PROCEDURE FACT SHEET

PRENATAL SCREENING OF DOWN SYNDROME
PERENATAL DIAGNOSIS OF SICKLE CELL DISEASE
CHROMOSOMAL ABNORMALITIES
MULTI FACTORICAL DISORDERS AND STRUCTURAL ABNORMALITIES
GENETIC DISORDERS
PRENATAL GENETIC COUNSELING
PRENATAL SCREENING
NUCHAL TRANSLUCENCY (NT) SCAN
FETAL BLOOD SAMPLING (FBS)
DOPPLER
3D SCAN
MATERNAL SERUM BIOCHEMISTRY (MSB)
ALPHA-FETOPROTEIN
FREEBETA hCG
ESTRIOL
CHORIONIC VILLOUS SAMPLING (CVS)
DNA ANALYSIS
AMNIOCENTESIS
INFECTION SCREENING
INTRAUTERINE FETAL THERAPY
GENETIC ANALYSIS
PRENATAL SCREENING OF DOWN SYNDROME

Down syndrome is the commonest form of chromosomal disorder worldwide.
Down syndrome is the commonest cause of severe mental retardation.
Every pregnant woman has a chance (risk of having a child with Down syndrome)
The vast majority of pregnancies affected by Down syndrome have no clearly identified risk factors.
The risk for Down syndrome is higher, when there is a previous Down syndrome in the family (immediate or extended).
Down syndrome occurs more commonly in pregnant women above 35 years.
Down syndrome is not caused by witch craft or sorceries.
Down syndrome is not related to dietary indiscretion or mistake of drugs or alcohol.
All pregnancies should be screened for Down syndrome through nuchal translucency scan and/or maternal blood analysis.
Only screen positive pregnancies are advised to have invasive test such as chorionic villous sampling or amniocentesis.

PERENATAL DIAGNOSIS OF SICKLE CELL DISEASE

Sickle cell disorder is the commonest single gene disorder among blacks.
Sickle cell disease gene is found in about 25-50% of Nigerian Population.
About 100,00 children are born annually with a serious Sickle cell disorder children.
If the mother and the baby’s father both carry the gene for sickle cell, for each baby there is:
1. A 25% (one in four) a chance that the baby will not be affected (that is, will not carry a disorder) a 50% (two in four) chance that the baby will be a carrier and a 25% (one in four) chance that the baby will have a disorder.
2. The chance of passing the gene to the unborn child be detected as early as 11 weeks of pregnancy, through either chorionic villous sampling or amniocentesis.
3. Early pregnancy diagnosis guarantees the peace of mind of a normal child down’s syndrome, Trisomy 18/13, and ONTD screening protocol in the first trimester and the combination of free Beta HCG and PAPP-A offers the best screening.

CHROMOSOMAL ABNORMALITIES

Chromosomes are units of genetic information. Each individual have a complete set of chromosomes that is referred to as normal chromosomal complement. Abnormalities however may arise from a deficiency in either the total number of chromosomes or the structure. Chromosome abnormalities are caused at conception when an abnormal sperm or egg from the other parent. The abnormal sperm or egg contains extra or missing chromosome material. These abnormal sperm or eggs appear to be present in everyone, but the risk of an abnormal conception increases significantly with the parents ages. Majority of fetuses that suffer chromosomal end up as spontaneous abortions, while the minority that are delivered suffers from varing forms and severity of birth defects especially of the heart. The most common chromosome abnormality is down syndrome and is the commonest cause of severe mental retardation.

Prenatal diagnosis of chromosomal abnormalities involves the use of both screening and diagnostic techniques. The screening method that is widely used all over the world is a combination of maternal age, nuchal translucency scan and maternal serum biochemistry. This is the combination we also use in the centre to produce the most accurate risk value in all pregnant women. Diagnostic test involves invasive procedures such as aminocentesis or chorionic villous sampling to obtain a fetal sample for laboratory analysis. A chromosome test is performed on cells from the placental tissue (chorionic villi) to determine if the fetus has a chromosome abnormality. The test can also reveal the chromosomal sex of the fetus.

MULTI FACTORICAL DISORDERS AND STRUCTURAL ABNORMALITIES

These are defects caused by an interplay of environmental factors and gene that is expressed usually as physical defects. The commonest physical defect are the open neural tube defects such as spinal bifida and heart defects (hole in the heart) such as ventricular septal defects. Approximately 99% of these defects may be detected through advanced ultrasound examination, testing for the fetal proteins such as alpha-fetoprotein (AFP) and acetylcholinesterase (AChE) in the amniotic fluid and maternal serum and coloured droppler imaging. Skull and spine defects which are too small or covered by skin (closed) cannot be detected by these tests. Ultrasound alone does not detect all of the anomalies. The 3D scan has a special advantage in the diagnosis of facial cleft such as cleft lip.

GENETIC DISORDERS

Genetic defects may occur either as a single gene defect or genetic syndromes. The commoner of the two groups are the single gene defects with examples as Tay-Sachs in the Jewish population, Sickle Cell disease in African-Americans and Latinos and Cystic Fibrosis in Caucasians.

Some couples may be carriers of genetic disorders for which prenatal diagnosis can be performed. In our centre, the commonest single gene defect diagnosed is the sickle cell disease.

PRENATAL GENETIC COUNSELING

Counseling is the most important aspect of our service. This is the provision of information to patients that will enable them to make an informed option about prenatal diagnosis. It is a very important aspect of prenatal diagnosis, during which the couple are allowed to freely discuss all concerns about prenatal diagnosis of the condition at risk.

Counseling is done both before (pre procedure) and after (Post procedure) any prenatal screening or diagnostic procedure. While we often offer detail explanations of results of screening test and the possible options available to confirm a suspicion, the final decision is made of the couple; to take or decline an invasive procedure.

Similarly, after an invasive procedure and release of result, counseling is usually made and the couple allowed to come to a real understanding of all aspects of the diagnosed condition and possible options.

PRENATAL SCREENING

Prenatal screening refers to procedures that can identify a subset of the general population that is at an increased risk of congenital abnormality. This subset is referred to as the high risk group. The type and timing of prenatal screening method depends on the abnormality at risk. For example, in genetic defect such as sickle cell disease, haematological screening is done for couples to identify their genotype, while in chromosomal abnormality, the maternal serum and ultrasound assessment of the fetus produce risk assessment.

INDICATION(S) FOR PRENATAL SCREENING

Pregnancy irrespective of background
Pregnancy exposed to harmful agents (teratogens) such as drugs, X-rays etc.
Pregnancy complicated by medical conditions such as diabetes mellitus, hypertension.
Pregnancy affected by infection (TORCHS).
History of previously affected pregnancies/fetus with either a medical or surgical condition.
Family history of congenital abnormalities e.g Down’s syndrome, cleft lip.
Abnormal fetal growth.

NUCHAL TRANSLUCENCY (NT) SCAN

This is the use of the ultrasound scan to measure the fluid at the back of the neck of the baby. All babies give the fluid at the back of the neck, which is best measured at between the 11-13+6 weeks of pregnancy. After this period, the fluid resolves in normal pregnancy. In fetuses affected by congenital abnormalities, there is an abnormal accumulation is chromosomal abnormalities such as Down’s syndrome, genetic syndromes as well as structural abnormalities such as cardiac defects. The measurement of the fluid has been shown to provide a better and reliable assessment of the risk of chromosomal abnormalities such as Down’s syndrome in the fetus, as well as some genetic syndromes and structural abnormalities.

The NT is essentially a screening test, with a detection rate for Down’s syndrome of about 80% (Maternal age alone picks up about 30% of babies with Down’s syndrome).

As a screening test, it will not tell you definitely whether or not your baby has Down’s be used to make an informed decision about whether to have an invasive test such as chorionic villous sampling or amniocentesis.

In every case of increased nuchal scan, a detailed heart scan is recommended. The nuchal translucency scan is also referred to as early anomaly scan because of the fact that over 80% of the major fetal structures can be identified and assessed at this period. Otherwise called the anomaly scan. It is a specialized screening and diagnostic scan (advanced scan) performed between the 18^th and 23^rd weeks of pregnancy, to detect structural congenital abnormalities in the fetus. Detailed attention is given to the major organs to include the face, brain, spinal cord, heart, bowels, kidneys and limbs. In skilled hands, it is able to detect virtually all forms of anomalities.

Irrespective of the NT scan, it is recommended that every pregnant woman also do the anomaly scan. More importantly, in women that missed the early trimester scan, the anomaly scan provides an opportunity to identify soft tissue markers for chromosomal abnormalities and genetic syndromes.

Counseling is provided at the end of the scan session, on the outcome of the scan and the prognosis for the fetus. We often times conduct cervical length assignment at the period of anomaly scan in pregnancies at a high risk of preterm delivery. This include twin pregnancies, previous history of preterm delivers etc.

FETAL BLOOD SAMPLING (FBS)

Is also referred to as cordocentesis. It involves the introduction and aspiration of fetal blood from the fetal umbilical cord, or liver under continous ultrasound guidance.

It is a second trimester procedure usually done after the 18^th week. It is very useful in the management of rhesus isoimmunization, when the fetal blood will be taken to determine the blood level as a measure of severity of the condition and also to transfuse blood when necessary.

DOPPLER

The Doppler flow study is essentially an assessment of the blood flow in various organs of the baby and the mothers uterus.

It is a specialized scanning of the blood vessels in the fetus to aid the screening of some conditions such as intrauterine growth retardation, the diagnosis of conditions like fetal anemia (blood shortage) and the management of conditions such as rhesus isoimmunization.

3D SCAN

This is the view of the baby in a 3 dimensional plane. It is complimentary to the 2D images and helps to pick up congenital structural anomalies especially surface abnormalities such as cleft lip/palate with absolute certainty.

It is fun to some women who wish to have a better appreciation of the fetus in pregnancy especially in the second trimester.

MATERNAL SERUM BIOCHEMISTRY (MSB)

In maternal serum biochemistry, certain biochemical substances are measured in the blood of the mother at specific times in pregnancy. These substances are called hormones. Their values vary depending on which abnormality is being assessed. MSB is essentially a screening method and it is not diagnostic of any abnormality.

There are2 specific periods in pregnancy that hormones are assessed namely first trimester (11-14 weeks) and second trimester (16-23 weeks). They are use either singly or in various combinations of hormones to produce a risk for congenital abnormality.

ALPHA-FETOPROTEIN

Alpha-fetprotein (AFP) is the best marker known for detection of open neural tube defects (ONTDS). It tends to be elevated in the blood of women and fetuses with ONTDS, and tends to be lower in the blood of women carrying fetuses with Down Syndrome and Trisomy 18/13.

FREE BETA hCG

Freebeta is the only biochemical market that can be used in both the first and second trimesters. In both trimesters, freebeta hCG is elevated in the blood of women carrying fetuses with Down’s syndrome (second trimester median MoM = 2.69) and reduced in the blood of women carrying fetuses with Trisomy 18/13 (seconf trimester median MoM = 0.20). in the second trimester, the comparable median Moms for intact Hcg are 2.03 and 0.36, causing greater overlap between affected and unaffected fetuses.

ESTRIOL

Estriol was originally added to AFP and hCG to enhance detection of Down’s syndrome. Estriol concentrations do not influence risk calculations for ONTDs. Researches have shown that estriol improves Down’s syndrome detection by only a marginal 1-2%, raising detection from 55% to 57%. Most researchers today agree that estriol increases the initial positive rate of a screening program without improving the detection rate of Down’s syndrome or Trisomy 18/13. Consequently we have deleted eristol to increase detection, to reduce unnecessary positives and cost.

There is a misconception that the use of three markers provides better detection than two markers. On the contrary, the combination of freeBeta and AFP achieves a 21-4% higher Down’s syndrome detection rate at a lower false positive rate than the “triple test”. In summary, scientific literature has documented the AFP/freeBeta protocol as the most sensitive and specific.

CHORIONIC VILLOUS SAMPLING (CVS)

Chorionic Villous Sampling (CVS) is the collection or aspiration of chorionic villi (placental tissue) from the developing pregnancy. Both the baby and placenta (after birth) originate from the same cell and so the genetic materials present in the cells of the placenta are the same as those of the baby. CVS is therefore a diagnostic test and not a screening test. CVS is performed in our centre usually between 10-14 weeks. It may however be done up till 44 weeks of pregnancy. Booking for the procedure is made only after we have a scan confirmation and dating of the pregnancy may occasionally rely on dating from last menstrual period (LMP).

The procedure is performed by a consultant in fetal medicine under continuous ultrasound guidance taking about 5-20 minutes. The preliminary scan confirms the date, placenta thickness and the best area for sampling. Although CVS can be performed either through the vaginal (transcervical) or abdomen (transabdominal), we perform only the transabdominal procedure in our centre for all cases. This has a comparatively better advantage over the transcervical procedure in terms of cleanliness of the sample and lower risk of complications especially abortion.

CVS has been proven to be a safe procedure for both mother and baby. However, spontaneous abortions can occur following CVS, either related to or independent of the procedure. The estimated risk of a spontaneous abortion related to the CVS procedure is about 1% (1 in 100 chances). Recent studies have shown limb reduction birth defects occur in less than 1 in 1000 pregnancies when CVS was performed after 9 weeks of pregnancy, which is not an increased risk. Bleeding, cramping, leaking of fluid from the vagina and infection may occur with CVS. Some women say CVS does not hurt at all, others feel some pressure or cramping. For a few women CVS cannot be performed.

With newer technologies, preliminary results can be obtained within 2 and 5 days, while final results of cell culture are obtained at about 10-14 days.

DNA ANALYSIS

In approximately 1% of cases, the test will need to be repeated. This is because the cells will not grow or amplify in the laboratory and the results are inconclusive.

The woman is advised to rest for about 30 days after the procedure and refrain from sexual activities or 14 days. These measures have been shown to reduce the risk of procedure related abortion.

We often discuss how to reach you during ……… following CVS so your test results can be reported. Mode of communication is entirely your choice.

Most couples are reassured by these tests because most tests will be normal. It the test results show your baby has a disorder, the nature of the disorder will be discussed with you. Prenatal diagnosis allows couples to make informed decisions and help with the management of their pregnancy supportive counseling is available.

AMNIOCENTESIS

Amniocentesis is a medical procedure in which a small amount of amniotic fluid is withdrawn from the amniotic sac surrounding the fetus in the uterus. This fluid contains cells from the fetal skin and amniotic membranes.

Traditional amniocentesis is performed in the centre after 15^th week of pregnancy by a consultant in fetal medicine. The procedure involves passages of a thin needle through the mother’s abdominal wall into the uterus at a safe distance from fetus. A small amount of amniotic fluid (5-10mls) containing cells naturally washed from the fetus is quickly withdrawn. It is very important that the procedure is ultrasound guided to avoid injury to the fetus.

Amniocentesis has been proven to be a very safe procedure for both mother and baby. It may however come with some risk. Miscarriages may occur spontaneously before and after amniocentesis, independent of the procedure. Medical studies have shown that there does not appear to be a statistically increased risk of miscarriage for women having amniocentesis compared to the risk for the women who have not had amniocentesis. The possible risk of a spontaneous abortion, is therefore, stated as being equal to or less than 0.5% (1 in 200 chance). The observed number of spontaneous abortions occurring after amniocentesis by an experienced physician using continous ultrasound has been shown to be less than 1 in 300.

Analysis of sample will take between 72 hours and 10 days depending on the test required. Some special genetic tests will be discussed with the patient, as well as the modality for release of results

Most parents are reassured by these tests because most test will be normal. If the test shows your fetus has a disorder, the nature of disorder will be discussed with you. Prenatal diagnosis allows couples to make informed decisions and helps with the management of their pregnancy. Supportive genetic counseling is available.

Infection screening

Infections in early pregnancy when the fetal organs are being laid down are recognized causes of birth defects. The organisms or infection types include syphilis, cytomegalovirus, herpes virus, rubella, toxoplasmosis and of recent Parvovirus B19.

We offer screening for these conditions on indications from medical history and of late as a routine in the center. Screening can be direct or indirect.

Intrauterine fetal therapy

The center maintains links with other centers outside country, where some forms of intrauterine fetal therapies can be carried out such as laser surgeries. however, we offer intrauterine fetal blood transfusion for some adverse fetal conditions, such as fetal anaemia resulting from rhesus isoimmunization, intrauterine saline infusion in selected cases of oligohydraminiuos, amniodrainage in selected cases of polyhydramnious e.t.c

Genetic Analysis

Prenatal paternity testing is offered through chorionic villous sampling or amniocentesis, while sex determination is carried out often as part of the resolution of some sex-linked conditions.

Training and research

We collaborate with recognized and standard overseas prenatal diagnosis centers and laboratories to provide accurate analysis of the specimens . continuous training and acquisition of knowledge remains the centerpiece of our practice.