In an earlier post, I wrote about the different types of tests used to detect hCG. While the results of These test are usually very accurate, false positive results can and do occur. Here I discuss some reasons why a urine pregnancy test might give a false positive result.
First, though, a few comments about what a false positive result actually is. Pregnancy tests are designed to detect hCG;the hormone produced by the placenta during pregnancy. If the hormone is truly present in the urine and the test detects it, then that result is a true positive result. In other words: hCG present = true positive test result. However, because hCG is usually only produced during pregnancy,many people consider a positive result to mean that a woman is pregnant. There's a big difference between those two meanings! To summarize:
- Pregnancy tests detect hCG
- hCG is usually (but not always) produced during pregnancy
- A positive pregnancy test indicates that hCG is present (even if the hCG is being made by something other than the placenta)
With that in mind, let's explore the causes of false positive urine pregnancy test results.
- Missed reaction time: The result of a pregnancy tests should be read when the manufacturer instructions say to read it. If the result is read after that time, a faint line is sometimes visible (possibly due to evaporation of the urine) that might be interpreted as a positive result. This would truly be a false positive result because hCG is not present.
- Biochemical pregnancy: A biochemical pregnancy is a real pregnancy but is one that ends very early after conception. If a pregnancy test is performed near the time of the expected period (or even several days later), a positive result can be obtained. This is actually not a false positive result because hCG is present and it was detected by a test designed to detect it! Even though the pregnancy has ended, hCG can still be detected in the urine for a few, or even several, more days. Biochemical pregnancies are quite common although many aren't even detected because the miscarriage occurs before the woman even knew she was pregnant and so had no reason to perform a pregnancy test. Indeed, the term "biochemical pregnancy" came into use only after urine pregnancy tests became sensitive enough to detect hCG close to the day of the expected period. Prior to that, the tests were not able to detect that rather low amounts of hCG that are associated with a biochemical pregnancy.
- hCG from sources other than the placenta: Although hCG is most commonly made only during pregnancy, there are other times that it is produced. Certain cancers sometimes make hCG; most notably a family of tumors collectively called trophoblastic tumors. The pituitary gland in the brain can also produce hCG although this is more common in women who have gone through menopause. Finally, people taking hCG as a weight-loss aid (a waste of money, by the way) or as part of fertility treatments can also have detectable hCG in their urine.
This is impressive! A study reported yesterday in the British Medical Journal describes a new blood test that could vastly decrease the number of invasive procedures that are currently used to confirm if a fetus has Down syndrome.
Current blood tests used for Down syndrome screening can identify up to 90-95% of Down syndrome pregnancies but about 5% of normal fetuses are incorrectly identified as having Down syndrome. That means that lots of women have follow-up tests, like amniocentesis, to definitively determine if their baby is affected. That's a problem because amniocentesis is an invasive procedure that can lead to the loss of the pregnancy. Current estimates put the risk of fetal loss due to amniocentesis at about 1 out of 300.
This new blood test measures the amount of DNA from chromosome 21 that is present in the mother's blood. Down syndrome is caused by having an extra copy of chromosome 21. We know that a pregnant woman's blood contains small amounts of her baby's DNA but that amount is very
low compared to the amount of her own DNA in her blood. Using a technique called massively parallel sequencing, this test looks for increased amounts of pieces of chromosome 21 in the mother's blood. In a Down syndrome pregnancy, the mother's blood will have more pieces of chromosome 21 because the fetus has an extra copy of that chromosome.
The study used blood collected from 753 women who were at high-risk of having a baby with Down syndrome. 86 of these pregnancies were carrying a fetus with Down syndrome and the test was able to correctly identify 100% of them. While that alone is impressive, even more exciting is that only 2.1% of the unaffected fetuses were incorrectly identified as having Down syndrome. Stated another way, in 98% of the cases Down syndrome could be ruled-out sparing the need for invasive follow-up testing. Like some of the existing blood tests used to screen for Down syndrome, this new test can be performed in the first trimester of pregnancy.
Although the test is not yet available, there is a company that is working on making it available soon.
This month the National Academy of Clinical Biochemistry (NACB) launched its blog, appropriately called the NACBlog. The first post is on the topic of fetal lung maturity tests and how the medical community might respond to the upcoming loss of a popular test of fetal lung maturity that is being discontinued by its manufacturer (disclaimer: I am the author of that post).
Seems like a good reason to talk about FLM tests here! So, how can a lab test evaluate a fetus' lungs?
First the basics:
- The lungs are one of the last organs to mature in a fetus. In order for them to work properly after birth the alveoli (i.e. air sacs) have to open up and stay open once the baby takes its first few breaths. This is not as easy as it seems because the inside lining of the alveoli has a thin coating of water and the surface tension of this water promotes their collapse. A collapsed alveoli doesn't work very well! Fortunately, our lungs secrete chemicals called surfactants that lower the surface tension of the water that coats the alveoli thus preventing the alveoli from collapsing.
- Having enough of these surfactants in the lungs at birth is extremely important because that's when the baby has to make a transition from getting its oxygen from mom to getting it from the air. If there's not enough surfactant then the alveoli may collapse and the baby may have a difficult time breathing. When this does happen it's called respiratory distress syndrome of the newborn, or just RDS.
- Lung surfactants begin to be made around the 25th week of pregnancy but there's usually not enough of it present to prevent RDS until the 37th week. That means babies born prematurely are at greater risk of developing RDS than those born at term.
- Because the fetus essentially "breathes" amniotic fluid in and out of its lungs, the amount of surfactant in the lungs can be determined by measuring surfactants in the amniotic fluid. In the lab, there are a few ways we can do just that using a sample of amniotic fluid.
Several fetal lung maturity tests have been developed since the 1970's but only a few are still in use today:
- This test looks for the presence of a lung surfactant called phosphatidylglycerol (usually just called PG).
- This is an agglutination test that uses antibodies to detect PG in amniotic fluid. If PG is present then visible agglutinates (clumps of particles) can be seen and the fetal lungs are considered mature.
- Lamellar Body Count
- In certain cells of the lungs, surfactants are packaged into granules called lamellar bodies and secreted from the cells into the alveoli. This test actually counts the number of lamellar bodies in amniotic fluid.
- The higher the lamellar body count, the more likely it is that the fetal lungs are mature.
- Lecithin/Sphingomyelin Ratio
- This was the first test of fetal lung maturity ever developed and is more commonly known as the L/S ratio. It's a measure of the ratio of two lung surfactants, lecithin and sphingomyeli, that's determined using a technique known as thin-layer chromatography.
- Lecithin is the most important lung surfactant and provides the greatest surface tension-lowering properties of all the surfactants. It increases dramatically in the last few weeks of pregnancy. Sphingomyelin is a minor lung surfactant and that amount of it in the lungs stays about the same throughout pregnancy so it serves as a good baseline against which the increasing amount of lecithin can be compared. A ratio that is 2.5 or greater is usually used to indicate lung maturity.
- Many doctors consider this to be the "best" fetal lung maturity test but that is not true.
- TDx FLM II
- This test measures the ratio of surfactant to albumin and so is sometimes called the S/A ratio.
- The test relies on a technique known as fluorescence polarization and is the most widely used fetal lung maturity test; unfortunately it will no longer be available to clinical labs at the end of this year because the manufacturer has decided to stop making it.
- The effect that the loss of this test will have on patients, doctors, and labs remains to be seen!
There a whole lot more to say about fetal lung maturity tests but those will have to wait for future posts.
It makes sense to kick off this blog with some information about pregnancy tests. Whether you do a home pregnancy test or have one performed in a healthcare setting they all test for the same hormone: human chorionic gonadotropin; more commonly referred to as hCG.
The tests that can be done at home are only performed on urine samples. hCG tests done in healthcare settings may use urine or blood samples. hCG tests performed on urine simply look for the presence or absence of hCG and give a positive (hCG is present) or negative (hCG is absent) result. Tests done on blood provide a measurement of the amount of hCG present in the blood. This type of test is most often done in clinical laboratories.
Many people ask: "How soon in pregnancy will a pregnancy test give a positive result?" While it's a straightforward question, the answer is surprisingly difficult to determine. That's because it's difficult to know with certainty precisely when fertilization of the egg occurs and when it gets implanted in the uterus. hCG is produced after implantation, after which it takes some time for enough hCG to be produced to become detectable in the blood and urine. Few people would argue that, in most women, a blood test gives a positive result somewhere between 9 and 11 days after fertilization (or about 1 to 3 days before the day of the expected period) and a urine test gives a positive result 1 to 2 days later.
Welcome to The Pregnancy Lab! We created this blog because of our interest in the biochemistry of pregnancy and the different laboratory tests used during pregnancy. It's our hope that this blog will become a resource for anyone interested in gaining a better understanding of laboratory testing during pregnancy.
We probably won't be posting something new every day but we do plan on adding content at least weekly. We'll also be inviting colleagues to post occasionally as well so do expect well-rounded discourse.
Feel free to add your comments and questions. We look forward to learning with you!