Low Fetal Fraction and Birth Weight in Women with Negative First-Trimester Cell-Free DNA Screening

2019 ◽  
Vol 37 (01) ◽  
pp. 086-091
Author(s):  
Mark A. Clapp ◽  
Margaret Berry ◽  
Lydia L. Shook ◽  
Penelope S. Roberts ◽  
Ilona T. Goldfarb ◽  
...  
Keyword(s):  
Birth Weight ◽  
First Trimester ◽  
Cell Free Dna ◽  
Free Dna ◽  
Increased Risk ◽  
Trimester Screening ◽  
Future Work ◽  
Primary Variable ◽  
Cfdna Screening ◽  
Fetal Fraction

Abstract Objective To determine the association between low fetal fraction and birth weight among women with a negative cell-free DNA (cfDNA) result for common aneuploidies in the first trimester. Study Design This is a retrospective cohort of women who delivered a singleton between July 2016 and June 2018 at a single institution and had normal cfDNA testing in the first trimester. The primary variable of interest was “low fetal fraction,” which was defined as fetal fractions less than 5th percentile among all fetal fractions in the cohort (fetal fraction < 5.34%). The primary outcomes were birth weight ≤ 5th and ≤ 10th percentiles. Multivariable logistic regressions assessed for the association between low fetal fraction and birth weight. Results A total of 7,478 women delivered a singleton at ≥24 weeks' gestation, of which 2,387 (32%) underwent genetic screening through cfDNA; the majority were in the first trimester (n = 2,052 [86%]). 2,035 met the inclusion criteria. Birth weight ≤ 5th percentile was significantly higher in the low fetal fraction group (6.9 vs. 3.2%; p = 0.04). A low fetal fraction was associated with higher odds of an infant with a low birth weight: adjusted odds ratio (aOR) of 2.32 (95% CI 1.15–4.67) for birth weight ≤ 10th percentile (p = 0.02) and aOR of 3.73 (95% CI 1.40–9.03) for birth weight ≤ 5th percentile (p = 0.004). Conclusion Low fetal fractions of ≤ 5th percentile were associated with an increased risk of birth weights ≤ 5th and ≤ 10th percentiles in women with negative cfDNA screening in the first trimester. Future work is needed to further investigate this relationship and to determine the potential clinical implications, such as third-trimester screening for growth restriction in women with low fetal fractions and negative cfDNA screening results.

Association of Fetal Fraction of Cell-Free DNA and Hypertensive Disorders of Pregnancy

2018 ◽  
Vol 36 (03) ◽  
pp. 311-316 ◽  
Author(s):  
Nathanael Koelper ◽  
Mary Sammel ◽  
Lorraine Dugoff ◽  
Whitney Bender
Keyword(s):  
Multinomial Logistic Regression ◽  
First Trimester ◽  
Chronic Hypertension ◽  
Hypertensive Disorders Of Pregnancy ◽  
Cell Free Dna ◽  
Free Dna ◽  
Hypertensive Disorders ◽  
Increased Risk ◽  
The Relationship ◽  
Fetal Fraction

Objective The objective of this study is to examine the relationship between fetal fraction and hypertensive disorders of pregnancy. Study Design This is a retrospective cohort study of women with singleton pregnancies who had cell-free DNA (cfDNA) screening at 10 to 20 weeks of gestation. The primary outcome was the development of gestational hypertension (gHTN), preeclampsia (PEC), and PEC with severe features. Multinomial logistic regression was performed to assess the relationship between fetal fraction and pregnancy outcomes of interest while controlling for potential confounders. Results Among 2,701 women meeting inclusion criteria, 387 (14.3%) were diagnosed with hypertensive disorders of pregnancy. First-trimester fetal fraction was significantly lower in women diagnosed with hypertensive disorders of pregnancy (10.9 vs. 12.4, p < 0.0001). An increased risk of gHTN and PEC, PEC with severe features with delivery > 34 weeks, and PEC with severe features with delivery ≤ 34 weeks was seen with lower first-trimester fetal fractions (odds ratio [OR]: 0.55, 95% confidence interval [CI] [0.36–0.83], p = 0.005; OR: 0.59, 95% CI [0.35–0.99], p = 0.048; and OR: 0.27, 95% CI [0.08–0.96], p = 0.044). The relationship between fetal fraction and hypertensive disorders of pregnancy was not statistically significant after adjusting for maternal age, race, body mass index, and chronic hypertension. Conclusion Fetal fraction of cfDNA at 10 to 20 weeks of gestation was not associated with the development of hypertensive disorders of pregnancy.

Cell-Free DNA Screening for Fetal Aneuploidy

2021 ◽  
pp. 115-120
Author(s):  
Ashley N. Battarbee ◽  
Neeta L. Vora
Keyword(s):  
Trisomy 21 ◽  
Dna Analysis ◽  
Chromosomal Abnormalities ◽  
Area Under The Curve ◽  
First Trimester ◽  
Outcome Data ◽  
Cell Free Dna ◽  
High Risk Women ◽  
Free Dna ◽  
Trimester Screening

In a prospective, multicenter blinded study at 35 international centers, the Noninvasive Examination of Trisomy (NEXT) study evaluated the performance of cell-free DNA screening for fetal trisomy compared to standard first trimester screening with nuchal translucency and serum analytes in a routine prenatal population. Among the 15,841 women who had standard screening and cell-free DNA analysis with neonatal outcome data, there were 68 chromosomal abnormalities (1 in 236). Of these, 38 were Trisomy 21 (1 in 417). Cell-free DNA analysis had a higher area under the curve (AUC) for trisomy 21, compared to standard screening (0.999 vs. 0.958, p = 0.001). Cell-free DNA analysis also had greater sensitivity, specificity, and positive predictive value compared to standard screening for trisomy 21, 18, and 13. While cell-free DNA analysis cannot detect all chromosome abnormalities, it performed better than standard screening for detection of trisomies 21, 18, and 13 in a routine population including low- and high-risk women.

scholarly journals Noninvasive Fetal Genotyping by Droplet Digital PCR to Identify Maternally Inherited Monogenic Diabetes Variants

2020 ◽  
Vol 66 (7) ◽  
pp. 958-965 ◽  
Author(s):  
Richard C Caswell ◽  
Tristan Snowsill ◽  
Jayne A L Houghton ◽  
Ali J Chakera ◽  
Maggie H Shepherd ◽  
...  
Keyword(s):  
At Risk ◽  
Digital Pcr ◽  
Monogenic Diabetes ◽  
Droplet Digital Pcr ◽  
High Birth Weight ◽  
Cell Free Dna ◽  
Pathogenic Variants ◽  
Free Dna ◽  
Increased Risk ◽  
Fetal Fraction

Abstract Background Babies of women with heterozygous pathogenic glucokinase (GCK) variants causing mild fasting hyperglycemia are at risk of macrosomia if they do not inherit the variant. Conversely, babies who inherit a pathogenic hepatocyte nuclear factor 4α (HNF4A) diabetes variant are at increased risk of high birth weight. Noninvasive fetal genotyping for maternal pathogenic variants would inform pregnancy management. Methods Droplet digital PCR was used to quantify reference and variant alleles in cell-free DNA extracted from blood from 38 pregnant women heterozygous for a GCK or HNF4A variant and to determine fetal fraction by measurement of informative maternal and paternal variants. Droplet numbers positive for the reference/alternate allele together with the fetal fraction were used in a Bayesian analysis to derive probability for the fetal genotype. The babies’ genotypes were ascertained postnatally by Sanger sequencing. Results Droplet digital PCR assays for GCK or HNF4A variants were validated for testing in all 38 pregnancies. Fetal fraction of ≥2% was demonstrated in at least 1 cell-free DNA sample from 33 pregnancies. A threshold of ≥0.95 for calling homozygous reference genotypes and ≤0.05 for heterozygous fetal genotypes allowed correct genotype calls for all 33 pregnancies with no false-positive results. In 30 of 33 pregnancies, a result was obtained from a single blood sample. Conclusions This assay can be used to identify pregnancies at risk of macrosomia due to maternal monogenic diabetes variants.

scholarly journals 610: Actual rates of recommended diagnostic testing after first trimester screening vs. same-day screening by cell free DNA

2016 ◽  
Vol 214 (1) ◽  
pp. S326 ◽  
Author(s):  
Arin Buresch ◽  
Mara Rosner ◽  
Barrie Suskin ◽  
Francine Einstein ◽  
Emnonila Bircaj ◽  
...  
Keyword(s):  
Diagnostic Testing ◽  
First Trimester ◽  
First Trimester Screening ◽  
Cell Free Dna ◽  
Free Dna ◽  
Trimester Screening

scholarly journals Association between fetal fraction on cell‐free DNA testing and first‐trimester markers for pre‐eclampsia

2018 ◽  
Vol 52 (6) ◽  
pp. 722-727 ◽  
Author(s):  
D. L. Rolnik ◽  
F. da Silva Costa ◽  
T. J. Lee ◽  
M. Schmid ◽  
A. C. McLennan
Keyword(s):  
First Trimester ◽  
Dna Testing ◽  
Cell Free Dna ◽  
Free Dna ◽  
Fetal Fraction

scholarly journals SIGNIFICANCE OF LOW MATERNAL SERUM Β-HCG LEVELS IN THE ASSESSMENT OF THE RISK OF ATYPICAL CHROMOSOMAL ABNORMALITIES

2021 ◽  
Author(s):  
Robin Wijngaard ◽  
Elena Casals ◽  
Imma Mercadé ◽  
Javier Laguna ◽  
Irene Madrigal ◽  
...  
Keyword(s):  
Chromosomal Abnormalities ◽  
First Trimester ◽  
Maternal Serum ◽  
First Trimester Screening ◽  
Cell Free Dna ◽  
Substantial Impact ◽  
Free Dna ◽  
Trimester Screening ◽  
Β Hcg ◽  
The Impact

Introduction: The introduction of prenatal cell-free DNA as a screening test has surpassed traditional combined first-trimester screening (cFTS) in the detection of common trisomies. However, its current limitation in detecting only common trisomies is affecting the diagnostic yield for other clinically significant chromosomal abnormalities. Methods: In efforts to optimize the detection of fetuses with genetic abnormalities, we have analyzed the relationship between the cFTS risk score and biomarkers with atypical chromosomal abnormalities. Furthermore, we have evaluated the impact of prenatal cell-free DNA screening on the detection of chromosomal abnormalities in our population. For these purposes, we performed a retrospective study of 877 singleton pregnancies who underwent chromosomal microarray analysis (CMA) between 2013 to 2020 and for whom first-trimester screening data were available. Results: The results demonstrated that low levels of free beta human chorionic gonadotropin (β-hCG) (≤ 0.37 MoM) and increased fetal nuchal translucency (NT) (≥ 3.5mm) were statistically associated with the presence of atypical chromosomal abnormalities. In fact, the risk of pathogenic CMA results increased from 6% to 10% when fetal NT was increased and from 6% to 20% when a low serum β-hCG level was detected in the high-risk cFTS group. Moreover, our results showed that altered serum levels of β-hCG can have a substantial impact on the early detection of clinically relevant copy number variants. Discussion/Conclusion: Traditional cFTS can potentially identify a substantial proportion of atypical chromosomal aberrations, and women with increased NT or low maternal serum β-hCG levels are at increased risk of having pathogenic CMA results. Our results may help clinicians and women decide whether invasive testing or prenatal cell-free DNA screening testing are more appropriate for each situation.

First-trimester screening-biomarkers and cell-free DNA

2019 ◽  
pp. 1-7 ◽  
Author(s):  
Ioan Suciu ◽  
Slavyana Galeva ◽  
Samira Abdel Azim ◽  
Lucian Pop ◽  
Oana Toader
Keyword(s):  
First Trimester ◽  
First Trimester Screening ◽  
Cell Free Dna ◽  
Free Dna ◽  
Trimester Screening

scholarly journals Not all low fetal fraction cell‐free DNA screening failures are at increased risk for aneuploidy

2021 ◽  
Author(s):  
Samantha Caldwell ◽  
Eyad Almasri ◽  
Lindsey Schmidt ◽  
Chen Xu ◽  
Brittany Dyr ◽  
...  
Keyword(s):  
Cell Free Dna ◽  
Free Dna ◽  
Increased Risk ◽  
Fetal Fraction

scholarly journals Cell-Free DNA in the Investigation of Miscarriage

2020 ◽  
Vol 9 (11) ◽  
pp. 3428
Author(s):  
Emily Colley ◽  
Adam J. Devall ◽  
Helen Williams ◽  
Susan Hamilton ◽  
Paul Smith ◽  
...  
Keyword(s):  
Chromosomal Abnormalities ◽  
First Trimester ◽  
Maternal Blood ◽  
Tissue Cell ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna ◽  
Genome Wide ◽  
Prenatal Test ◽  
Fetal Fraction

Approximately one in four pregnancies result in pregnancy loss, and ~50% of these miscarriages are caused by chromosomal abnormalities. Genetic investigations are recommended after three consecutive miscarriages on products of conception (POC) tissue. Cell-free DNA (cfDNA) has been utilised for prenatal screening, but very little work has been carried out in nonviable pregnancies. We investigated the use of cfDNA from maternal blood to identify chromosomal abnormalities in miscarriage. One hundred and two blood samples from women experiencing a first trimester miscarriage were collected and stored. The mean gestational age was 7.1 weeks (range: 5–11 weeks). In this research, samples without a genetic test result from POC were not analysed. CfDNA was extracted and analysed using a modified commercial genome-wide non-invasive prenatal test. No results were provided to the patient. In 57 samples, cytogenetic results from POC analysis were available. Chromosomal abnormalities were identified in 47% (27/57) of POC analyses, and cfDNA analysis correctly identified 59% (16/27) of these. In total, 75% (43/57) of results were correctly identified. The average cfDNA fetal fraction was 6% (2–19%). In conclusion, cfDNA can be used to detect chromosomal abnormalities in miscarriages where the ‘fetal fraction’ is high enough; however, more studies are required to identify variables that can affect the overall results.

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