Prenatal diagnosis

Prenatal diagnosis Dr Hiba Ahmed SuhailM.B. Ch. B./F.I.B.O.G.College of medicineUniversity of Mosul

Prenatal diagnosis: Prenatal diagnosis is the identification of a disease prior to birth.

The early prenatal diagnosis and detection of congenital abnormality allows both parent and medical cares to plan the management for the pregnancy as:
Reassurance of the parent
Termination of pregnancy when the anomaly is incompatible with life .
The time ,mode and place of delivery prepared to ensure good prognosis of the neonate .
Offer in utero treatment.

Congenital anomaly refer to fetal alformation or disorders conferred by birth (born with )

Incidence 2-3 per 100 pregnancies
The prenatal detection of the congenital abnormality is one of the aims of the routine antenatal care

Classification of common congenital abnormalities

• Structural abnormalities
• congenital heart disease
Neural tube defects
Cleft lipand palate
Clubbed foot
Chromosomal abnormalities
trisomy 21(Downs syndrome) ,trisomy 13 and 18
Monosomy X(Turners syndrone )
Genetic
Cystic fibrosis
Sickle cell anaemia
Thalassemia
Miscellaneous
viral infection


Test for fetal anomaly
Screening is performed in all women in order to identify women who are at high risk of a disorder.
They do not confer any risk to the pregnancy and are performed for disorders which there are accurate prenatal diagnostic tests.

Diagnostic tests are carried out on pregnancies that have been identified as high risk by a prior screening test. It is usually invasive with risk of miscarriage .

Difference between prenatal screening and diagnostic tests

• Diagnostic
• Screening
• Women at high risk
• All women
• Population tested
• To diagnose abnormality
• To Select a high risk group
• Purpose of test
• Ultrasound
• Amniocentesis
• Chorionic villous sampling
• cordocentesis
• Maternal history
• Maternal biochemistry
• Maternal virology
• Ultrasound
• Usual method of testing
• Patient aware of potential risks
• Diagnostic test should be available
• Prerequisite to test
• Small risk of miscarriage from invasive test
• Anxiety of a screen positive result
• Risk of test


• Prenatal diagnostic tests can be divided into:
• 1-non-invasive tests ultrasound scanning
•  maternal blood sampling
• 2- invasive tests  Amniocentesis
•  chronic villus sampling
• and placental biopsy
•  Fetal blood sampling
•  Fetoscopy

Ultrasound scan

At boking (11-14 weeks)
Anomaly scan at 18-22 weeks
Maternal serum tests
• Free fetal DNA can be extracted from maternal blood to determine fetal blood group in cases of alloimmunization , or to determine the sex of the fetus in X- linked disorders.
• Other studies
• 3 dimensional ultrasound scan and fetal MRI this permit the increased resolution required for certain fetal malformation like cleft lip and palate.

1-Non invasive prenatal diagnosis

2- Invasive prenatal diagnostic tests
• Cordocentesis
• Chorion villous sampling
• amniocentesis
• 20-40
• 10-40
• 15-40
• Gestation (weeks)
• Transabdominal
• Trans abdominal / trans cervical
• Transabdominal
• Route
• Fetal white blood cells
• Trophoblast cells
• Fetal fibroblast
• Cells sampled
• 1
• 1
• 1
• Procedure related risk of miscarriage (%)
• Not needed
• 24-48 hours
• FISH for chromosomes 13, 18, 21 and XY, 24-48 hours
• Direct karyotype result
• 24-48 hours
• 1-2 weeks
• 2-3 weeks
• Culture karyotype result
• None
• 1%
• None
• Mosaicism rate on karyotype


Structural anomaly (Neural tube defects)
Are most common major abnormalities . It occurs due to defect in formation of neurl tube defects during embryogebrsis.
The aetiology is multi - factorial ( envirumental , genetic , pharmacological and geographical factors implicated.
Anencephaly ( lethal ) , encephalocele ( prognosis related to size of defects )
Spina bifida usually affect spinal cord at the caudal level. The local effects (paralysis of legs, urinary and fecal incontinence ) depend on spinal levels and the number of spinal segments affected in the lesion.
When a parent or previous sibling has had an NTD, the risk of recurrence is 5-10%.

Screening test

Ultrasound
1- in first trimester can diagnose anencephaly , encephalocele.
2- At 20 weeks anomaly scan for spina bifda and hydrocephalous.
Mid trimester maternal serum alpha - fetoprotein ( AFP ) levels are increased in pregnancies affected by open NTDs.
Diagnostic test
In the past, in case of screen positive women, they referred for amniocentesis to detect the presence of acetylcholinestrase in the amniotic fluid.

Prevention of neural tube defects:

Periconceptional folate supplementation to the mother reduce risk
folic acid should be given for at least 3 months prior to conceptionand for the first trimester of pregnancy.
The dosage is 400 mcg for primary prevention and 4 mg for
prevention of NTD in :
• Women with previously affected baby with NTD
• with type 1 diabetes mellitus
• in mother use antiepileptic drugs
• multiple pregnancy
• mother with hemoglobinopathies .


Structural anomaly (Congenital heart disease) CHD
Anomalies of the heart and majors arteries are common heterogeneous
They range from asymptomatic to the lethal one or that required surgery
Risk factor:
• When a previous sibling or father is affected by CHD
• Offspring of women with type 1 diabetes.
• Drugs like lithium
• Viral infection like rubella
• Chromosomal abnormality
Can be detected by ultrasound at 20 weeks

Chromosomal abnormalities(Downs syndrome)

Down's syndrome (trisomy 21 ) it is an abnormal female gametogenesis either due to:
Non dysjunction in meiosis (90 %)
Un balanced translocation (6 %)
Mosaism (4%)

Screening

• Maternal age and history
Increase risk with advanced maternal age. Age over 35 years old 1:750 , previous history of Down's 1:100 these should offer prenatal diagnosis.
• 2. Maternal serum biochemistry
This iclude first trimester test of maternal serum HCG , estriol , inhibin ,PAPP-A , together with second trimester alpha feto protien (all are reduce except HCG)
3-Ultrasound for nuchal translucency
Measurement of subcutaneous collection of fluid in nuchal (behind neck) region of fetus at 10-13 weeks gestation, it increase in affected fetus
Diagnostic test
Women with positive screening test are offered invasive tests
• (Amniocentesis and chorionic villus sampling ) .


Genetics disorders (hemoglobinopathies )
Sickle cell anaemia and thalassaaemia are both autosomal recessive with a risk of 25% affection of the offsbling
Screening of at high risk populations (african in sickle cell anaemia and Mediterranian in thalassaemia) is by maternal serum electrophoresis
• Prenatal diagnosis by any invasive test (amniocentesis , CVS ,cordocentesis ) to take fetal cell for DNA study .

• parvovirus

• toxoplasmosis
• Cytomegalovirus
• Rubella
• Infected children
• Cat-litter
• Under-cooked meat
• Infected individuals
• Infected individuals
• Source
• Aplastic anaemia
• hydrops
• Microcephaly
• Ventriculomegaly
• Cerebral calcification
• Heart defects
• Growth restriction
• Hepatomegally
• Thrombocytopenia
• Mental retardation
• Microcephaly
• Ventriculomegaly
• Cerebral calcification
• Heart defects
• Growth restriction
• Hepatomegally
• Thrombocytopenia
• Mental retardation
• Cataracts
• Heart defects
• Growth restriction
• Hepatomegally
• Thrombocytopenia
• Mental retardation
• Features of congenital infection
Congenital infections