Low fetal fraction in early pregnancy associated with increased risk of adverse pregnancy outcomes, reveals research

Noninvasive prenatal testing (NIPT) for Down, Edwards, and Patau syndromes is made possible by the detection of fetal cell-free DNA (cfDNA) in maternal blood. Recent study titled "Fetal fraction of cell-free DNA in noninvasive prenatal testing and adverse pregnancy outcomes: a nationwide retrospective cohort study of 56,110 pregnant women" aimed to assess the association between fetal fraction and adverse pregnancy outcomes. The study conducted a retrospective cohort analysis of 56,110 pregnant women who underwent noninvasive prenatal testing (NIPT) between June 2018 and June 2019 within the Dutch nationwide implementation study (TRIDENT-2).

Findings and Association with Adverse Pregnancy Outcomes

The findings of the study indicated a significant association between fetal fraction and adverse pregnancy outcomes. When fetal fraction was analyzed as a continuous variable, a decrease in fetal fraction was associated with an increased risk of hypertensive disorders of pregnancy, small for gestational age neonates, and spontaneous preterm birth. Specifically, a decrease in fetal fraction was associated with increased risk of hypertensive disorders of pregnancy (adjusted odds ratio, 2.27), small for gestational age neonates <10th percentile (adjusted odds ratio, 1.37) and <2.3rd percentile (adjusted odds ratio, 2.63), and spontaneous preterm birth from 24 to 37 weeks of gestation (adjusted odds ratio, 1.02).

Association with Specific Pregnancy Complications

The study found no association between fetal fraction and fetal congenital anomalies, stillbirth, or neonatal death. However, when fetal fraction was below the 10th percentile, there were similar associations with adverse pregnancy outcomes.

Conclusion and Implications for Clinical Practice

The study concluded that in early pregnancy, a low fetal fraction is associated with an increased risk of adverse pregnancy outcomes. These findings suggest the potential for using noninvasive prenatal testing to predict and manage pregnancy complications. The authors emphasized that the identification of pregnant women at risk for adverse outcomes is crucial for timely preventive measures or intensified monitoring, and the potential clinical utility of fetal fraction as a screening parameter warrants further exploration.

Significance and Potential Implications of the Findings

The study is significant as it sheds light on the potential of NIPT in predicting adverse pregnancy outcomes and suggests that fetal fraction in NIPT could be a biomarker for placental health. The potential implications of these findings include utilizing NIPT for risk stratification of adverse pregnancy outcomes, which could enable tailored pregnancy management through intensified monitoring or preventive measures. The study was supported by a grant from the Netherlands Organisation for Health Research and Development (No.43002014), and the authors acknowledged the Dutch national prenatal screening registry Peridos and the Dutch national perinatal registry Perined for their collaboration and providing data for the study.

Key Points

- Study findings indicated a significant association between fetal fraction and adverse pregnancy outcomes. Decrease in fetal fraction was associated with an increased risk of hypertensive disorders of pregnancy, small for gestational age neonates, and spontaneous preterm birth. Specifically, a decrease in fetal fraction was associated with increased risk of hypertensive disorders of pregnancy (adjusted odds ratio, 2.27), small for gestational age neonates <10th percentile (adjusted odds ratio, 1.37) and <2.3rd percentile (adjusted odds ratio, 2.63), and spontaneous preterm birth from 24 to 37 weeks of gestation (adjusted odds ratio, 1.02).

- No association between fetal fraction and fetal congenital anomalies, stillbirth, or neonatal death was found. However, when fetal fraction was below the 10th percentile, there were similar associations with adverse pregnancy outcomes.

- The study concluded that in early pregnancy, a low fetal fraction is associated with an increased risk of adverse pregnancy outcomes, suggesting the potential for using NIPT to predict and manage pregnancy complications. The authors emphasized the importance of identifying pregnant women at risk for adverse outcomes for timely preventive measures or intensified monitoring. The potential clinical utility of fetal fraction as a screening parameter was highlighted for further exploration.

- The study is significant as it sheds light on the potential of NIPT in predicting adverse pregnancy outcomes and suggests that fetal fraction in NIPT could serve as a biomarker for placental health. The findings indicate potential implications for risk stratification of adverse pregnancy outcomes, utilizing NIPT for tailored pregnancy management through intensified monitoring or preventive measures. - The study was supported by a grant from the Netherlands Organisation for Health Research and Development (No.43002014), and the authors acknowledged the Dutch national prenatal screening registry Peridos and the Dutch national perinatal registry Perined for their collaboration and providing data for the study.

Reference –

Becking EC, Scheffer PG, Henrichs J, et al. Fetal fraction of cell-free DNA in noninvasive pre-natal testing and adverse pregnancy outcomes: a nationwide retrospective cohort study of 56,110 pregnant women. Am J Obstet Gynecol 2024;231:244.e1-18