Placenta and Intra-Uterine Growth Restriction

Question 1

Fertilization and beyond - Summary

• Sperm and Ovum meet in … Tube (… Tube) (usually a…) …-… hours after ovulation.
• Fusion occurs and 2nd … division occurs
• … reaction makes ovum impermeable to other sperm
• End- Zygote- has … (46 chromosomes)

Answer 1

• Sperm and Ovum meet in Fallopian Tube (Uterine Tube) (usually ampulla) 12-24 hours after ovulation.
• Fusion occurs and 2nd meiotic division occurs
• Acrosome reaction makes ovum impermeable to other sperm
• End- Zygote- has diploid (46 chromosomes)

Question 2

Zygote to Blastomere

• Zygote = A … … cell.
• The process of … is the step of embryogenesis where the zygote divides to produce a cluster of cells known as the …
• The … forms early in embryonic development and has two layers that form the embryo and placenta.

Answer 2

• Zygote = A fertilised egg cell.
• (The fertilized egg, known as a zygote, then moves toward the uterus, a journey that can take up to a week to complete until implantation occurs. Through fertilization, the egg is activated to begin its developmental process (progressing through meiosis II), and the haploid nuclei of the two gametes come together to form the genome of a new diploid organism.)
• The process of cleavage is the step of embryogenesis where the zygote divides to produce a cluster of cells known as the morula.
  
  • morula: A spherical mass of blastomeres that forms following the splitting of a zygote; it becomes the blastula.
• The blastocyst forms early in embryonic development and has two layers that form the embryo and placenta.
  
  • The human blastocyst possesses an inner cell mass (ICM), or embryoblast, which subsequently forms the embryo, and an outer layer of cells, or trophoblast, which later forms the placenta.

Question 3

Morula = A spherical mass of … that forms following the splitting of a …; it becomes the blastula.

Answer 3

Morula = A spherical mass of blastomeres that forms following the splitting of a zygote; it becomes the blastula.

Question 4

Morula -> Blastocyst

• In humans, the blastocyst is formed approximatelyy … days after fertilization.
• This stage is preceded by the morula.
• The morula is a solid ball of about … undifferentiated, spherical cells.
• As cell division continues in the morula, the blastomeres change their shape and tightly align themselves against each other.
• This is called compaction and is likely mediated by cell surface adhesion glycoproteins.

Answer 4

• In humans, the blastocyst is formed approximatelyy four days after fertilization.
• This stage is preceded by the morula.
• The morula is a solid ball of about 16 undifferentiated, spherical cells.
• As cell division continues in the morula, the blastomeres change their shape and tightly align themselves against each other.
• This is called compaction and is likely mediated by cell surface adhesion glycoproteins.

Question 5

Blastocyst

• The blastocyst possesses an inner cell mass (ICM), or …, which subsequently forms the embryo, and an outer layer of cells, or …, which later forms the p….
• The … surrounds the inner cell mass and a fluid-filled, blastocyst cavity known as the blastocoele or the blastocystic cavity.

Answer 5

• The blastocyst possesses an inner cell mass (ICM), or embryoblast, which subsequently forms the embryo, and an outer layer of cells, or trophoblast, which later forms the placenta.
• The trophoblast surrounds the inner cell mass and a fluid-filled, blastocyst cavity known as the blastocoele or the blastocystic cavity.

Question 6

Days 4-5 Fertilization

• The morula develops a cavity and becomes known as a …
• This thins out and becomes the … –start of the placenta
• The rest of the cells move (are pushed up) to form the inner cell mass. This creates an embryonic …
• The … has now reached the uterine lumen and is ready for implantation.

Answer 6

• The morula develops a cavity and becomes known as a blastocyst.
• Blastocyst thins out and becomes the trophoblast –start of the placenta
• The rest of the cells move (are pushed up) to form the inner cell mass. This creates an embryonic pole.
• The blastocyst has now reached the uterine lumen and is ready for implantation.

Question 7

Day 6-7 Bilaminar disc of the embryo

• Inner cell mass differentiates into two layers: E…(1) and H…(2)
• These two layers are in contact.
• (2) forms extraembryonic membranes and the primary … …
• (1) forms embryo
• … cavity develops within the epiblast mass

Answer 7

• Inner cell mass differentiates into two layers: epiblast and hypoblast.
• These two layers are in contact.
• Hypoblast forms extraembryonic membranes and the primary yolk sac
• Epiblast forms embryo
• Amniotic cavity develops within the epiblast mass

Question 8

Days 16 + Fertilization

• Bilaminar disc develops further by forming 3 distinct layers (this process is known as …)
  
  • Initiated by … streak.
  • The epiblast becomes known as …
  • The hypoblast is replaced by cells from the epiblast and becomes …
  • The epiblast gives rise to the third layer the …

Answer 8

• Bilaminar disc develops further by forming 3 distinct layers (this process is known as gastrulation)
  
  • Initiated by primitive streak.
  • The epiblast becomes known as ectoderm
  • The hypoblast is replaced by cells from the epiblast and becomes endoderm
  • The epiblast gives rise to the third layer the mesoderm.

Question 9

Embryo – the 3 germ layers

• The … degenerates. The … gives rise to all three germ layers.
• The embryo … to create the adult pattern

Answer 9

• The hypoblast degenerates. The epiblast gives rise to all three germ layers.
• The embryo folds to create the adult pattern

Question 10

The development / formation of the placenta

• The … cell mass - called the … - makes the placenta
• S.. cells invade devidua (endometrium)
• C… cells erodes maternal spiral arteries and veins
• Spaces (L…) between the fill up with maternal blood
• Followed by mesoderm that develops into fetal vessels
• Aiding the transfer of nutrients, O2, across a simple cellular barrier

Answer 10

• The outer cell mass - called the trophoblast - makes the placenta
• Syncytiotrophoblast cells invade devidua (endometrium)
• Cytotrophoblast cells erodes maternal spiral arteries and veins
• Spaces (lucanae) between the fill up with maternal blood
• Followed by mesoderm that develops into fetal vessels
• Aiding the transfer of nutrients, O2, across a simple cellular barrier

Question 11

Placenta formation

Answer 11

• Top - what should happen
• Bottom - pre-eclampsia and growth restriction (more narrow artery - higher resistance)

Question 12

Cytotrophoblast cells (CTB)

• … stem cells
• Invade the … blood vessels and destroy the epithelium
• Give rise to the … cells (STB)
• … in number as pregnancy advances

Answer 12

• Undifferentiated stem cells
• Invade the maternal blood vessels and destroy the epithelium
• Give rise to the syncytiotrophoblast cells (STB)
• Reduce in number as pregnancy advances

Question 13

Syncytiotrophoblast cells (STB)

• … differentiated cells
• … contact with maternal blood
• Produce … hormones

Answer 13

• Fully differentiated cells
• Direct contact with maternal blood
• Produce placental hormones

Question 14

The Placenta as an Endocrine Organ

• What two hormones? (… and …)
• What do they help to do?
  
  • 1 = maintenance of … and produces … and …
  • 2 = for growth and …, produces carbohydrate and …

Answer 14

• 1 = Human chorionic gonadotrophin (HCG)
  
  • maintenance of corpus luteum of pregnancy
  • produces progesterone and oestrogen
• 2 = Human placental lactogen HPL
  
  • growth, lactation
  • carbohydrate and lipid
• Many more!

Question 15

Placental Barrier

• Maternal blood in the la… in direct contact with …
• … layer of syncytiotrophoblast/cytotrophoblast/fetal capillary epithelium is all that separates the fetal and maternal blood
• Cytotrophoblasts … as the pregnancy advances
• The barrier … as pregnancy advances leading to a greater surface area for exchange (over 10m2 )

Answer 15

• Maternal blood in the lacunae in direct contact with syncytiotrophoblasts
• Mono layer of syncytiotrophoblast/cytotrophoblast/fetal capillary epithelium is all that separates the fetal and maternal blood
• Cytotrophoblasts decrease as the pregnancy advances (not needed)
• The barrier thins as pregnancy advances leading to a greater surface area for exchange (over 10m2 )

Question 16

Transfer Across the Placenta

• Gases – oxygen and carbon dioxide by simple diffusion
• Water and electrolytes
• …. hormones
• … poor – only by pino…
• Transfer of maternal antibodies Ig.. -starts at …. weeks – mainly after … weeks therefore lack of protection for premature infants

Answer 16

• Gases – oxygen and carbon dioxide by simple diffusion
• Water and electrolytes
• Steroid hormones
• Proteins poor – only by pinocytosis
• Transfer of maternal antibodies IgG -starts at 12 weeks – mainly after 34 weeks therefore lack of protection for premature infants

Question 17

Named Parts of the Decidua

Answer 17

Question 18

Placenta - Maternal vs Fetal surface

Answer 18

Question 19

Umbilical cord insertions

Answer 19

usually cord comes out middle but may vary

Question 20

What is Vasa Praevia? (pregnancy)

Answer 20

• velomentous cord insertion that runs across the cervical os
  
  • What is vasa previa? Vasa previa is an incredibly rare, but severe, complication of pregnancy.
  • The fetal vessels within the umbilical cord pass over the internal os. As the internal os dilates in labour the vessels are stretched and exposed and can rupture leading to massive fetal blood loss and death.
  • Diagnosed on Ultrasound using colour dopplers
  • Management deliver by Caesarean Section when the fetus is above 34 weeks.

Question 21

Clinical aspects of the placenta

• Position of the placenta within the uterus
  
  • Mainly … (at the top)
  • Anterior or posterior (front wall or back wall)
  • “low lying” or placenta … (near to the cervical os)

Answer 21

• Position of the placenta within the uterus
  
  • Mainly fundal (at the top)
  • Anterior or posterior (front wall or back wall)
  • “low lying” or placenta praevia (near to the cervical os)

Question 22

• What is Placenta Praevia?
• What can it cause?

Answer 22

• “low lying” placenta position (near to the cervical os)
• May lead to
  
  • Massive bleeding in pregnancy
  • Painless bleeding
  • Fetal death
  • Maternal death

Question 23

Clinical aspects of the placenta

• Failure of … invasion into maternal circulation at 12 and 18 weeks
  
  • Poor maternal fetal … of blood
  • Lack of oxygen and nutrients to the fetus
  • Leads to Fetal … …
  • Pre-… (raised Blood Pressure)

Answer 23

• Failure of trophoblastic invasion into maternal circulation at 12 and 18 weeks
  
  • Poor maternal fetal mixing of blood
  • Lack of oxygen and nutrients to the fetus
  • Leads to Fetal Growth Restriction
  • Pre-eclampsia (raised Blood Pressure)

Question 24

• What is Placenta Accreta?
• What is the treatment?

Answer 24

• Placenta accreta is a serious pregnancy condition that occurs when the placenta grows too deeply into the uterine wall.
• Placenta unable to separate at birth – uterus can not contract down and massive bleeding.
• Treatment hysterectomy.

Question 25

Placenta Accreta

Answer 25

**The placenta has invaded too deep into the myometrium and thus after birth the placenta can not separate and stays within the uterus. As a consequence the uterus can not contract down and massive bleeding can occur leading to the requirement to do a hysterectomy.**

Question 26

_Placental abruption_ * .... of the placenta during pregnancy. * Leads to disruption of the ... to the fetus leading to fetal distress and death * Bleeding can be ... but the ... fills up with blood. * Different to Placenta praevia where the blood is seen from the vagina. * Presents as: * ... * ... * ... * ...

Answer 26

* **Seperation** of the placenta during pregnancy. * Leads to disruption of the **blood** to the fetus leading to fetal distress and death * Bleeding can be **concealed** but the **uterus** fiills up with blood. * Different to Placenta praevia where the blood is seen from the vagina. * Presents as: * **Massive bleeding in pregnancy (often concealed)** * **Extremely painful** * **Fetal death** * **Maternal death**

Question 27

_Placenta in multiple pregnancies_

Answer 27

Question 28

_Development vs Growth_ * When is development? What happens? * What is growth?

Answer 28

* **First 12 weeks** fetal development occurs – **organs** formed * Then the baby needs to get bigger – **fetal growth**

Question 29

_Why do We Monitor Fetal Growth?_ * **Growth restriction is associated with** * ... * ... death * ... morbidity

Answer 29

* **Growth restriction is associated with** * **Stillbirth** * **Neonatal** death * **Perinatal** morbidity

Question 30

Confidential enquiries have demonstrated that most stillbirths due to Intra-Uterine Growth Restriction are ...

Answer 30

potentially avoidable and associated with suboptimal care

Question 31

_The Small-for-Gestational-Age Fetus (SGA) - Why do babies not grow to expected potential?_ * What is SGA? (either EFW or AC) * OR - of \< ... centile on the fetal growth scan * SGA is not synonymous with fetal growth restriction (IUGR)

Answer 31

* SGA = **estimated fetal weight or abdominal circumference** * OR \<**10th** centile on the fetal growth scan

Question 32

_Ultrasound measurements for growth_ * ... ... (AC) * ... ... (HC) * ... length (FL) * ... volume (LV) * D...

Answer 32

* **Abdominal circumference (AC)** * **Head circumference (HC)** * **Femur length (FL)** * **Liquor volume (LV)** * **Dopplers**

Question 33

_Causes of Small Babies_ * **3 main groups of SGA fetuses:​** * "..." baby ie. constitutionally small * ...-... mediated growth restriction * ... mediated growth restriction

Answer 33

* **3 main groups of SGA fetuses:​** * "**Normal**" baby ie. constitutionally small (Based on maternal size & ethnicity) * **Non-placenta** mediated growth restriction (eg. structural or chromosomal problem, fetal infection, inborn errors of metabolism) * **Placenta** mediated growth restriction (PET, hypertension, autoimmune disease, thrombophilias, renal disease, diabetes)

Question 34

_Causes of Non-placenta mediated growth restriction (3)_

Answer 34

* structural or chromosomal problem * fetal infection * inborn errors of metabolism

Question 35

_Causes of Placenta mediated growth restriction (6)_

Answer 35

* PET (pre-eclampsia) * hypertension * autoimmune disease * thrombophilias * renal disease * diabetes

Question 36

_Types of IUGR_

Answer 36

Symmetrical or Asymmetrical

Question 37

_Symmetrical Intra-Uterine GR_ * What groups out of the 3 for small babies? * What is reduced? (3)

Answer 37

* Groups 1 and 2 * HC , AC , FL all reduced

Question 38

_Asymmetrical Intra-Uterine GR_ * What group out of the 3 groups of small babies? * What is reduced?

Answer 38

* group 3 = placenta mediated growth restriction * AC reduced - head femur length normal - abdominal circumference very small

Question 39

_Trophoblast invasion_

Answer 39

Question 40

_Risk factors for IUGR_ * Maternal age \> ...yrs * Nulli.. * Low or high maternal ... * Diabetes / Renal disease / APLS * Most important modifiable factor = ... * Maternal SGA * More common in ... * Previous SGA infant * Previous ... * PAPP-A \< ... MoM at combined screening * Hypertension/PET = ... /recurrent APH this pregnancy

Answer 40

* Maternal age \> **40yrs** * **Nulliparity (first pregnancy)** * Low or high maternal **BMI** * Diabetes / Renal disease / APLS * **Smoking** * Maternal SGA * **IVF** * Previous SGA infant * Previous **stillbirth** * PAPP-A \< **0.4** MoM at combined screening * Hypertension/PET = **pre-eclampsia** /recurrent APH this pregnancy

Question 41

_Fetal growth restriction_ * Deficient ... invasion * Reduced placental ... * Fetal need ... supply * IUGR * Hy... * Fetal ... redistribution * Olig... * Abnormal ... * Fetal ... if not recognised

Answer 41

* Deficient placental invasion * Reduced placental reserve * Fetal need exceeds supply * IUGR * Hypoxia * Fetal vascular redistribution * Oliguria * Abnormal CTG * Fetal death

Question 42

_Diagnosis of Fetal Growth Restriction_ * Clinical ... – abdomen “looks smaller” * Clinical measurement of uterine size: ... - ... height (SFH)

Answer 42

* Clinical **suspicion** – abdomen “looks smaller” * Clinical measurement of uterine size: **Symphysis** - **fundal** height (SFH)

Question 43

Symphysis - Fundal height should be roughly the same as...

Answer 43

number of weeks pregnant (in cm)

Question 44

_Fetal Growth charts_

Answer 44

Question 45

_Symmetrical Fetal growth restriction - example graph_ * what groups? * What is reduced? *

Answer 45

* Groups 1 and 2 (small baby due to ethnicity or parents, or non-placental reason) * In symmetrical growth restriction the Head Circumference, The BPD ( biparietal diameter of the Head() and the abdominal circumference are ALL reduced

Question 46

_Asymmetrical Fetal growth restriction - example graph_ * What groups? * What is reduced?

Answer 46

* Group 3 - placental mediated GR * AC - abdominal circumference only dropped off

Question 47

Why is abdominal circumference a good representation of IUGR?

Answer 47

Fetal liver is there - liver stores glycogen if good growth - struggling - won't be able to store any so circumference will be smaller

Question 48

_Fetal growth restriction - Overview of what is reduced_ * Asymmetrical Growth Restriction: just ... growth affected * ... circumference reflects the size of the fetal ... * Causes: * ... insufficiency – no excess glycogen being deposited within the liver

Answer 48

* Asymmetrical Growth Restriction: just **abdominal** growth affected * **Abdominal** circumference reflects the size of the fetal **liver** * Causes: * **Placental** insufficiency – no excess glycogen being deposited within the **liver**

Question 49

_Consequences of hypoxia in the fetus_ * Blood flow (oxygen and nutrients) redirected to areas of greater importance * ... * Blood flow (oxygen and nutrients) redirected away from areas of lesser importance * ... (doesn’t eat!) * ... (placenta clears waste products) * ... (placenta brings O2)

Answer 49

* Blood flow (oxygen and nutrients) redirected to areas of greater importance * **Brain** * Blood flow (oxygen and nutrients) redirected away from areas of lesser importance * **Gut** (doesn’t eat!) * **Kidneys** (placenta clears waste products) * **Lungs** (placenta brings O2)

Question 50

_Ultrasound findings in IUGR_ * Small ... circumference (means a small ...) * Decreased ... fluid ( this is produced by the ...) * Increased blood flow to the ... (look at Middle Cerebral arteries in the brain – using the ... effect scan)

Answer 50

* Small **Abdominal Circumference** ( small **liver**) * Decreased **amniotic** fluid ( this is produced by the **kidneys**) * Increased blood flow to the **brain** (look at Middle Cerebral arteries in the brain – using the **doppler** effect scan)

Question 51

_Clinical features of IUGR_ * ... smaller than expected * Baby’s ... lessen to conserve ... * Fetal heart rate changes as ... develops (as seen on CTG) * Fetal ...

Answer 51

* **SFH** (symphysial fundal height) smaller than expected * Baby’s **movements** lessen to conserve **energy** * Fetal heart rate changes as **hypoxia** develops (as seen on CTG) * Fetal **death**

Question 52

_Management / Monitoring of FGR Baby_ * Serial ultrasound evaluation of fetal ..., ... volume and fetal d... * Timing delivery will depend on a combination of factors including * ... age * D.. studies * Other risk factors * The goal is to maximize fetal ... and growth but minimize the risks of ... mortality and

Answer 52

* Serial ultrasound evaluation of fetal **growth**, **liquor** volume and fetal **doppler** * Timing delivery will depend on a combination of factors including * **Gestational** age * **Doppler** studies * Other risk factors * The goal is to maximize fetal **maturity** and growth but minimize the risks of **perinatal** mortality and morbidity

Question 53

Fetal Dopplers are ...-... assessment of fetal ...

Answer 53

Fetal Dopplers are **non-invasive** assessment of fetal **circulation**

Question 54

_Fetal Dopplers_ * Non-... assessment of fetal circulation * Differentiating the fetus with pathological growth restriction and guides timing of intervention (eg, intensive monitoring, antenatal glucocorticoids, early delivery) that reduce ... mortality. * Looks at flow of blood and ... in the vessels * 1. ... artery doppler * 2. ... ... artery doppler * 3. ... venosus doppler * Where flow is normal, monitoring can continue * Where there are abnormalities in flow, may indicate expediting delivery

Answer 54

* Non-**invasive** assessment of fetal circulation * Differentiating the fetus with pathological growth restriction and guides timing of intervention (eg, intensive monitoring, antenatal glucocorticoids, early delivery) that reduce **perinatal** mortality. * Looks at flow of blood and resistance in the vessels * 1.**Umbilical** artery doppler * 2.**Middle cerebral** artery doppler * 3.**Ductus** venosus doppler * Where flow is normal, monitoring can continue * Where there are abnormalities in flow, may indicate expediting delivery

Question 55

_Fetal Dopplers - What 3 vessels do we look at?_

Answer 55

* Looks at flow of blood and resistance in the vessels * Umbilical artery doppler * Middle cerebral artery doppler * Ductus venosus doppler

Question 56

_Normal pregnancy middle cerebral artery VS in Fetal growth restriction_

Answer 56

* **left - normal - Pressure difference in systole and diastole usually very big** * **right - FGR - when baby is struggling, difference between top and bottom spike = a lot lower (compensating or not compensating)** * **​**This scan is demostrating the normal blood flow in the middle cerebral artery in the barin. * The peak corresponds to systole of the heart and during diastole the flow is negative ie below the line.

Question 57

_Wait or deliver in Intra-Uterine GR?_ * If we wait do to a lower chance of ... * Give ... to help * Reduces need for what route of delivery? * If baby is more likely to survive, particularly above ... weeks - may have to delivery if: * If there is decreased .... * Abnormality on the ... * ... abnormality

Answer 57

* If we wait due to a lower chance of **survival** * Give **steroids** to help * Reduces need for what route of delivery? - **C-section** * If baby is more likely to survive, particularly above **32** weeks - may have to delivery if: * If there is decreased **movements** * Abnormality on the **doppler** * **CTG** abnormality

Question 58

_Betamethasone/dexamethasone and IUGR_ * When given to the mother will cross the ... and stimulate the aveoli cells to produce ... gene * This stops the collapse of the alveoli cells by coating the cells and reducing the ... ... * Helps prevent ... ... Syndrome which leads to ... death in ... babies * Produced from ...-... weeks and usually the baby will have enough by 34 weeks in preparation for a term delivery * In ... babies it is lacking

Answer 58

* When given to the mother will cross the **placenta** and stimulate the aveoli cells to produce **surfactant** gene * **Surfactant** stops the collapse of the aveoli cells by coating the cells and reducing the **surface tension** * Helps prevent **Respiratory Distress** Syndrome which leads to neonatal death in premature babies * Produced from **24- 34** weeks and usually the baby will have enough by 34 weeks in preparation for a term delivery * In **premature** babies it is lacking