Yesterday’s post generated a lot of discussion on Facebook and off-line about the role of maternal age and the incidence of Down syndrome. Today, we consider the value of prenatal screening for Down syndrome in relation to the mother’s age.
Most women accepting prenatal testing for Down syndrome are not doing so in order to find out they are carrying a child with Down syndrome. Rather, most are seeking reassurance that they are not carrying a child with Down syndrome. And, as more and more mothers accept prenatal testing, most of them will get what they are looking for: a negative test result.
This is because the overwhelming majority of expectant mothers are not carrying a child with Down syndrome. Figure 1 takes the age-incidence rate in 5 year increments from the table included in the American Congress of Obstetricians & Gynecologists’ (ACOG) practice bulletin recommending that all women be offered both prenatal screening and diagnostic testing (ACOG Practice Bulletin No. 88):
Another way of showing the incidence rate based on the mother’s age is in the chart at the top from the American Academy of Family Physicians. As you can see, in younger mothers, the chance is close to 0% and even for mothers at age 40, the chance is only then nearing 1%. Because of this low-incidence rate, that is why even receiving a “positive” from the new blood test for Down syndrome, with its stated greater-than-99% accuracy, still results in mothers under the age of 30 having a greater chance that their test result is a false positive. Figure 2 shows this positive predicative value rate based on the ages in Figure 1:
To further explain, for a 15 year old, if she receives a positive NIPS result at a 99.5% sensitivity rate, she has a 4-in-10 chance of actually having a true positive, and a 6-in-10 chance of her result being a false positive. Similarly, at age 30, the mother has a 51/49 chance for true positive/false positive. Only when the mother’s age nears 45 does a “positive” NIPS result with a 99.5% sensitivity actually mean she has a 99.5% chance of a true positive.
But, these figures deal with positive results, when most women are considering prenatal testing in order to be reassured by receiving a negative result. How informative is NIPS with a negative result?
This question was prompted by a comment by Robert Resta on the blog post that I discussed on Tuesday. Resta is the same Genetic Counselor who noted that in this century, most Down syndrome pregnancies are occurring in women 35 and older, due to the increase in the number of women in that age group being pregnant coupled with the higher incidence rate once a mother turns 35.
Regarding a negative NIPS result, even at the stated 99.9% specificity rate (i.e. the ability to rule out those pregnancies not carrying a child with Down syndrome), Resta offered the following observation:
A 35 [year old] woman has less than a 0.5% chance of having a baby with Down [s]yndrome, so age alone as a screening tool has a negative predictive value of 99.5%. After a normal NIPS, she has a 99.9% chance of not having a baby with Down syndrome. Not exactly a great scientific achievement. Cognitively, most of us cannot distinguish between 99.5% and 99.9%.
This point is made even clearer when considering the negative predictive value of age in mothers under 35 years old.
Table 3 shows the negative predictive value (NPV) based on the incidence rate associated with maternal age:
So, what is the utility of offering a 15 year old, or a 20 year old, or a 25 year old, seeking reassurance from a negative NIPS result with a 99.9% specificity if, by their age alone, they already have a 99.9% chance of not having a child with Down syndrome? Similarly, how much reassurance is to be gained by the 30 year old by having learned she has a 0.01% greater chance of not having a child with Down syndrome based on a negative NIPS result as compared to her baseline 99.89% chance of not having a child with Down syndrome?
The very act of offering screening engenders anxiety for a low risk condition, and then we expect pregnant women to be grateful when a test tells them they are at low risk for the condition?
Would knowing that a negative NIPS result means a 0.5% further chance of not having a child with Down syndrome be worth paying $2,700 for the test?