Screening Flashcards
MSS1
When can it be done
When is it best done
What does it involve
Bloods Best 10 weeks (possible 9-13+6) Hcg PAPP-A NT scan Best 12 (possible 11+2-13+6)
MSS 2
When can it be done
When is it best done
What does it involve
Bloods only + age weight and gestation 14-20 weeks (best 14-18) Bhcg unconjugated oestradiol AFP Inhibin A
What are the booking bloods
FBC Group and screen Iron studies Rubella Hep B HIV Syphillis MSU - Asymptomatic bacteriuria
Cystic fibrosis
What is it
What is the pathology
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.
What is fetal Cell free DNA
- NIPT
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
T21
What are the manifestations
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
Fragile X chromosome
What is it
What are the manifestations
Who do you screen
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.
What is a MoM
Multiple of median
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
What is a Negative predictive value
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
What is a positive predictive value
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.
What is Turners syndrome
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.
Folate deficiency
causes and presentation
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)
routine Iron supplementation
Routine supplementation no benefit and ? increase perinatal death, SA constipation, diarrhoea and nausea
Rubella infection in pregnancy
Epidemiology
When is it significant / what is the risk of fetal transmission
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
Rubella transmission and sx
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
Fetal consequence of rubella infection
+ diagnosis
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
GBS screening
Who to treat in labour
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
How commonly do soft markers occur
What is the negatives about reporting them?
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.
What is the significance of an Absent nasal bone
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
What are are associations with Echogenic bowel?
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
What is Pyelectasis
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
Shortened long bones (humerus, femur)
Concerns? Significance?
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
What is a Echogenic intracardiac focus
What rate in normal population?
What rate in T21
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
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
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
Single umbilical artery
How to interpret?
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
What is a Cystic hygroma
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.
How to interpret
ventriculomegaly
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.
Second trimester nuchal fold
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.
Omphalocele
Risk
Mortality
Associated chromosomal abnormalities
• 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%
What is the prevalence of NTD
When does it occur
What is the pathophysiology?
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
What is spina bifida?
What does it mean if it is open?
closed?
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)
