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Best Practices for Integrating Cell-Free DNA-Based NIPT Into Clinical Practice

Introduction External Quality Assessment (EQA), which is also referred to as proficiency testing (PT) in some countries, is a means of assessing clinical analytical and interpretation performance with interlaboratory comparison and against international standards (ISO). EQA allows an independent appraisal of the laboratory's results and interpretation compared to the validated results and to the performance criteria. The aim of EQA is to be educational and to…

Maternal Constitutional and Acquired Copy Number Variations

Introduction Extracellular nucleic acids have already been known to exist in the blood circulation since 1948 . The observation of abnormally high concentrations of DNA in serum of cancer patients lead Stroun et al. to suggest that DNA found in the serum of cancer patients might be released by tumor cells . This hypothesis was confirmed when tumor-derived oncogene mutations were identified in the plasma and…

Noninvasive Prenatal Diagnosis of Monogenic Disorders

Introduction The groundbreaking discovery of the presence of cell-free DNA in maternal plasma was made in 1997 by Dennis Lo . In the years since that, gradual technological development has meant that we can now use a maternal plasma sample as a source of material for prenatal testing for many different applications. One obvious potential application for this is noninvasive prenatal diagnosis (NIPD) of monogenic disorders—so-called…

Noninvasive Fetal Blood Group Typing

Hemolytic Disease of the Fetus and Newborn Hemolytic disease of the fetus and newborn (HDFN) is a disease caused by maternal IgG alloantibodies against paternally inherited RBC alloantigens, for which the maternal cells are negative. The maternal alloantibodies are induced by fetomaternal hemorrhage (FMH) in a previous or current pregnancy or by prior incompatible blood transfusion. The risk for immunization by FMH is highest in the…

Genome-Wide Cell-Free DNA-Based Prenatal Testing for Rare Autosomal Trisomies and Subchromosomal Abnormalities

Acknowledgments I am indebted to my clinical laboratory and analytical teams and thank them for their support—Nicola Flowers, Olivia Giouzeppos, Grace Shi, Clare Love, Rebecca Manser, Ian Burns, Shelley Baeffel, Sera Tsegay, Tom Harrington, and LaiEs Carver. Research conducted at the Murdoch Children's Research Institute was supported by the State Government of Victoria's Operational Infrastructure Support Program. Introduction Cell-free DNA-based noninvasive prenatal testing (cfDNA-based NIPT) has…

The Role of Cell-Free DNA-Based Prenatal Testing in Twin Pregnancy

Introduction Due to an increasing trend of advancing maternal age at conception, and the increased use of assisted reproductive technologies (ART), the number of twin and higher order multiple pregnancies is increasing in many countries, despite the introduction of the single embryo transfer policy . Compared to singletons, twin pregnancies are at increased relative risk of many obstetric complications, including aneuploidy . This is probably the…

Why Cell-Free DNA-Based Noninvasive Prenatal Testing for Fetal Chromosome Anomalies Is Not Diagnostic

Introduction Since the commercial introduction of cfDNA-based prenatal tests in 2011, a plethora of studies with designs of proof of concept, validation, case reports, large cohort studies, and meta-analyses have been published. Although cfDNA-based prenatal screening for trisomy 21, 18, and 13 has made big steps forward from the very early stages of its use, it soon became evident that false-positive and false-negative results might occur…

Prenatal Screening for Common Aneuploidies Before and After the Introduction of Cell-Free DNA-Based Prenatal Testing

Prenatal Screening Before Cell-Free DNA-Based NIPT Aneuploidies Aneuploidies, the presence of an abnormal number of chromosomes, are conditions associated with significant morbidity and mortality. Aneuploidies affect approximately 1 in 160 live births , although the overall incidence is higher due to natural pregnancy losses and termination of affected pregnancies. The commonest aneuploidies affecting live births are trisomies 21, 18, and 13 and monosomy X. Trisomies describe…

The Technology and Bioinformatics of Cell-Free DNA-Based NIPT

Acknowledgments Carrie Haverty provided helpful comments on the manuscript. Introduction The primary challenge of cell-free DNA (“cfDNA”) based prenatal testing (commonly called noninvasive prenatal testing or NIPT) is to identify fetal chromosomal anomalies from maternal plasma samples, where maternal cfDNA molecules far outnumber their fetal counterparts. Further complicating this task is the fact that the relative amounts of fetal and maternal fragments (i.e.; the fetal fraction)…

Understanding the Basics of NGS in the Context of NIPT

Acknowledgments Clement Chu and Mark Theilmann provided helpful comments on the manuscript. Introduction The core goal of cell-free DNA based prenatal testing (at its introduction called “NIPT”) is to provide minimally invasive, clinically accurate, and financially accessible screening for fetal chromosomal aneuploidies in the early stages of pregnancy. This goal poses certain important constraints: minimal invasiveness means the test must operate from analytes in a maternal…

Vacuum-Assisted Birth

Description Vacuum-assisted birth is a method of assisting or expediting vaginal vertex birth through the application of a vacuum-assist device. Operative vaginal birth can be faster and safer than cesarean birth in many cases. Discussion here is limited to vacuum-assisted births with the fetus presenting within 45 degrees of directly occiput anterior. Indications Fetal —nonreassuring fetal status, acute fetal distress. Maternal —fatigue, prolonged second stage of…

Urodynamic Testing: Simple

Description Simple urodynamic testing involves the measurement of bladder function that is conducted using simple equipment readily found in an office setting. Indications Urinary incontinence (stress, urge, mixed, overflow). May be used as an adjunct to the evaluation of interstitial cystitis or other urinary complaints. Contraindications Active bladder infection. Known or suspected allergy to cleansing solutions or local anesthetics to be used. You’re Reading a Preview…

Urodynamic Testing: Complex

Description Complex urodynamic testing involves the measurement of bladder function that is conducted using specialized equipment or techniques. Indications Urinary incontinence (stress, urge, mixed, overflow). May be used as an adjunct to the evaluation of interstitial cystitis or other urinary complaints. Contraindications Active bladder infection. Known or suspected allergy to cleansing solutions or local anesthetics to be used. You’re Reading a Preview Become a Clinical Tree…

Trigger Point Injection

Description Injection of steroids or local anesthetics into selected fascial and subcutaneous locations thought to give rise to pain and other symptoms. Response to trigger point injection routinely persists longer than the duration of action of the agent used. This frequently extends to permanent relief after only one or two anesthetic injections. Because of the rapid response to trigger point injections, they can be useful as…

Transvaginal Ultrasonography

Description Transvaginal (also called endovaginal) ultrasonography is a technique for ultrasonographic visualization of the uterus and adnexa using an ultrasonographic probe placed in the vaginal canal. The superior resolution of transvaginal ultrasonography derives from the proximity of the ultrasonographic transducer, and the higher frequencies of sound waves used by these devices. In some cases, this resolution may be as small as 0.2 mm. The tradeoff of…

Subdermal Contraceptive Capsule Removal

Description Etonogestrel subdermal contraceptive implants provide reliable reversible contraception, but they must be removed after 3 years of use or if a return to fertility is desired. Indications Desired return of fertility or the completion of the useful life of the contraceptive implant. Contraindications Local skin infection, known or suspected allergy to the agents used for the removal process. You’re Reading a Preview Become a Clinical…

Subdermal Contraceptive Capsule Insertion

Description The etonogestrel implant (Nexplanon) is a single-rod progestin contraceptive placed under the skin of the inner upper arm that provides up to 3 years of reversible contraception. The implant is a 40- × 2-mm semirigid ethylene vinyl acetate rod containing 68 mg of etonogestrel (the 3-keto derivative of desogestrel). Contraceptive effectiveness is equal to or greater than that of most sterilization procedures. Indications Reversible contraception.…

Speculum Examination

Description Speculum examination of the vaginal canal and cervix is a vital part of any gynecologic examination. The use of a speculum also facilitates a number of gynecologic processes, including obtaining cervical cytology or cultures, colposcopy, intrauterine contraceptive device placement and removal, hysteroscopy, and others. When used properly it is an invaluable tool; when used artlessly, its use can result in pain, trauma, and lost information.…

Sonohysterography

Description Sonohysterography is a technique for ultrasonographic visualization of the uterine cavity using saline as a contrast and distending media. The technique is also known as saline infusion sonohysterography (SIS). It is well suited for the ultrasonographic detection of endometrial polyps, hyperplasia, cancer, leiomyomas, and intrauterine adhesions. It has replaced diagnostic dilatation and curettage for most women. Indications Similar to those for hysteroscopy or endometrial biopsy;…