Prenatal Diagnosis: Treating Babies In Utero Through Genetics

A lab worker removing test tubes.

There are a few thousand diagnosable genetic disorders and the diagnostic process for some of them starts with something as simple as a blood test.

Much of the new progress is due to the proliferation of new techniques for analyzing fetal DNA.

Fast facts: Prenatal Genetic Testing
  • Birth defects affect 1 in 33 babies born in the U.S. each year.
  • We can detect disorders at the chromosomal level and other mutations 12 weeks into pregnancy.
  • Unlike traditional fetal screenings, new maternal blood tests do not pose an increased miscarriage rate.
  • With noninvasive methods becoming more available, more prenatal genetic testing is expected.

“When I started my career several decades ago, the unborn baby was hidden from us quite securely,” says Yale Medicine's Maurice Mahoney, MD, professor emeritus of genetics and of obstetrics, gynecology and reproductive sciences at Yale School of Medicine. “Now, the diagnostic tests we can do with a fetus pretty much parallel what we can do with babies outside the womb.”

Much of this amazing medical progress is due to the proliferation of new techniques for analyzing fetal DNA. These permit gene sequencing—determining the precise order of a stretch of DNA—and identifying small segments of chromosomes where there is missing or extra genetic material, and doing so quickly at an acceptable cost.

“At Yale Medicine, we have one of the best gene sequencing set-ups in the country,” explains Dr. Mahoney. “We have invested time and effort into acquiring lots of sequencing machines and into using informatics [sophisticated computer analysis] to analyze genes.”

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Cracking the code

A decade ago, there were just a few hundred genetic disorders that could be diagnosed before a baby was born such as Down syndrome or Fragile X syndrome. Making these diagnoses required invasive procedures like amniocentesis, in which a sample of the amniotic fluid is extracted through a needle inserted into the mother’s uterus, or chorionic villus sampling (CVS), in which tissue is removed from the wall of an expectant mother's placenta.

Nowadays, there are a few thousand diagnosable genetic disorders and the diagnostic process for some of them starts with something as simple as a blood test.

“In the last two or three years, there have been rapid changes in the approach to fetal genetics,” Dr. Mahoney explains. “We have come to understand that the baby’s DNA is also the placenta’s DNA. Fetal DNA is released into the mother’s bloodstream from shed placental cells as cell-free DNA, fragments of genetic code. Now, we can use genetic sequencing techniques to analyze fetal DNA and maternal DNA in the mixture in which they sit.”

Fetal genetic testing is a sophisticated, scientific process similar to a very complex version of the game, Where’s Waldo? The geneticists take a maternal blood sample and compare DNA fragments they find in the blood to the mother’s complete genetic code. Whatever fragments do not match are fetal DNA fragments—which can be analyzed and screened for potential problems.

New methods

This genetic analysis opens up a number of new options for doctors. The older prenatal screening methods, still in use today, addressed just a handful of fetal conditions and typically stated that the chance that a fetus had a disorder was just a few percent.

With the new methods, geneticists can say that a fetus has a certain condition with a chance as high as 95 percent or, conversely, that a fetus does not have a certain condition with a chance over 99 percent.

“To establish a positive diagnosis, you still need to do a diagnostic test that requires an invasive procedure like amniocentesis or CVS,” Dr. Mahoney says. “But these new screening techniques can give us—and parents—vital information very early in a pregnancy that can help manage the next steps.

“We now can let people know they have a risk they might not have thought they had,” he says.