Chromosomal abnormalities occur when there is an alteration in the normal number or structure of chromosomes. These abnormalities can occur during any stage of fetal development, but are most commonly detected during prenatal screening tests in the first and second trimesters of pregnancy.
When does prenatal screening occur?
Prenatal screening refers to various medical tests that are done during pregnancy to check for potential problems with the fetus. Screening tests identify women who are at increased risk of having a baby with certain birth defects or chromosomal abnormalities. The two main types of prenatal screening are:
- First trimester screening – done between weeks 11-13 of pregnancy
- Second trimester screening – done between weeks 15-20 of pregnancy
Keep in mind that prenatal screening only estimates the chance or risk that the fetus has a chromosomal condition. A diagnostic test such as CVS or amniocentesis is needed to confirm whether the fetus is actually affected or not.
What chromosomal abnormalities can be detected with prenatal screening?
There are several chromosomal conditions that prenatal screening tests check for, including:
- Down syndrome – caused by an extra copy of chromosome 21 (trisomy 21)
- Trisomy 18 – caused by an extra copy of chromosome 18
- Trisomy 13 – caused by an extra copy of chromosome 13
- Turner syndrome – caused by a missing or partially missing X chromosome in girls
- Klinefelter syndrome – caused by an extra X chromosome in boys (XXY)
- Triple X syndrome – caused by an extra X chromosome in girls (XXX)
Down syndrome is the most common chromosomal abnormality, occurring in about 1 in 700 pregnancies. Trisomy 18 is the second most common, while trisomy 13 is less common, happening in 1 in 10,000 pregnancies. Turner syndrome, triple X, and Klinefelter syndrome are also rare.
First trimester screening
In the first trimester, there are two main screening tests available:
- Nuchal translucency (NT) scan: An ultrasound done between 11-14 weeks to measure the fluid at the back of the fetus’s neck. Increased fluid may indicate higher risk of Down syndrome or trisomy 18.
- Cell-free DNA screening: A blood test that analyzes DNA from the mother and fetus to detect increased risk for Down syndrome and trisomies 18 and 13. This noninvasive prenatal test (NIPT) is done after 10 weeks.
First trimester screening using the NT scan and cell-free DNA has a detection rate of over 99% for Down syndrome and about 95% for trisomy 18. It can identify 87% of trisomy 13 cases.
Detection rates of first trimester screening
| Condition | Detection Rate |
|---|---|
| Down syndrome | 99% |
| Trisomy 18 | 95% |
| Trisomy 13 | 87% |
Second trimester screening
Second trimester screening includes the following tests:
- Quad screen: A blood test done between 15-20 weeks that measures 4 pregnancy-related hormones to determine risk of chromosomal conditions.
- Detailed anatomy ultrasound: An ultrasound at 18-20 weeks that checks fetal anatomy for potential markers of genetic abnormalities.
The quad screen alone can detect up to 80% of Down syndrome pregnancies, and about 60-70% of trisomy 18 cases. When combined with ultrasound, the detection rate for Down syndrome is up to 85%. Second trimester screening does not reliably detect trisomy 13.
Detection rates of second trimester screening
| Condition | Detection Rate |
|---|---|
| Down syndrome | 80-85% |
| Trisomy 18 | 60-70% |
| Trisomy 13 | Not reliable |
When are diagnostic tests recommended?
Diagnostic tests like CVS (chorionic villus sampling) and amniocentesis are generally recommended in these situations:
- Screening tests show a high risk for a chromosomal abnormality
- Ultrasound reveals potential markers of genetic conditions
- Parents or doctor want diagnostic confirmation of a suspected condition
- One parent is a known carrier of a genetic disorder
- Parents have had a previous pregnancy with a chromosomal abnormality
These invasive tests can confirm with 99% accuracy whether a chromosomal condition is present. CVS can be done as early as 10 weeks, while amniocentesis is typically performed after 15 weeks.
Can chromosomal abnormalities be inherited?
Most chromosomal abnormalities occur randomly and are not inherited. However, in some cases, a rearrangement or abnormality of chromosomes can be passed from parent to child. Examples include:
- Balanced translocations: A segment of one chromosome breaks off and attaches to another chromosome. This does not usually cause problems in the carrier parent. However, unbalanced translocations can occur when the chromosomes with the translocation are passed to a child.
- Inversions: A segment of a chromosome is reversed end-to-end. Carriers of inversions are at increased risk for producing eggs or sperm with unbalanced chromosome arrangements.
- Fragile X syndrome: Caused by mutation of the FMR1 gene on the X chromosome. The premutation form can be passed from parent to child.
If one parent is known to be a carrier of a balanced translocation or inversion, prenatal diagnostic testing should be offered during pregnancy to check if the chromosomal rearrangement has been inherited by the fetus.
Can lifestyle factors influence chromosomal abnormalities?
Most chromosomal conditions occur by chance and cannot be prevented through lifestyle changes. However, there are some factors that are known to increase the risk of chromosomal problems in a pregnancy:
- Advanced maternal age: The risk of trisomy 21 and other chromosomal abnormalities increases with maternal age, especially over 35 years old.
- Paternal age: Though not as well defined as maternal age, increased paternal age may increase risks of conditions like Down syndrome.
- Cigarette smoking: Smoking raises risks of certain chromosomal abnormalities.
- Alcohol use: Drinking alcohol during pregnancy is associated with a higher risk of fetal chromosomal disorders.
- Obesity: Higher pre-pregnancy BMI may increase the likelihood of trisomy 21 in some studies.
- Diabetes: Poorly controlled diabetes is linked to higher risk of fetal anomalies.
- Folate deficiency: Not getting enough folate before pregnancy can increase risk of defects in brain/spinal cord development.
Following recommendations to get health conditions under control, taking prenatal vitamins, avoiding alcohol/smoking, and maintaining a healthy pre-pregnancy weight can help reduce risks of chromosomal problems.
Can chromosomal abnormalities be treated?
Unfortunately, there is currently no way to correct or “fix” chromosomal abnormalities before birth. Prenatal treatment is limited to managing potential pregnancy complications or delivery planning. Treatment after birth depends on the specific condition and symptoms present:
- Down syndrome: Therapies focus on developmental support, managing health problems, and enabling independent functioning.
- Trisomies 18 and 13: Due to the severity of health issues, treatment after birth is often focused on comfort care.
- Turner syndrome: Hormone replacement therapy at puberty to induce development of secondary sex characteristics.
- Klinefelter syndrome: Testosterone therapy starting in adolescence to develop male sex traits.
Early intervention programs after birth, medications, surgery for certain defects, educational support, physical and speech therapies, and assistive technologies can improve outcomes in some cases.
What is the prognosis for pregnancies with chromosomal abnormalities?
The outlook depends greatly on the specific syndrome and severity of symptoms. Some key points on prognosis:
- Around 50% of fetuses with trisomy 13 or 18 will be stillborn or die shortly after birth.
- Those with trisomy 13 or 18 who survive past the first year have a lifespan of less than 10 years.
- Life expectancy for Down syndrome is around 60 years with early intervention and good medical care.
- With hormone therapies, those with Turner syndrome typically have normal life expectancy.
- People with Klinefelter syndrome also have normal life expectancy but often experience infertility.
Early screening and detection of chromosomal abnormalities allows parents to be informed about risks and prognosis. This knowledge can guide pregnancy management decisions and delivery planning.
Conclusion
Chromosomal abnormalities can occur throughout pregnancy but are most commonly detected through first and second trimester prenatal screening tests. Down syndrome is the most prevalent chromosomal disorder. While some lifestyle factors can increase risk, most chromosomal conditions happen by chance and cannot be prevented. Prognosis varies widely based on the specific syndrome and severity of health issues. With early screening and proper management, outcomes for some conditions like Down syndrome continue to improve.