Clinical consequences of poor placentation II Flashcards
Why is it important to look at the causes of a small foetus?
- The causes of a small foetus each have different managements so it is important to differentiate between them.
- Can look at blood flow within the baby and the mother, which is measured via Doppler assessment. This can define placental insufficiency.
Define FGR.
- Notoriously difficult to define
- Definition is conceptual
- It is a condition in which the fetus does not reach its biological growth potential
Often equated to being small - It is difficult to measure the growth potential of a foetus and whether it is growing appropriately (some babies may be genetically predisposed to being small).
- Not all small fetuses are growth restricted
- Not all growth restricted fetuses are small
- A baby may be in the 50th centile (right in the middle) and then drop down to the 15th centile. It is still classified as a normally sized baby (not less than the tenth centile), but it has dropped the centiles significantly. This indicates a problem but it is not a small baby, strictly speaking, according to the standard reference values.
How is growth measured?
- Growth involves increment in a time interval
- Usual method is to plot fetal size against gestation
- Various centile cut-offs are used for diagnosis of SGA
- Have to look at how the baby grows over time. When looking at one point in time, the baby may be normally grown but then small further down the line. Equally, the baby may be small at the beginning and small at the end due to genetics.
- Therefore, growth charts are used. They give the average weight over a gestational window. Weight is shown on the y-axis, while the x-axis shows gestational age. As gestation increases, birth weight increases. The bottom part of the graph is classified as small for gestational age. Traditionally, this is less than the 10th centile. There are babies that are large for gestational age (above the 90th centile). Babies in between are called appropriate for gestational age. However, a baby can be appropriate for gestational age at first and remain appropriate for gestational age while dropping centiles (just not below the 10th centile). Therefore, it is important to incorporate a drop in centiles when diagnosing foetal growth restriction.
- As well as talking about the percentile, absolute birth weights can be used. Anything below 2500g is a low birth weight, anything below 1500g is a very low birth weight and anything below 1000g is an extremely low birth weight. It is possible to use cut-offs that are not gestation dependent, but it is more appropriate to use percentile as this gives it in context to gestational age. If a baby is born at 30 weeks and it is appropriate gestational age, the birth weight will be low (due to the gestational age). Therefore, it is not really appropriate to use a cut-off for all babies.
What are the 4 causes of smallness?
- There are four areas that are considered when there is a small baby that has been measured on the growth chart.
1) Pregnancy was dated incorrectly. Traditionally dated on last menstrual period. In the 80s, the length of the baby started being measured between 11 to 14 weeks. This is called the crown-rump length. When measuring the baby at this crucial stage, it allows the gestational age to be determined. This is very accurate (within five days of the actual conception date). If the pregnancy has not been able to be dated by ultrasound and last menstrual period is being used, it may be that the woman has an irregular cycle (doesn’t know the length) or abnormal bleeding in pregnancy and mistakenly thought this was a period when it was actually an implantation bleed or signs of a miscarriage threat that didn’t happen. Therefore, using last menstrual period is technically quite challenging. Equally, if the baby can’t be measured in the first trimester, the head circumference is used in second/third trimester. This is not as accurate, so sometimes the dating can be wrong.
2) Constitutional = The baby will not be big if the parents are both small. It can otherwise be that the parents are both short or have a slender stature. This is a healthy small.
3) Primary foetal/environmental problem. It can be that the baby has a problem, e.g. does the baby have a chromosome or genetic condition that is causing them to be small? Have they had an insult during the early stages of the pregnancy that has caused their development to be stunted?
4) Placental insufficiency = Is the placenta working well enough to meet the oxygen and nutritional needs of the baby? There are reasons why the placenta may not be perfused very well. As well as affecting the mum, it can equally affect the baby and cause it to be small.
What are the primary foetal/environmental causes of smallness?
1) Chromosomal conditions
(e.g. Trisomy 18, Triploidy)
Chromosomes provide the body with instructions to produce different proteins. Abnormalities in these chromosomes can cause poor messaging within the baby, resulting in it being small.
Trisomy 18 (Edward’s syndrome) = life-limiting condition babies tend to be very small. They classically have rocker-bottom feet (shaped like a rocker-bottom) and clenched hands.
The normal number of chromosomes per cell is 46. Babies with triploidy have an extra set of chromosomes (69 instead of 46). The top ultrasound image shows how a baby typically presents with triploidy. The head is much larger than the rest of the body. The test for Down’s syndrome involves measuring the fluid behind the neck and measuring placental hormones. In these babies, the placental hormones, particularly hCG, tends to be extremely high. This is because the placenta becomes abnormally big and abnormally vesicular. They are producing lots of hCG, which makes the mother very sick as hCG stimulates the vomiting centres. If the biochemistry from the Down’s screening shows very high hCG, triploidy may be picked up. An invasive test may be offered to check the baby’s chromosomes to confirm the diagnosis. Traditionally, this involves taking a placental biopsy (CVS = chorionic villus sample).
2) Insults from congenital infections
(e.g. Rubella, CMV). If this periventricular shadowing (bright spots around the ventricles) and enlarged ventricles (ventriculomegaly) was seen on a scan in a baby, it would instantly suggest CMV as this is pathognomonic of CMV. If this was the case, the patient would be offered an amniocentesis (needle test to sample amniotic fluid). The sample can then be sent to the lab to look for the CMV virus. If this result is positive, the outlook is bad for the baby as it is a brain-destroying virus and can cause severe disability.
3) Genetic syndromes. Single gene defects can include Russell-Silver syndrome, which is characterised by poor growth and reduced intellectual ability. This child also has low set ears, which is another feature.
4) Teratogens. There are other insults to a baby’s development, such as high alcohol intake during pregnancy causing foetal alcohol syndrome. Drug abuse, particularly cocaine and amphetamines, can cause small babies.
5) Maternal problem, e.g. cyanotic CHD. The cardiovascular system has to adapt to undergo massive changes to support the pregnancy. If the mum has a problem with the heart, such as cyanotic congenital heart disease, then the baby will also be hypoxic. Cyanotic means there is a lack of oxygen going around the body and the woman becomes blue. Equally, this can affect the baby. If the baby is lacking oxygen, they will be small.
What is placental insufficiency?
- Placenta function is nutrient and gas exchange (oxygen and carbon dioxide)
- Placental insufficiency = insufficient to support the baby’s needs of pregnancy (gas exchange and nutrition).
- Poor function leads to:
1) slowing of growth (not much energy for the baby to build up and grow). Metabolism reduces, so oxygen requirements reduce. The baby can go through certain stages with lack of oxygen.
2) Hypoxaemia = reduction in oxygen content of the blood. These low levels of oxygen then have an effect at the tissue level = hypoxia. If there is a complete lack of oxygen, the baby will have asphyxia. This is anaerobic metabolism (very dangerous) and cannot be supported for long.
3) This can result in stillbirth if it reaches this far. - Ultrasound used to find evidence of
1) Placental dysfunction
2) Fetal response to the dysfunction
(Important distinction to make between them).
How is placental insufficiency assessed in a clinical setting?
1) In a clinical setting, a risk factor based approach is still used. There is an algorithm that has been developed by the foetal medicine foundation (which produced the aspirin algorithm). This has a combined screening algorithm (not shown on this slide). This is because it has not been part of a randomised control trial yet. Hence, the risk factor based approach has been used.
There are a lot of risk factors and they are quite similar to the risk factors for PE. There is raised BMI, chronic hypertension, diabetes, renal impairment, antiphospholipid syndrome (an autoimmune condition), increased maternal age. There are other factors, such as the mother being a smoker (this is a teratogen) or drug misuse. Fibroids are benign, noncancerous overgrowths of the muscle within the uterus. Sometimes, this can use up more of the baby’s blood supply, so the baby ends up being small. Placental markers have been mentioned. Pregnancy associated protein-A is a placental function marker. If there are very low levels of PAPP-A, this would be a risk factor for a small baby, because placental function is inferred to be reduced due to lower levels of hormones. Also, if the baby is lacking oxygen, it can sometimes make their bowel look bright on an ultrasound. This is called foetal echogenic bowel. There are many reasons for this. It could be cystic fibrosis, it could be a bowel problem, it could be an infection, but one of the reasons is that it is not getting enough oxygen from the placenta and so it looks very bright; this is another risk factor for foetal growth restriction.
2) Previous history = many red flags to be aware of to then offer extra growth scans and Doppler scans. Also, if there has been a history of a growth restricted baby, it is likely to occur again.
3) Positive Uterine artery Dopplers measure blood flow to the uterus from the mum. If there is low resistance blood flow (lots of blood going to the womb with oxygen and nutrients), there would be optimum blood flow to the baby. If the uterine artery Doppler has high resistance (above a cut-off), there is less blood flow going to the placenta and this will be classified as screening positive if identified when a woman is screened at 20 weeks and the uterine artery Dopplers are usually measured. They will have extra growth scans to look out for the signs of having a small baby.
4) Abnormal placental echo-texture. Sometimes, the placenta may not look normal. This means that the placenta is very thick, globular with lakes (holes). The placenta is not functioning very well. Extra scans will be carried out because the placenta may not work very well as the pregnancy progresses.
5) AC/EFW below the 3rd centile. After conducting a scan, if the estimated foetal weight is below the third centile or the tummy (abdominal circumference) is below the third centile, the pregnancy would have to be monitored closely as this would suggest foetal growth restriction.
What is a Delphi procedure and what was the outcome?
- A consensus Delphi procedure was carried out in 2016.
- A Delphi procedure is where many definitions are listed and then clinicians (experts) rank them in order of importance/how strongly they agree. They were able to get a consensus for diagnosing FGR. It was subdivided into early and late FGR.
- Early foetal growth restriction was defined as babies younger than 32 weeks in absence of congenital anomalies. Have to ensure that there is nothing else wrong with the babies before putting them in this category. If they are less than 32 weeks and have a chromosomal or genetic problem, then it is not a placental mediated growth restriction. Also have to ensure there is no infection etc. After this, signs of placental dysfunction can be looked for. If there are signs, it can be determined that this looks like placental growth restriction and the baby can be classified this way. The main cut off is the estimated foetal weight or the abdominal circumference less than the third centile. This is absolute for both early and late growth restriction. Otherwise, the blood flow can be checked in the baby’s umbilical cord and the umbilical artery can be looked at. If there is absence of flow in the cord, it can be said that despite the baby maybe being more than the third centile, there is growth restriction because the cord is showing signs of growth restriction. If looking for other ways to define growth restriction, AC/EFW <10th centile can be combined with either problems with the umbilical cord Doppler (umbilical artery PI) or uterine artery Dopplers, which is the maternal blood flow. If either of these are high resistance (above the 95th centile) in combination with the 10th centile, then it can be classified as growth restriction.
1) AC/EFW < 10th centile can be combined with
2) UtA-PI > 95th centile and/or
3) UA-PI > 95th centile - If looking at late growth restriction, gestational age above 32 weeks, abdominal circumference or estimated foetal weight less than third centile is absolute. Any babies that have this are growth restricted. Otherwise, they can have two out of the three.
1) AC/EFW < 10th centile
2) AC/EFW crossing centiles > 2 quartiles on growth centiles
3) CPR < 5th centile or UA-PI > 95th centile - On the growth chart, if the baby drops from 75th centile to the 25th centile, this is crossing two quarters. This would be classified as a growth restricted baby if it was in combination with another point. If looking at blood flows in the baby, there are two blood flows that are important. Blood flow in the cord = umbilical artery Doppler. If this is high resistance, above the 95th centile, in combination with another point, this would be growth restriction. If measuring the umbilical cord artery and also the middle cerebral artery, putting them together produces the cerebroplacental ratio. This is another marker for growth restriction. The MCA is placed over the umbilical artery to produce a ratio. If the ratio produced is below the 5th centile, then it is classified as growth restriction.
- The cerebroplacental ratio is a measure of the umbilical artery vs the middle cerebral artery. It is MCA divided by umbilical artery. A high umbilical artery and a low MCA will produce a low ratio. A low ratio implies that there is redistribution happening. Towards term, the umbilical artery can be completely normal but on the higher end of normal (still within the normal range) and the MCA can still be normal but in the lower part of the range. The absolute values are within the normal range so it appears normal. However, calculating the ratio will show subtle redistribution that is not picked up from the traditional methods. This is why the CPR was introduced. If CPR is slow, it should be picked up as subtle redistribution and delivery should be considered (especially as the baby is at term).
- Can read the paper for more background. It is important to understand the definitions to identify these babies so they can be monitored closely. A time of delivery can then be chosen that is safe for the baby from a prematurity perspective without pushing them too far where they have stillbirths.
- These definitions are important. After classifying them, they would have to be followed up with blood flows to choose a suitable time for delivery. Have to hopefully get them further along in the pregnancy so that prematurity is not an issue.
GA – Gestational Age
AC – Abdominal circumference
EFW – Estimated Fetal Weight
UtA-PI – Uterine Artery Pulsatility Index
UA-PI – Umbilical Artery Pulsatility Index
CPR – Cerebroplacental
Outline the feto-maternal circulation.
- This diagram shows the foetal circulation as it is drawn anatomically.
- There is the descending aorta with the umbilical arteries coming off and going into the umbilical cord to the placenta. The umbilical arteries have deoxygenated blood. This is the only artery that has deoxygenated blood in the body. These umbilical arteries will disappear once the baby is born. The blood will keep going towards the placenta. It has to be of a low resistance so that it can get to the placenta easily and exchange the gases. It gets rid of the waste products in the placenta. The blood will come back oxygenated with nutrients by the umbilical vein. This is one of the only veins in the body that has oxygenated blood. The other vein is the ductus venosus. This is an important structure, only in foetal life, that shunts the blood from the umbilical vein straight into the right side of the heart through the foramen ovale and into the left side of the heart, where it is given into the systemic circulation. The first place that it will goes is into the head and neck veins, including the carotids. The important structures in the baby are the heart and the brain, so the baby will preferentially shunt that oxygenated blood into the important places. The cycle then repeats itself so that blood goes down the descending aorta again to reach the placenta via the umbilical arteries.
How do we know what the baby is doing with the oxygenated blood it receives from the placenta?
- Increased resistance can be inferred, but this informs about placental function (instead of the baby’s response). Even though there is high resistance, the baby may still get what it needs. However, with time, they may then need to respond to poor oxygenation. The blood flows that are looked at are the middle cerebral artery and the ductus venosus in the liver. With the middle cerebral artery, in a normal baby, there is normal blood flow (not low resistance, just normal). When the baby is lacking oxygen, it shunts blood to the important places (mainly the brain). In doing so, they redistribute the blood flow. There is cerebral redistribution, meaning low resistance. There is low resistance in this area, so lots of blood goes there and lots of gas exchange takes place. This provides enough oxygen to survive. Low resistance in the brain is bad, as it suggests that there is a lack of oxygen and the baby is compensating for this lack of oxygen. When the baby decompensates, the ductus venosus Doppler becomes abnormal. When the ductus venosus Doppler is abnormal, there is so much backpressure in the heart that the flow can’t reach the heart. The oxygenated blood can’t get into the heart efficiently. At this point, there is less oxygenated blood into the baby, it can’t compensate anymore and there will be a stillbirth. It is important to consider the uterines (the maternal side of placental function), the umbilical arteries (the foetal side of the placental function) and the baby’s response to any hypoxia which is the middle cerebral artery for compensating (getting the blood to where it needs to be) or whether the baby is decompensating with an abnormal ductus venosus.
How do we know what the baby is doing with the oxygenated blood it receives from the placenta?
- Increased resistance can be inferred, but this informs about placental function (instead of the baby’s response). Even though there is high resistance, the baby may still get what it needs. However, with time, they may then need to respond to poor oxygenation. The blood flows that are looked at are the middle cerebral artery and the ductus venosus in the liver. With the middle cerebral artery, in a normal baby, there is normal blood flow (not low resistance, just normal). When the baby is lacking oxygen, it shunts blood to the important places (mainly the brain). In doing so, they redistribute the blood flow. There is cerebral redistribution, meaning low resistance. There is low resistance in this area, so lots of blood goes there and lots of gas exchange takes place. This provides enough oxygen to survive. Low resistance in the brain is bad, as it suggests that there is a lack of oxygen and the baby is compensating for this lack of oxygen. When the baby decompensates, the ductus venosus Doppler becomes abnormal. When the ductus venosus Doppler is abnormal, there is so much backpressure in the heart that the flow can’t reach the heart. The oxygenated blood can’t get into the heart efficiently. At this point, there is less oxygenated blood into the baby, it can’t compensate anymore and there will be a stillbirth. It is important to consider the uterines (the maternal side of placental function), the umbilical arteries (the foetal side of the placental function) and the baby’s response to any hypoxia which is the middle cerebral artery for compensating (getting the blood to where it needs to be) or whether the baby is decompensating with an abnormal ductus venosus.
How does a doppler flow work? What are three pathological examples?
- The transducer sends an ultrasound signal to a flowing object. As the red blood cells are moving, they diffract the ultrasound and then it gets reflected back to the probe but there will be a change in the distance where the ultrasound signal has been and the quality of the ultrasound. When it is put into a computer, like an ultrasound machine that is receiving these images, it will give the flow of blood. This is how a Doppler flow works.
- This is an arterial blood flow shown in the diagram. There is a line at the bottom of the triangle which is important; forward flow = above line, reverse flow = below the line. When thinking about oxygenated and deoxygenated blood, it needs to go forward (either to the placenta from the umbilical arteries for gas exchange or in the ductus venosus, for instance, it needs to go forward as oxygenated blood needs to reach the baby).
- It is dependent on the cardiac cycle, hence the triangles. The peak of the triangle is systole (when the ventricles contract) and the trough of the triangle is diastole (when the heart is filling up with blood). There should always be forward flow so that the blood is going into the correct place and it is getting the oxygen that it needs, particularly in the umbilical artery. Particularly in the umbilical artery, if the baby has a low resistance, it has lots of blood going to the placenta. Going along, can see that the diastolic flow becomes less as the heart fills up. There is a lot of resistance in the placenta and it is trying to push the blood back when the heart is relaxed. In those spaces, there is less blood going to the placenta to get oxygen.
- There is absent end diastolic flow. This means that the blood is static in these segments here. It is not going towards the placenta and not getting the oxygen. Even worse, reversed end diastolic flow is reached. This is when deoxygenated blood is going backwards into the baby. At this point, it is very serious for the baby.
- This is an important concept to understand as Dopplers can be used as a way to interrogate placental function.
How does a Doppler appear in FGR?
- This can be compared to changes in foetal growth restriction. Can see the uterine arteries have a high resistance because this diastolic flow is much less than it was before. This implies poor placentation or poor cardiovascular adaptation from the uterine arteries. There is high resistance in those blood vessels, which means there is less blood going to the uterus and less oxygenated blood going to the uterus. This is the maternal side of the placenta. The foetal side of the placenta is the umbilical artery. Can see that the diastolic flows becomes less, showing high resistance (or high PI as it is called). Then, the diastolic flow becomes absent, then it becomes reversed. These are the typical changes that are seen in foetal growth restriction. When this happens, the baby will start to compensate for the reduced oxygen. This means that it redistributes the blood to the brain. The resistance in these blood flows becomes low, so there is low resistance. Looking at the previous one, there is higher resistance (this is a normal MCA). The baby will compensate and have low resistance blood flow. This means that the oxygen in the blood stays in the brain for a longer period of time. There is more blood going to the brain and more oxygenation to the important places. If there is so much resistance in the placenta, there can be back pressure on the heart. This will cause the heart to decompensate. The flow of the oxygenated blood from the ductus venosus into the heart becomes reduced and then reversed. When there is reversed oxygenated blood that the baby desperately needs, it is bad and it is important to get the baby out.
- Doppler blood flows allow detection of growth restriction and how the baby’s responding.
What are the methods of detecting FGR?
- Clinical: Symphysis-fundal height
- Serial ultrasound biometry
- Uterine artery Doppler screening
- There is a risk factor based approach. Women with risk factors will have serial growth scans to pick up any growth restriction.
- The baby has to be monitored in some way in women who do not have risk factors. Therefore, a tape measure tends to be used. The symphysis-fundal height will be measured, from the symphysis pubis to the to the top of the uterus. This is usually measured with the tape measure turned the other way so the numbers can’t be seen to remove bias. Usually, the number of centimetres translates to gestational age. For example, if a baby is 25 weeks and the symphysis-fundal height is 25 centimetres, the baby is appropriate for gestational age. However, more than two centimetres either side means the baby is abnormally small or large respectively. This is the method used to measure the growth of the baby in low risk pregnancies. Babies that are high risk for growth restriction will have serial growth scans.
- Now, the uterine artery Dopplers are carried out for all women at 20 weeks. If there is high resistance blood flow in the uterine artery Dopplers, it would infer that the uterus is not being perfused very well and there is a chance of growth restriction. A woman with a high uterine Doppler above the normal level (the cut-off is usually gestation dependent) will get serial growth scans.
Is the symphysis fundal height a good determinant?
- One trial with 1639 women was available
- Antenatal detection of small babies was lower in the fundal height group (28%) than abdominal palpation (48%)
- No evidence of improved outcome
- The symphysis-fundal height is not a good determinant. Many midwives are more likely to be accurate by just feeling the abdomen.
- The tape measure is no longer used at St. George’s; growth scans are carried out for all women. If the woman is high risk with risk factors or high uterine artery Dopplers, they will have serial growth scans, but all women will have a growth scan at ~36 weeks because it is much better than the tape measure.
