Screening

Question 1

MSS1
When can it be done
When is it best done
What does it involve

Answer 1

Bloods
Best 10 weeks (possible 9-13+6)
Hcg
PAPP-A
NT scan
Best 12 (possible 11+2-13+6)

Question 2

MSS 2
When can it be done
When is it best done
What does it involve

Answer 2

Bloods only + age weight and gestation 
14-20 weeks (best 14-18) 
Bhcg
unconjugated oestradiol
AFP
Inhibin A

Question 3

What are the booking bloods

Answer 3

FBC 
Group and screen
Iron studies 
Rubella
Hep B
HIV 
Syphillis
MSU - Asymptomatic bacteriuria

Question 4

Cystic fibrosis

What is it
What is the pathology

Answer 4

An autosomal recessive genetic disease of the exocrine
glands. Cystic fibrosis is characterised by epithelial secretory dysfunction associated with ductal obstruction resulting in airway obstruction; chronic respiratory infections; pancreatic insufficiency; maldigestion; salt depletion; and heat prostration.

Question 5

What is fetal Cell free DNA

- NIPT

Answer 5

Cell-free fetal DNA of placental origin is detectable in maternal plasma from early first trimester.
Screening test - T21, T18 Edward syndrome and T13 Patau syndrome.
These cell-free fetal DNA fragments are released and
comprise about 10% of the total cell-free DNA in maternal blood.
CfDNA testing for fetal aneuploidy works by sequencing a portion of each DNA fragment in maternal plasma (both maternal and fetal), mapping each DNA sequence to a reference genome to determine its chromosome of origin, and counting the number of fragments arising from each chromosome

Question 6

T21

What are the manifestations

Answer 6

hypotonia, short stature, brachycephaly, upslanting palpebral fissures, epicanthus, brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, Simian crease, and moderate to severe intellectual disability. Cardiac and
gastrointestinal malformations, a marked increase in the incidence of leukemia, and the early onset of Alzheimers

Question 7

Fragile X chromosome
What is it
What are the manifestations
Who do you screen

Answer 7

intellectual disability, behavioural and learning challenges and various physical characteristics.
Caused by the expansion or lengthening of the FMR1 gene on the X chromosome, known as a gene mutation.
When the gene lengthens it switches off production of a protein that is involved in brain development and other functions. It is also the most common single gene cause of autism worldwide.(no ethnic correlation)
Only women need be offered FXS screening. FXS screening is particularly important if there is a family history of intellectual disability.

Question 8

What is a MoM

Multiple of median

Answer 8

A multiple of the median (MoM) is a measure of how far an individual test result deviates from the median. MoM is commonly used to report the results of medical screening tests, particularly where the results of the individual tests are highly variable

Question 9

What is a Negative predictive value

Answer 9

The negative predictive value is the proportion of negative results in tests that are true negative results. The NPV is not intrinsic to the test—it depends also on the prevalence

Question 10

What is a positive predictive value

Answer 10

The positive predictive value is the proportion of positive results in tests that are true positive results. The PPV is not intrinsic to the test—it depends also on the prevalence.

Question 11

What is Turners syndrome

Answer 11

A syndrome of defective gonadal development in
phenotypic females associated with the karyotype 45,X (or 45,XO). Patients generally are of short stature with
undifferentiated gonads (streak gonads), sexual infantilism, hypogonadism, webbing of the neck, cubitus valgus, elevated gonadotropins, decreased estradiol level in blood, and congenital heart defects.

Question 12

Folate deficiency

causes and presentation

Answer 12

Macrocytic anaemia (raised 25% pregnancies) 
Raised MCV also check for drugs eg azathioprine and EtOH
At risk of folate deficiency include woman on anticonvulsants or folate antagonists (sulphasalazine) or haematological conditions eg haemolytic anaemia, sickle cell, thalassaemia, hereditary spherocytosis (prescribe 5mg daily)

Question 13

routine Iron supplementation

Answer 13

Routine supplementation no benefit and ? increase perinatal death, SA constipation, diarrhoea and nausea

Question 14

Rubella infection in pregnancy
Epidemiology
When is it significant / what is the risk of fetal transmission

Answer 14

1-2 % of woman are not immune - the risk of them contracting Rubella infection in pregnancy is 2/1000

Highest risk in the first 16 weeks
Risk of transmission
<11 weeks 90% (90% of these pregnancies will be affected badly)
11-16 weeks 55% (20% risk of severe complications)
16+ 45% risk of transmission
16-20 weeks risk of deafness only
20+ risk no increased risk

Question 15

Rubella transmission and sx

Answer 15

Transmission 10 days before the rash to 15 days after sx onset
1-5 day prodromal illness then rash 3-5 days. Rash face + neck to trunk and extremities Petechiae on soft palate that coalesce to papules - forschheimers sign

Question 16

Fetal consequence of rubella infection

+ diagnosis

Answer 16

microcephaly, IUGR, meningoencephalitis, cataracts, retinopathy, hearing loss, cardiac defects, hepatosplenomegly, thrombocytopenia w purpura, bone radiolucencies,
bluish red skin, adenopathy interstitual pneumonia
developmental delay
Dx- serology, viral culture of amniotic fluid, Fetal blood sample

Question 17

GBS screening

Who to treat in labour

Answer 17

20% woman colonised
Not routine screening
In labour treat PTB, PROM >18 hours, Intrapartum fever, or previous GBS baby
If previous GBS in urine then retest at 36 weeks - if positive then treat GBS in labour

Question 18

How commonly do soft markers occur

What is the negatives about reporting them?

Answer 18

11-17% of the population
higher prevalence in aneuploid fetuses and the likelihood of aneuploidy is significantly increased when more than one marker is present.
Inefficient for screening, a detailed evaluation of fetal anatomy should be performed whenever one or more soft markers has been identified.

information is anxiety-provoking for patients, requires considerable time for counseling, and may lead to invasive prenatal testing. Such testing may result in procedure-related loss of a normal fetus, and is costly.

Question 19

What is the significance of an Absent nasal bone

Answer 19

0.8% normal population
65% T21
The optimum time for nasal bone assessment is at crown rump length of 65 to 74 mm (13 to 13.5 weeks of gestation)
When the fetal profile is viewed in the midsagittal plane, the nasal bone synostosis appears as a thin echogenic line within the bridge of the nose. The nasal bone is considered present if this line is more echogenic than the overlying skin, and absent if it is not visualized, or less echogenic, than the overlying skin

Question 20

What are are associations with Echogenic bowel?

Answer 20

1-2% of the normal population
13-21% of T21
Fetal echogenic bowel refers to increased echogenicity (brightness) of the fetal bowel noted on second trimester sonographic examination
Also been associated with this finding: other chromosomal defects, fetal growth restriction, cystic fibrosis, congenital infection, intraamniotic bleeding, and gastrointestinal obstruction

Question 21

What is Pyelectasis

Answer 21

1-3% normal population
10-25% T21
Pyelectasis or mild hydronephrosis is a common finding in fetuses. Studies that defined pyelectasis as renal pelvic diameter of ≥4 mm at 15 to 19 weeks of gestation demonstrated pyelectasis

Question 22

Shortened long bones (humerus, femur)

Concerns? Significance?

Answer 22

Fetuses with Down syndrome have slightly shorter long-bones than their normal counterparts. A shortened humerus appears to be a better predictor of Down syndrome than a shortened femur (positive likelihood ratio 4.8 and 3.7, respectively)
Various criteria have been published for determining whether a femur or humerus is too short
These criteria overlap the range observed in unaffected fetuses and vary widely among different populations; therefore, each laboratory should develop specific standards for its own population. We consider abnormal an observed-to-expected length ratio (based on biparietal diameter) of less than 0.9.
In contrast, severely shortened (<5th percentile) or abnormal appearing long bones may be a sign of a skeletal dysplasia or early onset fetal growth restriction

Question 23

What is a Echogenic intracardiac focus
What rate in normal population?
What rate in T21

Answer 23

Normal 3-5%
28% in T21

Echogenic intracardiac foci, the same brightness as bone, usually occur as a single focus in the left ventricle, but multiple foci, biventricular foci, or a right ventricular location can also occur. This entity is different from diffuse, extensive myocardial calcification, which is rare and associated with myocardial dysfunction
The incidence varies across races/ethnicities (present in up to 30 percent of Asian fetuses), and decreases with advancing gestational age It is thought to be related to microcalcification and fibrosis of the papillary muscle or chordae, often disappears later in pregnancy or postnatally, and is not associated with myocardial dysfunction or structural anomalies. In an autopsy study of abortuses, stillbirths, and perinatal deaths, discrete central papillary muscle calcification was more common in fetuses with trisomy 13 than trisomy 21 (39 and 16 percent, respectively, versus 2 percent of normal controls)
When an echogenic intracardiac focus is identified in an otherwise normal second trimester fetus, a normal cell-free DNA test can be very reassuring and obviate the need for invasive testing

Question 24

What is a Choroid plexus cyst

What other feature makes T18 much less likely?

What is the risk of aneuploidy vs the risk of amnio

Answer 24

Choroid plexus cysts are most common in the second trimester.
They appear to result from filling of the neuroepithelial folds with cerebrospinal fluid The typical sonographic appearance is a small (usually less than 1 cm), sonolucent structure(s) with well delineated borders located within the choroid plexus. A wide range of appearances are possible from unilateral single cysts to bilateral septated and multiple cysts. A targeted scan for other fetal anomalies should follow imaging of these cysts.
In addition, if the fetus is able to unclench its hand and hold it open, trisomy 18 is not likely. In a meta-analysis including 748 fetuses with isolated choroid plexus cyst(s), the risk of trisomy 18 was 1/374 and the positive predictive value was 1/390
When isolated choroid plexus cyst(s) are detected in an otherwise low risk patient the risk of amniocentesis (1/250 chance of pregnancy loss) is higher than the risk that the fetus has trisomy 18 (less than 1/374). We suggested restricting amniocentesis to patients with additional sonographic abnormalities or high risk factors (ie, advanced maternal age [older than 32 years at delivery [62]], abnormal serum analyte screen) [63]. Some women may request amniocentesis after risk-benefit counseling. When choroid plexus cysts are identified in an otherwise normal second-trimester fetus, a normal cell-free DNA test can be very reassuring and obviate the need for invasive testing

Question 25

Single umbilical artery How to interpret?

Answer 25

There is a well-documented association between single umbilical artery (SUA) and an increased risk of aneuploidy when additional fetal malformations are detected. The rate of aneuploidy with isolated SUA is not known, but most experts do not recommend routine chromosomal analysis if there are no other malformations or other indications for genetic amniocentesis

Question 26

What is a Cystic hygroma

Answer 26

A cystic hygroma is a thin-walled, subcutaneous uni- or multilocular subcutaneous mass filled with lymphatic fluid and usually occurring in the posterior neck. It results from a localized area of lymphatic dysplasia with dilatation and/or leakage of lymph from the lymphatic vessels. It may be accompanied by generalized lymphedema. A small, unilocular cystic hygroma without accompanying diffuse lymphedema may be difficult to distinguish from other causes of nuchal thickening. By comparison, septations are characteristic of multilocular cystic hygromas and readily differentiate cystic hygromas from simple increased nuchal translucency. First trimester cystic hygromas are often associated with trisomies, whereas second trimester cystic hygromas are often associated with monosomy X.

Question 27

How to interpret | ventriculomegaly

Answer 27

Isolated ventriculomegaly is a risk factor for Down syndrome, but most children with isolated, mild ventriculomegaly have a normal outcome. Mild ventriculomegaly is detected in 4 to 13 percent of fetuses with Down syndrome and 0.1 to 0.4 percent of euploid fetuses The risk of abnormal outcome, such as Down syndrome, increases with the degree of ventriculomegaly, progression of ventriculomegaly, and presence of other anomalies.

Question 28

Second trimester nuchal fold

Answer 28

0.5-2% normal pregnancies 20-33% T21 The nuchal fold, rather than nuchal translucency, is measured in the second trimester. The nuchal fold is the measurement between the outer edge of the occipital bone to the outer margin of the skin and is taken in the axial plane. An increase in this measurement is also associated with aneuploidy.

Question 29

Omphalocele Risk Mortality Associated chromosomal abnormalities

Answer 29

• 1:4000 births • 25% mortality • 15% chromosomal abnormalities • 30% have other congential abnormalities • 60% of omphaloceles not containing liver are associated with fetal aneuploidy esp T18 T 13 • THe more other abnormalities the higher risk of a chromosomal disorder • Most common chromosomal abnormalities T18 63% T13 17% T21 4% Turners 6% Triploidy 5% Rare chromosomal deletions 5% • Associated structural abnormalities in 35-70%

Question 30

What is the prevalence of NTD When does it occur What is the pathophysiology?

Answer 30

5-10 / 10 000 Note defects occur week 5-6 of gestation (which is 3-4 weeks post fertilization) When the neural folds of ectoderm closes The neural tube develops into brain, spinal cord and meninges The mesoderm form the vertebral structures over the neural tube Failure of the neural tube to form means the mesoderm does not organise around it

Question 31

What is spina bifida? What does it mean if it is open? closed?

Answer 31

Spina Bifida - the neural tube does not completely close - can be open or closed Open - not covered by skin - 80% - associated with ventriculomegly Closed - covered by skin - 20% - is covered by skin, can have a hairy patch (eg lipomenigocoele, lipomyelomeningocoele)

Question 32

``` Types of NTD What do they mean? Occultia? Meningocele? Myelomeningocoele? anencephaly? Craniorachiachisis ? ```

Answer 32

occultia - small gap but no opening, nerves or spinal cord not damaged. Often asymptomatic - may have hair, dimple or birth mark over the lesion. Meningocele - sac of meninges protruding (not the nerves) least common, often spinal cord is ok. Myelomeningocoele - most severe - open or closed, bones form incompletely - meninges and spinal cord bulging out. Can damage exposed nerves -loss of power and sensation distally, no bladder or bowel control MSK deformities, seizures. Associated with arnold chiari II malformation where cerebellar and brain stem slips down into the foramen magnum. This results in hydrocephaly. Dx often antenatal (high AFP as leaks from fetus into amniotic fluid and maternal blood stream) Anencephaly - The neural tube fails to close cranially, Completely unfused - craniorachiachisis

Question 33

What are the risk factors for NTD?

Answer 33

90% of patients have no risk factors Folic acid deficiency Dietary deficiency Inadequate absorption - IBS, intestinal resection, celiac, liver diease Folic acid antagonists eg carbapezapine, valproic acid, MTX also trimethprim, sulphasalazine MTHFR is an enzyme that regulates intracellular folate levels - a genetic polymorphism reduces its activity and therefore increases their risk of NTD Appears to be a genetic component although no gene yet isolated Previous pregnancy with NTD (10X risk - 70% risk reduction) Either parent with a personal hx (10X risk) Family Hx if a second or third degree relative is affected (risk .5 to 1%) Antiepileptic drugs - consult neurologist as can affect antiepileptic action Diabetes - mixed recommendations Obesity 2X increased risk Poorly controlled diabetes Twins ? associations with pesticide exposure, HIV drugs, clomiphine

Question 34

What supplementation reduces the risk of NTD

Answer 34

Supplementation reduces NTD by 93% Some bodies say that all woman with child bearing potential take folic acid supplementation due to the high rate of unplanned pregnancy 0.4mg OD from 1 month before conception Population based fortification in flour of cereals/bread / rice / pasta reduces NTD High dose prophylaxis High risk are candidates for higher dose 1-4 mg daily from 3/12 before conception + continue for the first 12 weeks after which reduce the dose to 0.4mg Previous pregnancy with NTD (10X risk - 70% risk reduction) Either parent with a personal hx (10X risk) Family Hx if a second or third degree relative is affected (risk .5 to 1%) Antiepileptic drugs - consult neurologist as can affect antiepileptic action Diabetes - mixed recommendations Not recommended for obesity

Question 35

What syndromes are related to NTD ?

Answer 35

Associated syndromes eg T13 T 18 triploidy, meckel - gruber, Roberts HARD, amniotic bands

Question 36

Fever in T1 increases the risk of what?

Answer 36

Elevation of maternal temperature in T1 (spa baths, fever) increases the risk of NTD, CHD and oral clefts

Question 37

When can NTD be detected?

Answer 37

12-14 week USS will detect 90% anencephaly, 80% encephalocele, and 44% spina bidifa 20 week USS - 100% anencephaly and 95% spina bifida Obesity decreases detection rates

Question 38

AFP What does it do What is the pattern through pregnancy What is its value?

Answer 38

Fetal specific globulin, synthesised in the fetal yolk sac GI tract and liver unknown function Can be measured in the maternal serum, amniotic fluid or fetal plasma Rises in early pregnancy, peaks at 28-32 weeks then falls - the maternal serum level rises in advancing gestations likely because the increased fetoplacental permeability Secreted by the fetal kidney into the urine then into the AF - in the amniotic fluid it peaks 12-14 weeks then declines and becomes undetectable at term Measurements in the amniotic fluid may aid NTD diagnosis AFP peaks in fetal plasma 10-13 weeks then declines Best timing screening maternal serum AFP 16-18 weeks (15-20) Results are MoM for each gestational week, abnormal is over 2 or 2.5 MoM Ancencephaly over 95% detection FP 2-5% , SB 75-90%, false positives 1-3% 2009 metaanalysis 700000 woman Sensitivity 75% specificity 98% false positive 2.2% false negative 25%

Question 39

What affects AFP interpretation?

Answer 39

Gestational age (levels change throughout) Maternal weight - dilutional if high BMI T 1 and2 DM - The level of MS AFP is lower in diabetics so they need a lower cut off Also raised if abdo well defects, anaemia, nephrosis, teratomas, uropathy evelates AFP Twins elevates Normal levels higher in black woman - MoM should be adjusted Viability - fetal death raises MSAFP low in T21 and T18

Question 40

Unexplained AFP - what does it increase the risk for?

Answer 40

early fetal demise IUGR PET No evidence that intensive fetal monitoring will improve outcome

Question 41

After dx NTD what other fetal assessment needs to occur?

Answer 41

Fetal assessment after diagnosis 20% have associated abnormalities Cleft palate MSK renal and cardiovascular malformations Chromosomal microarray 6% chromosomal abnormalities - often if multiple abnormalities Microarray is preferred if structural abnormalities Appropriate if will change management Fetal MRI Confirm uncertain findings Help assess CNS abnormalities

Question 42

If delivery of a baby with NTD What are the considerations? MOD? Equipment?

Answer 42

Levels 3 paeds / paeds neurosurg Latex free gloves + equipment - associated with life threatening latex allergy Term is better Breech - for LSCS If cephalic no good evidence about MOD - if head is near normal size then meningocoele unlikely to cause dystocia LSCS if HC over 40 cm or BPD more then 12 cm

Question 43

Other postnatal considerations for a NTD baby?

Answer 43

Post Natal Work up for renal involvement - Check urinary tract function, U+Es Look for hydropcephaly may need a shunt Neurogenic bladder - tx anticholinergics ADHD Weight gain Faecal and urianry incontiencne UTI Hydrobephrotos - VUR Sexual dysfunction Orthopaedic abnormalitiy

Question 44

Recurrence NTD

Answer 44

Risk of recurrence is 2-4% if one affected sibling 2 affected siblings risk is 10% Anencepahly recurrence 2-5% Testing for MTHFR not recommended as can treat with folic acid supplementation

Question 45

What is the most common abnormality that causes miscarriage?

Answer 45

18% is Monosomy X (turners) | 75% of cases paternal X missing

Question 46

What does aneuploidy mean?

Answer 46

Any deviation from the diploid 46 chromosomes principal cause is non disjunction during cell division 99% embryos lacking a chromosome abort spontenously

Question 47

Trisomy Waht is the incidence of the main trisomy conditons?

Answer 47

Three chromosomes of one type This is caused by meiotic non disjunction of chromosomes Risk associated with increased age T21 1:800 18 1:8000 13 1:25,000

Question 48

What does mosaicism mean?

Answer 48

2 cell lines with 2 or more different genotype either autosomes or the sex chromosomes involved Less serious birth defects (then monosomy or trisomy) Result of non dysjunction in early cleavage of the zygote Loss of chromosomes by anaphase lagging - the chromosomes separate normally but then one of them is delayed and lost

Question 49

What are structural chromosomal abnormalities ?

Answer 49

These are a result of chromosome breakage This is caused by environmental factors eg irradiation, drugs, chemicals, viruses These can be translocations or deletions

Question 50

How do we clinically screen for risk of PET?

Answer 50

Past personal or family Hx Medical disorders eg HTN, renal disease or diabetes Current pregnancy factors eg multiple pregnancy Assess BP BMI

Question 51

What about biochemical screening for PET?

Answer 51

RANZCOG says there is not enough evidence Data is distorted by including multips who already have high postive predictive value with their own PET hx - improving the dataset outcomes They include PAPP-A, PIGF (placental growth factor) and uterine artery PI There is a 10% false positive rate 90-95% sensitivity - for a disease prevalence 3-4:1000 results not replicated only for early onset PET not at all effective with late PET (which is 2/3 of PET)

Question 52

FGR Long term and short term affects on the fetus

Answer 52

Short term Being growth restricted is implicated in half of stillbirths. Perinatal mortality increases with decreasing birth weight centile, with the adjusted perinatal mortality 3 times higher with a birth weight of <5-10th centile and nearly 15 times higher when birth weight is <1st centile. Implicated in Childhood morbidity, and of disease in adult life (obesity, type 2 diabetes and cardiovascular disease).

Question 53

What are risk factors for SGA? Major risk factor- serial USS and umbilical artery doppler for wellbeing 3X minor then uterine artery doppler at 20 weeks and make a plan for serial scans from there - if normal then consider 1X scan in T3 If +ve then serial growth scans

Answer 53

``` These major risk factors include previous small for gestational age infants, previous fetal death in-utero, current pre-eclampsia, current significant unexplained antepartum haemorrhage, diabetes mellitus with vascular disease, renal impairment, antiphospholipid antibody syndrome, systemic lupus erythematosis, smoking ≥ 11 cigarettes a day, daily vigorous exercise maternal age >40 ``` The RCOG guidelines also suggest that women with three or more minor risk factors, including previous pre-eclampsia, maternal age ≥35 years, daily vigorous exercise, BMI <20 or >35kg/m2 should be referred for a uterine artery Doppler at 20-24 weeks, and further ultrasound surveillance should be determined according to the normalcy of this uterine artery Doppler

Question 54

What biochemical marker is linked to FGR

Answer 54

Although low pregnancyassociated plasma protein A (PAPP-A) <5th centile at time of nuchal translucency screening (<0.4 MoM) has been found to be associated with an increased risk of SGA, the odds ratio (OR) for SGA infant (birth weight <10th centile) and severe SGA (birth weight <3rd centile were 2.7 and 3.7, respectively with the detection rate of SGA being poor at 12% and 16%, respectively A metaanalysis found that the most accurate predictor for birth weight < 10th centile was PAPP-A <1st centile (0.3MOM); LR+ 3.50 (2.53,4.82), LR- 0.98 (0.97,0.99). For birth weight <5th centile, the most accurate predictor was again PAPP-A <1st centile; LR+ 4.36 (3.27,5.80), LR- 0.97 (0.96,0.98).

Question 55

Prepregnancy screening History and examination Clinical examination?

Answer 55

History Medical problems, optimise, Medications - ensure safe medication in pregnancy Mental health status FHx Genetic inheritable conditions High risk - referral to genetic counselling low risk - should be made aware of the availability of carrier status evaluation (not funded) Vaccinations check immunity to Hep B rubella and varicella and vaccination if appropriate In pregnancy dTAp 28-32 weeks and influenza Examination BP BMI Heart sounds, if relevant breast exam and cervical smear

Question 56

Prepreg consult - what are the lifestyle recommendations

Answer 56

Balanced diet BMI (affects fertility, health of the oocyte and embryo quality - linked to still birth, miscarriage and anomaly) Moderate intensity exercise Excessive caffeine >300 mg/ day (3-4 cups) should be avoided Folic acid Minimum 1 month pre preg for first 12 weeks of pregnancy 0.8mg if no risk factors 5mg (High BMI diabetic, Prev NTD or FHx, AED) Iodine 150 mcg prior to planned pregnancy/ ASAP and throughout pregnancy and breastfeeding Stop smoking and drinking Travel avoid travel to affected areas If travelling to a zika infected country prevent mosquito bites, use condoms while having sex in that country Dont live somewhere with exposure to toxins or radiation

Question 57

How to counsel for diagnostic testing

Answer 57

a. A description of the conditions that can and cannot be detected through traditional screening processes and details of the testing process. This should include information about phenotypic variability of chromosomal conditions and the difficulties in being able to predict the extent of effect on a particular baby. b. A discussion of the differences between screening and diagnostic tests. c. Advantages and disadvantages of the different types of tests available (taking into account the gestation of the pregnancy). d. Practical aspects of testing; including the timing of tests and the approximate costs involved. e. The possibility that the screening and diagnostic pathway may reveal anomalies other than those expected. f. Details of support groups and sources of further information (see How to decide on antenatal tests for chromosomal abnormalities and other conditions and Antenatal screening for Down syndrome and other conditions (New Zealand). g. The understanding that, if a chromosome or genetic condition is diagnosed, a woman can choose whether to continue or terminate the pregnancy. Where a condition has been diagnosed, parents should be given sufficient information regarding the aetiology, associations, and implications of that diagnosis during pregnancy, the newborn period and beyond, in order to make informed decisions about their options.

Question 58

What is the biggest risk factor for T21 ?

Answer 58

The most important factor for having a child with trisomy 21 is maternal age. The chance of an affected newborn at term is approximately 1 in 300 for a woman aged 35 years, increasing to 1 in 100 by the maternal age of 40 years.7 The overall prenatal prevalence of trisomy 21 has increased with the trend to later childbearing in many developed countries

Question 59

What is the commonly detected abnormality?

Answer 59

Trisomy 21 comprises approximately half of the chromosome abnormalities detected prenatally. The next most common autosomal trisomies are trisomy 18 and trisomy 13. Together, trisomies 21, 18 and 13 make up about 66% of major aneuploidies currently detected by prenatal diagnosis

Question 60

When can cell-free DNA testing be performed?

Answer 60

From 10 weeks If have cellfree DNA testing they should still have an USS for structural assessment until 15-20 weeks

Question 61

``` T21 screening Options Gestations Sensitivity Specificity PPV ```

Answer 61

CFTS 11-13+6 Sensitivity 85% specificity 95% PPV 10% Second trimester screen 14-20 weeks Sensitive 7-% specificity 93% PPV 2-3% cfDNA after 10 weeks 99% sensitivity and specificity 45% PPV

Question 62

cfDNA Failure? if repeated?

Answer 62

1-5% no result | if repeated 50% have a result

Question 63

What are other USS findings that can contribute to aneuploidy detection in T1

Answer 63

tricuspid valve flow nasal bone ductus venosus waveform improve detection but te

Question 64

How to screen multiples?

Answer 64

Twins ALL USS 11-13 weeks for chorionicity, morphology + nuchal CFTS - less accurate 72-80% - nasal bone included helps increase to 90% labs need to know - gestation, chorioicity, demise, CRL of both Can do second trimester screen Can do cfDNA- higher no call rate, less data to back it Triplets - USS +/- nasal bone

Question 65

invasive testing When loss rate CVS Amnio

Answer 65

loss rate 1:900 depends on experience It is acceptable to go straight for invasive testing if the woman has been fully counselled Amnio From 15 weeks (before 14 weeks increase the risk of talipes) CVS from 11 weeks

Question 66

What tests can be done on amnio sample?

Answer 66

Conventional karyotype - cultured fetal cells to prepare stained metaphase chromosome for microscopic inspection FISH - rapid aneuploidy test - rapid assessment of common abnormalities T21,18,13, sex chromosome abnormalities as well as specific gene deletions eg giGeorge Chromosomal microarray - Genome wide oligonucleotide array - detects large and small deletions (they do not detect balanced translocations or single gene disorders) This is best if there are structural abnormalities microarray detect variants of uncertain or unknown significance in about 5%

Question 67

genetic carrier screening who is it for?

Answer 67

low risk people It is estimated that all individuals are carriers for at least three clinically severe recessive childhood disorders. Most of these are autosomal. 24% of adults with test postiive for at least one recessive disorder on expanded carrier testing

Question 68

What is the ethnicity increases the risk of different genetic abnormalities? CF Tay sachs Thalassaemia

Answer 68

CF - Northern european and Ashkenazi jews South East asians - thalassaemia Tay Sachs - Ashkenazi Jews

Question 69

What are the options for genetic testing pre pregnancy? | What methods are possible?

Answer 69

One step testing - same time - run results for each person Two step = cheaper - test female, then only test male for what she is a carrier for - takes longer

Question 70

How does ART affect CFTS

Answer 70

ART results in T1 in low PAPPA - more likely to have a false positive result in CFTS Higher rate of cfDNA failure 5.2 % vs 2.2%

Question 71

how good is the nuchal for screening for major anomalies

Answer 71

``` detects 50% of major anomalies 75 % of lethal abnormalities Most likely anencepahaly, abdominal wall defects megacystis body stalk anomalies ```

Question 72

what doppler should you not use in T1 ?

Answer 72

Pulsed Doppler ultrasound should not be used routinely in first trimester. If pulsed doppler examination is necessary, the Thermal Index should be <1.0 and exposure time minimised (ideally to 5-10 minutes).

Question 73

incidence of major structural anomaly

Answer 73

2-3% | detection rates 60%

Question 74

What is the ALARA principle

Answer 74

the “ALARA” (“as low as reasonably achievable”) principle - utilising the lowest amount of power exposure necessary to achieve the diagnostic purpose in clinical practice. This entails using ultrasound only if there is an appropriate clinical indication, minimising exposure time, using the lowest power and optimal gain settings to obtain the desired image, being mindful of operating modes which increase the potential for bioeffects (e.g. power or pulse wave doppler) and being aware of the Thermal Index (TI) and Mechanical Index (MI) on the ultrasound machine

Question 75

Is there harm from USS ?

Answer 75

It is widely accepted that ultrasound that induces a temperature rise in tissue of less than 1.5 degrees Celsius is not associated with harmful sequelae. Some clinical situations entail an increased risk of inducing a temperature rise beyond this limit and particular care must be taken when scanning febrile patients, fragile tissues of early gestation, poorly perfused tissues (e.g. eyes), or tissues with a high absorption co-efficient (e.g. bone). It is for this reason that pulsed Doppler should not be used routinely during the first trimester. If it is necessary, the TI should be <1.0 and exposure time minimised (ideally to 5-10 minutes)

Question 76

If both members of a couple are known carriers of the same autosomal recessive condition or a woman is a carrier of an X-linked condition, there are a number of options available What are they?

Answer 76

1. Having a child naturally and testing after birth to see if the child is affected. 2. Conceiving naturally and having diagnostic testing during pregnancy to determine if the fetus is affected. This is usually performed with an invasive test (amniocentesis or chorionic villus sampling). ``` 3. Conceiving the pregnancy by in vitro fertilisation (IVF) and testing embryos by preimplantation genetic diagnosis (PGD). Unaffected embryos would then be selected for achieving pregnancy. ``` 4. Using donor sperm, egg or embryo from unaffected individuals. 5. Adoption. 6. Not having children

Question 77

People of (Ashkenazi) Jewish decent are more likely for what conditions?

Answer 77

Tay Sachs disease, Niemann Pick disease type A, Fanconi anaemia group C, familial dysautonomia, Bloom syndrome, Canavan disease and mucolipidosis type IV in addition to the normal Thalassaemia CF SMA fragile X

Question 78

What is the incidence of being a carrier vs affected persons for CF SMA Fragile X

Answer 78

CF Carrier 1/35 Affected 1/5000 SMA 1/50 carrier 1/10 000 affected Fragile X Carrier 1/333 Affected 1/7000 males chance of a single gene condition is 1/500