TY - JOUR
T1 - Fetal fraction of cell-free DNA in noninvasive prenatal testing and adverse pregnancy outcomes
T2 - a nationwide retrospective cohort study of 56,110 pregnant women
AU - Becking, Ellis C.
AU - Scheffer, Peter G.
AU - Henrichs, Jens
AU - Bax, Caroline J.
AU - Crombag, Neeltje M.T.H.
AU - Weiss, Marjan M.
AU - Macville, Merryn V.E.
AU - Van Opstal, Diane
AU - Boon, Elles M.J.
AU - Sistermans, Erik A.
AU - Henneman, Lidewij
AU - Schuit, Ewoud
AU - Bekker, Mireille N.
N1 - Funding Information:
This work was supported by a grant from the Netherlands Organisation for Health Research and Development (No. 43002014). The funders of the study had no role in the study design, data collection, data analysis, data interpretation, writing of the manuscript, or the decision to submit the report.
Publisher Copyright:
© 2023 The Authors
PY - 2023
Y1 - 2023
N2 - Background: Noninvasive prenatal testing by cell-free DNA analysis is offered to pregnant women worldwide to screen for fetal aneuploidies. In noninvasive prenatal testing, the fetal fraction of cell-free DNA in the maternal circulation is measured as a quality control parameter. Given that fetal cell-free DNA originates from the placenta, the fetal fraction might also reflect placental health and maternal pregnancy adaptation. Objective: This study aimed to assess the association between the fetal fraction and adverse pregnancy outcomes. Study Design: We performed a retrospective cohort study of women with singleton pregnancies opting for noninvasive prenatal testing between June 2018 and June 2019 within the Dutch nationwide implementation study (Trial by Dutch Laboratories for Evaluation of Non-Invasive Prenatal Testing [TRIDENT]-2). Multivariable logistic regression analysis was used to assess associations between fetal fraction and adverse pregnancy outcomes. Fetal fraction was assessed as a continuous variable and as <10th percentile, corresponding to a fetal fraction <2.5%. Results: The cohort comprised 56,110 pregnancies. In the analysis of fetal fraction as a continuous variable, a decrease in fetal fraction was associated with increased risk of hypertensive disorders of pregnancy (adjusted odds ratio, 2.27 [95% confidence interval, 1.89–2.78]), small for gestational age neonates <10th percentile (adjusted odds ratio, 1.37 [1.28–1.45]) and <2.3rd percentile (adjusted odds ratio, 2.63 [1.96–3.57]), and spontaneous preterm birth from 24 to 37 weeks of gestation (adjusted odds ratio, 1.02 [1.01–1.03]). No association was found for fetal congenital anomalies (adjusted odds ratio, 1.02 [1.00–1.04]), stillbirth (adjusted odds ratio, 1.02 [0.96–1.08]), or neonatal death (adjusted odds ratio, 1.02 [0.96–1.08]). Similar associations were found for adverse pregnancy outcomes when fetal fraction was <10th percentile. Conclusion: In early pregnancy, a low fetal fraction is associated with increased risk of adverse pregnancy outcomes. These findings can be used to expand the potential of noninvasive prenatal testing in the future, enabling the prediction of pregnancy complications and facilitating tailored pregnancy management through intensified monitoring or preventive measures.
AB - Background: Noninvasive prenatal testing by cell-free DNA analysis is offered to pregnant women worldwide to screen for fetal aneuploidies. In noninvasive prenatal testing, the fetal fraction of cell-free DNA in the maternal circulation is measured as a quality control parameter. Given that fetal cell-free DNA originates from the placenta, the fetal fraction might also reflect placental health and maternal pregnancy adaptation. Objective: This study aimed to assess the association between the fetal fraction and adverse pregnancy outcomes. Study Design: We performed a retrospective cohort study of women with singleton pregnancies opting for noninvasive prenatal testing between June 2018 and June 2019 within the Dutch nationwide implementation study (Trial by Dutch Laboratories for Evaluation of Non-Invasive Prenatal Testing [TRIDENT]-2). Multivariable logistic regression analysis was used to assess associations between fetal fraction and adverse pregnancy outcomes. Fetal fraction was assessed as a continuous variable and as <10th percentile, corresponding to a fetal fraction <2.5%. Results: The cohort comprised 56,110 pregnancies. In the analysis of fetal fraction as a continuous variable, a decrease in fetal fraction was associated with increased risk of hypertensive disorders of pregnancy (adjusted odds ratio, 2.27 [95% confidence interval, 1.89–2.78]), small for gestational age neonates <10th percentile (adjusted odds ratio, 1.37 [1.28–1.45]) and <2.3rd percentile (adjusted odds ratio, 2.63 [1.96–3.57]), and spontaneous preterm birth from 24 to 37 weeks of gestation (adjusted odds ratio, 1.02 [1.01–1.03]). No association was found for fetal congenital anomalies (adjusted odds ratio, 1.02 [1.00–1.04]), stillbirth (adjusted odds ratio, 1.02 [0.96–1.08]), or neonatal death (adjusted odds ratio, 1.02 [0.96–1.08]). Similar associations were found for adverse pregnancy outcomes when fetal fraction was <10th percentile. Conclusion: In early pregnancy, a low fetal fraction is associated with increased risk of adverse pregnancy outcomes. These findings can be used to expand the potential of noninvasive prenatal testing in the future, enabling the prediction of pregnancy complications and facilitating tailored pregnancy management through intensified monitoring or preventive measures.
KW - adverse pregnancy outcomes
KW - cell-free DNA
KW - cell-free DNA screening
KW - cell-free fetal DNA
KW - fetal fraction
KW - gestational diabetes
KW - hypertensive disorders of pregnancy
KW - noninvasive prenatal testing
KW - pregnancy complications
KW - small for gestational age neonates
KW - spontaneous preterm birth
U2 - 10.1016/j.ajog.2023.12.008
DO - 10.1016/j.ajog.2023.12.008
M3 - Article
SN - 0002-9378
JO - American Journal of Obstetrics and Gynecology
JF - American Journal of Obstetrics and Gynecology
ER -