Chapter 3 - Fetal Medicine Flashcards
Pathogenesis of Trisomy 21
Results from non-disjunction of chromosome 21 at meiosis (95%). = 1% risk of recurrence
May also
be due to balanced translocation in parents (4%). = 10% risk of recurrence if the mother, less if in the father.
1% estimated due to
mosaicism.
Describe the risks of trisomy 21 with age
- <25yrs: 1:1500
- 30yrs: 1:910
- 3 5yrs: 1:380
- 4 0yrs: 1:110
- 4 5yrs: 1:30
Describe the features of trisomy 21
1) Typical appearance:
• flat nasal bridge
• epicanthic folds
• single palmar crease.
2) Intellectual impairment:
• 80% profound or severe
• mean mental age at 21yrs is 5yrs
• increased risk of early-onset dementia.
3) Congenital malformations:
• cardiac abnormalities (46%, e.g. VSD, atrial septal defect (ASD), and
tetralogy of Fallot)
• gastrointestinal atresias are common (e.g. duodenal atresia).
4) Increased risk of other medical conditions, including:
• leukaemia
• thyroid disorders
• epilepsy.
What is the second most common autosomal trisomy
Trisomy 18 (Edwards’ syndrome) due to non-disjunction at meiosis
--> Features: • craniofacial abnormalitie - small facial features, small chin, and low-set ears • rocker bottom feet. • Congenital malformations: • cardiac abnormalities- usually VSD • gastrointestinal abnormalities • urogenital abnormalities.
Which aneuploidy results in: craniofacial, including cyclopia; microcephaly.
• Congenital malformations (midline):
• holoprosencephaly (failure of cleavage of the embryonic forebrain)
• gastrointestinal abnormalities, especially exomphalos
• cleft lip and palate (midline).
Trisomy 13 (Patau’s syndrome)
Describe the cause and features of Turners
Loss of X chromosome resulting in; short stature, webbed neck, and wide carrying angle, non-functioning ‘streak’ ovaries and coarctation of the aorta BUT NO MENTAL IMPAIRMENT
Pathogensis of Klinefelters
47 XXY - caused by non-disjunction of the X chromosomes.
- Sterile
- hypogonadism
- tall
- loq IQ
A test which has a high detection rate
= Sensitive
A test with low false positives
= Specific
What is the combined screening test?
Scan + blood test at 11-13 weeks
- Scan looks at nuchal measurement +/- hypoplasia nasal bone and severe tricuspid regurg assessment
- Blood test = PAPP-A and hCG
**now the recommended **
Give the advantages and disadvantages of the combined test
Advantages
• Performance 90% detection for 5% FPR (75% for 3%).
• May detect other abnormalities such as anencephaly.
• An increased NT is also a marker for structural defects, e.g. cardiac
malformations.
•Result usually available in 1st trimester, allowing surgical termination
of pregnancy (TOP).
• Acceptable detection rate for all trisomies.
Disadvantages:
Expensive and difficult to perform nuchal scan.
Describe the triple and quad test
When Blood tests at 16wks. How • Dating scan (but not nuchal scan). • Blood tests at 15wks measuring: • oestriol • hCG • alpha-fetoprotein (AFP) • inhibin A (not if triple).
Lower detection rate and higher false positives than combined
When is the triple and quad test recommended
Recommended if NT scan not possible or gestation too advanced.
Describe the integrated screening tests
An alternative screening test with nuchal scan + bloods at 10 weeks and repeated bloods at 15weeks
- expensive so rarely used and has lower detection but lower false positives
What is the significance of a raised AFP
- Neural tube defects
- Abdominal wall defects.
- Congenital nephrosis.
- Upper fetal bowel obstruction.
- Placental or umbilical cord tumours.
- Sacrococcygeal teratoma.
- Multiple pregnancy.
- After bleeding in early pregnancy.
An elevated AFP should trigger closer fetal and maternal surveillance as
it is also a marker of adverse perinatal outcomes including:
• Fetal death.
• IUGR.
• Late pregnancy bleeding.
• Preterm delivery.
When does the anomaly scan occur?
W18-21
Anomaly scan detection of malformations is dependent on:
- The anatomical system affected.
- Gestational age at the time of the scan.
- Skill of the operator.
- Quality of the equipment.
- BMI of the mother
Anomaly scan is most effective at picking up ………….. anomalies and worst at detecting……..
best = neuro 76% worst = cardiac 17%
Anomaly scan features
Skull and brain + nuchal fold Spine Abdomen Limbs Heart Face
Most common neural tube defects
Spina bifida and anencephaly
What is anencephaly?
Absence of skull vault and cerebral cortex. It is incompatible with life, with
babies rarely living more than a few hours if they are not stillborn.
Types of spina bifida + which is the most common?
Spina bifi da occulta (mildest):
• split in vertebrae with no herniation of spinal cord
• v aries from asymptomatic to mild neurological symptoms.
Meningocele (least common):
• split in vertebrae with herniation of meninges and cerebrospinal
fluid (CSF)
• varies from normal neurological function to moderate symptoms.
Myelomeningocele (most severe):
• split in vertebrae allows herniation of spinal cord and meninges
• invariably have abnormal neurology at and below the lesion
• usually have an abnormal cerebellum and hydocephalus, which may
result in mental impairment.
Recommended doses of folic acid
- 400 micrograms/day for 3mths before conception, continued to 12wks.
- 5 mg/day for women with previously affected child or those taking anticonvulsants.
Lemon and banana sign are seen on fetal US in which detect
Spina bifida:
• defect seen in the vertebral bodies or tissue overlying the spine
• frontal bone scalloping (‘lemon sign’)
• abnormal shaped cerebellum (‘banana sign’)
• up to 95% detection rate for major defects
Risk factors for cardiac abnormalities
1) FH
2) Previous Hx
3) Meds - anti-convulsants or lithium
4) Increased thickness of nuchal translucency
True or false:
Most cardiac abnormalities are missed at routine anomaly scans.
TRUE, may be better detected later (22weeks)
Why is bilateral renal agenesis is lethal?
because of anhydramnios causing lung
hypoplasia.
Name 3 fetal urinary tract defects
1) Renal agenesis
2) Posterior urethral valve syndrome
3) Hydronephrosis
Keyhole bladder is seen in…..
Posterior urethral valve syndrome
- in male fetuses where folds of mucosa block the bladder
neck causing outfl ow obstruction. - The severity is variable; back pressure may cause irreversible renal
damage and oligohydramnios
Name 3 fetal lung defects
1) lung hypoplasia - often due to oligohydramnios from PROM or renal anomalies
2) Diaphragmatic hernia - 40% die postnatally due to lung hypoplasia and lots have other malformations
3) Congenital cystic adenomatoid malformation = alveoli are replaced by cysts (good prognosis)
Name 3 fetal GI defects
1) Exomphalos (omphalocele) = viscera inside a sac but often associated with chromosomal abnormalities
2) Gastroschisis = protrusion of the gut through an anterior abdo wall defect, not covered by a sac, usually occurs in young women (rare after 25yrs) but not associated with chromosomal abnormalities
3) GI obstruction - CF, trisomy
Double bubble sign on US
Duodenal atresia
No stomach bubble on US + polyhydramnios
Oesophageal atresia
signs not seen if TOF
Which soft markers on US require expert referral?
1) Increased nuchal fold
2) Two vessel umbilical cord
3) Echogenic intracardiac foci
4) Echogenic bowel
5) Choroid plexus cyst
6) Mild renal pelvic dilation
1) Increased nuchal fold increases the risk of chromosomal abnormalities + early sign of hydrops
4) Echogenic bowel increases the risk of chromosomal abnormalities + occasionally associated with increased
perinatal risk, cystic fibrosis, and bowel obstruction.
6) Mild renal pelvic dilation = increases the risk of chromosomal abnormalities
What are the indication for chorionic villus sampling?
- Karyotyping if high risk for aneuploidy
- For DNA analysis if parents are carriers of a gene mutation e.g. CF or thalasseamia
What are the risks of chorionic villus sampling?
- 1% risk of miscarriage
- Increased risk of vertical transmission
- Risk of false negatives
- Placental mosaicism 1%
When & what does chorionic villus sampling occur?
- 10-13 weeks
- Involves aspiration of some trophoblastic cells for karyotyping, fluorescent
in situ hybridization (FISH) and polymerase chain reaction (PCR).
When + how is aminocentesis conducted?
- Only from week 15 onwards
- Aspiration of amnionic fluid of cells from the skin and gut
Indications of aminocentesis ?
- Karyotyping for anueploidy
- DNA analysis for genetic mutations
- Enzyme assay for inborn errors of metabolism
- Fetal infection diagnosis e.g. CMV and toxoplasmosis
Which invasive fetal diagnostic test is safer in terms of risk of miscarriage?
Aminocentesis (risk very litter higher than would happen naturally)
Define fetal hydrops
- The accumulation of serous fluid in two or more fetal compartments e.g. pleural effusion, ascites or polyhdramnios
- Divided into non-immune and immune causes
What is the cause of fetal hydrops?
Due to an imbalance of interstitial fluid production and lymphatic return
- CFH
- Obstructed lymphatic flow
- Decreased osmotic pressure
- Immune: Blood group incompatibility
- Non-immune: fetal anaemia (parvovirus, thalassaemia, G6PD), Cardiac/chromosomal/genetic abnormalities, infections or twin to twin transfusion
Inx for fetal hydrops
1) US
2) Fetal blood or amniotic sampling
3) Kleihauer test
4) Antibody screen
5) Virology
6) Electrophoresis
How can you treat fetal anemia?
in utero blood transfusions
Define rhesus isoimmunization
Maternal IgG response crossing the placenta against fetal red cells causing destruction and anaemia; if severe,
precipitates fetal hydrops, which is often referred to as immune hydrops.
Describe rhesus blood groups
Consists of three linked gene pairs; one allele of
each pair is dominant— C/c , D/d , and E/e . There are only five antigens (d is
not an antigen; it merely implies absence of D).
Inheritance is Mendelian.
D gene is the most significant cause of isoimmunization, because 16% of white mothers are rhesus D –ve (d/d ). Incidence lower in Afro-Caribbean and Asian populations.
Other significant antigens include c, E, and atypical Kell antibody. Because of success of anti-D prophylaxis, these account for
up to 1/2 of cases.
Why is the first baby not affected by sensitizing events?
The first immune response mounted is IgM which do not cross the placenta so this pregnancy is not at risk but subsequent mount a IgG response by primed memory B cells which does cross the placenta and can cause haemolytic anaemia —> high CO leading to hydrops + rise in bilirubin leading neonatal jaundice or worse brain damage
Give 5 sensitizing events
- TOP or evacuation of retained products of conception
- Ectopic
- Vaginal bleeding after 12weeks or earlier if v heavy
- ECV
- Blunt abdo trauma
- Invasive uterine procedure (amniocentesis or CVS)
- IUD
- Delivery
How to manage a woman identified during booking bloods as rhesus negative
- Check partners antibodies to determine risk
- PCR of fetal cells in maternal blood can determine fetal blood group
- if <10IU/ml repeat every 4weeks
- if >10IU/ml assess for anaemia
- Measure peak systolic velocity (PSV) of the fetal middle cerebral artery weekly - It will become abnormal before the baby is anaemic/risk of hydrops. If raised fetal blood sampling is indicated.
- If fetal low haematocrit give irradicated rh-ve -ve CMV packed red cells into the umbilical vein or hepatic vein from 18weeks onward
- Postnatal anaemia/jaundice –> transfusion, phototherapy or exchange transfusion
How to prevent rhesus disease
Anti-D 1500IU to all rhesus -ve mothers at 28weeks + within 72 hours of rhesus sensitizing events + after delivery (give more if Kleihauer suggests)
What % of fetal haemolysis is due to rhesus antibodies?
Rhesus = 50%
As prevention is so successful, fetal haemolysis is rare and 50% is due to other antibodies e.g. anti-kell and anti-c
Describe the normal factors involved in the composition of amniotic fluid after 20weeks
Consists of fetal urine, volume depends on urine production, fetal swallowing and absorption; it varies with gestation (greatest betweek 24-36weeks).
Volume is measured by US, deepest pools in the 4 quadrants of the uterus
Definition of oligohydramnios
Reduction of amniotic fluid with the deepest pool <2cm or total of all 4 pools (AFI) <8cm
Describe the complications of oligohydramnios
Reduced volume –> lung hypoplasia, limb abnormalities e.g. talipes.
PROM –> infection and prematurity
Inx oligohydramnios
1) US
2) Speculum looking for ruptured membranes
- - If SROM check CRP, FBC and vaginal swabs
Mx oligohydramnios If SROM at 34–36 or more weeks
Induce labour unless CS indicated for another reason
Mx oligohydramnios If SROM <34–36 weeks
- Prophylactic oral erythromycin
- Monitor for infection
- Daily CTG
- ?induce at 34-36weeks
Mx oligohydramnios if IUGR
Mx according to umbilical artery doppler and CTG
Mx if isolated oligohydramnios
Intervention is not usual if umbilical artery Dopplers are normal.
Mx oligohydramnios if renal tract abnormal
Refer to fetal medicine
Causes of oligohydramnios
• SROM. • Reduced fetal urine production: ---IUGR ---fetal renal failure or abnormalities ---post-dates pregnancy. • Obstruction to fetal urine output: fetal abnormalities such as posterior urethral valves.
Define Polyhydramnios
The amniotic fluid is increased.
In general a deepest pool of >8cm or an AFI >22 is abnormal.
Causes of polyhydramnios
Increased fetal urine production:
• Maternal diabetes.
• Twin–twin transfusion syndrome (recipient twin).
• Fetal hydrops.
Fetal inability to swallow or absorb amniotic fluid
• Fetal gastrointestinal (GI) tract obstruction (e.g. duodenal atresia,
tracheo-oesophageal fi stula).
• Fetal neurological or muscular abnormalities (e.g. myotonic dystrophy, anencephaly).
• Other rare abnormalities or syndromes (e.g. facial obstruction).
• Idiopathic (usually mild).
Complications of polyhydraminos
1) Preterm due to uterine stretch
2) Malpresentation
3) Maternal discomfort due to distension
Inx of polyhydramnios
1) Maternal GGT
2) US fetus
Mx of polyhydramnios
• Severe polyhydramnios = fetal abnormality
- if massive (e.g. AFI >40), amnioreduction (drainage of excess fluid with a needle), or non-steroidal anti-inflammatory drugs (NSAIDs).
• If fetal abnormality, refer to fetal medicine centre.
• Twin–twin transfusion syndrome= fetal medicine
centre, usually with laser ablation of placental anastomoses.
- If preterm, assess risk of delivery with cervical scan and/ or fibronectin assay, and steroids.
- If unstable or transverse lie at term, admit to hospital: CS if labour ensues with an abnormal lie.
**NSAIDs cause fetal oliguria and can constrict the ductus arteriosus:
close supervision is therefore indicated.
Definition of IUGR
Pathologically small baby
SGA = below 10th percentile for its age
To minimise false positives:
- Ensure dates are correct
- Try to take maternal height, weight, parity, ethnicity and fetal gender into account
- www.gestation.net have optimised growth curves
Complications of IUGR
- Perinatal mortality is 6–10 times greater.
- Incidence of cerebral palsy is 4 times greater.
- 30% of all stillborn infants are growth restricted.
- Intrapartum fetal distress and asphyxia.
- Meconium aspiration.
- Emergency CS.
- Necrotizing enterocolitis.
- Hypoglycaemia and hypocalcaemia.
Causes of IUGR
Maternal • Chronic maternal disease: - hypertension - cardiac disease - chronic renal failure. - Substance abuse + smoking • Autoimmune diseases: antiphospholipid antibody syndrome. • Genetic disorders: phenylketonuria. • Poor nutrition. • Low socio-economic status. Placental (placental insuffi ciency) • Abnormal trophoblast invasion: - pre-eclampsia - placenta accreta. - Infarction. - Abruption. - Placenta praevia. • Tumours: chorioangiomas (placental haemangiomas). • Abnormal umbilical cord or cord insertion: two-vessel cord.
Fetal • Genetic abnormalities: - trisomy 13, 18, or 21 - Turner’s syndrome - triploidy. • Congenital abnormalities: - cardiac, e.g. tetralogy of Fallot, transposition of the great vessels • gastroschisis. • Congenital infection: - CMV - rubella - toxoplasmosis. • Multiple pregnancy.
Define the classifications of IUGR
• Symmetric growth restriction: describes a fetus whose entire body is
proportionately small and tends to be seen with very early onset + with chromosomal abnormalities.
• Asymmetric growth restriction: undernourished fetus who is compensating by directing its energy to maintaining the growth of vital organs e.g. brain and heart at the expense of
the liver, fat, and muscle = ‘head-sparing effect’ = normal
head size with small abdominal circumference and thin limbs.
= IUGR secondary to placental insufficiency.
Mx IUGR
- Early identification + intensive fetal monitoring to continue the pregnancy safely for as long as possible to minimise prematurity complications but deliver before compromise occurs.
LT outcome of IUGR
- Most grow normally in infancy
- 1/3 do not reach full predicted height and have childhood attention/performance deficit
- In adulthood: higher rates of of coronary heart disease, HTN, high cholesterol + abnormal glucose-insulin metabolism (Baker hypothesis)
Incidence of still born
1% of babies
1/3 of still borns are small for gestational age
When should preterm and high risk babies be delivered?
Preterm should only be delivered if displaying signs of distress to maximize maturity
After 36 weeks babies at high risk should be delivered
How do you monitor high risk babies?
1) US biometry
2) Amniotic fluid volume
3) Umbilical cord doppler
If abnormal and at term - deliver
If abnormal, growth restricted and preterm - give betamethasone 12mg IM + monitor umbilical cord doppler –> deliver if reversed diastolic flow or abnormal CTG
What does high resistance/pulsatility in the uterine artery indicate?
That the mother is at increased risk of developing early onset pre-eclampsia or having a baby with IUGR; therefore she should be offered extra monitoring in pregnancy
What does high resistance/pulsatility in the umbilical artery indicate?
Placental failure –> small baby
+ abnormal waveforms are an early signs of fetal impairment
+ can be used to time fetal rescue
What can screening the middle cerebral artery with a doppler indicate?
- Anaemia
- Head sparing IUGR (reduced resistance or pulsatility)
- May be more useful than umbilical at term
When is ductus venosus doppler monitoring used?
This waveform is a surrogate for cardiac function and used in T-T transfusion syndrome monitoring + to time delivery in compromised babies as an adjunct to CTGs and umbilical artery
Describe the stages of umbilical artery dopplers:
- End diastolic flow
- Absent end diastolic flow (AEDF)
- Reversed end diastolic flow (REDF)
• When the placenta is functioning normally, flow through the
umbilical artery is not impeded by end organ resistance; therefore
blood continues to flow forwards (away from the heart) during
cardiac diastole, seen on Doppler waveform as ‘end diastolic flow’
- As the uteroplacental unit begins to fail, the vascular resistance rises and the forward flow in diastole begins to be reduced (this can be numerically quantified and used for monitoring).
- When the resistance is very high, blood no longer fl ows forwards in diastole: this is called ‘absent end diastolic fl ow’ (AEDF).
• When the situation is critical, the resistance is so great that blood may flow back towards the heart during diastole: this is called
‘reversed end diastolic flow’ (REDF)
Describe a normal CTG
- HR 110-160/min
- Varies from baseline by 5-25bpm
- HR should speed up by at least 15bpm for 15seconds (accelerations) + at least 2 accelerations in 20mins (reactive)
- Should be no slowing from baseline (decelerations)
Why has routine antenatal CTG found not to be useful?
- Abnormal CTG is a late stage event and fetal death is almost imminent
When are CTGs useful?
To exclude current compromise:
• In acute conditions known to cause fetal compromise, e.g. abruption and in women reporting reduced fetal movements.
• Daily in the surveillance of chronic conditions that are associated with uteroplacental insufficiency such as pre-eclampsia, and in IUGR when there is AEDF.
