1. Blood and urine tests – we require 4 tubes of blood and 1 urine sample to perform these tests
a) Full blood count (FBC) – screens fo anaemia and thalassaemia. Tests for anaemia (haemoglobin level less than 11.5 g / dl), alpha- or beta- thalassaemia (MCV less than 80 fl is a good screening test). Haemoglobin electrophoresis is indicated if MCV is less than 80 fl, and would include the FBC and haemoglobin electrophoresis of the partner as well. DNA gene probes for thalassaemia may be indicated if alpha thalassaemia is suspected.
b) Infection screen for Hepatitis B, syphilis and HIV. If positive, there are strategies to reduce the risk of transmission of the infection to the baby.
c) Immunity screen for Rubella - If negative, consider rubella vaccination before the next pregnancy. It prevents the potential of contracting rubella during the first or second trimester of pregnancy that may affect the fetus severely.
d) Pre-exisiting diabetes mellitus – glucose and HbA1c levels.
e) Blood group and Rhesus type - This screens for Rhesus negative state in the mother. If the mother is Rhesus negative, injection with Rhogam injections during certain scenarios would reduce the risk of a blood problem to future, or even current, babies.
f) Screening for antibodies to atypical red blood cell antigens - This screens for potentially harmful antibodies in the mother that could cross the placenta and bind to the red blood cells of the fetus and possibly causing heart failure in the foetus, and also possible antibodies that may cause a reaction if an incompatible blood type is used for blood transfusion.
g) Screen for asymptomatic urinary tract infection with urine microscopy. If it shows possibility of urinary tract infection, a urine culture would be indicated and antibiotics may be necessary as it may reduce the risk of late miscarriages and preterm labour.
2. First Trimester Scan (FTS) between 11-13 weeks
The FTS is designed to screen for 4 groups of problems in pregnancy:
a) Risks of common chromosomal abnormalities (including Down syndrome [Trisomy 21], Edward syndrome [Trisomy 18] and Patau syndrome [Trisomy 13]) using Fetal Medicine Foundation (FMF) software. This allows the detection of 90% of Down syndrome, 90% of Edward syndrome and 90% of Patau syndrome.
b) Early structural abnormalities such as anencephaly (absence of skull), exomphalos (protrusion of intestines through an abdominal wall defect), megacystis (enlarged bladder), etc.
c) Risk of early pre-eclampsia requiring delivery 34 weeks (i.e. a serious condition during pregnancy characterised by high blood pressure with proteins in the urine). If left untreated, pre-eclampsia tends to progress and may become very serious. As the treatment of pre-eclampsia is delivery, we are most worried if the pre-eclampsia occurs early (i.e. before 34 weeks) which may require us to delivery early. If the risk of pre-eclampsia is raised, calcium supplementation of at least 1 g / day and low dose aspirin of 150 mg taken in the night may reduce the risk of this complication from 0.4% of the population to 0.04% of the population.
d) Risk of fetal growth restriction before 37 weeks which may require early delivery. If fetal growth restriction is detection, the fetus needs to be closely monitored with fetal movement chart, regular measurements of the fetus and regular Doppler studies of the blood flow within the baby, and also cardiotocography (CTG) later in the third trimester. When the fetal status is non-reassuring, early delivery may be indicated. Low dose aspirin of 150 mg taken in the night and calcium supplementation of at least 1 g / day may reduce the risk of fetal growth restriction. However, there is less data on low dose aspirin for prevention of this condition.
Further tests for chromosomal abnormalities
One needs to understand the different types of chromosomal abnormalities to decide which tests to do.
1. Large chromosomal abnormalities that are visible to the microscope are at least 5-10 MB in size.
a) Common chromosomal abnormalities which are usually random events that increase with increasing mother's age
i) Trisomy 21 or Down syndrome - Occurs in about 1:600-700 live births, increasing with mother's age (from 1:2000 for a 20-year-old mother to 1:100 for a 40-year-old mother). It ranges from mild to severe, with normal lifespan for the mild cases, with mild to severe intellectual disabilities and typical facial appearance, often with heart defects, and other abnormalities.
ii) Trisomy 18 and Trisomy 13 (Edwards and Patau syndromes) - Occurs in 1:5,000 for Trisomy 18 and 1:10,000 for Trisomy 13. Severe disorders with multiple abnormalities with > 90% dying while in the womb or within the first year of birth; < 10% survive longer than 1 year.
b) Sex chromosomal abnormalities (including 47XXX, 47 XXY, 47XYY) - Occurs in about 1:1,000 for each of the 3 sex chromosomal abnormalities. Most of these individuals are normal, but some may have deficits in social or intellectual skills. Individuals with 47XXY are often infertile. Some experts question if there is a need to screen for this group of conditions which does not usually result in serious manifestations while other experts advocate screening for this as early intervention after birth have been shown to improve outcomes (when compared to those who were not diagnosed at birth and hence did not have the early interventions).
c) 45XO (Turner syndrome) - More than 90% of Turner syndrome fetuses miscarry. Those born alive (about 1:2,000 to 5,000 live births) tend to be short with early menopause, may have difficulty to conceive and occasionally have developmental delay or behavioural problems. For the milder Turner syndrome children, early interventions like growth hormone and low dose estrogen have been shown to improve adult height, and cognitive and behavioural functions.
d) Triploidy - Occurs in 1-2% of pregnancies. This is a condition where there are 3 copies of every chromosome instead of the normal 2. Most embryos with triploidy miscarry early. Severe disorder with multiple abnormalities including the brain and skeleton, usually small in size with very little amniotic fluid and / or enlarged placenta.
e) Other chromosomal abnormalities - These are typically not detected by routine screening tests but are fortunately rare and account for < 30% of all the large chromosomal abnormalities.
2. Smaller chromosomal abnormalities are invisible to the microscope and range between 0.6 to 5-10 MB in size. These include microdeletion and microduplication syndromes. Depending on the specific condition, these may cause variable effects on the intellectual function, multiple structural abnormalities, and autistic spectrum disorders. Advances in technology now allow many conditions in this category to be diagnosed though some experts question if there is a need to screen for this group of conditions as current technologies only allow a small number of the rare microdeletions to be screened, and the screening tests have uncertain detection rates and low positive predictive values (i.e. probability that the fetus is affected if the test is high risk), and many may have a wide spectrum of severity of manifestations that may not be predicted accurately even if the genetic condition has been confirmed. This group of disorders does not appear to vary with mother's age, and appears to occur at about 0.84% prevalence. This group includes:
a) 22q11.2 deletion syndrome - This is the commonest micro deletion syndrome, occurring in about 1:2000 pregnancies, also known as DiGeorge syndrome. It may be associated with mild to moderate intellectual disability and schizophrenia, heart abnormalities, feeding difficulties, problems with immunity, and low calcium levels.
b) 4 other common deletion syndromes - They include 1p36 deletion syndrome, Prader-Willi syndrome, Angelman syndrome and Cri-du-chat syndrome. These are relatively rare, accounting for about 1:5000 to 1:20000 pregnancies.
c) Other microdeletion or microduplication syndromes - they could be grouped into 2 groups:
i) abnormal or pathogenic - Some of these conditions may be known to be associated with early onset of intellectual disability, multiple structural abnormalities and / or autism spectrum disorders. Other conditions may be associated with variable onset and severity (ranging from mild to severe) of disorder. Up to 1% of the population may have a microduplication or microdeletion syndrome.
ii) variation of unknown significance (VUS) where parents' blood may have to be further checked. Depending on whether the parents also carry the same microdeletions / microduplications, referral to a geneticist is usually required to discuss the possible outcomes of the baby.
One could choose no further test (which may be appropriate especially if abortion is not an option), an invasive diagnostic test such as chorionic villus sampling or amniocentesis (which is associated with 0.1-0.3% risk of miscarriage from the procedure), or a screening blood test at 10-12 weeks which evaluates the risk further (allowing detection of some, especially the common ones, but not all) before deciding if an invasive test is necessary. The test to choose for this category depends on individuals’ views on this.
This is a suggestion of an algorithm that may help you choose which test to do.