Transcript Options for prenatal diagnosis of chromosomal abnormalities

MID TRIMESTER ASSESSMENT
VIRAL INFECTIONS
NORMAN BLUMENTHAL
FRANZCOG
BLACKTOWN HOSPITAL
Question 1
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What percentage of pregnancies are
complicated by serious (major) birth
defects?
Serious Birth Defects
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complicate & threaten the lives of 35% of newborn infants
account for 20% of neonatal deaths
account for 30% of serious morbidity
in infancy and childhood
Ultimate aims of prenatal
diagnosis
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provide accurate diagnoses and
informative prognoses to the mother and
her family
with a low or no risk of miscarriage
as early as possible in the pregnancy
to allow informed decisions about the
pregnancy
Aims of prenatal diagnosis
To provide the options of
pregnancy termination
in-utero treatment
arrangements for the best method of delivery
and optimal peri-natal care
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Question 2
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What is the best available serum screening
test for neural tube defects and when it is
done?
Spina Bifida
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Increased AFP (> 2.5 MoM)
correlates with open skin defects
Increased risk of a fetus
with a NTD
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Family history of NTD in mother’s or
father’s close relatives
Pregnant women with IDDM
Pregnant women on anti-convulsant
medication
Current recommendations for
Folate (folic acid)
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Daily folate intake of 5mg for all women
who may become pregnant( 1 mth before)
Tablets available over the counter
– $2.50-$5.20 for 90 tablets
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Dietary folate
– 2 servings of orange, banana, strawberries
– 5 servings of asparagus, beans, beetroot, brussel sprouts, broccoli,
cabbage, cauliflower, leeks, parsnips, peas, potato, spinach
– 7 servings of wheat germ, wheat bran, wholegrain bread, pasta,
cereals
The Triple Screen
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Analytes: estriol, AFP, beta-HCG
Serum collected at 15-17 weeks gestation
Assayed in centralised laboratories
Risk of Down syndrome assessed by collating
serum results with patient’s age and previous
history
If risk >1:250 at term - recommend amniocentesis
The Triple Screen
Advantages:
Little skill required to collect blood
Assayed in centralised laboratories
- good QA
performed at 15-17 weeks gestation
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– subsequent karyotyping by amniocentesis
The Triple Screen
Disdvantages:
Requires pre-test and post-test counselling
Results highly dependent on gestational age
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– thus need a dating ultrasound beforehand
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Not reliable in twin pregnancies
Opportunities for karyotyping only at 16 wk
– thus if TOP required - cervagem IOL
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Not as enjoyable for the patient as NTS
The Triple Screen
Disdvantages:
detection rate approximately 65%
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Does screening do more harm than good?
– Screening raises parents expectations of
medicine, and their expectations of a perfect baby
– False positives cause anxiety and occasional
miscarriages of normal fetuses
– False negatives leave parents with an unwanted
Down syndrome child to bring up.
They often feel misled, betrayed by their
“statistics-quoting doctor”, and quite litigious
– Some patients become unreassurable, and have
an unnecessary procedure
Congenital defects: types and frequency
Type
% of births % all birth defects
Structural Malformations
3.0%
60%
Monogenic defects
1.4%
28%
Chromosomal disorders
Total
0.6%
5.0%
12%
100%
Ref: Prenat Neonat Med 1999;4:157-164
Normal 4 chamber view
Fetal Leg
Fracture in Osteogenesis Imperfecta
TRV Fetal Abdomen
Duodenal Atresia (DoubleBubble sign)
TRV Fetal Hand
Polydactyly
Fetal Feet:
Bilateral Club Foot
Placenta praevia
Question 3
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The 18-week morphology scan is good
and accurate in the assessment of Downs
Syndrome (T/F)?
Ultrasonic features of Trisomy 21 at the
18 week anomaly scan
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thickened nuchal fold
>6mm
short femurs:
actual:expected FL
<0.91
short humeri
renal pelvic dilatation
ventriculomegaly
sandal gap toe
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single umbilical artery
widened pelvic angle
echogenic bowel
hypoplasia/clinodactyly
of middle phalanx of
5th finger
presence of a simian
crease
echogenic focus LV
Comparison of screening parameters at 18 week
anomaly scan
Ultrasound screening for aneuploidy is not a useful
primary tool in the diagnosis of Down syndrome
in the second trimester
Because
– the findings are subtle
– they require much expertise and time for
detection
Ref: D’Alton ME, Craigo S, Bianchi D. Prenatal diagnosis. Curr Probl
Obstet Gynecol Fertil 1994;17(2):41-80
Accuracy of Midtrimester US screening for
detectable major fetal malformations
Routine scans <24 wk
Abn. fetuses detected
Anomalies detected
CNS
GU
Craniofacial
Cardiac
GI
Skeletal
Tertiary
Non-tertiary
2679 (36%) 4648 (64%)
19/54 (35%) 8/64 (13%)
67%
50%
50%
18%
50%
25%
40%
35%
0%
0%
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0%
Ref: Crane JP, LeFevre ML, Winborn RC et al A randomized trial of prenatal
ultrrasonographic screening: impact on the detection, management and outcome
of anomalous fetuses. Am J Obstet Gynecol 1994;171:392-399
INFECTIONS IN PREGNANCY
Infections pose a problem for
– mother
– baby
– both
Some infections
– antepartum
– intrapartum
– postpartum
VIRUSES
Question 4
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Genital Herpes:
a. Herpes is more likely to result in
transmission of the virus to the neonate if it
is recurrent as opposed to a primary attack.
b. Obvious herpetic lesions on the vulva in
labour, is an indication for Caesarean
section.
Herpes Simplex
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Recurrent painful genital ulcers
HSV 1 & 2
Transmitted to infant at time of delivery
More common in primary infection(50%)
< 5% with recurrent episodes
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Neonatal Herpes - acquired perinatally
– 95% of cases
– localised - eyes, skin, mouth, CNS
– disseminated - increased mortality
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Congenital Herpes - acquired transplacentally
– 5% of all cases
– skin vesicles, chorioretinits
– micro/hydrocephaly, micropthalmia
Treatment
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Antiviral e.g. Acyclovir/famcyclovir
Caesarean if lesions present
Recurrent attacks now debatable
CMV
50% of Austr. population immune(IgG pos)
• 2% of births
• Acquired by primary or recurrent infections
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• Primary infection occurs in 4% of pregn
Maternal Infection
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Asymptomatic
Mononucleosis like symptoms
– fever, fatigue, myalgia, pharyngitis,
diarrhoea, lymphadenopathy.
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Diagnosed by culture or antibody detection
Foetal
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Transplacental transmission
Primary infection
– 40% risk of infection
– 10% symptomatic at birth
– 10% symptomatic later
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Suspicion based on U/S
– IUGR, micro/hydrocephaly, periventricular
– calcifications, ascites, effusions, oligo/polyhydramnios
Recurrent Infection
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Less insiduous to neonate
- usually asymptomatic at birth
-10% hearing loss in future
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Diagnosis
- 4 x rise in antibody titre IgG, IgM
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Foetus
- amniotic fluid PCR
- umbilical cord sampling
Varicella Zoster
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Maternal infection
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may cause severe, possibly fatal chickenpox
of all adult chickenpox - 2% in pregnancy
25% of all chickenpox deaths
more severe - encephalitis, myocarditis, pneumonitis
Prevention
– zoster immune globulin in 72 hrs
– acyclovir if not given ZIG
Congenital malformations
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Highest risk of foetal damage 13-20 weeks
Skin scarring in dermatomal distribution
Limb hypoplasia
Eye defects - micropthalmia, cataracts
Neurological abnormalities
Noenatal Chickenpox
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Occurring within 7 days prior to delivery
Transplacental transmission if large amount
of virus with no maternal protective
antibodies yet present
30% infant mortality
Give ZIG to neonate within 72h of birth
Toxoplasmosis
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Protozoan parasite
Cat host - passed in cat faeces but must mature in soil
prior to becoming infective
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Undercooked meat, soil, animal contact
Prevalence varies France, S. America 80%
Australia 30-40% sero +ve
Congenital Infection
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Follows primary maternal infection
Chances of transmission
1st trimester - 25%
2nd trimester - 54%
3rd trimester - 65%
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Magnitude of foetal damage greatest in
early pregnancy
- Neurological abnormalities, chorioretinitus,
jaundice, rash
Diagnosis
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Difficult - maternal infection asymptomatic
Demonstrate seroconversion
Amniocentesis or foetal blood sample
Management
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Serial IgG and IgM
If seroconversion
- monitor foetus by serial ultrasound
- hydrops foetalis, IUGR
Question 5
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Which of the following statements regarding
Rubella and pregnancy are correct?
a. Congenital Rubella Syndrome may occur in
patients who are known to be immune to Rubella.
b. Rubella infection after 16 weeks of pregnancy
results in foetal damage in about 30% of cases.
Rubella
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90% women immune
Vaccine live - give postpartum
Congenital Rubella Syndrome
- before 16 weeks
- cataracts, glaucoma, deafness, cardiac
- after 16 weeks