Category Archives: Diagnostic Test

Diagnostic Test

Anti-Mullerian Hormone: The Blood-Based Biological Clock?


Many women choose to delay starting a family for various reasons, but how long is too long to wait? Is there some way to determine the time remaining on a woman’s “biological clock” to help guide family planning? A new biomarker measured in blood, anti-Müllerian hormone (AMH), has been proposed to do exactly that but there are some important limitations that must be considered before rushing out to the closest doctor’s office to request an AMH measurement.

First, some background. Women are born with approximately one million primordial ovarian follicles and only about one thousand of these remain when a woman reaches menopause. Over the course of a woman’s reproductive years, these primordial follicles come out of hibernation and develop into immature follicles by accumulating theca cells that produce testosterone and granulosa cells that convert testosterone to estradiol. Each cycle, in response to follicle-stimulating hormone (FSH), one of these immature follicles becomes the dominant, mature follicle that ultimately releases an egg through the process of ovulation. Some immature follicles exit the development pathway and become nonviable while others continue to develop for possible selection as the dominant follicle in a subsequent cycle. The key point is that the granulosa cells of these immature follicles produce AMH, which can be measured in serum or plasma as a direct reflection of the number of immature follicles. If more immature follicles are present, the serum/plasma AMH concentration will be higher. If fewer immature follicles are present, the AMH concentration will be lower. At first glance, measuring AMH would seem to be the ideal way to determine a woman’s reproductive lifespan – if AMH is high, many immature follicles remain and menopause is years away.

Unfortunately, it’s not quite that simple. While elevated AMH concentrations do reflect a large number of immature follicles, this doesn’t necessarily guarantee fertility. Polycystic ovary syndrome (PCOS) is a condition marked by the presence of many immature AMH-secreting follicles and women with PCOS typically have elevated serum/plasma AMH concentrations. AMH has been shown to inhibit the effects of FSH and AMH excess prevents immature follicles from reaching the final stages of development, resulting in impaired fertility for many women with PCOS. While an AMH concentration within the age-appropriate reference interval is a favorable indicator of fertility, higher is not necessarily better as very high AMH concentrations may indicate an underlying anovulatory condition.

At the other extreme, low age-specific serum/plasma AMH concentrations have been associated with impaired fertility in women in their 30s and may predict earlier menopause but low AMH concentrations are substantially harder to interpret in girls and younger women – precisely the population for whom an early estimate of reproductive lifespan would be most valuable. Low AMH concentrations in healthy women in their teens and 20s have not been associated with impaired fertility and survivors of childhood cancers with low AMH concentrations have achieved pregnancy. Furthermore, circulating AMH concentrations are reduced by lifestyle factors like oral contraceptive use and smoking, complicating the connection between AMH concentration and reproductive lifespan.

While studies of large numbers of women show that a low age-specific AMH concentration is associated with earlier menopause, it’s difficult to predict the age at menopause for an individual woman using a serum/plasma AMH concentration. The rate of decline in serum/plasma AMH concentrations varies from woman to woman, meaning that two women with identical AMH concentrations one year may have very different AMH concentrations the following year. Furthermore, the onset of menopause is a complex trait determined by genetic factors, environmental exposures and other influences like smoking, alcohol consumption and previous pregnancies. Ultimately, while AMH does reflect the number of immature follicles, its ability to predict onset of menopause and guide family planning decisions is questionable at the present time.

Currently, the most appropriate clinical use of AMH measurement is to predict response to ovarian stimulation in women undergoing in vitro fertilization (IVF). Women with a high AMH concentration (and a large number of immature follicles) who undergo IVF are at increased risk of ovarian hyperstimulation syndrome (OHSS), a potentially fatal condition marked by abdominal fluid retention, blood clots, altered electrolyte concentrations and kidney failure. Using a moderate ovarian stimulation protocol in women with a high AMH concentration has been shown to reduce the risk of OHSS while increasing the number of pregnancies and live births per IVF cycle started. At the other end of the spectrum, women with a low AMH concentration are enrolled in a more intensive stimulation protocol to maximize egg retrieval while those with undetectable AMH are offered alternate treatment options as the chance of IVF success is low.

It’s possible that one day AMH may be routinely measured to predict the onset of menopause but for now, its most promising uses are limited to PCOS diagnosis (still some kinks to be worked out there too) and customization of ovarian stimulation protocols to improve IVF outcomes while minimizing the occurrence of OHSS.

Direct to Consumer Laboratory Testing Survey


Recruiting Material visit
Direct-to-consumer (DTC) laboratory testing permits consumers to order laboratory tests directly from a clinical laboratory without necessarily having to work with their healthcare provider. Currently nearly 40 states allow consumers to order some or all of their laboratory tests. This model of lab testing is relatively new in the United States and little is known about its impact on consumers.

However, many health care providers are concerned that consumers do not have enough background knowledge and information to make sound decisions based on their test results. Consumers might not understand what tests to order or how to interpret the tests.   It is unclear how often consumers share their results with healthcare providers and what action, if any, is taken based on the results. In addition, frequent test ordering in a normal population increases the chances of false (positive and negative) results. False results may give consumers a false sense of security when tests are normal or result in unnecessary alarm when tests are abnormal.

Recently an article in the medical journal JAMA expressed the opinions of many in the medical field that DTC testing may actually increase the cost of healthcare in the US.

However, many feel that there is value in allowing consumers to order laboratory tests through DTC laboratories and that there is not enough data to conclude that DTC testing adversely affects patient health or healthcare costs. This was expressed in a response to the JAMA article.

In order to gather data on the effects of DTC laboratory testing, a survey is being conducted to identify the reasons American consumers use DTC laboratories. The survey will quantify how frequently consumers of DTC test services order tests, define the most frequently ordered DTC tests, identify resources consumers use to understand DTC test results, and evaluate consumer engagement with health care professionals based on DTC test results.

If you have ever ordered your own lab tests from a direct-to-consumer laboratory, you may be eligible to participate in a research study from Washington University about direct-to-consumer lab testing.

Visit here  or copy this link
https://www.surveymonkey.com/r/DTCtestingSurvey 
to learn more or contact Dr. Ann Gronowski at 314-362-0194.

Personalized medicine during pregnancy


Pregnancy dnaPersonalized medicine can be defined as customized disease prevention therapies and drug treatment protocols based on knowledge of an individual’s unique genetic makeup, metabolic profile and clinical presentation. So far, personalized medicine has focused on the prevention and treatment of conditions affecting adults such as cancer and cardiovascular disease.  However pregnancy is a unique situation where the unique characteristics of two individuals are being assessed: mother and infant. Remarkably few studies have addressed the therapeutic implications of recent advances in genetic technologies for the fetus. Focus has been more on prenatal diagnosis than on fetal treatment. As molecular technologies advance and costs decrease, targeted genetic testing and even whole genome sequencing of the fetus are likely to become more available. This brings with it a number of ethical issues especially as it relates to testing of the infant. For instance, there are questions of informed consent, confidentiality of results, the clinical significance of genetic polymorphisms and decisions to terminate pregnancy on the basis of these test results.

Nonetheless, there have been some interesting advances in personalized medicine, for both mother and fetus, during pregnancy. This is the focus of an upcoming symposium at the AACC meeting to be held tomorrow, July 29th, at 10:30 am in Atlanta, Georgia.  

Predicting Response to Drugs:  Sixty-four percent of women in the US are prescribed more than one drug during pregnancy (excluding vitamins). A better understanding of how drugs are metabolized during pregnancy and how they affect the fetus is clearly needed. Cytochrome P450 is the predominant class of oxidative enzymes that catalyze many types of drugs. Interestingly, the expression of a number of P450 genes is altered during pregnancy. Most notably, CYP1A2 has been shown to be decreased by 65% by the 3rd trimester. In the past several years, several studies have examined the ability to predict a woman’s response to drugs used during pregnancy, like tocolytics and anti-emetics, based on their genotype. A study by Haas, et. al. demonstrated that CYP3A5 high-expressing women had lower circulating concentrations of Nifedipine, a common tocolytic. A study by Lehmann, et. al. demonstrated that a genotype for serotonin receptor subunits 5-HT3A and 5-HT3B may play a role in hyperemesis severity and response to anti-emetics. This type of genotyping is not yet ready for prime time, but it holds promise for better utilization of medications during pregnancy.

Assessing the Fetus: We have blogged previously about cell free fetal DNA (cffDNA) in maternal blood and its utility in predicting fetal trisomy. cffDNA can also be used to assess fetal Rhesus D (RhD) status. This method can be used to determine the fetal RhD genotype when the mother has clinically significant alloantibody to the D antigen AND the father is heterozygous for RhD or is not available for testing. Testing such as this is useful because instead of treating all RhD-negative women with RhD immunoglobulin, treatment can be targeted to mothers that carry RhD-positive fetuses. This type of approach can conserve supplies of therapeutic anti-D, prevent unnecessary administration of a human-derived blood product to a vulnerable patient group, and avoid subjecting RhD-positive infants to intensive antenatal monitoring to predict and treat fetal anemia. Interestingly, despite the fact that the American College of Obstetricians and Gynecologists support the use of cffDNA for RhD assessment, it is not a widely used clinical tool in the United States.

Predicting Viability: Not all personalized medicine is genetic. Personalized medicine can also be used to guide treatments. With this in mind, there are several publications that suggest novel uses for hCG testing. The first takes advantage of “semi-quantitative” urine hCG devices. These devices are similar to home pregnancy devices, but they essentially contain multiple detection strips with different cutoffs that can give the reader a rough estimate of the urine hCG concentration (>25, >100, >500, >2000 or >10,000). Several studies have examined the use of these devices in a home setting following medical abortion as a replacement for clinic follow-up. If the woman is able to demonstrate decreasing hCG concentrations at home, she can avoid a return visit to the clinic. This can reduce the burden on the healthcare setting, but it could also help women for whom getting to a clinic is difficult because of work or family commitments or who live in a remote geography. Both studies demonstrate that use of semi-quantitative hCG devices in this setting had 100% sensitivity to detect unsuccessful abortions. The second interesting use for hCG measurement is in the prediction of fetal viability. Several studies have suggested that urine and serum concentrations of hyperglycosylated hCG (hCG-H) are low in women with pregnancy failure. These studies suggest that measurements of serum or urine hCG-H to detect failed pregnancy is 60-70% sensitive and 97-100% specific (links here and here). These studies are small and there is not currently a readily accessible assay for hCG-H, but it is intriguing to think about the possibility of a test that could distinguish viable from non-viable pregnancies especially in an emergency setting when physicians are making treatment decisions and have to take into account potential risks to the fetus.

Can a personalized approach improve IVF success rates?


Test Tube Baby

This post was written by Robert D. Nerenz, PhD, an assistant professor of pathology and laboratory medicine at the University of Kentucky, in Lexington.

In the United States, an estimated one in seven couples experience infertility and for many of these couples, in vitro fertilization (IVF) represents their best chance of achieving pregnancy. However, IVF cycles constitute a significant expense (approximately $12,500 per cycle), disrupt patients’ daily lives and only result in a healthy, live birth 30% of the time! Furthermore, the majority of IVF cycles performed in the United States involve the transfer of multiple embryos. This is of particular concern because multiple embryo transfer carries a finite risk of a multiple gestation pregnancy. Bringing multiple infants to term is associated with an increased risk of poor fetal and maternal outcomes including decreased birth weight, increased rate of fetal death, preeclampsia, gestational diabetes and preterm labor. Clearly, there is a significant need to improve IVF success rates while also minimizing the likelihood of multiple gestation pregnancies.

One strategy that may accomplish both of these goals is to perform “single embryo transfer” by implanting one embryo that has a high likelihood of producing pregnancy and, ultimately, a live birth. This is the focus of an upcoming symposium at the AACC meeting to be held July 29th at 10:30 am in Atlanta, Georgia. Fertility clinics around the world currently attempt to do this by observing embryos under a microscope and choosing the best embryo on the basis of its physical appearance. Unfortunately, this approach does not provide any information about the embryo’s genetic status. This is an important limitation because aneuploidy (the gain or loss of a chromosome) is the most common cause of pregnancy loss. It is also estimated to occur in ≥10% of clinical pregnancies and becomes more frequent with increasing maternal age.

To ensure that aneuploid embryos are not selected for transfer, several research groups have developed methods collectively known as comprehensive chromosome screening (CCS). CCS involves culturing embryos for 5-6 days, removing a few cells from the trophectoderm (the outer cell layer that develops into the placenta), isolating the DNA from those cells and assessing the copy number of each chromosome using techniques such as quantitative PCR, comparative genomic hybridization, or single nucleotide polymorphism arrays. Following determination of the embryos’ genetic status, only embryos with the normal number of chromosomes are chosen for transfer. In multiple prospective, randomized controlled trials described here and here, CCS has been shown to increase the pregnancy rate and decrease the frequency of multiple gestation pregnancies. As a result, CCS is beginning to make the transition from the research setting to use with patients.

The ability to transfer only euploid embryos represents the most promising application of novel technologies to IVF but ongoing research is focused on other ways to improve the IVF success rate. Many different groups are analyzing the culture medium that embryos are grown in prior to implantation. It is hoped that this will provide information about the embryos’ metabolic health and might help identify which embryos are most likely to result in pregnancy and live birth. Other groups are evaluating endometrial gene expression profiles to assess endometrial receptivity and ultimately determine the best time to perform embryo transfer. While both of these approaches have technical limitations and are not quite ready for primetime, they have the potential to greatly improve our current standard of care and may be ready for clinical use in the near future.

Preimplantation Genetic Diagnosis and Screening


BlastocystPreimplantation genetic testing is a way of examining the genetic features of a developing embryo during the process of in vitro fertilization, before pregnancy. After the egg is fertilized with sperm, the embryos develop to the cleavage-stage. On day 3 after fertilization, a single blastomere is removed from the embryo for genetic evaluation using techniques such as PCR, FISH, or comparative genomic hybridization.

Preimplantation genetic diagnosis (PGD) is used to select embryos without certain genetic disorders. This testing including three major groups of disease: sex-linked disorders, single gene defects, and chromosomal disorders.

Preimplantation genetic screening (PGS), is not used to detect disease, but as a screen to select embryos for such things as: matching HLA type in order to be a tissue donor for an affected sibling, selecting gender, selecting embryos with the least predisposition for developing certain cancers, and selecting embryos with a higher chance of implantation and therefore increase the likelihood of achieving pregnancy. Medscape has an excellent overview of PGD and PGS.

For women of advanced maternal age or couples with known genetic mutations, the ability to screen for embryos free of certain genetic mutations is reassuring. However, as with many medical interventions associated with human reproduction, PGS has raised ethical questions. For instance, as stated earlier, PGS can be used to select for a preferred gender. In some cases this is to avoid a sex-specific disease. Other times this is done for so-called "family planning" or "gender balance." In other words, selecting a gender because of personal preference. Some feel this is discriminatory and should not be allowed. In other cases, embryos have been tested so that the resulting child would be compatible to serve as a stem cell donor for a sick sibling (much like the popular fiction book "My Sister's Keeper").   There have also been cases where parents have requested the selection of affected embryos so that the child has the same minor disability, such as deafness or dwarfism, as the parents. Some preimplantation genetics laboratories agree to do this type of testing and some do not.

The New York Times recently ran an article discussing this issue. The article states that:

"In the United States, there are no regulations that limit the method’s use. The Society for Assisted Reproductive Technology, whose members provide preimplantation diagnosis, says it is 'ethically justified' to prevent serious adult diseases for which 'no safe, effective interventions are available.' The method is 'ethically allowed' for conditions 'of lesser severity' or for which the gene increases risk but does not guarantee a disease."

The January issue of Clinical Chemistry published a Question and Answer piece entitled "The Ethical Implications of Preimplantation Genetic Diagnosis." A podcast interview with two of the authors is also available.

The paper summarized the opinions of an ethicist, an attorney, and the director of a preimplantation genetics laboratory. The ethicist indicated that in the past, PGD has focused mainly on reducing the risk of transmitting serious diseases. In the future, he sees a shift away from lifesaving interventions to more ‘eugenically’ inspired interventions. That is, looking for traits that parents do not want in their children and selecting for traits that they do want in an attempt to pass them on. The morality of eugenics is a key moral as this technology moves forward.

Indeed it will be interesting to see where the future of this technology lies. Although it is practiced routinely, the indications, utility, and outcomes of PGD and PGS are still being defined.

Screening or diagnostic test. What is the difference?


Today was an interesting day at work.  A genetic counselor I work with emailed me that a pregnant patient wanted to have "every single Down syndrome screening test that was available."  While this was problematic in and of itself (more about that later), this patient also planned to have an amniocentsis regardless of the results of the screening test.

Do you see a problem with this line of thinking?  If not, read on.

Let's start with what a screening test is.  I've written about this before here, but to recap: a screening test is NOT the same as a diagnostic test.  A test that screens for Down syndrome doesn’t identify if a woman is pregnant with a baby that has Down syndrome; it identifies women who are pregnant with babies that are at increased risk of having Down syndrome.  In other words, the screening test puts tested women into one of two camps: those without increased risk and those with incrased risk.  Women who screen positive and who are at increased risk are offered a diagnostic test that can confirm if their baby does or does not have Down syndrome.  A screening test cannot do that.

The diagnostic test for Down syndrome is determining the karyotype of the fetus in order to identify how many copies of chromosome 21 have been inherited (unaffected fetuses have 2 copies; affected fetuses have 3 copies).

The results of a Down syndrome screening test are used to identify women who should be offered diagnostic testing (karyotype).  Women who have a positive screening test result are offered amniocentesis in order to obtain  the amniotic fluid required for karyotyping the fetus.  However, because amniocentesis is an invasive procedure, there is a small risk of miscarriage (usually less than 0.5 percent).

The problematic request of the patient to have more than one Down syndrome screening test should now be apparent for two reasons:

  1. Her desire to have every available screening test is illogical if she has already made up her mind to have an amniocentesis and diagnostic testing.  The fetal karyotype is THE definitive (i.e. diagnostic) test and so screening for a disorder makes no medical or economic sense because, regadless of the results, the diagnostic test will still be performed.
  2. Requesting all available screening tests is a complete waste of health care resources.  Granted, the number of Down syndrome screening tests available is a source of much confusion for both physicians and patients.  That said, patients (with help from their doctors) should choose the screening test that is best for them.  Choosing multiple screening tests is not a wise idea.  Consider what might be done if the results of these tests don't agree with each other.

Consumers of health care often (mistakenly) believe that more testing is better.  Few take the time to consider that tests may have downstream consequences that they might not be prepared for.  In this case, the patient had already decided to have the "best" test.  That is her choice and one that I support.  What I don't support is the wasted time, money, and effort required to perform tests that are, in this specific situation, meaningless.

The gestational diabetes mellitus debate continues


Discussion_icon_noshadowI have just returned from the annual meeting of the AACC where I attended a very interesting debate on the diagnosis of gestational diabetes mellitus (GDM). I've written about the current controversy in diagnosing GDM before and you can read about those here and here. Basically, the controversy boils down to one issue: should recently recommended criteria for identifying pregnant women with GDM be globally implemented or not? 

Arguing for that position was Dr. Donald Coustan from Brown University and regional principal investigator for North America of the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. He correctly pointed out that lack of a universal testing strategy when screening for GDM makes it impossible to compare clinical studies on GDM. He reviewed how the new IADPSG glucose cutoffs came into being (they were based on risk of adverse infant outcomes) that he advocates referring to as the ADA criteria because the ADA is recommending the use of the new testing method.

Arguing against the use of the ADA criteria was Dr. Sean Blackwell from the University of Texas Health Science Center at Houston, TX. He agreed with several of Dr. Coustan points. Among them that:

  1. The HAPO study was well conducted.
  2. There was a positive association between glucose concentration and adverse infant and maternal outcomes at lower glucose cutoffs than are currently used to diagnose GDM.
  3. There is benefit in having a single, universal screening test for GDM.
  4. There is evidence that, as currently defined, treatment of GDM improves outcomes.

He had two major problems with use of the new ADA criteria. The first was that its use would double the number of women diagnosed with GDM (from about 7% to 16%). The second was that the HAPO study was an observational study, not a treatment trial and, as such, there is no evidence that treating these additional women for GDM is effective or safe.

Dr. Coustan argued that the increase in the number of GDM diagnoses is not surprising given that, in the US, 31% of adult US women have either diabetes or pre-diabetes. He also argued that the Australian Carbohydrate Intolerance Study of Pregnant Women (ACHOIS) study demonstrated that treatment of women with mild GDM reduced adverse outcomes such as large for gestational age newborns, macrosomia, and preeclampsia.

Dr. Blackwell pointed out that most of the additional 10% of women that would be diagnosed with GDM under the ADA criteria would, by definition, have "milder" GDM and would only require nutritional modification and glucose monitoring rather than drugs to control their GDM. These women would have glucose control similar to those of obese women without diabetes. Further, he added that several studies in obese women without diabetes have failed to demonstrate that nutritional interventions have any impact on any infant health outcome.

The moderator of this debate was my co-blogger, Ann Gronowski. Prior to its start, she polled the audience of (mostly) laboratorians to see which testing strategy they currently offered at their institutions. Most indicated they offered the current ACOG criteria (advocated by Dr. Blackwell). At the end of the debate, the audience was asked if they would support switching to the new, ADA criteria. The majority response was "yes." Dr. Coustan argued his points effectively.

It's my belief that the evidence, while not complete, is strong enough to support widespread adoption of the ADA criteria when screening for and diagnosing GDM.

A new way to detect gestational diabetes mellitus? Not so fast.


In May I wrote about recommendations made by the International Association of Diabetes in Pregnancy Study Groups (IADPSG) for glucose tolerance testing in pregnancy.  Those recommendations advocate for the use of a 75-gram oral glucose tolerance test to detect gestational diabetes mellitus (GDM) in pregnant women between 24 and 28 weeks gestation and were based on findings of the Hyperglycemia and Adverse Outcomes (HAPO) study.  That study clearly demonstrated that the risks of adverse maternal and fetal outcomes continually increased as maternal glucose concentrations increased.  The American Diabetes Association adopted the IAPDSG criteria and recommends that approach to identifying women with GDM.

In the September 2011 issue of Obstetrics and Gynecology, the American Congress of Obstetricians and Gynecologists (ACOG) opt to stick to their guns.  The ACOG continues to recommend the "two-step" approach to screen and diagnose GDM.  Step one is a screening test using either patient history, clinical risk factors, or with a 50 gram glucose administered orally followed by the measurement of blood glucose 1 hour later (a result greater than 140 mg/dL is considered abnormal).  Those with an abnormal screening test go on to have the diagnostic test: a 100 gram oral glucose tolerance test with blood glucose measured over 3 hours.

The ACOG rightfully acknowledges that while the treatment of mild GDM decreases adverse infant outcomes there is no evidence to indicate that use of the IADPSG recommendations would result in any significant improvements in outcomes.  Of course, lack of evidence doesn't mean that there is no benefit, it simply means that any benefits have not yet been demonstrated.  The fact that widespread adoption of the IADPSG screening test would double the number of women diagnosed with GDM was also noted by the ACOG.  This increase is notable because it would lead to a considerable increase in health care costs and likely overwhelm health care delivery systems.

In contrast to the ACOG, the National Academy of Clinical Biochemistry (NACB) have published guidelines that recommend the approach advocated by the IADPSG.  Confused yet?  Disagreement among professional groups is not unusual and consensus is not easy to come by.  As usual, a lot more research is required before widespread agreement is achieved.

A new way to detect gestational diabetes mellitus


Diabetes definition At first glance, screening pregnant women for gestational diabetes mellitus (GDM) seems like it should be straightforward.  After all, the tests are designed to identify pregnant woman with high concentrations of glucose (sugar) in their blood and laboratory tests that measure glucose are accurate and precise.  So what’s the problem?

For one, experts don’t agree on how best to screen pregnant women for GDM.  While nearly everyone agrees that both mom and baby can have adverse outcomes if GDM goes undetected and untreated, there is lack of consensus on the best way of identifying GDM.

Consider how it has been done for several years here in the United States using either a 1 or 2 step process.  In the 2-step approach, a screening test is done first followed by a diagnostic test if the screening test is abnormal.  To do the screening test, blood glucose is measured 1 hour after the non-fasting patient drinks a 50-gram dose of glucose.  A glucose result that is greater than 140 mg/dL is usually used as the cutoff although a lower cutoff of 130 mg/dL is also used (again, no consensus).  A woman that has an abnormal screening test (i.e. glucose concentration greater than the cutoff) will go on to have the diagnostic test.  In the 1-step approach the screening test is skipped completely and only the diagnostic test is performed.

The test used to diagnose GDM is the oral glucose tolerance test (OGTT).  The OGTT requires women to be fasting and then drink either a 75- or a 100-gram dose of glucose.  Blood samples are collected every hour for 2 or 3 hours if using the 75- or 100-gram dose, respectively.  The test is considered positive, and GDM confirmed, if 2 or more of the glucose results are above designated cutoffs (which differ depending upon the glucose dose given).

Now, new criteria have recently been advocated.

The International Association of Diabetes in Pregnancy Study Groups (IADPSG) has made recommendations for glucose tolerance testing in pregnancy based on the results of the Hyperglycemia and Adverse Outcomes (HAPO) study.  That study clearly demonstrated that the risks of adverse maternal and fetal outcomes continually increase as maternal glucose concentrations increased.  Importantly, the relationship between glucose concentration and risks were continuous.  That is, there were no obvious glucose cutoffs above which risks increased.  The new recommendations from the IADPSG address this issue.

The IADPSG advocates for the use of the 75-gram OGTT in pregnant women between 24 and 28 weeks gestation.  The test is performed following an overnight fast of at least 8 hours and blood is collected at 1 and 2 hours after the glucose load.  A diagnosis of GDM is made when any of the following glucose results are met:

  • Fasting: greater or equal to 92 mg/dL
  • 1 hour: greater or equal to 180 mg/dL
  • 2 hour: greater or equal to 153 mg/dL

A couple of questions are called for here: 

  1. Why were those cutoff selected?  These are the glucose concentrations above which the adverse risks of hyperglycemia were 1.75-fold higher than for women whose glucose results were lower.  Other thresholds were considered but higher cutoffs missed lots of women with adverse pregnancy outcomes and lower cutoffs identified 25% of women as having GDM.
  2. What is the impact will this test have on the prevalence of GDM?   It will definitely increase.  Currently, about 7% of pregnant women are diagnosed with GDM in the US each year.  Using the IADPSG approach that will more than double to about 18% of pregnant women.

Although the American Diabetes Association adopted the IAPDSG criteria and recommends that approach to identifying women with GDM, it does recognize that there is the potential for harm.  For example, more interventions such as earlier delivery and increased C-section rates are likely to occur due to the increase in the prevalence of GDM.  Also, an increased number of women being diagnosed with GDM will be accompanied by a rise in health care costs.  Despite those considerations, the ADA supports the new criteria in light of the increased rates of obesity and diabetes throughout the US and the world.