The association of <i>HBB</i>-related significant hemoglobinopathies and low fetal fraction on noninvasive prenatal screening for fetal aneuploidy

Putra, Manesha; Idler, Jay; Patek, Kara; Contos, G.; Walker, Carol; Olson, Danielle N.; Hicks, Melissa A.; Chaperon, J; Korzeniewski, Steven J.; Patwardhan, Sanjay; Sokol, Robert J.

doi:10.1080/14767058.2019.1689558

Cited by 5 publications

(10 citation statements)

References 18 publications

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“…In the subgroup analysis of women with sickle cell trait, we also observed lower FF when compared to non‐carriers. These observations were similar to previous findings in women who were affected by HBB‐ related hemoglobinopathies, albeit our current study has a smaller effect size 11 . This lends support to our hypothesis that carriers of pathogenic variants in HBB have a subclinical increase of maternal cell necrosis that leads to a dilutional effect on FF.…”

Section: Discussionsupporting

confidence: 93%

“…Both of these cohorts were then compared to a control group of women who had low‐risk NIPS results (i.e., negative for trisomy 21, 18, 13 and sex chromosome aneuploidies) and were not carriers for any pathogenic variants in HBB or HBA1/HBA2. A subgroup analysis was performed among women with sickle cell trait (a subgroup of HBB‐ hemoglobinopathy carriers) because our previous study showed larger impact size among this group 11 …”

Section: Methodsmentioning

confidence: 99%

“…A subgroup analysis was performed among women with sickle cell trait (a subgroup of HBB-hemoglobinopathy carriers) because our previous study showed larger impact size among this group. 11 Multivariable linear regression was used to adjust for the systematic impacts of maternal age, gestational age and BMI to yield a "corrected FF" for each patient. Regression coefficients were 0.01% for each year of maternal age, 0.32% for each week of gestational age, and −0.27% for each unit of BMI.…”

Section: Methodsmentioning

confidence: 99%

“…9,10 We also previously reported the association of clinically significant beta-chain hemoglobin gene (HBB)-related hemoglobinopathies, especially sickle cell anemia, and low FF. 11 We speculated that this association could be due to an increase in maternal cell necrosis (from increased sickling or chronic anemia) causing a dilutional effect on FF.…”

Section: Introductionmentioning

confidence: 99%

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The impact of HBB‐related hemoglobinopathies carrier status on fetal fraction in noninvasive prenatal screening

et al. 2022

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Objective We evaluated whether there is an association between β‐globin (HBB) pathogenic variants and fetal fraction (FF), and whether the association has a clinically relevant impact on non‐invasive prenatal screening (NIPS). Method A whole‐genome sequencing NIPS laboratory database was retrospectively queried for women who underwent NIPS and carrier screening of both HBB and the α‐globin genes (HBA1/HBA2). Women affected with either condition were excluded from the study, yielding a cohort size of 15,853. A “corrected FF” was obtained via multivariable linear regression adjusted for the systematic impacts of maternal age, gestational age and BMI. Corrected FF distributions of HBB and HBA1/HBA2 carriers were each compared to non‐carriers using the Kolmogorov‐Smirnov test. Results In this cohort, 291 women were carriers for HBB alone, and 1016 were carriers for HBA1/HBA2 alone. The HBB carriers had a lower corrected FF when compared to non‐carriers (p < 0.0001). There was no difference in corrected FF among carriers and non‐carriers of HBA1/HBA2. Conclusion Carriers of pathogenic variants in the HBB gene, but not the HBA1/HBA2 genes, are more likely to have lower FF when compared to women with structurally normal hemoglobin. This decrease in FF could result in an elevated test‐failure rate if FF thresholds were used.

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Section: Discussionsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The impact of HBB‐related hemoglobinopathies carrier status on fetal fraction in noninvasive prenatal screening

et al. 2022

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“…More papers containing enough samples are needed to support this conclusion. Maternal diseases or severe immune maternal disorders, such as systemic lupus erythematosus ( 52), B12 deficiency (53), severe thrombocytopenia and neutropenia (54), significant HBB-related hemoglobinopathies (45), and preexisting hypertension (41) may also be associated with elevated maternal circulating cell-free DNA concentration or repeated detection failure owing to a low FF, while the FF improved after the disease was treated or suppressed.…”

Section: Maternal Characteristicsmentioning

confidence: 99%

Factors Affecting the Fetal Fraction in Noninvasive Prenatal Screening: A Review

Deng

Liu

2022

Front. Pediatr.

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A paradigm shift in noninvasive prenatal screening has been made with the discovery of cell-free fetal DNA in maternal plasma. Noninvasive prenatal screening is primarily used to screen for fetal aneuploidies, and has been used globally. Fetal fraction, an important parameter in the analysis of noninvasive prenatal screening results, is the proportion of fetal cell-free DNA present in the total maternal plasma cell-free DNA. It combines biological factors and bioinformatics algorithms to interpret noninvasive prenatal screening results and is an integral part of quality control. Maternal and fetal factors may influence fetal fraction. To date, there is no broad consensus on the factors that affect fetal fraction. There are many different approaches to evaluate this parameter, each with its advantages and disadvantages. Different fetal fraction calculation methods may be used in different testing platforms or laboratories. This review includes numerous publications that focused on the understanding of the significance, influencing factors, and interpretation of fetal fraction to provide a deeper understanding of this parameter.

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Advances in the Influencing Factors and Clinical Application of Fetal Fraction of the Non-Invasive Prenatal Testing

陈

2024

ACM

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The association of HBB-related significant hemoglobinopathies and low fetal fraction on noninvasive prenatal screening for fetal aneuploidy

Cited by 5 publications

References 18 publications

The impact of HBB‐related hemoglobinopathies carrier status on fetal fraction in noninvasive prenatal screening

The impact of HBB‐related hemoglobinopathies carrier status on fetal fraction in noninvasive prenatal screening

Factors Affecting the Fetal Fraction in Noninvasive Prenatal Screening: A Review

Advances in the Influencing Factors and Clinical Application of Fetal Fraction of the Non-Invasive Prenatal Testing

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