Imaging the Growing Fetus Flashcards
What is the first sign of pregnancy and how is pregnancy diagnosed?
First sign of pregnancy
• Missed period
• Hormones:
− Progesterone → causes constipation and heart burn
− hCG → causes nausea and vomiting. Women with twins have worse nausea
− Estrogen
Diagnosis of Pregnancy
• Pregnancy tests detect hcG in urine → ELISA
• hCG in the blood should double every 48 hours
What are the general features of ultrasound?
• Widely used since 1980s • Safe • Wealth of experience • Use: diagnosis, screening, surveillance, monitoring • Types: − 2D → thin slices, one at a time − 3D → takes volumes of echoes and digitally remodels to produce a more lifelike image − 4D → above plus real fetal movement
How is ultrasound used during a normal first trimester?
• Transabdnominal and transvaginal – transvaginal probes early on can help you get closer to the pregnancy for better views – useful for overweight women
• Earliest indication of pregnancy is thickened endometrium
• This is not diagnostic of pregnancy as could indicate:
− Late luteal phase
− Decidual reaction in ectopic pregnancy
− Retained products of conception
First indicators of pregnancy
• Gestation sac
− Day 12-13 development (day 27 since LMP)
− Represents the chorionic cavity or the developing pregnancy
− Circular bright ring surrounded by a black circle (fluid is sonniluscent)
− Transvaginally → visible time of LMP
− Transabdnomially → visible form 5 weeks LMP
• Gestation sac suggests presence of pregnancy, but doesn’t tell us if it is developing normally
• Next think to look for is the yolk sac
− Visible from around 27 days post LMP
− Initially, very close to the fetus
− By 45 days further apart due to growth of yolk stalk and enlargement of amniotic cavity
− Not visible after 11 weeks
Viability
• Pregnancy is viable from when heart pulsations can be visualized within the gestation sac
• Transvaginally → 5 weeks post LMP
• Transabdnominally → 6 weeks post LMP
Give a brief view of embryogenesis
- All major organs form within weeks 6 to 10
- Transformation to a reocgnisable fetus on an ultrasound occurs at 10 weeks
Embryogenesis
• Complex process of differentiation, migration and folding giving formation of a trilaminar embryo 3 weeks post fertiliastion
• Origins of major organs form early:
− Neural plate develops from ectoderm D18-19, neural tube closes by D27 forming the brain and spinal cord
− Heart formation: mesenchyme cord canalizes in week 5, then dilates and constricts to form 4 chambers weeks 4-7
What is teratogenesis and what are some examples of teratogens?
• Teratogens are substances that cause developmental toxicity/birth defects
• Overall risk of birth defects is 3-5%
• 10% of birth defects may be due to exposure to a teratogen
• Exposure to teratogens can increase risk of birth defects, but outcomes depend on multiple factors:
− Duration of exposure
− Genetic predisposition
− Dose (Cant stop women taking medication needed to stay healthy, so recommend lowest dose)
− Gestation period (many women often don’t know they are pregnant during time major organs are forming. Thought if you are exposed to a teratogen early on, you get ‘all or nothing’ – later on, may be more subtle effects)
− Other environmental factors
egs)
• Alcohol → fetal alcohol syndrome.
− Need to drink quite high levels of alcohol
− Leads to intellectual characteristics such as difficulty storing and retrieving information, struggle with abstract concepts, trouble staying on task
− Distinct facial features → smooth philtrum, thin upper lip, flat midface
• Isotretanoin → Vitamin A derivative used to treat acne
− Causes hearing/visual disturbance, facial dysmorphism, learning difficulty
• Warfarin → anticoagulant
− Causes nasal hypoplasia, limp hypoplasia, developmental delay
• Sodium valproate → anti-epileptic
− Causes facial appearance abnormalities, spina bifida and learning difficulties
Give an example of a first trimester complication
Ectopic pregnancies:
• Pregnancies that have implanted outside the uterus
• Majority occur on the fallopian tube → fimbrial, ampulla, isthmic ectopic pregnancies
• Can also be abdominal
• Risk of death through rupture
• Treatment is surgery or methotrexate (anti-metabolite affecting folate development, stops the trophoblast developing)
• Some may resolve spontaneously
What are diagnostic tests for first pregnancy complications
Hormone:
• hCG → doubles in normal pregnancy every 48 hours.
− Absolute levels of hCG diagnostic – if you have high hCG, should be able to see a pregnancy in the uterus, if you cant, may be ectopic
• Progesterone → low in miscarriage
Ultrasound
• Pregnancy in uterus if hCG is high
• Can see ectopic pregnancy
• If nothing is visible in the uterus, need to raise questions about viability/ectopic
What does the first trimester booking visit involve?
• Women ‘book’ pregnancy with healthcare services around 10-12 weeks gestation
• Offered screening for:
− Detection of pre-existing disorders → HIV, Syphillis, hepatitis, haemoglobinopathy, urine screen, hypertension
− Detection of fetal disorders → major structural abnormality only
− Growing interest in screening for the later complications of pregnancy
First trimester ‘booking’ visit involves: • Ultrasound scan: − Confirm pregnancy is in utero − Confirm viability (heart) − Number of fetuses − Data pregnancy (from LMP) − Major structural abnormality, eg) anencephaly • Offered screening for aneuploidy
Why do we screen for chromsomal disorders in the first trimester, and what kinds of chromsomal disorders
- Risk increases with maternal age
- With aneuploidy, high natural loss rate at 30% between 16 weeks and term
- Downs syndrome is the most common (Trisomy 21) → 1:600 live births
- Pataus (Trisomy 13) → 1:5000. Compatible with live birth, but children don’t normally live beyond a year
- Edwards (Trisomy 18) → 1:3000
Describe the historical screening for Downs Syndrome
• Historically, only way was amniocentesis or chorionic villus biopsy → requires a needle to take out amniotic fluid or trophoblast cells
• Risk of miscarriage:
− Amniocentesis (done from 14+5 weeks onwards) → 1%
− CVB (done from 11 weeks) → 1-2%
Describe the combined and quadruple tests for Downs syndrome
• Because of the high risk of the test, people looked to see if we could screen for Down’s
• The ones currently offered on the NHS are:
− Combined test → NT, PAPPA, hCG (10 weeks) → 6.1% false positive
− Quadruple test → AFP, E3, hCG, Inhibin A (14-20 weeks) → 6.2% false positive
Key: • NT = Nuchal Translucency: − Measures the fluid layer on the back of the neck − Fluid layer should be less than 3.5mm → thicker indicates Downs risk − Detection rate of 75% when used alone − False positive is 5% • PAPPA = Pregnancy Associated Plasma Protein A − Low in pregnancies with Downs • hCG − High in pregnancies with Downs • AFP = Alphafetoprotein − Low in pregnancies with Downs • E3 = estriol − Low in pregnancies with Downs • Inhibin A − High in pregnancies with Downs
What tests are done if the combined/quadruple tests indicate you are high risk?
Based on screening, women given result – not told ‘yes or no’ – they are given a risk
• High risk = greater than 1:150
• Based arbitratility on:
− Risk of miscarriage with invasive testing (1%)
− Number of women likely to accept testing
− Detection rate
• Choice is personal
• These high risk women are offered invasive testing in the form of qPCR and a full karypte
− qPCR:
➢ Uses short tandem repeats to detect copy number
➢ Targets specific whole chromosome markers
➢ Tests for chromsomes 21, 13, 18, and X
➢ Rapid results (2 days)
− Full karyotype
➢ 10 day culture
➢ G banding by microscopic visualization
➢ Resolution 5-10Mb (very low – just looking for large bits missing, translocations eg.. across the whole genome. Relies on proficiency by technician).
− FISH
➢ Specific areas, eg) Digeorge can detect known microdeletions and mutations
What new technologies can be used to detect chromosomal abnormalities?
New technology for screening (replacement for combined and quadruple test)
• Cell free fetal DNA (non-invasive)
− A proportion of cell free DNA in maternal plasma is derived from the fetus
− Amount increases with gestation (up to 50% later on)
− Currently in clinical use for:
− Fetal sex determination (Eg, haemophilia 9+ weeks)
− Fetal blood type (eg, Rhesus disease after 16 weeks)
Can a blood test for free fetal DNA be used to detect aneuploidy?
• Clinical use already for sex/blood group
• Uses chromosomes 21, 18 and 13
• MELISSA study: no false positives, high sensitivity and specificity for T21, T18 (lower for 13)
• Technology also being demonstrated for fetal genotype as well as karyotype
Is it in clinical use?
• Autumn 2011 → offered privately in the US
• Sept 2012 → reported by British press
• Likely to be offered in screen positive women , to reduce the number of invasive tests → expensive, costs £400 per test.
How can we screen for placental complications in the first trimester?
• Pre-eclampsia/FGR or severe disease
• Clinically diagnosed in the 3rd trimester but pathology occurs in the 1st
• Can we screen early?
− Use of 1st trimester serum markers eg) PAPP-A, AFP
− None perform well enough at present, may be better with ultrasound:
− PAPP-A → low (2.5MoM) poor prognosis
− PGF → low levels appear to be associated with FGF. Doesn’t perform very well as a screen, may be better as diagnostic test with women already presenting with problems.
What are some structural defects detected during second trimester screening?
Omphalocoele
• Gut stays outside after exteriorization and rotation, does not return
• It is often associated with chromosomal problems
• May be offered further screening or offer of termination
Gastroschisis
• Abdominal wall defect – isn’t a failure to return, it is a hole that means the bowel hangs out
• Looks like a cauliflower on the scan
• Not associated with chromosomal problems
• Wouldn’t be offered termination as the baby will be fine
