Prenatal diagnosis or screening is testing for diseases or conditions in a fetus or embryo before it is born
Such diseases include Thalassaemia, Sickle cell anaemia, cystic fibrosis, haemophilia, fragile X syndrome, Neural tube defects, birth defects etc.
Three are 3 main purposes of prenatal diagnosis:
1. To enable timely medical or surgical treatment of the condition before or after birth
2. To give the parents, the chance to abort the fetus with the diagnosed condition
3. To give the parents, the chance to prepare themselves psychologically, socially, financially and medically for a baby with a health problem or for a likelihood of a stillbirth
Prenatal diagnostic tests are of two types:
1. Non-invasive and
2. Invasive
Non-invasive Techniques:
• Ultrasonography
• Fetal blood cells in maternal blood
• Maternal serum alpha feto protein (AFP)
• Maternal serum beta HCG
• Maternal serum estriol
AS the invasive techniques carry the miscarriage risk drives a need for non-invasive alternatives
Invasive Techniques:
• Amniocentesis
• Chorionic villus sampling
Ultrasonography
• Can be safely done at any stage of pregnancy and
• May be repeated as and when required for assessing
o Fetal wellbeing and
o Anatomical defects can be visualized by this modality
Maternal serum AFP:
Increased level of alpha fetoprotein indicate neural tube defect (anencephaly, spina bifida)
Maternal serum Beta HCG:
Very high levels of HCG suggested triploblastic disease (molar pregnancy)
The absence of a fetus on ultrasonography along with an elevated HCG suggests Hyadatiform mole.
Maternal serum Estriol:
The amount of maternal serum estriol depends upon a viable fetus, a properly functioning placenta and maternal wellbeing.
In the third trimester, if the estriol drops then the fetus may be threatened and an early delivery may be necessary.
Estriol levels tends to be lower in
• Down’s syndrome and
• Adrenal hypoplasia with anencephaly.
Amniocentesis:
Usually done in early pregnancy (about 14 – 16 weeks)
A sample of amniotic fluid makes possible the prenatal diagnosis of chromosomal anomalies and certain metabolic defects.
The diagnosis of
1. Chromosomal anomalies is made by culture and karyotyping of fetal cells from the amniotic fluid and
2. Metabolic defects are diagnosed by biochemical analysis of the fluid
• Tay – Sach’s disease,
• galactosemia,
• Maple syrup urine disease,
• alpha thalassemia
Amniocentesis is called for in the following circumstances if the parents are prepared to consider abortion:
1. A mother aged 35 yr. or more (high risk of Down’s syndrome with advanced maternal age)
2. Patients who have had a child with Down’s syndrome or other chromosomal anomalies
3. Parents who have had a child with metabolic defect detectable by amniocentesis
4. When determination of the sex is warranted, given a family history of a sex linked genetic disease e.g. certain muscular dystrophies
5. For the detection of neural tube defects there is now the possibility of widespread screening by determination of alpha fetoprotein levels in the maternal serum.
Chorionic villus sampling (CVS):
Is typically performed in the 11th to 12th weeks of pregnancy
It should not be carried out before the 11th week in view of the increased risk of limb abnormalities associated with CVS prior to this date, which may be due to placental trauma at this critical stage of development.
Depending on placental site, CVS can be carried out either
• Trans-cervical or
• Trans-abdominally.
Chromosome analysis is carried out either as a direct preparation or following brief culture
In experienced hands the procedure-specific risk of miscarriage is up to 1%
For the detection of neural tube defects screening is done by the determination of alpha fetoprotein levels in maternal serum.
• If the test is positive, it can be confirmed by amniocentesis
For assessment of risk of aneuploidy as trisomy 21, 13, and 18:
Individualized risk first is calculated, taking into consideration, the following:
1. Maternal age,
2. Certain biochemical parameters in maternal serum
o human chorionic gonadotrophin (HCG) and
o pregnancy-associated plasma protein A (PAPP-A)
• between the 11th and 14th weeks of pregnancy
3. First trimester ultra-sonographic appearances of increased nuchal translucency in the fetus
If the risk is estimated to be high, decision may be made to carry out invasive method for confirmation of aneuploidy
(Prior to the above biochemical parameters, the so-called triple test was offered, measuring
a) alpha fetoprotein (AFP),
b) HCG and
c) Free estriol between 15 and 20 weeks
A further biochemical parameter, Inhibin A, when added to the triple test, yields the so-called quadruple test)
Accurate assessment of gestational age is essential for interpreting the biochemical parameters. This often involves using the last menstrual period, which can be a source of a high level of error
References:
• Khan MK, 2012. Prenatal Diagnosis (PND); CBMJ: July vol 1, no.2: pg 1 – 2
• Park’s Textbook of Preventive and Social Medicine, 23rd ed.
• Peter W, Johannes S (2010). The Prenatal Diagnosis of Genetic Diseases: Dtsch Arztebl Int. 2010 Dec; 107(48): 857–862
Eugenics: http://www.ihatepsm.com/blog/eugenics
Negative Eugenics and Positive Eugenics: http://www.ihatepsm.com/blog/eugenics
Euphenics: http://www.ihatepsm.com/blog/euphenics
Euthenics: http://www.ihatepsm.com/blog/euthenics
Genetic Counselling: http://www.ihatepsm.com/blog/genetic-counselling
Neonatal Screening: http://www.ihatepsm.com/blog/neonatal-screening
Prenatal Diagnosis: http://www.ihatepsm.com/blog/prenatal-diagnosis
Gene therapy: http://www.ihatepsm.com/blog/gene-therapy
Erythroblastosis Foetalis: http://www.ihatepsm.com/blog/erythroblastosis-foetalis
Role of Genetic Predisposition in Common Disorders: http://www.ihatepsm.com/blog/role-genetic-predisposition-common-disorders
Difference between ‘Eugenics’ and ‘Genetic Counselling’: http://www.ihatepsm.com/blog/difference-between-%E2%80%98eugenics%E2%80%...
FAQs in Genetics and Health (lecture): http://www.ihatepsm.com/category/genetics-and-health