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

Background: The relationship between fetal fraction and birth weight in twin gestations is poorly understood. Objective: To investigate the relationship between first trimester 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 12/2011 – 2/2022, excluding those with positive screen results for chromosomal aneuploidy. CfDNA testing was performed by a single lab using massively parallel sequencing (MPSS). Baseline characteristics and birth weight of pregnancies with normal fetal fraction were compared to those with low (<5%) and high (>95%) fetal fraction using univariable analyses and multivariable regression. Results: A total of 1041 twin pregnancies were included. Chronic hypertension, elevated BMI, 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 [IQR] fetal fraction 12.2% [9.8, 14.8] versus 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 birthweight < 10th percentile, suggesting that first trimester fetal fraction may not predict impaired fetal growth in twin gestations.