Questions and Answers About Prenatal Screening

Introduction

The Germano de Sousa Laboratory Medicine Center is certified by the Fetal Medicine Foundation (FMF) for Prenatal Diagnosis • First-Trimester Combined Screening, and is therefore an FMF Reference Laboratory for First-Trimester Prenatal Diagnosis.

 

If you have any additional questions, please email us at prenatal@cm-lab.com or call 212 693 530

 

We also recommend reading the article on Prenatal Diagnosis.

Table of Contents

• What Is Prenatal Screening—First-Trimester Combined Screening?
• What does the ultrasound exam involve?
• What does the biochemical screening test involve?
• Who is this test intended for?
• When should the Prenatal Screening—First-Trimester Combined Screening—be performed?
• How are the test results reported?
• What is a positive screening result?
• What is a negative screening result?
• What is a definitive diagnosis?
• What does amniocentesis involve?
• What is a chorionic villus sampling (CVS)?
• What is trisomy 21, or Down syndrome?
• What is trisomy 13 or Patau syndrome?
• What is trisomy 18 or Edwards syndrome?
• What are Open Neural Tube Defects (ONTD)?
• What are the advantages of first-trimester combined screening?
• Prenatal Care
• What is the detection rate?
• Why should you have the biochemical test performed at an FMF-certified laboratory?
• How long does it take to receive the results?
• Where can you have your blood collected for the biochemical test?
• What tests should you have done before getting pregnant?
• Tests Before Pregnancy
• What tests are performed during pregnancy?
• Routine Tests by Trimester

What is Prenatal Screening—First-Trimester Combined Screening?

Prenatal Screening—First-Trimester Combined Screening is an early screening test designed to assess the risk of the fetus having Trisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome), and Trisomy 13 (Patau syndrome).

It detects 97% of cases, with a false-positive rate of 3%, making it a crucial factor for the couple to consider when deciding whether or not to undergo amniocentesis.

This screening combines information from the ultrasound exam and the biochemical test.

What does the ultrasound exam involve?

The ultrasound examination allows for the accurate determination of gestational age through the crown-rump length (CRL) and enables the precise measurement of the nuchal translucency (nuchal translucency—TN/NT) and assess the presence of the nasal bone (ON/NB).

What does the biochemical screening test involve?

The biochemical screening test measures the levels of two substances in the mother’s blood: PAPP-A (Pregnancy-Associated Plasma Protein A) and free ß-hCG (free ß-subunit of human chorionic gonadotropin), both of which have high sensitivity and specificity for screening for the aforementioned anomalies.

Who is this test intended for?

The risk of Trisomy 21 (Down syndrome), as well as Trisomy 18 and 13, increases with maternal age, especially after age 35; however, it is not uncommon for young women to have children with Down syndrome.

The Fetal Medicine Foundation (FMF) recommends that a first-trimester risk assessment be performed for all pregnant women, regardless of their age.

If we consider only maternal age (>35 years) as a criterion for screening for aneuploidies, this will allow for the detection of only about 30% of cases.

When maternal age is combined with the first-trimester ultrasound examination (TN/NT), these tests together allow for the detection of about 75% of cases.

By considering maternal age, the ultrasound exam, and the biochemical test (first-trimester combined screening), approximately 95 to 97% of cases can be detected.

When should Prenatal Screening—First-Trimester Combined Screening—be performed?

Prenatal Screening—First-Trimester Combined Screening—should be performed between the 11th week and the 13th week plus 6 days of gestation.

How are the test results reported?

The result is expressed as a risk: High Risk—positive screening; Low Risk—negative screening. The result indicates the risk that the fetus has of being born with trisomy 21 or other chromosomal abnormalities.

What is a positive screening result?

If your test result is positive, it means there is a high probability that your fetus has a malformation (there is a 3% false-positive rate). In these situations, you can discuss the possibility of having an amniocentesis with your doctor.

What is a negative screening result?

If your test result is negative, it means you have a low probability of having a fetus with these birth defects, but it does not guarantee a healthy baby.

In these situations, you should not need to have an amniocentesis unless you wish to. You should consult with your doctor.

What is a definitive diagnosis?

A definitive diagnosis of the mentioned birth defects can only be made through invasive tests, such as chorionic villus sampling or amniocentesis, which allow for the collection of cells from which the baby’s karyotype is analyzed.

These are invasive procedures that require the insertion of a needle into the uterus and, as such, carry an inherent risk of miscarriage (0.5 to 1.0%). They should only be performed in pregnancies considered to be at risk for chromosomal abnormalities.

What Is Amniocentesis?

Amniocentesis involves obtaining a sample of amniotic fluid through a puncture in the mother’s abdominal wall, guided by ultrasound so that the specialist can direct the needle with precision, without risk of harming the fetus or the placenta. This procedure is usually performed after the administration of local anesthesia.

The amniotic fluid contains cells from the baby, which, after a period of culture, allow for the analysis of the chromosomes.

What is a chorionic villus sampling (CVS)?

Chorionic villus sampling enables prenatal chromosomal diagnosis.

Instead of amniotic fluid (as in amniocentesis), this test involves the extraction of a small sample of chorionic villi—that is, a sample of the placenta.

What is trisomy 21 or Down syndrome?

Trisomy 21 is a genetic disorder caused by the presence of an extra chromosome 21 and is also known as Down syndrome or Mongolism.

Down syndrome is the most common chromosomal abnormality found in live-born infants and is the most frequent cause of intellectual disability in children. It affects approximately 1 in every 700 births in the absence of screening.

It is characterized by morphological and organ abnormalities, including low-set ears, nasal hypoplasia, epicanthal folds, a widely spaced gap between the thumb and index finger, a palmar crease, cardiac malformations, and hearing and vision impairments. Life expectancy does not exceed 50–55 years.

The risk of trisomy 21 increases with maternal age, especially after age 35. Most babies with Down syndrome are born to young, healthy parents with no known risk factors.

Down syndrome is not usually hereditary; a child can be born with trisomy 21 even when there are no cases in the family.

What is trisomy 13, or Patau syndrome?

Trisomy 13 is caused by the presence of an extra chromosome 13 and affects about one in every 20,000 pregnancies.

It is also known as Patau syndrome. In most cases, it is associated with advanced maternal age.

A fetus with trisomy 13 is associated with typical morphological characteristics: severe mental retardation, and serious malformations (of the central nervous system, heart, kidneys, and eyes).

Most newborns die within the first month of life or during the first 6 months.

What is trisomy 18 or Edwards syndrome?

Trisomy 18 is caused by the presence of an extra chromosome 18 and affects about one in every 8,000 pregnancies.

It is also known as Edwards syndrome. Fetuses with trisomy 18 are associated with typical morphological characteristics: Mental retardation, choroid plexus cysts, ACIU, cleft palate, limb malformations, esophageal atresia, heart malformations, kidney malformations, exomphalos, diaphragmatic hernia. It has a higher incidence in females.

In most cases, the risk increases with maternal age.

What are Open Neural Tube Defects (NTDs)?

Neural tube defects (NTDs) are a group of malformations of the brain and spinal cord. In the absence of prenatal screening, about 1 in every 2,000 babies is born with an NTD.

Anencephaly and spina bifida are the most common NTDs. Anencephaly is a very serious defect that occurs when the skull and brain do not develop properly, and the baby dies within hours or days after birth.

Babies with spina bifida have an opening in the neural tube and exhibit abnormalities of varying severity. In most cases, they have severe malformations that require hospitalization and surgery.

The most common are weakness or paralysis of the legs, loss of bladder or bowel control, hydrocephalus (excess intracranial fluid), and, less commonly, mental retardation.

To prevent neural tube defects, pregnant women should take folic acid.

First-trimester prenatal screening does not detect neural tube defects.

What are the benefits of first-trimester combined screening?

First-trimester combined screening confirms an intrauterine pregnancy during the first trimester and provides an exact gestational age (to within 3 to 5 days). It can also provide an early diagnosis of multiple pregnancies.

It can detect increased nuchal translucency (NT) and screen for congenital heart defects.

It has high detection rates for Trisomy 21 and low false-positive rates for Trisomy 21.

Pregnant women prefer early prenatal diagnosis and, if necessary, early medical termination of pregnancy.

It provides earlier reassurance regarding the current pregnancy.

Prenatal screening reduces the anxiety that parents typically experience, allowing the pregnancy to proceed smoothly.

Prenatal Care

The health of the mother and the fetus should be monitored throughout the pregnancy.

From a medical standpoint, pregnancy is divided into three trimesters. The first trimester is of great importance, as this is when prenatal screening (first-trimester combined screening) should be performed.

It is during the first trimester that many health problems affecting the mother and the fetus can be detected and mitigated. Undergoing this screening in the first trimester allows pregnant women to feel confident that their pregnancy is safe, and if any problems arise, they can seek early advice from their doctor.

What is the detection rate?

According to the Fetal Medicine Foundation (FMF), an organization that promotes research in the field of fetal medicine, the first-trimester combined screening has a detection rate of 97% (in conjunction with ultrasound), with a 3% false-positive rate.

Why should you have the biochemical test performed at an FMF-certified laboratory?

It is essential that it be performed in a laboratory specialized for this purpose, since, technically, the measurement of the indicated substances should only be carried out using a specific type of technology.

It has been found that results can vary significantly depending on the equipment and methodology used, so accuracy is indispensable here as well.

Risk calculation is a mathematical formula that incorporates all these ultrasound and laboratory findings, taking into account the mother’s age, weight, race, smoking habits, and gestational age.

The choice of software is equally important, as it must account for variations in these factors throughout pregnancy. These factors do not all change in the same way over the course of pregnancy.

How long does it take to receive the results?

When you come to the lab for the biochemical screening, please bring your ultrasound report with you; the biochemical results are entered into the software to calculate the risk along with the measurements taken during the ultrasound exam. This way, you’ll receive the risk assessment on the same day, alleviating anxiety; and in the event of a positive result, you can decide together with your doctor whether to undergo amniocentesis.

You can also have the biochemical screening done at the lab, and the results will be sent directly to your doctor (an FMF-certified ultrasound technician), who will calculate the risk.

Where can you have your blood collected for the biochemical test?

You can have it done at any of our collection points or laboratories.

Check our website under “Collection Points.”

What tests should you have done before becoming pregnant?

When a woman is planning to become pregnant, she should consult her obstetrician-gynecologist and undergo a series of tests beforehand to assess her overall health and ensure a safe pregnancy.

The future father should also undergo tests to screen for infectious and general health conditions.

Tests Before Pregnancy

What tests are performed during pregnancy?

During pregnancy, the doctor monitoring the pregnancy prescribes a series of tests.

The most specific tests are designed to assess immunity to toxoplasmosis, rubella, cytomegalovirus, or other potential infections that may arise during pregnancy, in order to safeguard the well-being of both the mother and the fetus.

Tests are also performed for hepatitis B, syphilis, and HIV.

Blood glucose levels are assessed, and screening is performed for gestational diabetes, which can cause problems with the fetus’s development and growth.

Urinalysis helps confirm proper kidney function. A urine culture detects possible urinary tract infections, which are often asymptomatic in pregnant women.

A complete blood count (CBC) determines red blood cell count and iron stores, as well as blood type and Rh factor.

Routine Laboratory Tests by Trimester

1st Trimester - <13 weeks

• ABO blood group and Rh factor typing
• Screening for irregular agglutinins (indirect Coombs test)
• Complete blood count.
• Fasting blood glucose
• VDRL—Syphilis Screening
• Rubella serology—IgG and IgM (if status is unknown or the patient is not immune at the preconception consultation)
• Screening for Human Immunodeficiency Virus (HIV) infection—HIV-1 and HIV-2
• Hepatitis B screening, including for pregnant women with a history of prior vaccination, using HBsAg testing
• Screening for asymptomatic bacteriuria, performed via urine culture with optional antibiotic susceptibility testing (AST)
• First-Trimester Biochemical Screening, PAPP-A (Pregnancy-Associated Plasma Protein A) and free β-hCG (free β-subunit of human chorionic gonadotropin), with high sensitivity and specificity for screening for trisomies 21, 18, and 13.

Second Trimester—Between the 18th and 20th weeks

• Rubella Serology (IgG and IgM, in non-immune women)

Between the 24th and 28th weeks

• Complete blood count
• PTGO with 75 g (samples collected at 0, 1, and 2 hours)
• Toxoplasmosis Serology—IgG and IgM (for non-immune individuals)
• Urine culture with antibiotic susceptibility testing (AST) if indicated
• Screening for irregular agglutinins (indirect Coombs test) in Rh-negative women*

*Within 4 weeks prior to administration of anti-D immunoglobulin

3rd Trimester—Between the 32nd and 34th weeks

• Complete blood count
• VDRL
• Toxoplasmosis serology—IgG and IgM (in non-immune women)
• HIV 1 and 2
• Hepatitis B screening, HBsAg test (only for pregnant women who were not vaccinated and are not immune in the 1st trimester).
• Urine culture with optional antibiotic susceptibility testing (AST)

Between the 35th and 37th weeks

• Collection (outer third of the vagina and anorectal area) for specific testing for Group B β-hemolytic Streptococcus