Reproductive Genetics

Chromosome Testing

Most people have 46 chromosomes in the cells of their bodies, 23 inherited from the pregnant person and 23 from the father. The chromosomes carry all of a person’s “genes” and the genes determine many of our physical and health characteristics. Chromosome testing is offered prenatally by amniocentesis or CVS to check the baby for Down syndrome (caused by an extra chromosome, see below) or other chromosome disorders. It may be offered to couples who have a history of miscarriage to check for more subtle chromosome changes which can sometimes be responsible for repeated pregnancy loss.

Cystic Fibrosis (CF) Carrier Testing

Cystic fibrosis (CF) is a life-long disease that causes problems with digestion and breathing. A person can only have Cystic fibrosis if they inherit a mistake in the copy of the CF gene inherited from both the pregnant person and father. CF carriers have a mistake in one copy of the gene and do not have any CF symptoms. Even if no one in your family has ever had CF, you could still be a carrier. 

Learn more about CF screening and testing

Hemoglobin Screening

Sickle cell disease and Thalassemia are both abnormalities of hemoglobin. Hemoglobin is the substance in blood that carries oxygen and gives blood its red color. Sickle cell anemia is usually diagnosed early in childhood due to low blood count and frequent attacks of pain called crises. It is treated with daily penicillin, folate, pain medicine as needed, and occasionally transfusions. Thalassemia is also usually diagnosed early in childhood due to a very low blood count. It is a very serious disease and is treated with blood transfusions as needed. Both sickle cell disease and thalassemia are caused by a mistake in both copies of the hemoglobin A gene.

Tay-Sachs Disease and Other Ashkenazi Disorders

Certain genetic disorders are more common in people of Ashkenazi (Eastern European) Jewish descent. These include cystic fibrosis, Tay-Sachs disease, Canavan disease and several others. Each of these diseases is caused by different genes, but all are inherited the same way. In order to inherit one of these disorders, there must be a mistake in both copies of the gene that is responsible for the disorder. Carriers have a mistake in one copy of the gene and do not have any symptoms. Your baby can have one of these diseases only if both parents are carriers for that disease.

Fragile-X Syndrome

Fragile X is an inherited condition that causes mental disabilities. It is more common and more severe in males, but can occur in females too. Symptoms range from mild learning disabilities to severe mental disabilities and autism. Fragile X is caused by a repeating sequence of the genetic code in a gene on the X chromosome. Carriers have 50 to 200 copies of this sequence and do not have any symptoms, but the number of copies can expand when it is passed from a carrier parent to a child. 

Spinal Muscular Atrophy

Spinal Muscular Atrophy (SMA) is a genetic disease that affects approximately every 1 in 10,000 newborns. Spinal muscular atrophy is a lifelong disorder that often presents in infancy with progressive muscle weakness. Individuals with SMA usually inherit two non-working copies of a gene called SMN1. Typically, both parents must be carriers for SMA, to have an increased chance of having a baby with the condition.

Learn more about SMA testing

First Trimester Screening

This test is done during pregnancy between 11 and 14 weeks of gestation. It combines a blood test for hCG (the pregnancy hormone) and a specific protein (pregnancy associated plasma protein A or PAPP-A) with an ultrasound measurement of the back of the baby’s neck (nuchal translucency or NT). While there is a range of values for these in normal pregnancies, women with higher than average NT measurements, or higher or lower than average hCG or PAPP-A values may be at risk for having a baby with Down syndrome or another rare chromosome problem called Trisomy 18. The first trimester screen cannot tell for certain whether the fetus does or does not have these problems, but it can identify women who have a greater than average risk.

Quad Screening (Second Trimester)

The Quad Screen is done during pregnancy usually between 15 to 18 weeks of gestation. It measures levels of four substances (alpha-fetoprotein (AFP), hCG, unconjugated estriol, and dimeric inhibin) in a pregnant patient’s blood. These substances come from the fetus and placenta and are found in the blood of all pregnant women. It is normal for the levels of these substances to vary among different women, but some women with particularly high or low values of the various substances may be at increased risk for having a baby with Down syndrome, Trisomy 18, or an opening in the babies body caused by a neural tube defect (NTD) or an abdominal wall defect. The Quad Screen cannot tell for certain whether the fetus does or does not have a birth defect, but it can identify women who have a greater than average risk.

Prenatal Ultrasound

Ultrasound uses sound waves to create pictures of the baby before it is born. Most of the organs and bones of the baby can be seen with ultrasound. This technology is used early in the pregnancy to establish how far along a pregnancy is, or to make sure an early pregnancy is viable. Nuchal translucency measurements for the 1st Trimester Screen (above) are done at 11-14 weeks of pregnancy, and detailed evaluation of the baby’s anatomy is usually done between 18 and 20 weeks. Also at 18 to 20 weeks, most ultrasound exams include a “screen” for subtle indications (“soft signs”) that may indicate an increased risk for Down syndrome. Some of these include skin swelling at the back of the neck, slightly shorter than average upper arm or upper leg bones, or a small bright spot (echogenic intracardiac focus, EIF) seen on the ultrasound of the baby’s heart. There are no known risks from ultrasound.

Cell-Free Fetal DNA (Also Called: NIPT, Cell Free, NIPS, cfDNA)

Cell-free fetal DNA (cfDNA) is a screening test that can be done during pregnancy, any time after 10 weeks of gestation. This blood test (which is drawn on the pregnant person) uses advanced technology to assess the floating fragments of DNA from both the pregnant person and their baby to screen for increased risks of specific chromosome conditions called trisomies (extra chromosomes in the developing baby). The conditions cfDNA commonly screens for include; Trisomy 13, Trisomy 18, and Down syndrome. This screening can also provide information about fetal sex. 

CfDNA screening is recommended for patients who will be over the age of 35 at delivery or for those who have an increased risk of having a child with a chromosome abnormality either because of their history or due to ultrasound testing results. This testing is highly accurate in finding a pregnancy affected with one of the trisomy conditions, but no screening test is 100% accurate. If you receive a positive cfDNA result, follow up testing is needed to confirm the result. 

Learn more about cell-free DNA screening

Common Prenatal Diagnosis Procedures, Amniocentesis, or Chorionic Villus Sampling, may be appropriate for women who are at an increased genetic risk for one of several reasons. The most common ones include:

• Pregnant person age 35 or older on delivery date
• Positive 1st Trimester Screen or Quad Screen
• Concerning findings noted by prenatal ultrasound
• Both parents carry a recessive gene (cystic fibrosis, sickle cell, etc.)
• One parent carries a chromosomal rearrangement
• Pregnant person carries Fragile X or another X chromosome disease gene
• Prior child with a chromosome abnormality

Amniocentesis

Amniocentesis or “amnio” usually is done after 16 weeks of pregnancy. The procedure involves obtaining amniotic fluid from around the fetus. This fluid contains fetal cells that can be used for genetic tests. The level of AFP in the fluid is also a very good test to check for neural tube defects. Amniocentesis is done under ultrasound guidance through the pregnant person’s abdomen using a very thin needle. Though women are usually nervous before about having amniocentesis, most say afterwards that the procedure is quick, easy and surprisingly painless. As with any medical procedure, there is a small risk. The risks of amniocentesis include bleeding, infection, leakage of fluid, and miscarriage. The chance of miscarriage from amniocentesis is no greater than 1 in 500. The other complications are very uncommon.

Chorionic Villus Sampling (CVS)

The chorionic villus sampling (CVS) procedure involves obtaining a sample of fetal cells (chorionic villi) from the placenta. It is performed between 10 and 13 weeks of pregnancy. The procedure can be done through the cervix with a thin plastic tube, or it can be done through the pregnant person’s abdomen with a needle, depending on the location of the placenta. It is done under ultrasound guidance. An advantage of CVS is the ability to obtain genetic information about the fetus in the first trimester of pregnancy. CVS cannot provide any information about neural tube defects, so if you are at risk for a neural tube defect, amniocentesis, rather than CVS will be offered. The risks of CVS include bleeding, infection, and miscarriage. The miscarriage rate from CVS is less than 1%. Though CVS is an accurate test, it occasionally yields false abnormal results that require amniocentesis for interpretation.

Both amniocentesis and CVS involve obtaining fetal cells, growing them in the laboratory, and performing the necessary genetic tests. Because the cells must be grown and even the most common tests are complex, results typically take 10-14 days, but may take longer if special or unusual tests are required.