Prenatal Genetic Testing for Pregnancy Over 35

The risk of pregnancy complications rises with maternal age. Along with the increased chance of miscarriage and other issues, the risk of genetic diseases and disorders more than double when the mother is over 35. Genetic testing may involve non-invasive or invasive procedures to help check for these disorders and support informed pregnancy and parenting decisions. Always consult with a genetic counselor or healthcare provider to understand your need and options for genetic testing.

Advanced age pregnancy, formerly called geriatric pregnancy, refers to pregnancy at the age of 35 years and older. Individuals who are experiencing an advanced age of pregnancy are at higher risk for pregnancy complications that may significantly affect both maternal and fetal health. Healthcare providers will more closely monitor these patients to help identify conditions of concern and to guide decisions about the pregnancy.

Women and other individuals assigned female at birth (AFABs) with advanced aged pregnancy will typically experience 2 to 3 more ultrasounds than normal, which will help to closely monitor fetal growth and development. Those with significant risk factors may be recommended for more frequent ultrasounds, as much as every 4 to 6 weeks. Genetic testing may also be used to help assess the risk for Down syndrome or other genetic disorders.

Purpose of genetic testing

Genes are basic units of DNA that are passed down from parents to a child that define our physical and biological traits, affecting how we grow and continue to develop. Chromosomes are tightly-coiled, ribbon-like structures that contain these genes. Inheriting genetic defects or exposure to environmental stressors that cause genetic damage can lead to conditions such as sickle cell anemia (an inherited condition) or attention deficit hyperactivity disorder (due to epigenetics).

Caring for a child with a genetic condition will usually require long-term planning and mental and emotional preparation. Genetic diseases or disorders are also often impossible to treat and difficult to manage in severe cases. This is why the likelihood of transferring inherited disorders to a child may concern some hopeful parents. Through genetic testing, individuals can determine if a fetus has inherited certain genetic conditions, so they can make informed decisions regarding their pregnancy and parenting choices.

Genetic testing in advanced age pregnancy

The American College of Obstetricians and Gynecologists recommends that healthcare providers offer genetic testing to all pregnant women and AFABs, especially those experiencing advanced age pregnancy. Individuals with an advanced age pregnancy are at an increased risk of miscarriages, other pregnancy complications (such as gestational diabetes), and an almost 4 times increase in the risk of genetic disorders compared to a pregnant 20-year-old person. For this reason, it is important for individuals ages 35 and up to be evaluated for pregnancy complications, including the risk of genetic disorders in the fetus.

Genetic testing methods for pregnancy can be classified into two main groups — invasive and non-invasive. Invasive procedures for genetic testing include amniocentesis, chorionic villus sampling (CVS), and fetal blood sampling. The non-invasive procedure is simply called non-invasive prenatal testing (NIPT) or screening (NIPS). A few commercial at-home genetic tests are also available for use.

Amniocentesis

Amniocentesis is an invasive procedure in which amniotic fluid (fluid surrounding the fetus) is collected using a long needle inserted transabdominally (through the abdomen and into the uterus). Ultrasound is used to help closely guide the procedure.

The fluid contains fluids and cells from the fetus that can be used for genetic testing for Down syndrome, cystic fibrosis, or spina bifida, as well as evaluation for infections. The procedure can also be performed at or after 15 weeks' gestation, and can also be used for treatment to reduce amniotic fluid levels in individuals who have too much.

Chorionic villus sampling

The fetal membrane, which surrounds the fetus during pregnancy, is made up of two layers of tissue — the amnion tissue (innermost layer) and the chorion. The chorion is adjacent to the placental membrane, and the chorionic villi extend from the chorion and help transfer essential vitamins and minerals from maternal blood to the fetus.

Similar to amniocentesis, chorionic villus sampling (CVS) involves using a needle or a tube to gather a sample, in this case, tissue from the chorionic villi. Unlike amniocentesis, CVS does not detect a fetus with neural tube defects (such as spina bifida). However, CVS sampling can be performed earlier in pregnancy (between 10 and 14 weeks), via the cervix or transabdominally, with the help of ultrasound imaging.

Fetal blood sampling

Fetal blood sampling is also performed under ultrasound guidance and is safer between 20 and 28 weeks of pregnancy. Blood is collected from vessels in the umbilical cord (percutaneous umbilical blood sampling) or the heart or liver of the fetus. In addition to genetic testing, the procedure is also used for various other purposes, such as to assess for and treat blood problems, check for infections, or to deliver medicine to the fetus.

Non-invasive prenatal testing or screening (NIPT/NIPS)

In NIPT/NIPS, maternal blood samples are gathered to assess small pieces of DNA floating freely (rather than being bound in a cell). These pieces of DNA, called cell-free fetal DNA (cfDNA), are released from cells after they die and are broken down. Placental cfDNA is identical to that of the fetus and helps with screening for genetic disorders. This is a low-risk procedure, however, abnormal findings may indicate the need for confirmatory testing using more invasive procedures.

At-home genetic tests

At-home genetic tests are also a non-invasive and convenient option to help screen for chromosomal abnormalities. Commercial tests by companies like INVITAE, Juna Diagnostics, and Luna Genetics help detect genetic and chromosomal disorders by analyzing the cfDNA in the blood, and can also help identify gender. However, at-home tests do not replace the guidance and care of a healthcare provider. Always consult with your doctor for advice on testing and evaluating results of at-home tests.

Benefits, risks, and limitations of prenatal genetic testing

As with every procedure, invasive methods can increase the risk of miscarriage. Amniocentesis has 0.13% risk of pregnancy loss when performed by skilled providers and up to 2% risk of vaginal or fetomaternal bleeding and amniotic fluid leaks. In CVS, the main complications also include pregnancy loss, in addition to limb defects and intrauterine infections. However, the risk of complications is often lower than the possible health concerns resulting in provider recommendation of the procedure, and they are relatively safe in most patients.

NIPT/NISP is a low-risk procedure helping to screen for genetic conditions resulting from extra or missing chromosomal copies, such as Down syndrome (trisomy 21, or an extra 21st chromosome). NISPs/NISTs have not been approved for diagnostic testing and should only be used to screen for possible genetic conditions. Unfortunately, this procedure has been shown to falsely alert for abnormalities when there were none. NISP/NIST results must be confirmed using more invasive testing procedures (such as amniocentesis or CVS).

Pregnant individuals over 35 may be recommended for genetic testing. Non-invasive procedures may be helpful as an initial screening for genetic concerns, and additional confirmatory testing should be conducted to inform the decision-making processes. All invasive procedures carry risks, which must be considered in light of the need to evaluate potential maternal and fetal health concerns. Always consult a genetic counselor or healthcare provider to discuss your needs and options for prenatal genetic testing.