At a time when the NHS seeks to make £20 billion of efficiency savings through the Quality, Innovation, Productivity and Prevention (QIPP) programme it has never been more important to move care into the community. It is essential to budgets that any inappropriate care or unnecessary appointments are avoided and BIVDA does a lot of work promoting point of care testing as a viable way of achieving this.
Traditionally diagnostic tests on blood and other physical samples are performed remotely by a laboratory – typically in the UK this means sending samples to the pathology department at the local hospital. However, improvements in both simplification of tests and their procedure, coupled with innovations in technology which allow laboratory style equipment to be made compact and portable, mean that many tests which were done in a laboratory can now be done in a GP’s office or community setting.
The use of point of care tests in the home has become widespread nowadays as patients with diabetes measure their blood glucose, those with asthma can record breath sounds for analysis and patients taking warfarin can monitor their blood coagulation. However despite all these developments the original home testing kit is probably still the most widely used – that’s the home pregnancy kit. So today I’m taking a look at how the pregnancy test has developed over the centuries because it didn’t just open the door for women to take a more active role in their pregnancy options but also opened the door for testing to take place outside of the laboratory and in the home.
When this test first made it into US homes in 1978 women had to mix their urine with antibodies in test tubes. American women’s mag Mademoiselle told its readers ‘For your $10, you get pre-measured ingredients consisting of a vial of purified water, a test tube containing, among other things, sheep red blood cells…as well as a medicine dropper and clear plastic support for the test tube, with an angled mirror at the bottom.’ (Mademoiselle, April 1978, p. 86)
The anticipation, or agony, of the two minute wait which women face now while waiting for their results – which has long represented our view of the test and has even been depicted in recent Hollywood blockbusters Juno and Knocked Up – was a staggering two hours back in 1978. Also, the chances of accuracy were considerably lower: 97% for positive results but only 80% for negative results. The introduction of home pregnancy tests allowed women to become more active participants in their healthcare and enabled that to happen in a private environment. They also led to the much earlier detection of pregnancy which still today allows for quicker decisions regarding pregnancy options and all the health benefits associated with that. Like with any other change in health status, the sooner a diagnosis is made the better the outcome is likely to be for the patient – or both of them in this case.
Nowadays, however, the pregnancy test is accurate, simple and quick. Most people know how they work – you urinate on a stick and wait for the little box to tell you the results via a blue line or a red dot. What is happening is that the Human Chorionic Gonadotropin (hCG) in the urine is being bound to an antibody and an indicator (the pigment in your blue line). hCG is a hormone created by the development of the placenta, which starts to develop as soon as the egg is fertilised. One of the most important developments since the days of test tubes and two hour waits is that hCG can now be quantified. This means that ectopic and failed pregnancies can be more effectively detected and monitored – although this would be done by a clinician, not in the home. While hCG levels double every couple of days in a normal healthy pregnancy, hCG levels develop more slowly in ectopic or failing ones.
The tests today have extremely high accuracy rates of 97% for both positive and negative results. Although the home test is now entrenched as part of the modern pregnancy experience, they weren’t wholly received positively – some critics questioned the moral standing of a woman who needed to perform this particular test at home! However, since 1978 they have been offering a fast, private and accurate first opinion. This is how BIVDA envisages many other point of care tests in the future; trusted tools which, where appropriate, can provide people with the right information to make a decision about their healthcare. Not just for diagnosis – as we know, sometimes a diagnosis is best received where much needed counselling services are provided – but for the monitoring of long-term conditions, as has been pioneered by patients with diabetes for some time now. The benefits are not just for patients but for the NHS as well. As more care is administered in the community some pressure can be alleviated from primary and secondary care resources.
But it was a long time in the making. Below is a timeline mapping out the advances which led to the world’s most common home test; from the growth of barley seeds to the death of the rabbit.
1350 BCE – Ancient Egypt
A woman who might be pregnant would urinate on wheat and barley seeds over the course of several days. If the barley grew it was thought to mean a male child. If the wheat grew it meant a female child. If both do not grow, she was thought not to be pregnant. This theory was tested in 1963 and found that 70% of the time, the urine of pregnant women did promote growth!
From the Middle Ages until the 17C – Europe
In Europe, the colour of urine was inspected; In a 1552 text, pregnancy urine was described as: “clear pale lemon colour leaning toward off-white, having a cloud on its surface.”
Ernest Starling named chemical messengers in the body “hormones.”
American public health advocates started to encourage women to see their doctors as soon as possible after pregnancy was suspected but most still didn’t see one until well into pregnancy.
Ludwig Fraenkel named the hormone that promoted gestation, progesterone. Progesterone was isolated (an important step in the study of hormones) in 1934.
Scientists recognized that there is a specific hormone (now known as human chorionic gonadotropin (hCG)) that is only found in pregnant women. This is the hormone modern pregnancy tests use for detection today.
Aschheim and Zondek described the first test for hCG in urine (known as the A-Z test).
A woman’s urine was injected into an immature rat or mouse. In the case of pregnancy, the rat would be ‘in heat’ despite its immaturity. This test implied that during pregnancy there was an increased production of the hormone.
Hormone research blossomed in this period. Scientists in several different laboratories developed bioassays (special tests using animals or live tissue) to identify hCG by injecting samples to induce ovulation in rabbits, frogs, toads, and rats. These tests were expensive, required the sacrifice of several animals, and slow, often taking days to get results.
Popular childbirth books began to encourage women to visit a doctor’s office for confirmation of pregnancy rather than relying on “old wives’ tales” for the diagnosis.
A “hemagglutination inhibition test” for pregnancy was developed by L. Wide and C.A. Gemzell. Because it used cells in the testing process, this test was an immunoassay rather than a bioassay. The test used purified hCG, mixed with a urine sample and antibodies directed against hCG. In a positive pregnancy test, the red cells clumped, displaying a particular pattern. This test was much faster and cheaper than the old bioassay, but still relatively insensitive, especially for early diagnosis of pregnancy. The test also cross-reacted with various medications.
Important disease research in this period led to more knowledge about how hormones, steroids, and antibodies work in the human body. In the next decade, NICHD scientists would transfer these principles to their studies of reproductive hormones such as hCG.
A. R. Midgley described the first radioimmunoassay for hCG, but the test still could not differentiate between hCG and luteinizing hormone. Several other laboratories reported improvements on this test, but did not solve this basic problem.
Two things came together in this period along with the so-called sexual revolution: increased research on reproductive health and a heightened desire (brought on by both improved prenatal care and legal abortion) to detect pregnancy as early as possible. Beginning in the 1970s, prenatal care and prenatal testing became more routine in most Western healthcare systems.
Tests available to doctors and technicians included Wampole’s two-hour pregnancy test. The test could be done as early as four days after a missed period. In the packaging materials, the man pictured performing the test wore a laboratory coat, indicating that it was not intended for home use. Besides the equipment in the kit, (two test tubes, a plastic rack, a bottle of “control solution,” a bottle of “hCG-antiserum” and a bottle of “cell suspension”), testers would need a small funnel and filter paper or centrifuge, clean pipettes or syringes, and saline solution in addition to a urine sample.
Scientists at NIH learned more about the properties of hCG.
Vaitukaitis, Braunstein, and Ross published a paper describing the hCG beta-subunit radioimmunoassay that could finally distinguish between hCG and LH, therefore making it potentially useful as an early test for pregnancy.
Though the test was not yet widely available, NIH scientists spread the word about the new radioimmunoassay. At first, the test was found most useful for clinicians in testing and following patients being treated for hCG-secreting tumors. The sensitive radioimmunoassay could tell the doctors if the chemotherapy treatments had worked.
Several articles in the American Journal of Public Health stated that public health would be better served if the average consumer could purchase a home pregnancy test and use it reliably in her own home.
By the end of 1977, home pregnancy tests were ready for the American market.
Home pregnancy tests were available and fully advertised in major women’s magazines.
Taking the test at home, noted a 1979 article in Family Planning Perspectives, both protected the privacy of a woman who might not want her doctor to know she is sexually active and gave women a new opportunity to take an active role in their own health care.
Advances in the technology of pregnancy tests included the development of new types of antibodies and the use of enzyme labels in place of radioactive labels.
The next generation of home pregnancy tests was ushered in with FDA approval of Clearblue Easy’s digital pregnancy test. In place of a thin blue line, the indicator screen will now display either “pregnant” or “not pregnant.”
If you would like to know more about #TestingTuesday, or if you are an interested patient group, please contact Gemma Scotcher on email@example.com or follow us @bivda
More information can be found about point of care testing from the BIVDA Point of Care Directory and from NHS Health Checks
An unabridged version of the pregnancy test timeline can be found from The Thin Blue Line
You can also read more about the hCG test at Lab Tests Online