Q&A: Advancing maternal age and role of prenatal genetic testing

The mean maternal age at first birth has been increasing in the United States in recent years, from 24.9 years in 2000 to 27 years in 2019, according to two CDC reports.

As the mean maternal age approaches 35 years — which is the standard cutoff age indicating advanced age — risks for certain adverse events rise. Specifically, pregnant people older than 35 years have a greater risk for gestational diabetes, miscarriage, genetic disorders and other conditions, according to the Cleveland Clinic.

To assess for genetic disorders, prenatal testing has become increasingly available, which may help people with older maternal age in their family planning decisions.

Healio spoke with Daniel F. Roshan, MD, FACOG, FACS, a maternal-fetal medicine specialist and director at Rosh Maternal & Fetal Medicine in New York City, to learn more about the shift in average maternal age and the role of prenatal genetic testing.

Healio: How is advanced maternal age defined?

Roshan: It is a term used for mothers who are older than age 35 by the due date. The way medical professionals came up with it was they calculated risk associated with amniocentesis. So, mothers at age 35 have a higher risk for Down syndrome or chromosomal problems; the chance for Down syndrome itself is 1%. Therefore, they said 35 is a good age to start offering invasive testing like amniocentesis or chorionic villus sampling. That was the arbitrary thing that they set up.

Now, the risk of amniotic fluid loss with amniocentesis is much lower because sonograms are so much better, and doctors are using disposable kits that are sterile, and they use it only once since the needle is disposable. They clean the maternal belly so the chance of infection and the complications that used to happen in the old days that made the risk of amniotic fluid loss higher. Those risks are basically eliminated. Now, most doctors have started saying that the risk of amniotic fluid loss from amniocentesis is one in 2,000. Frankly, we think that most of the losses that happen with amniocentesis if everything is done correctly probably would have happened anyway. Overall, the risk of amniotic fluid loss from amniocentesis has decreased a lot.

Healio: As the average maternal age at delivery has been increasing, should the medical community reevaluate advanced maternal age as a concept?

Roshan: We don’t like the name “advanced” because it’s not sensitive toward mothers — there’s nothing advanced about age 35. I recommend that all doctors don’t use “advanced maternal age” but instead use the maternal age indication.

Since there is a decreased risk associated with amniocentesis, that age doesn’t need to be the cutoff anymore. Some people want to know everything for sure — even in their 20s — and they want amniocentesis. Now, we have noninvasive prenatal testing (NIPT). The accuracy of NIPT for Down syndrome is amazing, it’s about 99% accurate. It also detects trisomy 18 and 13 at 80% accuracy and some other chromosomal problems. With the invention of the NIPT, even if the maternal age is high but the sonogram and NIPT are OK, many doctors started just going by NIPT and sonograms alone and discussed amniocentesis or chorionic villus sampling. That’s a lot of help, especially for patients who don’t want to do invasive testing.

But because of NIPT, most of the doctors who started doing just NIPT are not doing any more first trimester and second trimester screening for biomarkers. And NIPT, as I said, has a high accuracy for detecting Down syndrome and other chromosomal problems, so when many people do that and when the sonogram looks good, they’re happy and they move on. There are many new options for screening right now, so we can’t just use age alone. But as the age goes up, the chance of chromosomal problems, miscarriages and structural defects might be going up.

Healio: Is the risk for chromosomal abnormalities with older maternal age clinically significant?

Roshan: As age goes up, the chance of chromosomal problems goes up. So, at age 20, let’s say the risk is one in 1,480 pregnancies, then at age 35, it’s one in 353. At age 40, it’s one in 85. It’s basically due to a phenomenon called aneuploidy. When the chromosomes are dividing, they don’t divide evenly as the age goes up.

Healio: Is there anything clinicians whose patients are planning to get pregnant at an older age should know about advanced maternal age?

Roshan: Clinicians should know that as the age goes up, the chance of chromosomal problems goes up, and they should consider testing one way or another, whichever way makes the patient happy. They could see a genetic counselor, they could see an OB/GYN doctor, they could see a high-risk maternal-fetal medicine specialist to go over all the options out there to test the baby and make sure everything is OK. The options right now are NIPT, amniocentesis, chorionic villus sampling and sonograms. Every patient decides for themselves, and doctors can’t decide for patients. Some patients hold the ethical belief that they wouldn’t terminate a pregnancy for any reason, and some patients say, “If anything is wrong, I would like to terminate. I don’t want to deal with anything abnormal.”

These are patients’ choices based on their ethical beliefs or religion or other things. Our job is to give counsel and guide them on what options patients have, and then they can pick and choose for themselves what makes them happy and how much they want to know and how much they don’t want to know.

Healio: Are there any gaps in research related to maternal age?

Roshan: Everything is well-studied now. There are tables that calculate the risk based on age, and then obviously there are other factors that get involved — prior history, family history, genetic history and so forth. I think that advances are pretty good as of now.

There is more carrier testing also going on that is much less expensive. Those are for checking if the couple is carrying any genetic problems that the fetus has to be tested for. Most of them are autosomal recessive, so both people have to be carrying it. If both carry it, then they have the option to check the fetus for that genetic problem through chorionic villus sampling or amniocentesis. Some known carriers don’t want to bother with terminations and just go through IVF pregnancies and reimplantation genetic diagnosis to make sure they’re very healthy.

Today, with carrier frequency testing, NIPT and the ease of doing an amniocentesis or chorionic villus sampling, the advances have been quite good.

References:

• Cleveland Clinic. Advanced Maternal Age. my.clevelandclinic.org/health/diseases/22438-advanced-maternal-age. Updated Feb. 28, 2022. Accessed Dec. 9, 2022.
• Martin JA, et al. Natl Health Stat Report. 2021;doi:10.15620/cdc:100472.
• Mathews TJ, et al. NCHS Data Brief. 2016;(232):1-8.