Week 8

Question 1

History Anti-D

Answer 1

In 1932 the three most characteristic clinical signs of Rh haemolytic disease of the fetus and newborn HDFN hydrops fetalis, severe neonatal jaundice and delayed anaemia of the newborn were identified as being caused by the same process
In the early 1940s Philip Levine identified that the cause of HDFN was antibodies to the D antigen
In 1969 postnatal anti-D immunoglobulin was first introduced
Between 1976 and 1991 this guidance was extended to include anti-D immunoglobulin administration following potentially sensitising events PSE
The 2002 guidance further extended the previous guidance to include routine antenatal anti-D prophylaxis RAADP
The widespread intro of anti-D immunoglobulin prophylaxis saw a dramatic fall in deaths attributed to RhD HDFN between 1977 and 1989. This fall in the death rate from RhD HDFN is mainly due to the introduction of anti-D immunoglobulin prophylaxis
Anti-D prophylaxis administered postnatally and following potentially sensitising events during pregnancy has reduced the UK maternal RhD sensitisation rate to 1.0-1.5%

Question 2

Anti-D immunoglobulin prophylaxis

Answer 2

The anti-D immunoglobulin prophylaxis policy has been so successful that it is hailed as one of the major achievements in obstetrics in the twentieth century
It’s predicted that the universal introduction of RAADP will prevent a further 17 late fetal and neonatal deaths in the UK each year

Question 3

Blood groups

Answer 3

A+
A-
B+
B-
AB+ can receive from everyone
AB-
O+
O- can be donor to everyone

Question 4

RhD factor and pregnancy

Answer 4

Blood types can be categorised as either RhD positive or RhD negative
Being RhD negative is usually only of consequence during pregnancy
If a RhD negative woman is pregnant with a RhD positive fetus she maybe have a potentially harmful immune response resulting in the formation of anti-D antibodies

Question 5

Genetic determinants of blood RhD factor

Answer 5

The RhD positive gene is more common than the RhD negative gene and is more dominant
If one of the two genes is RhD positive and the other RhD negative your blood type is RhD positive
It takes a pair of RhD negative genes to make your blood type RhD

Question 6

Anti-D formation

Answer 6

If fetal red cells cross the placenta and enter the maternal blood stream the spleen is activated by the fetal RhD positive red blood cells to produce anti-D antibodies
The presence RhD positive fetal red blood cells in maternal circulation stimulates the production of anti-D antibodies

Question 7

Anti-D

Answer 7

Anti-D immunoglobulin prophylaxis is administered to prevent maternal sensitisation with anti-D antibodies

Question 8

If anti-D is not given

Answer 8

Anti-D antibodies can cross the placenta and bind to the fetal RhD positive red cells
If this happens without the anti-D immunoglobulin injection the maternal anti-D antibodies will become permanent and irreversible. This is known as maternal sensitisation
It’s unlikely that the first pregnancy will be affected
However in a future pregnancy if the baby is RhD positive the maternal immune response will be greater
The maternal anti-D antibodies will cross to the fetal circulation and destroy fetal red blood cells. This leads to haemolytic disease of the fetus and newborn HDFN

Question 9

Maternal sensitisation

Answer 9

A woman is considered sensitised if she develops antibodies such as anti-D in her blood
Once sensitisation occurs its irreversible
The antibodies which are formed as a result of the sensitisation do not affect the mothers health
And only rarely affect first pregnancy
However they could affect future pregnancies where the baby is RhD positive

Question 10

Impact of sensitisation on pregnancy

Answer 10

During the pregnancy that results in a woman becoming sensitised the anti-D antibody is rarely produced at a high enough level to cause haemolytic disease of the fetus and newborn HDFN
Any future pregnancies may however be at risk of developing HDFN if the baby is RhD positive
The anti-D antibody which resulted from the earlier sensitisation can cross the placenta and attach and destroy RhD positive fetal red cells causing HDFN
The anti-D antibody resulting from maternal sensitisation will only attack RhD positive fetal red blood cells

Question 11

Fetomaternal haemorrhage

Answer 11

During pregnancy the placenta normally prevents maternal and fetal blood mixing
Fetomaternal haemorrhage FMH is the term used to describe any bleed from the fetus into maternal circulation
It’s the most common in the third trimester and around the time for birth
It’s often occurs with a potentially sensitising event such as vaginal bleeding but may also happen in the absence of any obvious potentially sensitising event

Question 12

Sensitised

Answer 12

The timing, rate and severity of the maternal immune response will vary between individuals
The level of antibody present can be detected by laboratory tests on maternal blood samples
The higher the levels the greater the significance for a pregnancy
If a women is sensitised anti-D immunoglobulin will have no effect
It should therefore not be given to a women with immune anti-D in their blood even if they experience a potentially sensitising event

Question 13

How maternal sensitisation occurs

Answer 13

Certain events during pregnancy are known to increase the risk of fetal maternal haemorrhage and maternal sensitisation these are known as potentially sensitising events PSEs
Gestation is an important factor for determining how a potentially sensitising event is managed
If anti-D immunoglobulin is required it should be given within 72hours of a potentially sensitising event occurring
The decision to give anti-D immunoglobulin in response to a potentially sensitising event should not affect or be affected by routine ante or post natal anti-D immunoglobulin prophylaxis

Question 14

Potentially sensitising events

Answer 14

Any vaginal bleeding
Blunt abdominal trauma
Invasive antenatal testing (amniocentesis, CVS)
External cephalic version
Miscarriage or termination of pregnancy
Ectopic pregnancy
Intrauterine death
Stillbirth and birth of a RhD positive baby

Question 15

Management of potentially sensitising events

Answer 15

The management of a potentially sensitising even varies according to gestation
Prior to 12 weeks gestation anti-D immunoglobulin is only occasionally indicated following a potentially sensitising event
Between 12 and 20 weeks gestation a minimum dose of anti-D immunoglobulin 1500iu is recommended
At 20 weeks gestation and onwards a minimum dose of anti-D 1500iu is also required however more anti-D immunoglobulin may be required depending upon the size of FMH this will be determined by laboratory tests

Question 16

management of potentially sensitising events 2

Answer 16

Anti-D immunoglobulin is most effective if given within 72 hours of a potentially sensitising event. However if a woman has not received anti-D immunoglobulin within this time it may still offer some protection if given up to 10 days after the potentially sensitising event occurred
Before the 12 weeks gestation, anti-D immunoglobulin should be considered if PV bleeding is heavy or persistent and/or associated with severe pain, particularly when approaching 12 weeks gestation
Anti-D immunoglobulin is always indicated following surgical intervention to remove products of conception (miscarriage and termination of pregnancy)
Anti-D immunoglobulin should always be given in cases of termination of pregnancy whether by surgical or medical means. In some cases anti-D immunoglobulin is also offered if early pregnancy loss, due to miscarriage or ectopic pregnancy if managed medically

Question 17

Sensitisation

Answer 17

Is irreversible there’s no treatment for it
Anti-D immunoglobulin should not be given to sensitised woman in the event that it is inadvertently administered the only consequence is the unnecessary exposure of the woman to a blood product
Sensitisation is only likely to cause problems for a women should she become pregnant with a RhD positive baby or require blood transfusion. It may be difficult to cross match blood and transfusion reactions could occur if RhD positive blood is given inadvertently eg during an emergency
This will usually mean regular monitoring of the anti-D antibody level in the woman’s blood. Usually the higher the antibody level the greater the risk of harm to the baby
There is no effective treatment that can change the levels of antibody produced and levels are likely to rise during the pregnancy if the fetus is RhD positive

Question 18

Management of pregnancies at increased risk due to maternal sensitisation

Answer 18

Some RhD negative women will be known to be sensitised before their first visit or it will be discovered during pregnancy. Although this does not affect woman’s health the baby is at risk of developing HDFN
Sensitised women require specialised care during pregnancy to monitor the health of their baby. They should be referred to a consultant obstetrician/fetal medicine department and have a haematologist or transfusion specialist involved in planning their care
Specialist investigations such as serial ultrasound including middle cerebral artery Doppler scanning can be used to monitor the health of the developing baby. Repeated testing of the woman’s antibody levels during pregnancy can help to predict the risk to the baby from HDFN
Babies of women known to have anti-D antibodies should be delivered in a hospital with neonatal care facilities it should be recognised that a future pregnancy with a RhD positive baby is likely to be at even greater risk of HDFN

Question 19

Management continued

Answer 19

Middle cerebral artery:
-measurement of Doppler flow through MCA can help identify babies with anaemia. Babies with anaemia have increased blood flow and should be referred to a fetal medicine unit
Fetal medicine unit:
-in the most serious cases intrauterine blood sampling may be indicated to determine the fetal haemoglobin level. If a fetus is found to be very anaemia a intrauterine blood transfusion may be required
Neonatal care:
-babies born to sensitised women are at risk of HDFN. They need to be assessed at birth by a paediatrician and may require treatment
Future pregnancies:
-women should be counselled about the likely risk of HDFN. In future pregnancies this should include follow up appointments with an obstetrician and/or haematologist/transfusion specialised and liaison with their general practitioner

Question 20

Booking visit

Answer 20

A maternal blood sample should be taken early in pregnancy ideally at the first antenatal clinic visit and before 16 weeks of gestation. This is to establish ABO and RhD type of the woman and to screen for the presence of red cell antibodies
If known the gestation of the fetus and any transfusion or anti-D administration history should be included on the request form to assist the effective interpretation of results

Question 21

Fetal DNA testing

Answer 21

We can now test whether the fetus of a women who is Rh negative is Rh positive or Rh negative
This test can be done from 11+2 weeks up to 24 weeks
The test is sent in a normal group and save bottle, the bottle must be handwritten.
The form can have a sticker on it but there must be a EDD from a scan on the form otherwise the sample will. Be rejected
The results will be put as an alert of Badgernet and a copy sent to woman
If the fetus is predicted Rh negative then the woman doesn’t need to have any antenatal or post natal anti-D—A cord sample needs to be sent at delivery for confirmation of blood group
If the fetus is predicted Rh positive then antenatal and post natal anti-D must be continued- A cord sample and Kleihauer must be sent at delivery

Question 22

Routine antenatal care

Answer 22

At the 28 week antenatal clinic visit a maternal blood test must be taken to recheck the ABO and RhD type and to screen for presence of any clinically significant antibodies the woman should then be offered routine antenatal anti-D prophylaxis RAADP
RAADP is given as a single dose at 28 weeks
The blood test must be taken before the woman is given RAADP
If anti-D immunoglobulin has previously been given for a potentially sensitising event, antibody screening should still be undertaken and the 28 week dose of RADDAP should still be given

Question 23

Routine postnatal care

Answer 23

Women who do not receive RAADP at 28 weeks eg. As a result of a missed appointment may still benefit from treatment at a later stage of gestation
The individual circumstances should be discussed with medical staff
Should the woman decline RAADP this should be recorded in her case notes
Postnatal care:
-at birth a cord blood sample should be taken from the baby to check for:
—the ABO and RhD type
A maternal blood sample should be taken no sooner than 30-45 minutes after the placenta has separated. Anti-D immunoglobulin is never administered to a baby

Question 24

Anti-D informed decision making

Answer 24

Health care professionals have a responsibility to support RhD negative women to make a fully informed decision about the use of anti-D immunoglobulin in pregnancy
Administration of anti-D immunoglobulin and RAADP in particular will benefit a small number of women and may carry some risks. Both health care professionals and the woman herself should be aware that the decision to accept or reject anti-D is hers

Question 25

Notes

Answer 25

Fit for purpose Information provided should use readily understandable language and include: -the reason anti-D immunoglobulin is offered -the potential benefits -the potential risks -the option to decline anti-D immunoglobulin -a list of potentially sensitising even and action to be taken in relation to them -sources of further information about anti-D immunoglobulin -a statement offering the opportunity to discuss anti-D immunoglobulin prophylaxis further

Question 26

Potential benefits of anti-D immunoglobulin

Answer 26

Although there are some theoretical concerns about anti-D immunoglobulin crossing the placenta entering the fetal circulation and causing harm to the unborn baby this has never been observed clinically Known side effects of anti-D immunoglobulin occur infrequently and include: localised pain at the injection site, fever and/or malaise and allergic reaction There are some RhD negative women who do not need or will not benefit from receiving anti-D immunoglobulin. However for these women the decision to decline anti-D immunoglobulin maybe difficult Examples of such circumstances: -women who are certain that the father is also RhD negative -women who are certain this will be their final pregancy

Question 27

Level of information

Answer 27

HCP should ensure that all women understand the information they have been given.some women will require more detailed info. Provision of this information is the responsibility of the healthcare professional The overall chance of a woman benefitting from RAADP is around 1 in 5790 this represents the risk of her becoming sensitised and going on to have a pregnancy affected by HDFN The chance of benefitting through avoiding sensitisation alone is around 1 in 228 In most sensitised pregnancies the baby will not develop clinically significant HDFN. However HDFN can be very serious and in around 10-12% of sensitised pregnancies the fetus will require one or more intrauterine blood transfusions. At present RhD HDFN causes about 37 fetal and neonatal deaths each year in the UK and around same number babies are born with developmental problems caused by HDFN

Question 28

Level of information continues

Answer 28

All human plasma use in the manufacture of anti-D immunoglobulin is screened for viruses known to be transmitted by blood. Anti-D immunoglobulin is only manufactured from plasma donated in countries outside the UK. This is to minimise any potential risk of vCJD. The risk of viral transmission by anti-D immunoglobulin is considered to be exceptionally low Transmission of Hep C via contaminated anti-D immunoglobulin is known to have occurred in the Republic of Ireland and in Germany between 1977 and 1979 prior to the introduction of hep c screening of blood donors and following intravenous administration of the product

Question 29

Level of information 3

Answer 29

Severe allergic reactions caused by anti-D immunoglobulin are rare Paternal RhD blood group testing is not usually offered routinely but if requested must be determined by formal lab tests If father is RhD negative all babies born to couple will be RhD- and woman cannot become sensitised to the RhD antigen. Sensitive counselling may be required to establish that women is certain of identity of this babies father prior to paternal RhD blood group testing Sensitisation is only likely to impact on future pregnancy women who seem certain that this will be their last pregnancy should be counselled on the risk should an unplanned pregnancy occur For those who will be sterilised at birth or soon afterwards anti-D immunoglobulin is of no benefit

Question 30

Ordering and administration of anti-D

Answer 30

Anti-D immunoglobulin is given as a standard dose It’s requested from blood bank on a named patient basis To request anti-D you must send a pink transfusion request form and tick the box for anti-D If the request is urgent hand the form to biomedical scientist and state that its urgent and patient is waiting and they’ll issue anti-d soon as Before administering anti-D it’s imperative to ensure the women has been confirmed as RhD- Anti-D made from human plasma and is subject to same ID checks and stringent documentation that are applied to the administration of other blood products In order to be effective it must be given as intramuscular injection Late administration, omission or administration of anti-D to wrong patient must all be reported via DATIX and the SHOT reporting system

Question 31

Management continued

Answer 31

Decline RAADP Some women may not accept RAADP: -personal choice -women who choose to be sterilised following delivery -women sure that father is RhD negative -where women is sure she wont have another child Difficult for women to be certain about these factors and the decision to decline should only be made after careful consideration and counselling

Question 32

Adverse reactions and drug interactions

Answer 32

As with any blood product occasional undesirable effects may occur all adverse effect must be recorded and the patients GP informed If anti-D given in community setting it’s recommended that where practicable the woman should be observed for 20 mins after admin Passively acquired antibody (present in anti-D preparation) can interfere with the maternal responses to live virus vaccines such as MMR Live vaccines such as MMR should not be given within 3 months of injection In postpartum period MMR may be given with anti-D provided that separate syringes are used and products are administered to separate limbs If not given simultaneously MMR given 3 months after

Question 33

Notes 2

Answer 33

Any muscle can be used for administration , care when injecting gluteal area and to women with higher BMI to ensure its intramuscular not subcutaneous Muscle more vascular so it’s absorbed more effectively Record must include: -first and last name women, DOB, unique ID/hospital number and whether consent was given -name of product, dose, batch number, route, site , time and date of admin -name and signature of staff who administered it Accurate documentation important to enable clinicians to plan future treatment. It also allow s lab staff to accurately interpret test results to help determine whether any anti-D present is passive or active

Question 34

Adverse events relating to anti-D administration

Answer 34

SHOT (serious hazards of transfusion) advise that improving HCP knowledge and understanding of guidance on anti-D immunoglobulin is key to changing practise and improving patient outcomes SHOT data shows a steady increase over the last 10 years in reported incidence involving anti-D immunoglobulin administration There is evidence to suggest that poor compliance with guidelines for anti-D immunoglobulin administration is a contributing factor to maternal sensitisation in the UK Evidence shows a consistent failure to recognise potentially sensitising events in pregnancy and a failure to manage them appropriately when they do occur For RAADP to be effective it must be administered in the third trimester of pregnancy

Question 35

The fetal period

Answer 35

Growth and physiological maturation of the structures created during the embryonic period Period involving preparation for the transition to independent life after birth

Question 36

From fertilisation to birth

Answer 36

Preembryonic period- 1-2 weeks Embryonic period- 3-8 weeks Fetal period 9 to 38 weeks Pregnancy weeks calculated from date of LMP. I.e conception weeks +2 so term is pregnancy 40 weeks

Question 37

Respiratory system

Answer 37

The lungs develop relatively late Embryonic development creates only the bronchopulmonary tree Functional specialisation occurs in the fetal period Important implications for pre term survival

Question 38

Lung development in the foetal period

Answer 38

Weeks 8-16: pseudoglandular stage bronchioles Weeks 16-26: canalicular stage respiratory bronchioles Weeks 26-term: terminal sac stage. Alveoli type I and type II cells. Surfactant

Question 39

The lungs during T2 and T3

Answer 39

Gas exchange conducted at placenta but lungs must be prepared to assume full burden at birth “Breathing” movements: conditioning of the respiratory musculature Fluid filled: crucial for normal lung development

Question 40

Respiratory distress syndrome

Answer 40

Often affects infants born prematurely Insufficient surfactant production If preterm delivery is unavoidable or inevitable -glucocorticoid treatment (of the mother) -increases surfactant production in fetus

Question 41

Developmental disorders/birth defects

Answer 41

Present at birth Structural/functioal/metabolic Wide range of causes Single gene defects, chromosomal, polygenic, teratogenic, unknown

Question 42

Teratogens

Answer 42

Congenital infection: TORCH, rubella, Zika virus, CMV Drugs and environmental pollutants/insecticides -vit A, pesticides, medications (sodium valproate for epilepsy), alcohol, recreational drugs Maternal metabolic disease. DM Radiation exposure

Question 43

Classify by timing

Answer 43

Preembryonic (pre wk2): lethal or no effect Early effects (2-4 weeks): scattered pattern Later effects (4-8 weeks): localised defect Fetal period (>9weeks): organ growth and functional maturation affected)

Question 44

Terminology congenital anomalies occur when normal development is disrupted

Answer 44

Deformation: late changes in previously normal structures (mechanical effect) eg talipes Disruption: secondary disturbance due to early influence of external factors eg amniotic bands Sequence: primary defect leads to a cascade of further anomalies eg potter sequence Malformation: primary disturbance of embryogenesis

Question 45

Antenatal screening and diagnostic tests

Answer 45

Screening: -Noninvasive -Blood tests and obstetric ultrasound scanning Chance of condition Diagnostic: -invasive -amniocentesis/chorionic villus sampling CVS Definitive result

Question 46

Combined test and quadruple test

Answer 46

Combined: -needs to be done before 14 weeks -maternal age + nuchal translucency (measure amount fluid in nuchal fold)+serum free betahCG and PAPP-A -reports chance of T21 and T18/T13 Quadruple: -maternal age, betahCG, unconjugated E3, inhibin A and AFP -tests for T21 only

Question 47

Non invasive prenatal test NIPT

Answer 47

Fetal DNA fragments extracted from maternal plasma DNA technology sequences the fragments and mapped to the genome Number of reads from the chromosomes of interest undergo statistical analysis

Question 48

Genetics

Answer 48

Single gene: mutation, deletion Chromosomes: translocation, duplications, microdeletions

Question 49

Trisomy 21

Answer 49

Non-disjunction 94%: at meiosis so at fertilisation true aneuploidy trisomy 21. One embryo not viable no chromosomes because of the non disjunction at meiosis Robertsonian translocation 5%: bit of 21 on 14 , some offspring not viable, some translocation carrier, some translocation Down’s syndrome (2 chromosome21 , chromosme 14 and chromosome 21+14)

Question 50

Di George syndrome

Answer 50

Deletion of a section of chromosome 22, 22q11.2 Characterised by a range of anomalies involving a range of structures -craniofacial and pharyngeal region Includes failure of development of 3rd and 4th pharyngeal (branchial) pouches during embryonic development

Question 51

CHARGE syndrome

Answer 51

CHD7 (chromodomain helicase DNA-binding domain, ATP dependent chromatin remodeller) CHARGE syndrome: CHD7 heterozygous mutation CHD7 expression essential for the production of Multipotent neural crest cells -coloboma: part eye tissue missing -heart defects -choanal atresia- nasal choanae occluded -growth and developmental retardation -genital hypoplasia -ear defects

Question 52

20 week screening scan

Answer 52

Screening for 11 conditions that -benefit from treatment before or after birth -need treatment in a specialist setting after birth -could mean the baby may die shortly after birth -lead to a discussion about pregnancy options Assessment of craniofacial development, femur, spine and abdominal circumference plus cardiac development

Question 53

Spina bifida and anencephaly

Answer 53

The CNS is derived from the neural tube The neural tube fuses along its length Defects in closure of the neuropores underlie serious and common birth defects of the central nervous system Caudal NT defect results in spina bifida Cranial NT defect results in anencephaly

Question 54

Spina bifida

Answer 54

Can occur anywhere along the length most common in lumbosacral region Neurological defects can occur Hydrocephalus nearly always occurs Multifactorial: -genetic, environmental, maternal, nutritional status -folic acid supplementation prevents NTDs Meningocele and myelomeningocele

Question 55

Cleft lip and palate

Answer 55

Difficulty feeding Hearing problems Dental problems Speech problems Can be an isolated finding but often associated with trisomies 13 and 18 (and often rarer symptoms)

Question 56

Development of nose and upper lip

Answer 56

3 different tissue types Maxillary prominences grow medially pushing the nasal prominences closer together in the midline Maxillary prominences fuse with medial nasal prominences Medial nasal prominences then fuse in midline

Question 57

Cleft lip and palates

Answer 57

Primary palate: intermaxillary segment Secondary palate: palatal shelves Lateral cleft lip- primary palate Cleft lip and palate- 1 and 2 palates

Question 58

Gastroschisis

Answer 58

Anterior body wall closure defect, lateral to umbilicus Normal development of GIT Incidence increasing Associated with younger mothers, smoking and recreational drug use

Question 59

Omphalocoele

Answer 59

Persistence of physiological herniation of midgut Normal developmental process doesn’t complete, not normal development GIT Commonly associated with other abnormalities 20% chromosomal abnormalities eg Edward’s T18

Question 60

Congenital heart defects

Answer 60

Occur when there is a structural defect of the chambers, great vessels. Theres an obstruction, there’s a communication between pulmonary and systemic circulation Additional complexity in embryonic development due to the differing circulatory needs of the fetus as compared to the newborn (mature) Congenital heart defects are the most common birth defect Often associated with chromsomal abnormalities Worldwide incidence 1% 90% survival to adulthood Compared to just 20% in the 1950s

Question 61

Importance of congenital anomaly

Answer 61

Affect 3% liveborn infants Causing perinatal and neonatal death and disability Lifelong impact to child/family -20-30% admissions to tertiary care emotional and physical wellbeing financial cost

Question 62

Prevention

Answer 62

Removal of risk factors and addition of protective factors Good diet and nutrition -folic acid/iodine supplementation Avoidance of teratogenic drugs/substances/agents Vaccinations. Rubella Screening for infections eg syphilis Maternal age- increased age a significant risk factor

Question 63

Urinary system

Answer 63

Fetal kidney function begins in week 10 Fetal urine is a major contributor to amniotic fluid volume Fetal kidney function is not necessary for survival in utero but without it there is oligohydramnios Amniotic fluid is important for stimulating lung development

Question 64

Importance of amniotic fluid volume

Answer 64

Oligohydramnios- too little, placental insufficiency, fetal renal impairment, abnormality Polyhydramnios- too much, fetal abnormality eg inability to swallow

Question 65

Nervous system

Answer 65

Nervous system is first to begin development and last to finish Corticospinal tracts required for coordinated voluntary movement begin to form in the 4th month Myelination of brain only begins in 9th month -eg corticospinal tract myelination incomplete at birth as evidence by increasing infant mortality in the 1st year

Question 66

Sensory and motor systems

Answer 66

No movement until 8th week Thereafter a large repertoire of movements develop “Practising” for post natal life suckling, breathing

Question 67

Implications “quickening”

Answer 67

Maternal awareness of fetal movements from 17 weeks onwards Low cost, simple method of antepartum fetal surveillance

Question 68

Development of lungs and brain

Answer 68

9 weeks: lungs begin functional adaptation 16 weeks: cerebellar development, corticospinal tracts begin to form 20 weeks: myelination begins in spinal cords 24 weeks: terminal air sacs appears; some surfactant production 28 weeks: characteristic gyri and sulci appear as cerebellar hemispheres grow larger than skull 36 weeks: greatly increased surfactant production, myelination begins in brain

Question 69

Deformation

Answer 69

Talipes: club foot Congenital hip dislocation

Question 70

Disruption

Answer 70

Amniotic bands- strips of amniotic membrane Poland anomaly- absent pectoral muscle interruption of the subclavian artery

Question 71

Sequence

Answer 71

Potter sequence: -bilateral renal agenesis or bilateral multicystic dysplastic kidneys -reduced fetal urine excretion -oligohydramnios causing fetal compression Potter facies: low set ears, beaked nose, prominent epicanthic folds and downward slant to eyes, pulmonary hypoplasia causing respiratory failure, limb deformities Pierre robin sequence: -mechanical theory -begins with mandibular hypoplasia -tongue cannot drop -impacts on development of palate

Question 72

Fetal alcohol syndrome

Answer 72

There is no known safe level of alcohol consumption during pregnancy Facial Skeleton derived from neural crest cells populating the pharyngeal arches Neural crest migration as well as development of the brain are known to be extremely sensitive to alcohol Incidence of FAS and alcohol related neuro developmental delay= 1/100 births Features: small head, low nasal bridge, epicanthal folds, small eye openings, flat midface, short nose, thin upper lip, smooth philtrum, underdeveloped Jaw

Question 73

Congenital rubella syndrome

Answer 73

Infection of the fetus with rubella virus Viral infection affects development of organs of special senses, heart plus a range of others Microcephaly, patent ductus arteriosud PDA, cataracts

Question 74

Normal growth

Answer 74

Three phases of fetal growth and development: -first: 4-20 weeks: increases in fetal weight, protein content and DNA content (cellular hyperplasia) -second: 20-28 weeks: increased in protein and weight and lesser increases in fetal DNA content (hyperplasia and concomitant hypertrophy) -Third: 28 weeks to term: continued increases in fetal protein and weight but no increase in DNA (hypertrophy)

Question 75

Fetal growth- definitions

Answer 75

Fetal growth restrictions (FGR) -failure of a fetus to achieve his or her growth potential Small for gestational age (SGA) -birth weight <10th centile for gestational age -centiles are based on local populations -can be adjusted for sex, parity, race, maternal weight and height Large for gestational age LGA: -birth weight >90th centile Low birth weight LBW: -birth weight less than a certain threshold eg 2500g Neonatal indices: -ponderal index, skin fold thickness, MAC/HC ratio

Question 76

Fetal growth restrictions- consequences

Answer 76

3-10% all births Significant cause of perinatal mortality and morbidity -still birth or neonatal death within 7 days birth 85% of unexplained stillbirths may be due to FGR LBW infants are more likely: -to die within first year of life -suffer from neonatal problems (birth asphyxia, hypoglycaemia, hypothermia) -fetal origin of adult disease

Question 77

Fetal programming “barker hypothesis”

Answer 77

Most show catch-up growth in childhood though may have smaller size in adulthood However IUGR can have lifelong impact Evidence to suggest curves are u shaped Babies born to GDM mothers in adulthood are at increased risk of IGT, diabetes and obesity Early exposure to increased insulin levels leads to metabolic and epigenetic differences

Question 78

Fetal programming 2

Answer 78

Good evidence that increased risk in adult life of: -obesity -type 2 diabetes -BP, stroke, heart disease -secondary to changes in growth, metabolism and vasculature -however postnatal factors are also important Due to “thrifty phenotype” programming: -evolved to offer advantage in a “famine environment” but problems in industrialised society

Question 79

Intergenerational effects

Answer 79

Mothers who were small for gestational age SGA themselves are more likely to have -SGA babies -increase perinatal mortality Rodent models: -maternal undernutrition F0 increase adiposity, glucose intolerance and cardiovascular risk in F1 and F2 generations -after undernutrition for 12 generations, takes 3 generations of normal diet to restore normal foetal growth and development

Question 80

Mechanisms for transgenerational effects

Answer 80

Epigenetics: heritable changes in gene expression by mechanisms other than underlying DNA sequences -DNA methylation -histone modification -micro RNA Maternal mitochondria: food restriction can alter number and function. Directly passed onto to offspring through ova

Question 81

LGA definition and causes

Answer 81

Definitions: -large for gestational age (LGA) birth weight >90th centile -macrosomia -birth weight>4500g Causes: -gestational age: pregnancies that go beyond 40 weeks increase incidence -Fetal sex; male infants tend to weigh more than female -excessive maternal weight gain and obesity -multiparity (have 2-3x vs primaparas) -erythroblastosis fetalis -hydrops fetalis -genetic disorder of overgrowth (eg Beckwith-Wiedemann syndrome, Sotos syndrome) -maternal diabetes (pre existing or gestational) Pathophysiology: -increased maternal glucose concentrations -increased fetal insulin concentrations -increased fetal growth factors

Question 82

Growth regulation

Answer 82

Genetic and environmental Environmental complex with multiple levels: -maternal -fetal -placental Successful placentation required for regulation Placental and fetal growth regulated by combination of substrate availability and endocrine or paracrine signalling -IGF1 and IGF2 major stimulus

Question 83

Maternal factors

Answer 83

Ethnicity Maternal stature/BMI -maternal v paternal influence Drugs -cigarettes, alcohol, drugs of abuse Nutrition Maternal hypoxia -cyanotic heart disease, chronic respiratory disease, altitude

Question 84

Maternal undernutrition

Answer 84

Dutch famine 1940s -late gestation —> decreased birthweight (started pregnancy at normal nutritional status) -early gestation—> not growth restricted But prenatal programming: when these babies become adults they are more likely to deliver growth restricted babies Developing world- IUGR major cause of perinatal mortality/morbidity: -maternal undernutrition -synergistic with low age, maternal anaemia, chronic disease/HIV and placental malaria

Question 85

Fetal factors

Answer 85

Genome -chromosomal disorders Growth factors: -insulin like growth factors, thyroxine Congenital infection: cytomegalovirus CMV, toxoplasmosis, rubella

Question 86

Placental factors

Answer 86

Primary placental problems -abnormality of placenta structure/function Secondary placental problems: -hypertension, chronic renal disease, vasculitis, pro-thrombotic disorders Multiple gestation: growth discordance less SA available for growth

Question 87

Malplacentation in IUGR

Answer 87

Majority of blood flow to uterus is supplied by uterine arteries (supplying Arcuate and spinal arteries) Shape of uterine artery waveform is unique and changes with gestation: early-high vascular impedance and low flow. Mid- high flow low resistance Poor trophoblast invasion of maternal spiral arteries: -increased impedance to flow and decreased placental perfusion -change in Doppler indices- diastolic notch etc Preeclampsia

Question 88

Asymmetrical v symmetrical patterns of IUGR

Answer 88

Asymmetrical: -uteroplacental insufficiency- decreased glycogen stores so decreased abdominal circumference Symmetrical: -early growth insult, chromosomal viral infection-disrupted regulation of growth processes or disruption at cell hyperplasia stage Patterns are seen but generally not helpful in predicting cause or outcome thus need to distinguish between small and healthy- small and not well IUGR IUGR is a combination of reducing growth velocity and placental insufficiency (abnormal uterine and/or raised umbilical artery PI)

Question 89

How do we manage foetal growth clinically

Answer 89

Antenatal visit Fetal growth assessment: symphsio-fundal height Ultrasound: fetal head circumference, abdominal circumference, femur length Fetal wellbeing assessment: -short term wellbeing- cardiotocograph CTG foetal HR -long term wellbeing- resistance to flow in arteries. Umbilical artery Doppler, middle cerebral artery Doppler, ductus venosus Doppler, liquor volume

Question 90

Risk factors for SGA

Answer 90

History: -age, parity, BMI, maternal substance exposure, exercise, weight gain, diet, SGA, hypertension, diabetes, renal disease Current pregnancy: -threatened miscarriage, fetal anomaly, pre eclampsia, pregnancy induced hypertension, placental abruption

Question 91

Monitoring babies that have estimated foetal weight <10th centile

Answer 91

Monitoring throughout pregnancy with umbilical artery Doppler and if they are <10th centile with normal umbilical artery Dopplers then push to have delivery at term If evidence of increased flow in umbilical artery Doppler then they are monitored more frequently to try and deliver at 37 weeks More significant abnormalities in umbilical artery Doppler eg have absence or reversed end diastolic flow then frequency of monitoring is increased and monitored closely with intent to deliver at 30-32 weeks

Question 92

Gestational diabetes

Answer 92

GDM is defined as any degree of glucose intolerance with its onset (or first recognition) during pregnancy 5% pregnancies Pre-existing risk: pancreatic Beta cell dysfunction (deficient insulin production) on background chronic insulin resistance (deficient receptors/altered insulin signalling pathway) present before pregnancy Pregnancy is a state of insulin resistance- hormonal, inflammatory, cytokines, adipokines changes (eg hPL, TNFa, resistin and others). Resistance increases with advancing gestation

Question 93

Screening

Answer 93

Screen from early pregnancy 16-18 weeks if: -past history of GDM or glucose intolerance Screen from 24-26 weeks if: -family history of diabetes (first degree relative) -PCOS -BMI>30 -ethnicity:Asian, black, Middle Eastern -previous macrosomia >4500g -previous unexplained stillbirth -on steroids (eg prednisolone) Screen urgently if arises in current pregnancy: -significant glycosuria (3+ at any time or 2+ on two or more occasions) -polyhydramnios and macrosomia Screen via: -OGTT (overnight fast then 75g glucose load, test at 2 hrs) -random blood glucose profile >36 weeks

Question 94

Complications of GDM- maternal

Answer 94

Pre eclampsia Pre term labour Instrumental delivery- C section Diabetes in later life

Question 95

Complications- foetal

Answer 95

Macrosomia Shoulder dystocia: anterior foetal shoulder stuck on maternal pubic symphysis delaying birth compromised blood flow to heart Polyhydramnios Perinatal mortality and morbidity: -neonatal hypoglycaemia, jaundice, polycythemia, hypocalcaemia Fetal programming and increased risks of adult diseases

Question 96

Management GDM

Answer 96

Multidisciplinary: -obstetrician -diabetologist -diabetic nurse -dietician Regular monitoring and strict control: -blood sugars up to 7 times a day Medical management: -diet -oral agents eg metformin -insulin Tight glucose control reduces risk of

Question 97

Obstetric management GDM

Answer 97

Regular growth scans Regular BM monitoring Deliver around 38 weeks- placenta wont work as well for as long Offer GTT 6 weeks postnatal: glucose tolerance test assess future risk diabetes