Woman & Doctor
First Trimester Screening
 
Kelsey McLaughlin, PhD

First trimester screening tests are used to estimate a woman’s chance of having a baby with birth defects relating to chromosomal or genetic anomalies. This screening involves testing the mom’s blood for levels of certain proteins and checking the baby’s anatomy through an ultrasound scan.

Keep reading to learn more about first trimester screening tests.

What is first trimester screening?

 

The first trimester screening tests are used to screen as many women as possible through non-invasive testing to determine which women have a higher chance of having a baby with a chromosomal disorder, compared to the average woman.

The results from the test will indicate that a woman is ‘positive’ or ‘negative’. This means that the chances of having a baby with a chromosomal disorder are higher than the average women (positive) or lower than the average woman (negative). ​

Pregnant women are considered ‘screen positive’ if the calculated risk of having a baby with Down Syndrome is more than a 1 in 350 chance, or more than a 1 in 100 chance of having a baby with Trisomy 13 or Trisomy 18. This is the same as saying women ‘screen positive’ if the chances of their baby having Down Syndrome is greater than 0.3% or the chances of their baby having Trisomy 13 or Trisomy 18 is greater than 1%.

The results from these screening tests are not definitive, meaning that they will not be able to tell for certain which babies have a chromosomal disorder. The real purpose of first trimester screening is to let doctors know which women need more in-depth diagnostic testing. Doctors will only be able to definitively tell if a baby does have a chromosomal disorder through a diagnostic test, which is more invasive.

Haematology
Sleeping Baby

What are chromosome anomalies?

When the father’s sperm fertilizes the mother’s egg, the baby receives genetic material from each parent.

 

Every cell in the body contains 46 chromosomes in total, or 23 pairs of chromosomes, that contain all of our genes and DNA. In each pair of chromosomes, one chromosome is inherited from the mother and one chromosome is inherited from the father.

If a baby has a chromosomal anomaly, this means that there is an abnormality in the baby’s chromosomes that impacts physical or developmental function. The two main causes of chromosomal anomalies are:

 

  1. Abnormal number of chromosomes: we normally have 46 chromosomes that form 23 pairs. Anomalies can be due to having too few or too many chromosomes.

  2. Abnormal chromosome structure: chromosomes have a very specific physical structure. Anomalies can be due to physical changes in the structure of a chromosome, which includes missing chromosome portions.

 

Chromosomal anomalies impact approximately 1% of all pregnancies, with Down Syndrome being the most common anomaly in Canada, occurring in 1 out of every 800 births.

 

The most common chromosomal anomalies are Down Syndrome (Trisomy 21), Edwards Syndrome (Trisomy 18) and Patau Syndrome (Trisomy 13). In these conditions, the baby has inherited an extra chromosome (referred to as 'tri'somy). Babies with Down Syndrome inherit an extra copy of Chromosome 21, while most babies with Edwards Syndrome and Patau Syndrome have an extra copy of Chromosome 18 and Chromosome 13, respectively.

What are the components of first trimester screening?

First trimester screening involves the combining blood tests, ultrasound of the baby and mom’s age to calculate the risk of the baby having a chromosomal abnormality.

 

An important clinical trial, known as the FASTER trial, determined that this is a highly effective strategy for detecting Down’s Syndrome in the first trimester of pregnancy. Testing is typically completed between 11 - 14 weeks of pregnancy and is non-invasive, meaning that testing is not associated with health risks for mom or the baby.

Here are the components of the test:

     1. Blood test

Doctors will test mom's blood for levels of two different proteins that are related to the health of the placenta.

​Pregnancy-associated plasma protein (PAPP-A)

PAPP-A is a protein that is released mainly from the developing placenta and is associated with the baby’s development. In normal pregnancy, PAPP-A levels increase in the mom’s blood throughout pregnancy as the placenta and baby grow. Women with low levels of PAPP-A in the first trimester are at higher risk of having a baby with a chromosomal abnormality. Low levels of PAPP-A are associated with a higher risk of preterm delivery, impaired fetal growth  and pre-eclampsia; however, levels of PAPP-A are typically the lowest in women who have a baby with a chromosomal abnormality.

 

beta human chorionic gonadotropin (β-hCG)

β-hCG is a hormone produced by the placenta that peaks in the first trimester of pregnancy. β-hCG is responsible for maintaining the health of the newly developing placenta and baby until the placenta is able to produce its own hormones. When women take an at-home pregnancy test, this test detects β-hCG in the urine to indicate that a pregnancy exists. Pregnant women with fetal Down’s Syndrome have higher levels of β-hCG, compared to women without chromosomal abnormality.

     2. Ultrasound of the baby

An ultrasound between 11 and 14 weeks of pregnancy looks for any major physical abnormalities the baby might have. In particular, doctors will check fluid levels that naturally pools at the back of the baby’s neck – this measurement is known as nuchal translucency. Babies with Down’s Syndrome typically have more fluid at the back of the neck, or higher nuchal translucency levels. ​This screening in the first trimester does not assess the presence of neural tube defects.

Together with mom’s age, maternal blood test levels and the ultrasound of the baby, calculate the risk of the baby having a chromosomal abnormality.

 

This screening is not perfect - if 100 babies had Down Syndrome, first trimester screening would correctly detect approximately 82-87 of these women; 13-18 women would be missed.

Why does maternal age matter?

Maternal age above 35 is associated with higher risks of adverse pregnancy outcomes, including miscarriage, gestational diabetes, and chromosomal abnormalities. In Canada, women above 35 are 3 times more likely to have a baby with a chromosomal defect, and women above 40 are 9 times more likely, compared to women aged 20-34 years old. The chances of having a baby with a chromosomal anomaly are:

 

  • Women aged 25: 1 in 475

  • Women aged 35: 1 in 180

  • Women aged 40: 1 in 60

 

Scientists believe that as women age, there are changes to the structure of her eggs located in the ovaries. A study in mice found that the proteins that keep the chromosomes stable inside the egg decrease in level over time. If the chromosomes in the egg are not stable and in correct formation, the division of chromosomes when the egg is fertilized is more likely to be uneven and the chances of the baby having a chromosomal anomaly is higher.

 

This is an important area of research, since maternal ages in Canada and around the world are on the rise. The average Canadian maternal age at first birth in 1920 was 25 years old and is currently over 30 years old. The Canadian Institute for Health Information estimates that 1 in every 5 births in Canada is to a mom over 35 years old.

Ultrasound
Pregnant Woman

What's the difference between screening and diagnostic tests?

Women who have a higher chance of having a baby with a chromosomal disorder that the average woman (screen 'positive' women) have the option of undergoing diagnostic tests. Diagnostic tests are the only way for doctors to definitively tell if a baby does have a chromosomal disorder.

The comparisons between screening and diagnostic tests are listed below:

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Why is testing for chromosomal anomalies done so early in pregnancy?

Screening for chromosomal anomaly is typically done in the first trimester for a few reasons:

     1. Babies with chromosomal anomalies exhibit differences in the first trimester in blood proteins and on ultrasound                findings, compared with babies without chromosomal anomalies, and

     2) Identifying women at higher risk of having a baby with a chromosomal anomaly in the first trimester provides time             for additional testing, discussion and management options.​

Is first trimester screening mandatory?

No - first trimester screening tests are optional. It is a personal decision to know the chances of having a baby with a chromosomal anomaly.

Summary

 

First trimester screening provides an estimate of a women’s risk of having a baby with chromosomal anomalies, including Down Syndrome (Trisomy 21), Patau Syndrome (Trisomy 13) and Edwards Syndrome (Trisomy 18). This non-invasive testing includes measuring proteins in the mom’s blood, an ultrasound of the baby and incorporates maternal age. Women who ‘screen positive’ in the screening test may decide to undergo further invasive diagnostic testing to receive an official diagnosis of chromosomal anomaly or no chromosomal anomaly.

Disclaimer

Every woman and every pregnancy is unique. Pregnant women should speak to their healthcare provider to ensure maternal and fetal safety. This article is meant to provide readers with current information and opinions. All medical and treatment decisions should be discussed with your healthcare provider.

This article was written by Dr. Kelsey McLaughlin and edited by Dr. Melanie Audette.