ACOG/SMFM Professional Guidance on the Role of NIPT as a First Tier Screening Test
The ACOG/SMFM practice bulletin that addresses prenatal screening for fetal chromosomal anomalies clearly states that both aneuploidy screening and diagnostic testing “should be discussed and offered to all patients regardless of maternal age or risk for chromosomal abnormality”
Aneuploidy screening
Serum screening with or without NT ultrasound or
cfDNA screening
Diagnostic testing (CVS or amniocentesis)
Notes
Standard serum screening remains a first-line option along with cell-free DNA screening, also known as noninvasive prenatal testing (NIPT), because additional chromosomal and single gene defects may be picked up with NT and performance may be more comparable to NIPT if the higher NIPT test failure rates are considered
While younger women may have a higher risk for fetal microdeletion syndromes than aneuploidy, ACOG does not recommend NIPT for microdeletions | Women who want information regarding microdeletions should be offered microarray testing using CVS or amniocentesis
What Is NIPT?
NIPT is a blood test that utilizes cell-free DNA technology (cfDNA) to predict the risk for fetal genetic disorders during pregnancy. In 2011, NIPT was introduced as a screen for T21 (trisomy 21 or Down syndrome). Today, NIPT cover the most common aneuploidies (T21, T13 and T18), as well as sex chromosomes and may also include some microdeletions and single gene genetic disorders
How Does It Work?
DNA fragments (outside of cells) can be found floating in the blood of all individuals
In every pregnant woman, there are fragments from
Her own DNA
Fragments of placental DNA (generally thought to derive from the outer cytotrophoblast rather than the inner mesenchymal layer)
A maternal blood sample is obtained ≥10 weeks (with some labs offering testing beginning at 9 weeks) of pregnancy
Usually performed at 11 to 13 weeks
Fetal Fraction
The percentage of fetal DNA found in maternal blood is known as the fetal fraction | Typical range 3 to 13% of maternal cfDNA
The fetal fraction is critical to the success of NIPT | Minimum required approximately 2 to 4%
Sensitivity drops with lower fetal fraction and if too low, test failure will result
Technologies
Generally, NIPT utilizes next generation sequencing and bioinformatics algorithms to interrogate DNA fragments that have been extracted from maternal samples
SNP-based: Bioinformatic algorithms combine risk from individual targeted single nucleotide polymorphisms (SNPs) to differentiate maternal from placental DNA fragments
SNP is the only analysis that can report on zygosity and individual fetal fractions in the case of twins (dependent on laboratory)
Quantification method: Bioinformatic algorithms determine the amount of DNA from chromosomal regions of interest | E.g. if too much chromosome 21 DNA is detected, then a ‘screen positive’ result for T21 will be generated
What Disorders Are Included?
T13, T18 and T21
Most effective at screening for T21
Chromosomes X and Y (fetal sex usually available)
Sex chromosome conditions (depending on the lab)
Monosomy X (Turner syndrome)
47,XXX (Triple X syndrome)
47,XXY (Klinefelter syndrome)
47,XYY (Jacob’s syndrome)
Microdeletions (also known as copy number variants or CNVs) are available with more extensive panels | CNVs occur in 0.4% of pregnancies and are not related to maternal age
22q11.2 deletion syndrome (DiGeorge syndrome) | 1,3000 to 1,4000 live births | May be more prevalent prenatally and cases may be missed at birth (see ‘Related ObG Topics)
1p36 deletion syndrome | 1 in 5,000 to 1 in 10,000 live births
4p16.3 deletion syndrome (Wolf-Hirschhorn syndrome) | 1 in 50,000 live births
5p15.2 deletion syndrome (Cri du Chat syndrome) | 1 in 20,000 to 1 in 50,000 live births
15q11.2 deletion syndrome (Angelman syndrome/Prader-Willi syndrome) |1 in 12,000 to 20,000 (AS) | 1 in 10,000 to 30,000 (PWS)
SYNOPSIS:
NIPT is a screening test only and not diagnostic. Cell-free DNA (cfDNA) is also commonly used with an understanding that the DNA is derived from placenta and not the fetus. NIPT utilizes next generation sequencing and bioinformatics algorithms to look at the DNA fragments in the mother and fetus, as a way of determining the likelihood of certain genetic conditions in the fetus. While there are multiple panels available, there is consensus regarding the clinical utility of NIPS screening for T13, T18 and T21. Patient education, especially around the concept of positive predictive value (PPV) is a priority. Calculator tools are available from professional societies (see ‘Learn More – Primary Sources’ below) or ideally laboratories should be able to provide obstetric professionals with real world test performance results.
NIPT Screening Performance
Detection rates
The following detection rates are based on recent meta-analysis (see ‘Learn More -Primary Resources’ below)
T21: >99% detection rate for T21
98% detection rate for T18
99% detection rate for T13
Combined false positive rate of 0.13%
cfDNA is the most sensitive and specific screen for T21, T18 and T13
Sensitivity and specificity are superior to standard screening for T21 and other common aneuploidies
Positive Predictive Value (PPV)
Trisomies
NIPT generally has very high negative predictive values (NPV) | From ages 20 to 45, NPV is >99% (NSGC GSF calculator)
PPV is also generally high but can vary based on age | Lower background risk will lower PPV
PPVs have been reported up to approximately 90% for T21 but tend to be lower for T18, T13 and monosomy X
Abnormal ultrasound will increase PPV
Microdeletions
NIPT for microdeletion syndromes can have high sensitivity and specificity but still have very low PPV because the particular syndrome is a priori so rare | For example
Cri du Chat Syndrome (Using NSGC GSF calculator – see ‘Learn More – Primary Sources’ below)
Even if sensitivity and specificity are both >99%, the chance of a positive results being a true positive (i.e. PPV) is ≤1%
Negative predictive value will generally always be high for a rare disorder
22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome, found in 1 in 3000 to 4000 live births | Appears to be more common prenatally with a prevalence of approximately 1 in 1000 of otherwise normal pregnancies (see ‘Learn More – Related Entries)
PPV in a low risk population (see ‘Learn More – Primary Sources’) has been reported to be approximately 1 in 20 and higher in pregnancies at higher risk (e.g. congenital heart disease consistent with 22q11.2DS)
Note: NIPT is a screening test and not diagnostic | Regardless of PPV, screen positive results require patients be offered invasive diagnostic testing to confirm results
Some women may opt for a cfDNA screen after a positive serum analyte screen instead of an invasive test. This is a valid option for patients who do not want an invasive test
However, patients should be counseled that a cfDNA screen will not give a diagnosis and may delay a formal diagnosis
cfDNA will not identify all babies with chromosomal abnormalities
Residual risk of a chromosomal abnormality after an abnormal traditional screen followed by a normal cfDNA screen is around 2%
Reasons for a False Positive Result
There is a high likelihood that a positive T21 NIPT screen is truly positive (approximately 90%)
However, confirmatory testing is necessary because false positive results are possible
Confined placental mosaicism (since NIPT only looks at the placental DNA)
Vanishing twin that was aneuploid but surviving twin is normal
Maternal condition such as cancer (NIPT results will usually show multiple chromosomal aneuploidies)
Unknown
NIPT Test Failure
Low fetal fraction
BMI: 10% of patients >250 lbs will have a fetal fraction <4% | May be caused by (1) dilutional effect or (2) elevation in maternal DNA due to inflammatory processes
Early Gestational age <9 weeks
Other reasons for no result include
Laboratory failure | IVF pregnancy | Maternal drug exposure to LMWH | Racial background (e.g. Black and South Asian vs white) | Fetal aneuploidy (e.g. T13 or T18 and sex chromosome aneuploidies)
Follow-Up for ‘No Call Result’
Inform patients that there is an increased risk of aneuploidy | Effect may be due to smaller placentas
Offer genetic counseling, detailed ultrasound evaluation and diagnostic testing
Repeat screening “may be considered’
Success rate 75 to 80% (less with high BMI)
Repeat screening is not advised for the following
Ultrasound anomalies present
Later gestational age where further delay may complicate access to reproductive options
Note: It is preferred that the laboratory report the fetal fraction
Single Gene and NIPT
NIPT also has the capability to identify single gene disorders
Ability to identify single gene variants that would likely not be detected with carrier testing
Generally serious autosomal dominant disorders that may be absent in the parents, but pathogenic variants may spontaneously occur in the fetus (de novo) such as Cornelia de Lange syndrome or Achondroplasia
Some of these conditions are associated with advanced paternal age (≥40 at time of conception)
Single gene screening is clinically available, although currently not recommended by ACOG
Note: ACMG provides healthcare professionals with open access ‘ACT Sheets’ to guide next steps following a positive NIPT report (see ‘Learn More – Primary Sources’ below)
What is the Best Strategy for Fetal Aneuploidy Screening?
BACKGROUND AND PURPOSE:
Multiple strategies for aneuploidy screening are currently being evaluated
cfDNA has superior performance characteristics compared to standard first trimester screening (NT + markers) but may miss fetal anatomic/chromosomal anomalies that can be initially detected on ultrasound
Kagan et al. (Ultrasound Obstet Gynecol, 2017) compared the performance of first trimester standard combined screening with an approach that uses the combination of a detailed ultrasound exam and cfDNA analysis
METHODS:
Prospective randomized control trial of normal first-trimester ultrasound exam at 11 to 13 weeks’ gestation (2015-2016)
Subjects were randomized into two groups of assessing aneuploidy risk
Standard screening
Ultrasound and cfDNA screening if ultrasound is normal
Blood was retained for standard serum markers in case the cfDNA result was inconclusive
Primary outcome
Number of false positives in screening for trisomy 21
False positive defined as normal karyotype if risk for trisomy 21 was >1:100, irrespective of the method of risk calculation
RESULTS:
688 women with normal first-trimester ultrasounds were randomized into each group (1) Standard screening cohort and (2) ultrasound + cfDNA cohort
All 7 cases of DS were detected on ultrasound based on enlarged NT or fetal anomalies, as were trisomy 13 and 18 cases
When comparing risk assessment using standard screening vs ultrasound + cfDNA cohorts, there were no major demographic differences
The ultrasound + cfDNA cohort median risk for trisomy 21 was 1 in 10,000
None of the cases had a risk above 1:100 [95% CI 0.0 – 0.5%]
The standard screening cohort median risk for trisomy 21 was 1 in 3,786
> 1:100 risk was identified in 17 (2.5%) pregnancies (95% CI 1.5 – 3.9%)
CONCLUSION:
A first-trimester screening for trisomy 21 using ultrasound, NT measurement, and cfDNA in women without ultrasound anomalies is associated with a significant reduction in the false positive rate compared to standard screening
This study suggests first trimester serum markers (β-hCG and PAPPA) should not be used
By including a detailed ultrasound, disadvantages of cfDNA only testing only are overcome
Anatomic assessment provided by ultrasound
Saving blood for markers if necessary can address the problem of inconclusive cfDNA results
What Is the Best Follow-Up Diagnostic Test After a High-Risk NIPT Result?
BACKGROUND AND PURPOSE:
DNA that circulates in the maternal compartment is mostly derived from placenta (cytotrophoblast layer) and not the fetus
Fetal and placental cells both originate from the fertilized oocyte, but diverge early in pregnancy into distinct tissues
Placenta can tolerate different cell lines (mosaicism) and may not perfectly match the fetal chromosomal complement, resulting in false positive and negative NIPS results
There are other causes that may result in false positive and negative NIPS reports, such as vanishing twin or maternal chromosomal anomalies
Therefore, there is universal agreement that a positive cfDNA report requires confirmation based on invasive testing with either CVS or amniocentesis
Grati et al. (Prenatal Diagnosis, 2015) used an extensive database to determine how often placental DNA (CVS results) matched fetal DNA (amniocentesis results), broken out by chromosome and cellular layer, to determine whether amniocentesis and/or CVS is the more appropriate confirmatory test.
METHODS:
Data on 52,673 karyotypes were analyzed to determine frequency of mosaicism involving cytophoblasts, for trisomies 21 (T21), 18 (T18), 13 (T13) and monsomy X (MX)
Karyotypes were obtained from cytorophoblast (outer layer, DNA source for NIPS), mesenchyme and confirmatory amniocentesis
RESULTS:
Using cytotrophoblast karyotype as a proxy for NIPS, authors posited the following
After a high-risk NIPS result, mosaicism on confirmatory CVS requiring a follow up amniocentesis would be:
2% in T21
4% in T18
22% in T13
59% in MX
When mosaicism is detected by CVS, the likelihood of fetal confirmation by amniocentesis would be:
44% in T21
14% in T18
4% in T13
26% in MX
CONCLUSION:
For T21/18, confirmatory CVS may still be an option, especially if there is a clinical indication to obtain early results
Small but still real risk for inconclusive results
For MX/T13, amniocentesis seems most appropriate for follow-up after high risk cfDNA result due to high likelihood of a mosaic result on confirmatory CVS
The authors state “If an ultrasound anomaly suggesting the suspected karyotype anomaly is found, CVS could be offered to the patient regardless of risk of need for a secondary procedure because an early diagnosis may be preferable.”
This study by Sotiriadis et al. (Prenatal Diagnosis, 2017) sought to calculate the proportion of pathogenic results that would be picked up by array comparative genomic hybridization (aCGH) compared to NIPS.
METHODS:
Comparative Retrospective Study
RESULTS:
This study included 2,779 fetuses that underwent invasive prenatal diagnosis using aCGH, with indications including large NT, standard 1st and 2nd trimester screening, fetal anomalies, maternal age, personal or family history of genetic issues, patient request or other (e.g. infection). Patients who were referred for screen positive NIPS were excluded. The investigators assumed a simulated NIPS panel comprised of common aneuploidies, trisomies 21, 18, 13, but also sex chromosome aneuploidies including monosomy X, 47, XXX, 47, XYY, and 47, XXY. NIPS would detect 28.0% (95% CI 14.3-47.6) of detectable aCGH pathogenic results for NT between 95th to 99th centile, 14.3% (95% 5.0-34.6) for NT > 99th centile, 34.2% (95% CI 21.1-50.1) for high-risk first-trimester results, 52.4% (95% CI 32.4-71.7) for second-trimester markers and 50.0% (95% CI 26.8-73.2) for advanced maternal age. Overall, the rate of aCGH pathogenic/likely pathogenic results was 5.0% of which 44.0% (95% CI 36.0-52.2) would have been missed by NIPS alone. This paper yet again reinforces the fact that NIPS is a screening test only and, particularly in the age of aCGH, approximately half of pathogenic findings detectable with invasive testing will be missed.
Does cfDNA in First Trimester Signal Subsequent Preeclampsia?
PURPOSE:
This study by Silver et al. (American Journal of Perinatology, 2017) sought to determine if a relationship exists between first trimester cell-free total DNA in maternal plasma and the development of preeclampsia.
METHODS:
Nested Case-Control Study
RESULTS:
Data on 350 women, 50% with and 50% without preeclampsia, who were enrolled in the Combined Antioxidant and Preeclampsia Prediction Studies, were analyzed. While some women did have higher cell-free total DNA than others (Black and Hispanic women had higher levels than white women), there was no correlation between levels and subsequent development of preeclampsia. The authors conclude that cfDNA is not a good prenatal risk assessment marker for preeclampsia.
SMFM Guidance – The Role of Prenatal Ultrasound and NIPT
SUMMARY:
SMFM has released, as part of their Consult Series, a document on the role of prenatal ultrasound in the context of cfDNA screening. The summary recommendations are as follows:
Negative cfDNA at 11-14 weeks: (evidence level 1B)
First trimester ultrasound only for NT measurement not recommended
Negative cfDNA and isolated ‘soft marker’: (evidence level 2B)
Diagnostic testing is not recommended solely for this indication
Describe ‘soft marker’ finding as ‘not clinically significant’ or ‘normal variant’
Negative 1st or 2nd trimester screen and isolated ‘soft marker’: (evidence level 2B)
Describe ‘soft marker’ finding as ‘not clinically significant’ or ‘normal variant’
Structural abnormality on ultrasound (evidence level 1A)
Offer diagnostic testing using microarray
Do not offer routine screening for microdeletions using cfDNA (evidence level 1B)
Key Points:
Examples of ‘soft marker’ include echogenic intracardiac focus or choroid plexus cysts
‘Isolated’ implies a single finding and the absence of any other pathology
If multiple ‘soft markers’ are identified
Refer for genetic counseling, consideration of diagnostic testing
prenatal risk assessment should be limited to expert centers and individuals
Counseling Women with NIPT Results Suggesting Cancer
PURPOSE:
This study by Giles et al. (Prenatal Diagnosis, 2016) surveyed genetic counselors on their current methods and management needs for counseling women whose prenatal cfDNA screening indicate maternal neoplasm.
METHODS:
Anonymous Online Survey Answered by Board-Eligible/Certified Genetic Counselors through the NSGC.
RESULTS:
343 participants completed the entire survey. Despite the fact that 95% of participants previously knew that NIPT could be used to uncover maternal neoplasm, the majority (51.8%) did not feel adequately prepared or comfortable discussing the ramifications of a test report suggesting an increased risk for maternal neoplasm based on NIPT findings. This study substantiates the urgent need for management guidelines on this topic.
Other findings may not be apparent until postnatal life:
Dysmorphic features: epicanthal folds, single palmar crease, low set ears
Decreased muscle tone
Intellectual disability: usually in the mild (IQ ~70) to moderate range (IQ ~50)
Most individuals with Down syndrome can participate in numerous group and individuals activities, but may need some level of supervision throughout their lives
Individualized education programs can help children with Down syndrome reach their potential
Special education services at school can range from inclusion in the typical classroom with extra help to small group instruction
Hearing loss (up to 75%)
Sleep apnea (50-75%)
Eye disease, such as cataracts (50-70%)
Endocrine disease: thyroid, diabetes
Hirschsprung disease
Leukemia is slightly increased in this population, typically requiring lower doses of chemotherapy treatments
Plaques are frequently seen in older adults with Down syndrome (50+ years) but their presence does not mean that Alzheimer’s disease will necessarily develop – other treatable causes of decline are investigated first
CAUSE:
Down syndrome (DS) is a condition caused by the presence of an extra chromosome (#21) at the time of conception. In 90% of cases, it is the result of nondisjunction during meiosis (Trisomy 21), which is usually a sporadic occurrence. In 4-5% of DS affected individuals a chromosomal imbalance is the cause, inherited from a parent who has a balanced karyotype (i.e. Robertsonian translocation). A small proportion of affected individuals, < 1%, are diagnosed with mosaic DS.
KEY POINTS:
ACOG requires all women be offered prenatal screening (biochemical/cfDNA) or invasive testing (amniocentesis;CVS) to detect an increased risk for DS, or to diagnosis it, respectively
Children with Down syndrome are more similar to other children than they are different
Overall, this condition is present in approximately 1 in 800 live births. Risk increases with maternal age
At maternal age 25, the risk is 1/1250
At maternal age 35, the risk is 1/365
At maternal age 40, the risk is 1/110
At maternal age 45, the risk is 1/32
If there is a family history or previous DS pregnancy, refer for genetic counseling
Data is limited on obstetrical management of an ongoing pregnancy with trisomy 21
Increased risk of fetal loss (5.9%), growth restriction (17.5%) and anomalies (75.0%)
Non-reassuring fetal surveillance (35.9%) appears to be associated with placental insufficiency and not necessarily related to structural anomalies
Data suggests a role for antepartum surveillance
Note: ACMG provides healthcare professionals with open access ‘ACT Sheets’ to guide next steps following a positive NIPS report for trisomy 21 (see ‘Learn More – Primary Sources’ below)
Klinefelter Syndrome: A Wide Range of Clinical Findings
WHAT IS IT?
Klinefelter syndrome is also known as XXY syndrome
Present in 1 in 500 to 1 in 1000 newborn males
A sex chromosome abnormality that involves the presence of two or more X chromosomes and one Y chromosome
Majority are 47,XXY karyotype
Remaining cases are 48, XXXY or mosaic 46,XY/47,XXY
Prenatally, usually no obvious physical features detectable on ultrasound
In infancy, possible minor findings:
Hypospadias and small or undescended testes
Clinical features may be subtle and often a diagnosis is not made until adolescence, adulthood, or not at all:
Tall stature
Small and atrophic testes
Gynecomastia (excess breast tissue)
Evidence of androgen deficiency such as decreased body hair
Increased risk for breast cancer and autoimmune disorders (e.g. lupus)
Intellectual development:
Individuals who have a 47,XXY karyotype usually have normal intelligence
Starting in childhood, educational support may be needed to address learning disabilities, delayed speech and language development
Individuals who have more than two X chromosomes are likely to have more severe symptoms
Treatment:
Testosterone replacement is available and is usually started in early puberty
Treatment should be under the care of an endocrinologist and ideally with the collaboration of a multidisciplinary team
Recent data suggest treatment early in childhood may have a positive impact on neurodevelopment and social behaviors
Removal of excess breast tissue is an option for cosmetic reasons and to reduce the risk for breast cancer
Fertility treatment now available using assisted reproductive technology (ART), including testicular sperm extraction with intercytoplasmic sperm injection (TESE-ICSI)
Academic educational support to assist with language-based learning disabilities (LLD) and motor planning issues
CAUSE:
Klinefelter syndrome is a condition caused by an abnormal karyotype (2 or more X chromosomes and one Y chromosome) that is present at the time of conception. It usually is the result of non-disjunction during meiosis and is either of maternal (55%) or paternal (45%) origin. It is a sporadic condition, not inherited.
KEY POINTS:
ACOG requires all women be offered prenatal screening (biochemical/cfDNA) or invasive testing (amniocentesis; CVS) to detect an increased risk or to diagnose aneuploidy, respectively
Currently, the only way to prenatally diagnose Klinefelter syndrome is through invasive testing (amniocentesis or CVS)
Klinefelter syndrome is now included on some cfDNA screening tests
Invasive testing is necessary to confirm any positive result on screening using cfDNA
If there is a history of Klinefelter syndrome, refer for genetic counseling
Bicuspid aortic valve and coarctation of the aorta
Renal defects (i.e. horseshoe kidney)
Other findings may not be apparent until postnatal life
Short stature is usually the most consistent finding, approximately 8 inches less than what would be expected for her family
Genetic mechanism resulting in short stature still unknown, however the absence of the SHOX gene, located on short arm of X chromosome, which helps coordinate bone development, is likely an important factor
Wide or webbed neck
Low-set ears
Low hairline at the back of the head
Broad chest with widely spaced nipples
Lymphedema, especially of the hands and feet
Absent, delayed, or partial spontaneous pubertal development (30%)
Absent or decreased fertility, depending on what percentage of cells have only one X chromosome, as two X chromosomes are required for ovarian development and function
Intellectual development:
Females who have a 45,X karyotype usually have normal intelligence although there may be some learning disabilities, particularly with mathematical and spatial concepts, some difficulty in social situations
Treatment and monitoring:
Cardiology monitoring
Growth hormone and hormone replacement therapy
Academic support for potential learning challenges
Fertility assessment
CAUSE:
Turner syndrome (45,X) is a condition caused by an abnormal karyotype that is present at the time of conception and results from a sperm or egg that is capable of undergoing fertilization, but has no X chromosome. As this appears to be a random event, Turner syndrome is generally not inherited and risk of recurrence in subsequent pregnancies is minimal.
KEY POINTS:
ACOG requires all women be offered prenatal screening (biochemical/ cfDNA) or invasive diagnostic testing (amniocentesis/ CVS)
Turner (45,X) syndrome is included on some cfDNA screening panels but is associated with a higher false positive rate compared to Down syndrome
Confirmatory testing (amniocentesis or CVS) should be offered all women with a positive cfDNA screening report
Presently, invasive testing is the only way to diagnose fetal Turner syndrome
There is data supporting the use of amniocentesis rather than CVS for confirmation
Present in 1/1500- 1/2500 live births
Estimated to account for 3% of all conceptions
Despite relatively functional outcomes, approximately 99% of cases are miscarried or stillborn
Mosaic Turner syndrome has a better chance of survival
ACMG provides ACT sheets to assist healthcare professionals with ‘next steps’ following a positive NIPS report for 45,X (see ‘Learn More – Primary Sources’ below)
Can a Laboratory Patent Non-Invasive Prenatal Screening?
In March 2016, Sequenom asked the United States Supreme Court to review a US Federal Court ruling that Sequenom’s patent (U.S. Patent No. 6,258,540) for noninvasive prenatal diagnosis analyzing cell-free fetal DNA (cfDNA/NIPS/NIPT) in maternal blood did not meet the U.S. Supreme Court’s criteria for patent eligibility.
Following a major case involving Mayo Collaborative Services and Prometheus Laboratories, patents using methods that start and end with “a naturally occurring phenomenon” will not be patent eligible if the methods used to measure a sample are routine, conventional and well understood laboratory applications. In other words the federal court did not find Sequenom’s patent “new and useful”.
As technology advances, the courts will have to continue to wrestle with how to interpret patent eligibility criteria. Their interpretation will lead to limited or expansive criteria. The full effects on the development of new medical diagnostics remain to be seen, but with the hope that these new technologies will continue to enable healthier lives.
OBG Project CME requires a modern web browser (Internet Explorer 10+, Mozilla Firefox, Apple Safari, Google Chrome, Microsoft Edge). Certain educational activities may require additional software to view multimedia, presentation, or printable versions of their content. These activities will be marked as such and will provide links to the required software. That software may be: Adobe Flash, Apple QuickTime, Adobe Acrobat, Microsoft PowerPoint, Windows Media Player, or Real Networks Real One Player.
Disclosure of Unlabeled Use
This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications.
The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the planners. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.
Disclaimer
Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information
presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.
Jointly provided by
NOT ENOUGH CME HOURS
It appears you don't have enough CME Hours to take this Post-Test. Feel free to buy additional CME hours or upgrade your current CME subscription plan
You are now leaving the ObG website and on your way to PRIORITY at UCSF, an independent website. Therefore, we are not responsible for the content or availability of this site
