Prenatal Genetic Screening – So many choices

Medicine is always changes, and its hard to keep up with the changes.  One good example is prenatal genetic screening.  It originally started as a screening test for anencephaly and spina bifida, and has now progressed to a wide variety of tests (all with their own acronyms of course):

NT – Nuchal translucency, a first trimester ultrasound.  Assigns a risk for Downs Syndrome, may identify a risk for congenital heart disease.

FTS – First trimester screen (labs and NT scan).  Better prediction that NT alone, fewer positive tests in women with normal fetuses.

IPS – Integrated prenatal screen (labs in the first trimester and second trimester and NT scan).  Even better test, but the results are delayed until the second trimester.  May identify placental dysfunction concerns.

SIPS – Serum integrated prenatal screen (labs only, no ultrasound).  In women under 35 the detection rate is similar to the detect rate for IPS in women over the age of 35.

Quad Screen – second trimester labs only.  Not the preferred screening test, as it has a high false positive rate.  More women will be labelled at risk, but have a normal fetus.

NIPT – Non invasive prenatal test (maternal sample any time after 10 weeks, screen for fetal DNA fragments).  Only test that is looking at DNA, not hormones released by the placenta.  Very low false positive rate, but often cost money out of pocket as it is not yet covered by many plans.

Details on each test can be seen here.

What do these tests have in common?  The lab parts actually don’t test the baby, they test the placenta.  Ultrasound is the only test that is actually looking at the baby.  Excluding NIPT, the other tests look a variety of hormones that are produced by the placenta.  The concentration of these hormones varies with gestational age, and by the number of fetuses.  It is important to understand that these are screening tests, they don’t give you a diagnosis, but a risk of there being a problem.  This can lead to anxiety and more testing (ultrasound and possibly amniocentesis).  However, the benefit of these tests is on a population basis, as most women will test negative.  That means they are at low risk for the problem, and can be reassured.

These tests are fairly limited in what they look for.  Humans have 23 pairs of chromosomes, one inherited from each parent.  Downs syndrome mean the fetus has trisomy 21 (an extra chromosome 21).  The other two common syndromes we screen for are trisomy 18 and 13.  Spina bifida and anencaphaly are defects of the neural tube, leaving openings at the top of the fetal skull or in the spine.  That is all these tests look for.  Some times the placenta will be identified to have a pattern of hormones that is associated with an increased risk of complications later in pregnancy, but these tests don’t identify all or even a significant number of these placentas.  These tests don’t identify genetic problems inherited from parents.  They don’t predicted developmental problems.  They won’t identify pregnancies at risk for autism.

For the individual women with positive tests, it can be scary.  However, it is important to remember that a screen positive does not mean that there is anything wrong with your baby.  Rather is highlights an increased risk, but in most cases things will still be fine.  For example, the test is considered positive at about a risk of 1 in 200 that the baby will have a common chromosome problem.  That means 199 babies with the same results will be normal, only one will be affected.  Even a result of 1 in 2 risk is not a diagnosis.  Have the the amniocentesis will reveal a normal fetus.

The hard part is to determine how mush risk you are comfortable with, and how badly you want to know the diagnosis.  If you are unwilling to continue a pregnancy with a baby with Down’s syndrome, your threshold to do an amniocentesis may be different than for a couple who would continue the pregnancy.  That is because there is a risk to the procedure – a 1 in 200 risk of complications.  This includes infection, rupture of membranes and loss of the the pregnancy all together.  The role for NIPT comes in here, it is a great screening test, and is nearly as good as a diagnostic test.  Again it is most useful for its negative results.  If a women has a different screening test that is positive for Downs syndrome, she can choose NIPT before an amniocentesis, because a negative NIPT is very reassuring.  If the test comes back positive, we still recommend an amniocentesis to confirm the diagnosis prior to making any decisions about terminating a pregnancy.

The reason to choose genetic screening is personal.  Some women choose the test for the reassurance it offers.  Some choose the test because they know they would terminate a fetus affected with Downs syndrome.  Some choose the test because they don’t want to be surprised by a life altering diagnosis at the birth of their child.  As a physician, the test help me evaluate the pregnancy.  If there are markers of Downs syndrome on ultrasound, it is nice to compare to the screening results because it affects the risks we estimate.  If we identify a baby with Downs syndrome, we monitor the pregnancy differently because they are at increased risk for structural problems, and an increased risk of stillbirth.  We make sure there is a pediatrician at the birth to help the infant if there are any problems.  The test is not a seek and destroy mission, but rather a chance to provide couple more information and choices as they become parents.


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