterone
Maternal placenta: use cholesterol to produce progesterone
Foetal adrenals: use cholesterol and pregnenolone from the placenta to produce DHEA-S
Conjugation: placenta processes steroids from all three sources
Maternal cortisol: converted to cortisone
Maternal/foetal DHEA-S: converted to oestrone and then oestradiol
Foetal 16aOH-DHEA-S: converted to 16aOH-oestrone and then oestriol
Which receptors does the human placenta not express
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.
describe how estriol is synthesised during pregnancy
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.
Which is then converted to 16aOH-oestrone in the placenta and then to estriol
Explain the increased blood clotting tendency
The maternal blood tends to clot more readily; this starts early in pregnancy, and is greatest at term. It is thought that this is protective against losing too much blood at delivery, but may also be important in view of the interactions between the placenta and maternal blood throughout pregnancy.
Explain the 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.
Explain the increased basal body temperature
Basal body temperature increases by ~0.5°C in the second half of the menstrual cycle after ovulation. This reverses during menstruation, and is sustained into the first trimester of pregnancy, probably by the thermogenic roles of progesterone.
As the fetus increases in size, it contributes to maternal temperature, and normal maternal temperatures may exceed 38°C.
Explain the increased breast size
The breasts of the mother undergo a number of changes during pregnancy. These are dependent on increased hormone levels in the maternal circulation (human placental lactogen, prolactin, and ostrogens are all involved); the changes (including an increase in size) start in the first trimester and continue through the rest of pregnancy, so the changes are generally greatest by the time of delivery.
Explain the increased vaginal mucus production
A common and normal change in pregnancy, clear mucus is produced throughout most of pregnancy. If the mucus is not clear (bloodstained, coloured or has an offensive odour), medical advice should be sought.
Explain the morning sickness
‘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
Explain the altered brain function
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.
Explain the altered appetite
The maternal appetite may be altered throughout pregnancy; two major factors are thought to be involved, and their may be others. As the size of the uterus increases during the later stages of pregnancy, it imposes steadily increasing pressures on the gastro-intestinal system, including the stomach. This can decrease the distensibility of the stomach, and in late pregnancy the mother may need to have up to 6 smaller meals per day, rather than 3 bigger meals.
Explain the altered fluid balance and urination frequency
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.
Explain the altered emotional state
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.
Explain the altered joints
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.
Explain how the maternal immune system is suppressed during the pregnancy
Firstly, a number of factors that can suppress the maternal immune system are produced at the utero-placental interface. These co-operate to modify the maternal immune system, including decreasing the Th1 responses and increasing the Th2 system. These changes are relatively subtle, but co-operate to have an overall effect.
The second major system is that the placenta expresses some very unusual Human Leukocyte Antigens (HLA) on the surface that is in contact with maternal tissues. Unlike the HLA with which we are most familiar (HLA-A, HLA-B, HLA-D), which are very polymorphic and exist in millions of potential variants. the placental HLA are almost invariant. HLA-G has five known sequence variants.
Describe the function of HLA-G
In addition, the structure of HLA-G is quite simplistic compared with other HLAs, and the current view is that HLA-G (and perhaps other HLAs) provide an immunological signal that shows that the tissue is human – but little or no information on which human it is from. The presence of the ‘human’ marker means that the maternal immune system recognises the tissue as being human, and not as being ‘non-self’; in addition, HLA-G can suppress the activity of some leukocytes and can down-regulate the maternal immune system within the uterus.
