Category Archives: DNA


Cell-free DNA screening tests in the general obstetrical population

DNAIt has been several years since cell-free DNA (cfDNA) tests for the detection of fetal aneuploidies became available. The first clinical studies of these tests were reported in women who, because of age or other reasons, were already at increased risk of having an affected pregnancy (i.e. “high risk” women). While these studies demonstrated the superior performance of cfDNA tests compared to traditional biochemical tests, their application to women at low risk was not encouraged because of lack of evidence regarding how well they would work in that population. A recent report on cfDNA screening tests in the general obstetrical population now provides much needed evidence.

Investigators at Brown University described several clinical utility aspects of cfDNA screening for common aneuploidies through the implementation of a statewide program called DNAFirst that offered cfDNA screening tests to the general pregnancy population in the state of Rhode Island. The clinical utility aspects that were investigated were a comparison of screening uptake rates before and after the DNAFirst program, an evaluation of a reflexive serum testing protocol for cfDNA tests that failed to produce a result, and explored women’s decision-making.

Over 11 months, 2,681 women agreed to undergo screening through 72 providers. Prior to undergoing testing, the women received information about cfDNA testing by primary obstetrical care providers. The median maternal age was 31 years and 79% of the women were younger than 35 years of age. There were 16 positive (i.e. abnormal for trisomy 21, 18, or 13) cfDNA results, 12 of which were confirmed as true positive and 4 of which were false-positive. 2,515 women had a negative screening result and all were true-negatives. 150 tests failed to produce a result (none of which were known to have trisomy). Collectively, these data produced a sensitivity of 100%, a positive predictive value of 75% and a false-positive rate of 0.15%. By comparison, the most effective biochemical screening test (the Integrated test) has a 90% detection rate, a 3% false-positive rate, and a positive predictive value of only 6%.

A small number of women who participated in the study (113) completed a survey asking them about their understanding of cfDNA testing. Women reported receiving information from their care provider in 9 minutes or less. While 85% understood that the test identified Down syndrome, 15% incorrectly thought it identified all genetic problems. 79% understood that a negative result did not rule out Down syndrome but 13% thought it did. These survey results suggest that most women do understand the basic concepts of cfDNA screening.

The study’s authors concluded that cfDNA screening tests perform very well in the general pregnancy population and that women understand the basic concepts of screening. Further, the tests were easily incorporated into routine practices. They encouraged clinical laboratories to offer cfDNA screening tests to improve access to better aneuploidy screening for the more than 2 million pregnant women in the United States who choose to undergo such testing each year.

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.

Conventional aneuploidy screening remains “most appropriate” choice for general population

OpinionThe American Congress of Obstetricians and Gynecologists (ACOG) have updated their guidance on cell-free DNA (cfDNA) screening tests for fetal aneuploidy. In it, they state that any patient (i.e. women at high-risk OR low-risk for having an affected pregnancy) may choose cfDNA testing but they caution that conventional screening tests are more appropriate. This document replaces an earlier opinion, published in 2012, which clearly stated that cfDNA screening tests should not be offered to the general obstetrical population because they are considered to be at low-risk.

So ACOG went from recommending that cfDNA testing not be performed on low-risk women to say that they may choose cfDNA testing. Why the subtle change? Well, as ACOG correctly notes, the landscape of cfDNA is changing rapidly. New studies are published frequently and those that have examined the performance of cfDNA tests in  low-risk women have reported that the test performs just as well in them as it does in high-risk women.

However, they make an important point about a metric that doesn't get the attention it deserves. The positive predictive value (PPV). See here for background. Because the prevalence of fetal aneuploidy in low-risk women is lower than it is in high-risk women, a "positive" or "abnormal" test result in low-risk women is more likely to be a false-positive result. For example, a positive result in a 25-year-old woman gives a 33% chance that the fetus is affected but that chance increases to 87% in a high-risk woman.

The report also calls out the "no result" problem. cfDNA tests fail to produce a result in 1-8% of samples tested, usually due to a low amount of fetal DNA in the blood sample. It's becoming clear that women with samples that fail to produce a result are at increased risk of having an affected fetus. According to ACOG, these women she be offered diagnostic testing such as fetal karyotyping using amniotic fluid obtained by amniocentesis.

Other notable points contained within the updated guidance include:

  • Caution about not routinely performing microdeletion screening (offered by some labs) because it has not been fully validated in clinical studies.
  • Clearly indicating that a negative or normal result does not rule out the possibility of an affected fetus.
  • Providing genetic counseling to patients about test limitations and that decisions such as pregnancy termination should not be based on these screening tests.
  • A reminder that cfDNA tests do not screen for neural tube or ventral wall defects

This certainly won't be the final say that ACOG has on cfDNA aneuploidy screening tests. Indeed, they state that "It will be critical to remain abreast of this rapidly changing technology to provide patients with the most effective, accurate, and cost-conscious methods for aneuploidy screening."

Momentum grows for use of cell-free DNA Down syndrome screening tests in all pregnant women

Low risk

The use of cell-free DNA (cfDNA) testing to screen for fetal aneuploidies has been the topic of several posts on this blog. Large clinical studies that have evaluated the performance of cfDNA tests have all arrived at the same conclusion: cfDNA testing is superior to traditional biochemical screening tests for the detection of trisomy 21 (Down syndrome) and other trisomies. However, most of these studies have tested women who are considered to be at high risk (e.g. over 35 years of age or who have had an abnormal biochemical screening test) of having an affected fetus. Fewer studies have evaluated test performance in women considered to be at low risk. Because of limited data in low-risk women, the majority of professional societies recommend restricting the use of cfDNA screening tests to only high-risk women. 

This is certainly going to change, and sooner rather than later.

The New England Journal of Medicine recently published a very large, well-designed study that compared the performance of a cfDNA screening test to a biochemical screening test (the first trimester combined test) in an unselected population of almost 15,841 women.

The results were rather unsurprising. There were 38 pregnancies affected by Down syndrome. All 38 (100%) were identified by cfDNA testing but only 30 (79%) were identified by biochemical testing. While that was a significant difference in the detection rate there was a greater significant difference in the false-positive rates. There were 854 false-positive results from biochemical screening and only 9 from cfDNA screening. These numbers translate into a false-positive rate of 5.4% and 0.06% for biochemical and cfDNA screening, respectively.

As the proportion of true positive results divided by the number of all positive results, the positive predictive value answers the question: "What is the probability of an affected fetus given a positive result?” In this study, these predictive values were 3.4% for biochemical screening and 80.9% for cfDNA screening. Clearly, cfDNA offers a huge improvement.

I must stress (as I’ve done several times before) that cfDNA tests are screening tests. The better performance of cfDNA tests has, unfortunately, created the perception that cfDNA tests produce conclusive results and, as such, are diagnostic tests. This could not be further from the truth. Just as with a positive biochemical screening test, a positive result from cfDNA testing should be followed by invasive diagnostic testing. Consider, for example, that the positive predictive value of the cfDNA test that was reported in this study for the 14,947 low-risk women was 50%. That’s a coin toss! Without a doubt it is vastly better than biochemical screening but no woman should make a decision to terminate her pregnancy based on cfDNA testing alone.

So is cfDNA testing an appropriate Down syndrome screening strategy for low-risk women? Yes, it is. It’s just a matter of time before professional societies recognize that fact. Indeed, the International Society for Prenatal Diagnosis did just that in their new position statement

Stay tuned…

The ugly stepsister: false positive NIPT test results

Positive Negative

© Stuart Miles –

NIPT (non-invasive prenatal testing) continues to get lots of attention lately. Indeed, we've written about it extensively on this blog. None of this is suprising because NIPT is a new technology that is continually evolving. Two years ago, I wrote about NIPT here and provided information showing it's excellent diagnostic sensitivity and specificity. To be clear: these tests are more accurate than traditional biochemical screening for detecting fetal aneuploides but they are still screening tests, meaning that positive (or abnormal) test results must be confirmed with diagnostic testing.

As is commonplace, with time comes experience and the lens of scruitiny has recently been focused on the positive predicitive value (PPV) of NIPT. What's a PPV? It's the proportion of true positive results divided by the number of all positive results. For NIPT testing, it answers the question: "What is the probability that a positive result means that the fetus is affected?" It is very important to stress that the PPV of any test is not intrinsic to the test. The PPV is also dependent on the prevalence of the condition in the tested population. If the condition is very rare in the tested population, then the PPV will likely be low, meaning that a positive result is more likely to be a false positive. The opposite is also true (positive test results are more likely to be "true" when the condition is highly prevalent).

NIPT is done to screen for fetal aneuploidies (extra copies of specific chromosomes) such as Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and Patau syndrome (trisomy 13). The prevelance of each of these disorders is influenced by the woman's age. As examples, the prevalence of each in a 35-year-old woman with a fetus at 10 weeks’ gestational age is 1:185, 1:470, and 1:1,500, respectively. As you might expect, the less prevalent a condition is, the more likley a positive result will be falsely positive.

This has been demonstrated for NIPT. A study published earlier this year evaluated the concordance of NIPT and cytogenetic results among cases with positive or negative NIPT results. The study examined test results from 109 consecutive specimens that were either prenatally and/or postnatally studied by fluorescence in situ hybridization, karyotyping, and/or oligo–single-nucleotide polymorphism microarray (as the definitive, or diagnostic, test). NIPT testing was performed with the Panorama (Natera, San Carlos, CA), Harmony (Ariosa Diagnostics, San Jose, CA), MaterniT21 (Sequenom, San Diego, CA), or Verifi (Illumina, Redwood City, CA).

The PPV for T21 was highest at 93% followed by a 64% PPV for T18.  The PPV for T13 was only 44%. Given the prevalence of each of these conditions, these data aren't all that surprising but they are still rather alarming. Why? Because several studies have claimed NIPT tests are >99% specific (e.g. ~1% false-positive rate). As the authors of the study described here state: "To an average clinician, the claim that a test is >99% specific leads him or her to expect that the false-positive rate will be <1%."

As I stated this above and in several other posts on this blog (but is worth emphasizing again): NIPT is a screening test, not a diagnostic test and it cannot be considered a replacement for diagnostic testing.

More on noninvasive prenatal testing for fetal aneuploidy

We have written about nonivasive prenatal testing (NIPT) on this blog several times.  Because they are so new, the landscape around these tests is continually evolving.  The American College of Obstetricians and Gynecologists (ACOG) published guidelines on these tests in December of last year.  Just this week, the American College of Medical Genetics and Genomics (ACMG) released its policy statement on the same topic.  Note that the ACMG refers to these tests as "noninvasive prenatal screening" (NIPS) tests to emphasize that this is what they are: screening, not diagnostic tests.

The ACMG calls for caution before these tests become widely integrated into prenatal care due to the current lack of data obtained from prospective clinical trials.  While they acknowledge that NIPS tests have high sensitivity and specificity there are limitations to the technology and false-positive and false-negative results do occur.

A particular concern, and one that doesn't get as much attention as it should, is that most of the fetal DNA in the mother's blood sample originates from the placenta and not the fetus and it may not accurately reflect the fetal karyotype.  They emphasize (as have others), that abnormal NIPS test results must be confirmed by invasive diagnostic tests such as amniocentesis.

The policy statement also lists several limitations to NIPS tests.  Among them:

  • They only detect aneuploidies (and some detect sex chromosome abnormalities).
  • Certain chromosome abnormalities are not detected.
  • The tests take longer to perform and result than more well-established tests.
  • Data on the performance of the tests in twin and triplet pregnancies is not well established.

A recent paper published in the journal Obstetrics and Gynecology has a similar ring to it.  The authors make several interesting observations:

  • First, they point out that well-established tests were developed in academic settings and came into use gradually and only after independent clinical studies generated data to support their use.  In contrast, NIPT (also developed in academic settings) was quickly licensed to commercial enterprises that have brought them to market without FDA review (as these are "lab-developed tests," FDA appoval is not required).
  • From the analytical perspective, there are currently no guidelines regarding quality control and quality assurance for NIPT; a vital component of any lab test.
  • The performance of NIPT in actual clinical practice settings (i.e. not a clinical study) is currently not well known or documented.  This is especially true for populations of women that have not been represented in the clinical studies (e.g. woman at low risk for having a fetus with an aneuploidy).
  • The more well-established tests are able to detect fetal anomalies besides aneuploidy (e.g. open neural tube defects).

The authors also reflect on how NIPT should be incorporated into clinical care.  They agree with the ACOG recommendations that the tests should not be offered to low-risk women but they go a bit further and state that the most appropriate use of NIPT is as a second screening test used for those who have an abnormal result from convential, more well-established screening tests.  The latter point is something I have commented on before and I could not be in more complete agreement.

    Should DNA-based tests for Down syndrome screening replace biochemical tests?

    In a previous post I described the clinical performance of DNA-based screening tests for fetal aneuploidies like Down syndrome.  Overall, these tests have excellent detection rates (~99%) with very low false-positive rates (~0.2%).  In other words, these tests are about 99.0% sensitive and 99.8% specific.

    With performance like that one might expect these to be considered diagnostic tests.  They are not! Although quite good, test results must not be interpreted as definitive evidence that a fetus does or does not have an aneuploidy.  Recent recommendations from the American College of Obstetricians and Gynecologists (ACOG) are quite clear on that issue.

    In those same recommendations, ACOG also states that DNA-based screening tests may be performed only on women who are at increased risk of having a fetus with aneuloidy.  Among the indications listed for women considered to be at increase risk are:

    • Maternal age 35 years or older at delivery
    • Fetal ultrasound findings suggesting aneuploidy
    • A previous aneuploid pregnancy
    • Abnormal biochemical screening test results
    The ACOG is right to avoid recommending that DNA-based screening tests are acceptable to use regardless of risk factors.  Unfortunately, many women who are not at increased risk are using these new tests as a primary screening test and that's not a good idea.

    To understand why, considered a population of 100,000 pregnant women from the general population and assume that the prevalence of Down syndrome is 1 in 500 pregnancies.  That means that there would be 99,800 unaffected pregnancies and 200 pregnancies with Down syndrome.  The table below compares the results of the most commonly used biochemical screening test (the Quad test) to a DNA-based screening test.

    Quad vs DNA performance
    Clearly, the DNA-based test has several advantages over the Quad test.  Its positive predictive value is nearly 17 times greater than the Quad's and a positive DNA-based test result substantially increases the odds of having an affected fetus.  So why not use the DNA-based test as a primary screening test?  For the following reasons:
    • No studies have been published that have evaluated the performance of DNA-based tests in women who are not at increased risk of having a fetus with an aneuploidy
    • DNA-based tests are not widely available
    • The time it takes to report results of DNA-based testing is about 3 times greater than it is with biochemical testing
    • DNA-based tests are considerably more expensive than biochemical tests
    • Relative lack of insurance coverage for DNA-based tests
    Until these these limitations can be resolved, it makes more sense to use DNA-based testing as a secondary screening test.  In other words, it is only done after one of the risk factors described by ACOG (above) are met.  Doing so greatly improves the performance of both tests (see figure below).  A limitation of this approach is that the detection rate is that of the biochemical test which is not as high as it is with the DNA-based test.  Still, given the current limitations of DNA-based testing, this 2-step testing approach makes the most sense.
    DNA as secondary test

    Molecular testing for Down syndrome: proceed with caution

    Ann recently posted about massively parallel genomic sequencing using maternal blood as a
    screening test for Down syndrome.  In it, she described a recently published, multi-center clinical study that validated this molecular test in just over 1,600 women.  The test detected 98.6% of the Down syndrome fetuses and had a false-positive rate of 0.2%.  Notably, this performance is considerably better than current biochemical marker Down syndrome screening tests.

    However, there are some important limitations to this new test.

    1. It’s expensive and available from only one company.  The Sequenom Center for Molecular Medicine, located in Grand Rapids, MI, developed the test and is currently the only place in the US that can do it.  It's marketed as the MaterniT21 test and costs $1,900 for the uninsured and ~$235 for those with insurance.  Biochemical screening tests cost much less.
    2. After the blood sample arrives in the lab, test results are available in about 10 days.  Results for biochemical screening tests take about 1 day.
    3. The test can only be performed in singleton pregnancies (not twins, triplets, etc).  Biochemical screening tests work best in singleton pregnancies, too, although risks can be estimated from a twin pregnancy.
    4. The test fails to work in about 2% of cases, usually as a result of there not being enough fetal DNA detected in the mother's blood.  This is more likely to be the case in overweight women who have a higher blood volume which dilutes the amount of the fetal DNA.  The concentrations of the markers used in biochemical screening tests are also effected by maternal weight but there are effective ways to account for that so that the final result is not affected.
    5. The test is only validated for the detection of Down syndrome and not other fetal aneuploidies such as trisomy 18 or trisomy 13.  The test does have the capability of detecting these disorders and, if they are detected, will be reported.  However, because the test has not been thoroughly investigated for detecting T18 or T13 a negative result doesn't rule out their presence.  Biochemical screening tests can detect these disorders although the detection rates are lower than they are for Down syndrome.
    6. The test does not detect open neural tube defects (e.g. spinal bifida) that are usually screened for using biochemical screening tests.

    I have no doubt that as the technology required to do massively parallel genomic sequencing becomes less expensive, tests like the MaterniT21 will become more affordable and mainstream.  Most of the limitations I described above will also be addressed with time and technological improvements.  As Ann indicated, this is the dawn of a new era in screening for fetal disorders.

    Screening for Down syndrome: Beginning of a New Era?

    DNADavid has written previously about the different types of screening tests for Down syndrome (trisomy 21). Although these tests have certainly gotten better over time, even the best among them is subject to less than perfect sensitivity (90%) and a false positive rate of between 2 and 5%. Given the prevalence of Down syndrome, this means that out of 16 women that screen positive for Down syndrome, only one will carry an affected infant. Therefore, 15 women are unnecessarily subject to potentially dangerous amniocentesis procedure. Recently, there have been reports of some molecular testing that may change the way we screen women for Down syndrome forever.

    In 1997, researchers discovered that DNA from a fetus actually circulates in the blood of the mother during pregnancy. It goes away very rapidly after the baby is delivered. This amazing observation meant that it might be possible to diagnose certain diseases in the fetus by simply taking a sample of mom's blood. Since then, many studies have been done to try to develop a method to screen for Down syndrome using maternal circulating fetal DNA.

    In 2008, two papers were published, from different laboratories, which described the detection of trisomy 21 using "massively parallel genomic sequencing" (MPGS). In this method, DNA fragments are isolated from a sample of mom's blood. These include a mix of mom's DNA and infant DNA. The ends of the DNA fragments get a small piece of adapter DNA attached to it which allows the fragments to hybridize to a surface coated with the complimentary adapter DNA sequence. All the fragments bound to the surface are then simultaneously amplified. After amplification, the DNA is sequenced. With the help of bioinformatics, the researchers are able to determine what chromosome the DNA fragment came from. The number of sequences that originate from a particular chromosome is counted and tabulated for each chromosome. If a fetus has an extra chromosome, then the percentage of chromosome 21 fragments is higher than expected.  Early studies suggested that this method might work with high sensitivity, but the studies were small.

    Recently, a very large validation study was published that demonstrated that this method is not only sensitive, but also had a very low false positive rate. 

    The study involved women at high risk of delivering an infant with Down syndrome from 27 prenatal diagnostic centers worldwide. The authors compared fetal karyotyping (the gold standard for diagnosing Down syndrome) to MPGS in 212 Down syndrome and 1484 matched normal pregnancies. Their research demonstrated that MPGS was able to detect Down syndrome with 98.6% sensitivity and only a 0.20% false positive rate. This represents a huge improvement over currently available methods.

    Currently, MPGS is only available at specialized centers and is quite expensive. However, with the advent of studies such as this, the availability and price of MPGS is bound to come within reach. Hopefully, within the next 10 years, we will see the end of maternal serum screening for Down syndrome as we currently know it.

    Screening tests for group B strep infection

    StreptococcusThe most common cause of life-threatening infections in newborns comes from a bacteria known as Streptococcus agalactiae (more commonly referred to as group B streptococcus or GBS).  This was stressed in a recent meta-analysis that reported that GBS infection remains an important, global cause of infant mortality.

    The overall infection rate was 0.53 per 1,000 live births and, on average, about 10% of infected infants died.  Infants born in Africa were more likely to be infected (1.21 per 1,000) and die (22%) from the infection than infants born in the Americas or Europe (0.67-0.57 per 1,000 with 11 and 7% fatality rates).

    It doesn't have to be this way because GBS infection is treatable with antibiotic therapy.  Indeed, in more developed countries, therapy is provided to women who carry the bacteria which prevents their baby becoming infected during delivery.  However, in poorer countries this is less likely to happen due to fewer resources.

    Providing therapy to every pregnant women is not practical because not all women are colonized with GBS and so a key preventative strategy is to identify those women who do carry the bacteria.  The most sensitive test is culture performed on samples collected from the vagina and rectum.  The Centers for Disease Control and Prevention (CDC) published guidelines in 2010 that called for the routine GBS screening in all pregnant women at 35 to 37 weeks of gestation.  Testing needs to happen close to delivery (normally at ~40 weeks) because women can be colonized with GBS at anytime.  That is, a negative test result obtained earlier in pregnancy wouldn't rule-out the possibility that colonization then occured sometime after testing.  Women with a positive culture are treated with antibiotics during labor to prevent the transmission of GBS to their infant.

    Although culture is considered the gold standard test for GBS screening, it is not perfect because some infants born to culture-negative women still get infected with GBS.  Also, culture techniques give results in 1–3 days, a time frame that may not be useful should an expectant mother go into labor prior to having the culture test performed.  For these women, DNA-based tests can be used.

    These tests detect the presence of GBS using a DNA amplification technique like PCR and give results in a few hours rather than days.  Currently, these types of tests are not as sensitive as culture (i.e. they can give false-negative results) and so they aren't recommended for routine screening of women who are not in labor.  Their sensitivity is improved by using an enriched sample (one where the bacteria are allowed some time to multiply in a growth media), the use of this type of sample is impractical for women in labor when results are needed quickly.

    Until an effective vaccine to prevent GBS infection is available, laboratory testing will remain an essential tool for identifying and preventing GBS.