2 - Pregnancy Flashcards
How long does human pregnancy last approximately?
9 months
How many cases of pregnancy have complications per year?
What is a trimester and how many are there in pregnancy?
Trimester = three month period
Pregnancy is typically divided into three trimesters
In what trimester of pregnancy is spontaneous loss of pregnancy most common?
The first trimester
- 1/3 of all conceptions do not complete the first trimester
When is the end of the second trimester?
26-27 weeks
What is the absolute limit of infant survival in the absence of modern neonatal intensive care?
the end of the second trimester = 26-27 weeks
(in the absence of modern neonatal intensive care)
What is the absolute limit of infant survival with modern neonatal intensive care?
The absolute limit is about 22 weeks of pregnancy and 50% survival is at about 25 weeks
What is ‘term’?
Normally stated as 280 days since the beginning of the last menstrual period (40 weeks)
The word ‘term’ covers gestational ages from 37-41 weeks of gestation, with deliveries either side of this being ‘pre-term’ or ‘post-term’.
When do abdominal changes become more apparent during pregnancy?
Abdominal changes become more apparent during the second trimester, and the major changes are during the third trimester
Summarise the main maternal changes of 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
The first eight items in the list show clear directionality of change (increase or decrease), whereas the others are all affected as pregnancy progresses, but vary between individuals.
Generically summarise the first weeks of pregnancy, concentrating on ovarian and uterine events
This summary of the earliest events of pregnancy reflects an average of the timings
Variability in length of the menstrual cycle makes it difficult to identify (in a normal pregnancy) the exact timings of ovulation and fertilisation.
What is the convention when counting the start of pregnancy for O&G doctors?
The convention is that pregnancy is counted from the first day of the last menstrual period (LMP)
Other events are then dated from this time
When would an embryologist consider the start of pregnancy?
An embryologist would start the count from fertilisation
How big of a difference would there be between gestational age derived from LMP and gestational age in an IVF pregnancy?
2-2.5 week difference
GA from LMP
Counted from first day of last menstrual period
GA in IVF Pregnancy
Could be counted from:
- addition of sperm to oocyte (fertilisation)
- insertion of ferilised oocyte into mother, 3-5 days after fertilisation (embryo transfer)
What GA should be used when making decisions as to whether to treat pre-term infants?
GA from fertilisation
What GA is conventionally used when discussing maternal changes?
GA - LMP (first day of Last Menstrual Period)
How much weight is gained by the mother during pregnancy?
Overall weight gain in pregnancy is variable
Average: 10-15 kg
What does weight gain in pregnancy include?
- weight of fetus
- amniotic fluid
- placenta
- increased fluid retention
- increased nutritional stores (to feed the baby after delivery)
When does most of the weight gain occur during pregnancy?
Weight changes are concentrated into the second and particularly, the third trimester
Outline how the levels of the main hormones of human pregnancy change throughout the duration of pregnancy
Human Chorionic Gonadotrophin (hCG)
- peak levels in maternal plasma in first trimester
- declines thereafter
- hCG is also produced by the placenta like the other hormones, but the regulation of its production is different
Placental Lactogen
- increases as pregnancy progresses
- parallels the increased size of the placenta
- produced by the placenta
Oestrogens (mainly oestriol)
- increases as pregnancy progresses
- parallels the increased size of the placenta
- produced by the placenta
- level can go up to 20nM (greatly exceeds level during normal menstrual cycle)
Progesterone
- increases as pregnanacy progresses
- parallels the increased size of the placenta
- produced by the placenta
- level can go up to 1µM (greatly exceeds level during normal menstrual cycle)
- key hormone in allowing pregnancy to continue
Administration of what hormone antagonist will lead to loss of pregnancy at all gestational ages?
Low progesterone levels or administration of a progesterone antagonist will lead to loss of pregnancy at all gestational ages
Why are there very low levels of FSH and LH throughout pregnancy?
High levels of steroids suppress the HPG (hypothalamic-pituitary-gonadal) axis
This leads to very low levels of LH and FSH
This is important as this results in no cyclic ovarian and uterine functions
What are the sources of progesterone during pregnancy?
From fertilisation (at about 8 weeks):
- corpus luteum is main source of progesterone
- this production is sustained by the rapidly increasing hCG levels
- placenta also makes progesterone
- placenta is small at this stage of pregnancy and so its contribution to maternal progesterone is limited
About 6 weeks of gestational age:
- corpus luteum gradually starts to produce less progesterone, despite very high hCG levels
6-9 weeks of gestational age:
- placenta increases in size
- gradually contributes more to maternal progesterone
About 9 weeks:
- corpus luteum ceases to make steroids
About 10 weeks of gestational age:
- placenta is source of all progesterone
The placenta produces progesterone constitutively at increasing levels for the rest of pregnancy
What is the ‘luteo-placental shift’?
The change is source of progesterone (from the corpus luteum to the placenta) in order to sustain pregnancy
Summarise the production of steroids during human pregnancy
Early Weeks of Pregnancy:
- corpus luteum produces progesterone
- corpus luteum produces oestrogens (mainly 17β-oestradiol
Luteo-Placental Shift:
- production of oestrogens changes as outline in the figure attached
- complex interaction between the placenta and the fetal adrenal glands
What complex interaction regarding production of oestrogens in pregnancy occurs following the luteo-placental shift?
PRODUCTION OF OESTROGENS IN HUMAN PREGNANCY, FOLLOWING THE LUTEO-PLACENTAL SHIFT
COMPLEX INTERACTION BETWEEN THE PLACENTA AND FETAL ADRENAL GLANDS
Human placenta does not express the enzyme CYP450 17A1 (also known as CYP 17 or CYP450 17,20-lyase)
- this enzyme converts pregnenolone to androgens
Therefore, conversion of prenenolone to androgens takes place in the fetal adrenal glands
- fetal adrenal glands are large and well-developed even in the first trimester
The weak androgen produced is dehydroepiandrosterone, DHEA
DHEA is sulphated as well to give DHEA-S, which is inactive
Hence, a female fetus is not exposed to an androgen during development
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.
Outline the increased blood clotting frequency associated with pregnancy
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.
Outline the decreased blood pressure associated with pregnancy
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.
Outline the increased basal body temperature associated with pregnancy
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.
Outline the increased breast size associated with pregnancy
Breast changes are dependent on increased hormone levels in the maternal circulation
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.
Outline 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.
Outline the increased nausea and vomiting (morning sickness) associated with pregnancy
‘Morning sickness’ is a misnomer - can be at any time of day
Affects up to 80% of pregnancies
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
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.
Outline the altered brain function associated with pregnancy
Steroids affect the brain
‘Baby brain’
esp. progesterone
Outline the altered appetite associated with pregnancy
Size of the uterus increases during the later stages of pregnancy
Imposes steadily increasing pressures on the gastro-intestinal system, including the stomach
Can decrease the distensibility of the stomach
In late pregnancy the mother may need to have up to 6 smaller meals per day, rather than 3 bigger meals.
Outline the altered fluid balance and urination frequency associated with 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.
Outline the altered emotional state associated with 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.
Outline the altered joints associated with 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.
Outline the altered immune system associated with pregnancy
This is perhaps the most complicated aspect of pregnancy, as the concept of immunological ‘self’ and the rejection of ‘nonself’ tissues has been established for decades. Such rejection (eg of a transplanted organ) is activated within a few days.
Pregnancy requires the survival of a ‘non-self’ entity for a period of 9 months, with no signs of a rejection reaction in normal pregnancy.
These differences have caused considerable problems in understanding the immunology of human pregnancy, but in recent years a change in the paradigms used to describe the immune system has been useful.
Much detailed information has been published, so only the key points will be included here. Two major systems seem to be involved in the immunological aspects of human 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.
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.
What regulates the development of structures needed for the fetus?
Genetic control
- therefore dependent on inheritance
- chromosomal abnormalities provide the clearest evidence of such genetic regulation
What is the only viable condition which involves the loss of a chromosome?
TURNER’S SYNDROME
45 chromosomes with one X chromosome (45 XO)
What does the loss of any autosome result in for an embryo?
Loss of any autosome ( chromosomes 1-22) leads to non-viability
45 YO also leads to non-viability
By what point of gestation have all the structures expected of a baby born at term developed?
By around 26 weeks
What is early development of the human embryo vulnerable to?
TERATOGENS
Factors that can affect the details of development, although the primary structures will be present
Name two complications of human development that occur in early stages of fetus development
Spina bifida
Cleft palate
All these risks are mainly in the first trimester of pregnancy. There are few known risks to the fetus specifically in the second trimester. The main risks to the fetus in the third trimester are those concerned with birth.
What are the 4 main organs/systems that develop relatively 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.
Summarise the stages in development of a fertilised human oocyte to an embryo, then to a fetus
What is embryology?
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.
What is the ‘Conceptus’?
Conceptus – everything resulting from the fertilised egg
What is the ‘fetus’?
Fetus – the baby for the rest of pregnancy
What is the ‘embryo’?
Embryo – the baby up to week 8 of development
What is the ‘infant’?
Infant – less precise, normally applied after delivery.
Outline the preimplantation development of a human embryo
The cells of the embryo are undergoing mitotic (cleavage) division, deriving their nutrients from the secretions of the Fallopian tube.
Outline the two separate meanings of the term ‘embryo’
During this first week (PF), the whole conceptus is the embryo.
After differentiation to form a blastocyst, the embryo refers to the cells that contribute to (or are) the baby alone; other tissues have separate identities.
What is the process of pregnancy mainly concerned with once the main structures of the baby have formed?
The rest of pregnancy is more concerned with growth of the fetus, and the maturation of the structures that have been developed.
Outline the normal trajectory of growth of a fetus during human pregnancy
Summarise embryonic development during the first trimester of human pregnancy
All of this takes place in a low oxygen environment (~3%)
Week 8 of embryonic development = Week 10 of gestation
Outline the functions of the human placenta
FUNCTIONS OF THE HUMAN PLACENTA
5 MAIN GROUPS
Exchange of nutrients and waste products
- nutrients = maternal to fetal
- waste products = fetal to maternal
- between the vascular systems of the mother and fetus/embryo
Connection (or anchorage)
- placenta must make strong connections with underlying maternal decidua to last 9 months
- placents is in contact with maternal arterial blood, so anchorage is essential
Separation
- fetal and maternal vascular systems must remain separate
- placenta ensures this
Biosynthesis
- placenta is very synthetically active
- it is second only to the liver in terms of range of functions it performs
Immunoregulation
- interactions between placenta and maternal tissues ensure no rejection of conceptus
- is not the uterus doing this because ectopic pregnancies prove that uterine linings are not essential for pregnancy
Describe the main structural features of the 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 (point 1).
Anchorage to the maternal decidualised endometrium is also shown (point 2). 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.
This figure also shows that the maternal and fetal blood supplies are separated from each other, despite being in close proximity.
What are cotyledons?
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.
By how many days after fertilisation is the conceptus almost completely implanted?
Approximately day 9 post-fertilisation (Figure 3.13), the conceptus is almost completely implanted within the maternal decidualising endometrium.
Describe the structure of the conceptus at the time of implantation
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.
What happens to the structure of the conceptus following implantation, with regards to the 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 shown in Figure 3.14.
What happens to the overall structure of the placental villi during pregnancy?
The overall structure of a placental villus does not change throughout pregnancy (Figure 3.15), 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.
Outline the different stages of contact between the conceptus and maternal throughout pregnancy
At the earliest stages of pregnancy, the conceptus is in contact with maternal endometrial cells (Figure 3.13).
As it grows, it makes transient contact with the maternal capillaries (Figure 3.14), but the rapidly proliferating cytotrophoblast cells form a shell around the conceptus (Figure 3.16), isolating it from maternal blood by about 4 weeks post fertilisation.
Why happens to the decidual glands in the first trimester of human 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 at this time, it is the source of the nutrients (glands: histotrophic nutrition) rather than maternal blood (haemotrophic nutrition) that is different.
Outline the remodelling of uterine spiral arteries during human pregnancy
The cytotrophoblast shell (Figure 3.18, labelled as CT) remains in place until about 8 weeks post-fertilisation, which is 10 weeks gestational age.
The spiral arteries are blocked by cytotrophoblast plugs.
During weeks 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 the structure shown in Figure 3.19, with 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).
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.
A further point to note from Figure 3.19 is the remodelling of the spiral arteries by cytotrophoblast cells (points E and F), 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.
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.
What regulates the growth of the placenta?
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.
What part of pregnancy/delivery poses the greatest maternal risk?
Delivery of the placenta
Outline the major maternal risks of pregnancy/delivery
LABOUR AND DELIVERY
PLACENTA DELIVERY
- 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 necessary for drugs to be given to ensure this happens correctly
- the placenta must be carefully checked to ensure that no pieces are missing after delivery
What can happen if any placental tissue is left within the uterus 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.
What are the main risks to the infant during pregnancy/delivery?
GAMETE PRODUCTION DEFECTS
- the most severe risks to the infant are caused by defects in the production of gametes
- loss of any autosome is not compatible with life, and any pregnancies with a 43 XX or 43 XY chromosome number will miscarry early
- 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.
PLACENTAL ISSUES
- 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 (Section 3.1)
EARLY DELIVERY
- 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
- 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.
How can infant risks from labour be minimised?
Can be minimised by monitoring of fetal health and delivery by Cesarean section if this is indicated.
What is 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.
What options are there for defining stillbirth?
VIABILITY LIMIT
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.
Why does stillbirth occur?
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).
When does stillbirth typically occur during gestation?
It is important to note that 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.
Outline the epidemiology of stillbirth
RATES VARY GREATLY BETWEEN COUNTRIES, AND WITHIN COUNTRIES
Lowest rates of stillbirth (0.2% – 0.5% of deliveries) = Europe and North America
Higher rates (up to 4.5% of deliveries) = 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.
What is the preferred method for detection of stillbirth?
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 Cesarean section if complications in the infant are detected.
If fetal compromise is detected, then Cesarean section as soon as possible is needed.
