Screening in pregnancy Flashcards
What are 4 types of fetal screening offered during pregnancy?
- Infectious diseases e.g. HIV, hepatitis B, syphilis
- Screening for inherited conditions affecting haemoglobin - thalassaemia, sickle cell disease
- Screening for chromosomal abnormalities
- Screening for physical anomalies on ultrasound
How are structural anomalies detected during pregnancy?
20 week (18-21 week) ultrasound ‘anomaly’ scan
What are 11 conditions that are looked for on a fetal anomaly scan at 20 weeks?
- Anencephaly
- Open spina bifida
- Cleft lip
- Diaphragmatic hernia
- Gastroschisis
- Exomphalos
- Serious cardiac abnormalities
- Bilateral renal agenesis
- Lethal skeletal dysplasia
- Edwards’ syndrome, or T18
- Patau’s syndrome, or T13
What proportion of fetuses have congenital malformations in the UK?
2.5%
What are 12 exampes of genetic disorders that can cause congenital abnormalities?
- Down syndrome (trisomy 21)
- Edwards syndrome (trisomy 18)
- Patau syndrome (trisomy 13)
- Triploidy
- Sex chromosome abnormalities
- XO (Turner syndrome)
- XXY (Klinefelter syndrome)
- XYY
- XXX
- Apparently balanced rearrangeemnts (translocations or inversions)
- Unbalanced chromosomal structural abnormlities
- Gene disorders e.g. fragile X syndrome, Huntington chorea, Tay-Sachs disease
What are 5 types of congenital structural disorders?
- Congenital heart disease
- Neural tube defects e.g. anencephaly, encephalocele, spina bifida
- Abdominal wall defects e.g. exomphalos, gastroschisis
- Genitourinary abnormalities
- Lung disorders
What are 5 examples of genitourinary structural disorders?
- renal dysplasia
- polycystic kidney disease
- pyelectasis
- posterior urethral valves
- Potter syndrome
What are 3 examples of structural lung disorders?
- Pulmonary hypoplasia
- Diaphragmatic herniae
- Cystic fibrosis
What are 12 examples of congenital infection?
- Toxoplasmosis
- Syphilis
- Rubella
- Cytomegalovrius
- Herpes simplex virus
- HIV
- Beta-haemolytic streptococci group B
- Chickenpox
- Erythrovirus
- Zika
- Hepatitis
- Listeria monocytogenes
What are 4 aims of prenatal diagnosis of congenital abnormalities?
- To identify early those which are incompatible with life or that are likely to result in significant handicap so as to prepare the parents, involve other specialist clinicians and offer option of termination of pregnancy if appropriate
- Identify conditions which may influence timing, site or mode of delivery
- Identify fetuses who may benefit from early neonatal paediatric intervention
- To identify fetuses who may benefit from in utero treatment
Why might couples opt to continue pregnancies in the face of severe defects which have resulted in either intrauterine or early neonatal death?
May find it easier to cope with their grief having held their child
What should our approach be when identifying conditions likely to cause long-term handicap and suffering for both the child and their parents?
parents must decide what is acceptable to them; we can only advise, guide and respect their final wishes, irrespective of our own personal opinions
provide written info for parents to absorb, may need to arrange follow up appointment a few days later
What increases the likelihood of autosomal trisomy, especially trisomy 21?
advancing maternal age
What are 6 factors that increase the risk of structural abnormalities?
- Increased maternal age
- Family history e.g. DMD, cysstic fibrosis, sickle cell disease
- Greater chance if parents have had previously affected child e.g. spina bifida
- Consanguinity - increases chance of single gene abnormalities, especially autosomal recessive
- Maternal pre-existing diabetes - increased risk of cardiac and neural tube defects
- Maternal epilepsy - increased chance of structural abnormalities (esp if taking teratogenic drugs)
What is the background risk of a child having spina bifida, and how is this affected if the mother has already had a child with spina bifida?
0.2%; increased to 2%
What are 2 conditions that a child is at increased risk of if the mother has pre-existing diabetes?
- Cardiac anomalies
- Neural tube defects (anencephaly, encephalocele, spina bifida)
What should counselling for screening involve?
make it clear most tests (especially those for chomosomal problems) will only identify those at ‘high or low risk’ for a condition, rather than whether condition is actually present
couple must understand that if they were placed in the ‘high risk’ group, further tests would then be offered and they should be aware of what that would involve
should ideally have given thought to what they would do should the pregnancy be affected
What type of screening test is the key one that is performed in the first trimester?
combined screening test for Down syndrome: measuring thickness of nuchal fluid behind fetal neck (nuchal translucency) + biochemistry (free beta-hCG and pregnancy-associated plasma protein A (PAPP-A)
What is the combined screening test in first trimester used to detect?
Risk of Down syndrome
What is the sensitivity of combined testing for Down’s syndrome?
up to 90% sensitivity when using cut off of 1 in 150 as high risk
but only identify those at increased risk, not absolute certainty
How does the combined screening test for Down syndrome work in dichorionic vs monochorionic twin pregnancies?
each twin given an individualised risk in dichorionic, but in monochorionic, risk is calculated as an average of that allocated to both twins
What are the 2 types of test which can be used to definitively diagnose Down syndrome?
- Amniocentesis
- Chorionic villous sampling
What are 2 reasons why it might not be possible to obtain a first trimester screening test?
- Poor fetal position
- Pregnancy already beyond 14 weeks’ gestation
In addition to informing about risk of Down syndrome, what else can nuchal translucency be used to indicate?
increased NT is a marker for structural defects e.g. cardiac malformations
What is the advantage of having the combined screening test in the first trimester?
allows surgical termination of pregnancy
At what point in the first trimester is the combined test performed?
11 - 13+6 weeks
What, in addition to Down syndrome, can be detected by the combined screening test in the first trimester?
all trisomies - Edward, Patau
What does measurement of nuchal translucency involve?
ultrasound of subcutaneous tissue between skin and soft tissue overlying cervical spine with the fetus in neutral position
In addition to the combined tests in the first trimester, what are 4 other types of tests for Down syndrome?
- Serum integrated test
- Integrated test
- Triple test
- Quadruple test
What does the serum integrated test for Down syndrome involve?
- dating scan (but not nuchal)
- PAPP-A at 10 weeks
- Quadruple test at 15 weeks measuring:
- oestriol
- hCG
- AFP
- inhibin A
What is the detection rate of Down syndrome for the serum integrated test?
85%
What is the integrated test for Down syndrome? 3 parts
- Nuchal scan 10-13 weeks
- PAPP-A at 10 weeks
- Quadruple test at 15 weeks measuring:
- oestriol
- hCG
- AFP
- inhibn A
What is the detection rate of Down syndrome with the integrated test?
85%
What does the triple test for Down syndrome involve?
blood test at 16 weeks for oestriol, hCG, AFP
+ normal dating scan (11-13 weeks) (but not nuchal scan)
What does the quadruple test for Down syndrome involve?
blood test at 16 weeks measuring oestriol, hCG, alpha-fetoprotein, inhibin A
+ normal dating scan (not nuchal scan)
What is the detection rate of Down syndrome with the triple test?
71%
What is the detection rate of Down syndrome with the quadruple test?
75%
What are 2 things that can increase the performance of the combined screening test for Down syndrome?
- Presence of additional risk factors: nasal bone (absent or hypoplastic) +
- tricuspid regurgitation
at 11-13+6 weeks
What is a disadvantage of the combined screening test for Downs yndrome?
expensive and difficult to perform nuchal scan
What is the recommended and best screening test for Down syndrome?
Combined screening test (nuchal scan + blood test PAPP-A and beta hCG) at 11-13 weeks
What other abnormality can a combined test directly reveal?
anencephaly
What can an elevated level of matern serum AFP be used to indicate?
greater than 2.2 multiple of median (MoM) can be used as screening tool for open neural tube defects
In addition to open neural tube defects, what are 7 other conditions that are associated with an elevated AFP level?
- Abdominal wall defects
- Congenital nephrosis
- Upper fetal bowel obstruction
- Placental or umbilical cord tumours
- Sacrococcygeal teratoma
- Multiple pregnancy
- After bleeding in early pregnancy
What are 4 adverse perinatal outcomes that AFP is a marker of, that should trigger closer fetal and maternal surveillance?
- Fetal death
- IUGR
- Late pregnancy bleeding
- Preterm delivery
What are 8 features that must be assessed as a minimum standard required for the 18-21 week anomaly scan?
- Skull shape and internal structures
- Spine - longitudinal and transverse views
- Abdominal shape and content at the level of stomach, kidneys, umbilicus/abdo wall, bladder
- Arms (tree bones and hand)
- Legs (three bones and foot)
- Heart - 4 chamber view, outflow tracts (PA and aorta)
- Lungs
- Face and lips
What are 4 internal skull structures that should be assessed on the 18-21 week anomaly scan?
- Cavum pellucidum
- Cerebellum
- Ventricular size at atrium <10mm
- Nuchal fold
What testing may be offered for those in whom it is not possible to obtain a first trimester screening test?
serological testing may be offered - quadruple testing (oestriol, beta-hCG, inhibin A, AFP)
What happens to AFP levels in Down syndrome vs in a neural tube defect or gastroschisis?
- Down syndrome: lower
- NTD/ gastroschisis: raised
What should finding a raised AFP on serological screening prompt?
ultrasound scan looking for neural tube defect or gastroschisis
What is the non-invasive prenatal screening test (NIPT)?
based on analysis of cell-free fetal DNA (cffDNA) extracted from maternal blood, used to screen for various chromosomal disorders and identify fetal rhesus blood type if required
What is non-invasive prenatal screening testing (NIPT) used for?
screen for various chromosomal disorders an identify fetal rhesus blood type if required
What is the benefit of NIPT and how often is it used?
much more sensitive and specific than conventional test
currently recommended as option to women who have been identified by other screening methods (combined screening test) but who wish to avoid invasive diagnostic procedures. however not yet widely available
What are 3 things that reduce the accuracy of non-invasive prenatal screening testing (NIPT)?
- Multiple pregnancy
- Obesity
- Women at less than 10 weeks’ gestation
What ultrasound screening test is offered to all women during pregnancy?
anomaly ultrasound scan between 18 and 21 weeks gestation
Why is the ultrasound scan for structural fetal anomalies at 18-21 weeks gestation?
maximises likelihood of obtaining satisfactory images, whilst allowing those in whom major or lethal abnormalities have been detected to consider termination of pregnancy
What are 3 drawbacks of the fetal anomaly scan at 18-21 weeks gestation?
- Despite highly skilled operators and optimal machinery, sometimes abnormalities not evident at this gestation and cannot be identified
- Maternal obesity reduces quality of images obtained
- Identification of minor abnormalities or ‘soft markers’ that are often associated with but not diagnostic of other problems, especially chromosomal abnormalities - found in 5% of detailed scans
In what proportion of detailed routine anomaly scans are soft markers of other problems e.g. chromosomal abnormalities identified (despite not always being assoicated with other problems)?
5%
What are 4 examples of soft markers that are relatively frequently detected on the fetal anomaly scan, and are associated with but not diagnostic of other problems?
- Choroid plexus cysts
- Mild renal pelvic dilatation
- Echogenic cardiac foci
- Mild cerebral ventricular dilatation
What increases the likelihood that a soft marker noted on the anomaly scan is associated with a chromosomal problem?
if noted in isoaltion, chance of chromosomal problems low; if more than once seen, or is in conjunction with structural defect, chromosomal problem more likely
What is a choroid plexus cyst?
a small, fluid-filled space that occurs in a gland in the brain called the choroid plexus. This gland is located on both the left and right side of the brain, and it makes fluid within the brain and spinal cord.
What proportion of fetuses with Down syndrome (trisomy 21) will have a normal detailed anomaly scan?
about two thirds
How commonly do Patau and Edwards syndrome show abnormalities on the fetal anomaly scan?
usually do show some anomaly, but usually non-specific and not diagnostic
What is the usual longer term effect of Edwards and Patau syndrome?
usually fatal in perinatal period, do not pose same lifelong implications as for trisomy 21
What are the 2 diagnostic tests which can be offered if screening has identified a mother at ‘high risk’ of carrying a baby with chromosomal abnormality
- Amniocentesis
- Chorionic villous sampling (CVS)
What are the 2 risks associated with both amniotcentesis and chorionic villous sampling?
- Miscarriage
- Rhesus sensitisation
What is given to women undergoing amniotcentesis or CVS due to the risk of rhesus sensitisation?
rhesus negative women rquire 250 IU of anti-immunoglobulin D
At what point in gestation may diagnostic amniocentesis be performed?
after 15 weeks’ gestation
What does amniocentesis involve?
- Passing a thin needle transabdominally into the amniotic cavity, under continuous ultrasound guidance, to extract 10-15ml of amniotic fluid
- Previously, amniocyte culture was used to obtain karyotype results but this was replaced with quantitative fluorescence polymerase chain reaction (QFPCR) to exclude more common aneuploidies
- Most recently, micrarray analysis allows examination of many more segments of genome, may detect small changes not identified before
What is the risk of miscarriage with amniocentesis?
1%
At what point in gestation may chorionic villous sampling be performed?
may be performed after 10 weeks gestation
What does chorionic villous sampling involve?
passing a needle transabdominally, or occasionally transvaginally, under direct ultrasound guidance to take a sample of placental tissue
What is the rate of miscarriage of chorionic villous sampling?
1.5-2%
What are the 3 infectious diseases that are screened for in pregnancy?
- Hepatitis B
- Syphilis
- HIV
How and when are infectious diseases screened for in pregnancy?
blood test taken as soon as possible, ideally before 10 weeks
Who receives screening for haemoglobinopathies and what are they?
- thalassaemia - all pregnant mothers
- sicke cell disease - if high risk due to FH/ live in high risk area
How are haemoglobinopathies (sickle cell disease and thalassaemia) screened for in pregnancy?
blood test as early as possible in pregnancy, ideally before 10 weeks
