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Am J Perinatol 2025; 42(05): 605-611
DOI: 10.1055/a-2413-2353
Original Article

First-Trimester Cell-Free DNA Fetal Fraction and Birth Weight in Twin Pregnancies

Molly R. Siegel 
1   Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, Massachusetts
,
Kaitlyn James
1   Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, Massachusetts
,
Bryann Bromley
1   Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, Massachusetts
,
Nathanael C. Koelper
2   Department of Obstetrics and Gynecology, Women's Health Clinical Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
,
Stephen T. Chasen
3   Division of Maternal-Fetal Medicine, Weill Cornell Medical College, New York, New York
,
Laurie Griffin
4   Department of Obstetrics and Gynecology, The Warren Alpert Medical School at Brown University, Providence, Rhode Island
,
Ashley S. Roman
5   Department of Obstetrics and Gynecology, NYU Grossman School of Medicine, New York, New York
,
Meghana Limaye 
5   Department of Obstetrics and Gynecology, NYU Grossman School of Medicine, New York, New York
,
Angela Ranzini
6   Division of Maternal-Fetal Medicine, MetroHealth, Cleveland, Ohio
,
Caitlin Clifford
7   Division of Maternal-Fetal Medicine, University of Michigan Health, Ann Arbor, Michigan
,
Joseph R. Biggio
8   Division of Maternal-Fetal Medicine, Ochsner Health, New Orleans, Louisiana
,
Akila Subramaniam
9   Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama
,
Angela R. Seasely
9   Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama
,
Jessica M. Page
10   Division of Maternal-Fetal Medicine, Intermountain Health, Salt Lake City, Utah
,
Sara S. Nicholas
11   Axia Women's Health Main Line Perinatal Associates, Wynnewood, Pennsylvania
,
Jay Idler
12   Division of Maternal-Fetal Medicine, Allegheny Health Network, Pittsburgh, Pennsylvania
,
Rashmi Rao
13   Department of Obstetrics and Gynecology, UCLA, Los Angeles, California
,
Raj Shree
14   Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington
,
Graham McLennan
15   Clinical Affairs, Sequenom Inc, LabCorp, San Diego, California
,
Lorraine Dugoff
16   Division of Reproductive Genetics, Department of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
17   Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
,
on behalf of the Twin cfDNA Study Consortium › Author Affiliations Funding This work was supported by Labcorp.

Clinical Trials The study was registered with ClinicalTrials.gov (identifier: NCT04488393).
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Abstract

Objective

The relationship between fetal fraction and birth weight in twin gestations is poorly understood. This study aimed to investigate the relationship between first-trimester cell-free DNA (cfDNA) fetal fraction and birth weight <10th percentile in twin gestations.

Study Design

This is a planned secondary analysis of the Twin cfDNA Study, a 17-center retrospective cohort of twin pregnancies screened for aneuploidy using cfDNA in the first trimester from December 2011 to February 2022, excluding those with positive screen results for chromosomal aneuploidy. cfDNA testing was performed by a single laboratory using massively parallel sequencing. Baseline characteristics and birth weight of pregnancies with normal fetal fraction were compared with those with low (<5%) and high (>95%) fetal fraction using univariable analyses and multivariable regression.

Results

A total of 1,041 twin pregnancies were included. Chronic hypertension, elevated body mass index, and self-identified Black race were associated with fetal fraction <5th percentile. There was no difference in median fetal fraction between those with birth weight <10th percentile in at least one twin (median [interquartile range (IQR)] fetal fraction: 12.2% [9.8, 14.8] vs. those with normal birth weight (≥10th percentile) in both twins (median [IQR] fetal fraction: 12.3% [9.7, 15.2] for normal birth weight, p = 0.49). There was no association between high or low fetal fraction and birth weight <10th percentile for one (p = 0.45) or both (p = 0.81) twins, and there was no association between high or low fetal fraction and birth weight <5th percentile for one (p = 0.44) or both (p = 0.74) twins. The results were unchanged after adjustment for potential confounders.

Conclusion

In this large cohort, there was no association between the extremes of cfDNA fetal fraction and birth weight <10th percentile, suggesting that first-trimester fetal fraction may not predict impaired fetal growth in twin gestations.

Key Points

  • No association between fetal fraction and small for gestational age birth weight in twins.

  • Results suggest that fetal fraction does not predict birth weight in twin gestations.

  • These results differ from the relationship between fetal fraction and birth weight in singletons.

Keywords

cell-free DNA - twin gestations - birth weight

Note

Portions of this work were presented as a poster presentation at the 69th Annual Society for Reproductive Investigation Meeting in March 2022, in Denver, CO.




Publication History

Received: 15 July 2024

Accepted: 10 September 2024

Accepted Manuscript online:
11 September 2024

Article published online:
01 October 2024

© 2024. Thieme. All rights reserved.

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333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

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