Early second-trimester plasma cell free DNA levels with subsequent risk of pregnancy complications

Abstract

Objective: To investigate the association between cfDNA levels measured during non-invasive prenatal testing (NIPT) and the risk of pregnancy complications in a Chinese population.

Methods: This was a retrospective cohort study of 831 pregnant women who underwent NIPT at 12-22 weeks of gestation. Maternal plasma cfDNA levels and pregnancy outcomes were obtained from NIPT Screening System and hospitalization records, respectively. Logistic regression analysis was performed to investigate the relationship between cfDNA levels and pregnancy complications (after adjusting for confounding factors).

Results: Maternal cfDNA levels were significantly higher in women diagnosed with intrahepatic cholestasis of pregnancy (ICP) and preeclampsia (PE) compared to pregnant women with non-pregnancy complications (NPC) (median cfDNA 7.07, 6.42 vs. 5.99 ng/mL). Increase in cfDNA levels were associated with an increased risk for ICP (adjusted-OR = 1.20, 95% CI: 1.07-1.34) and PE (adjusted-OR = 1.14, 95% CI: 1.02-1.26). In addition, increase in cfDNA levels were associated with risk of GDM, and was dependent on maternal age (maternal age ≥ 35 years: adjusted-OR = 1.16, 95% CI: 1.04-1.29; maternal age < 35 years: adjusted-OR = 0.85, 95% CI: 0.73-0.99).

Conclusion: Maternal plasma cfDNA levels measured during NIPT are associated with pregnancy complications (ICP, PE and GDM). Maternal age may be an important effect modifier for the association between plasma cfDNA levels and GDM.

Keywords: Cell free DNA; Gestational diabetes mellitus; Intrahepatic cholestasis of pregnancy; Maternal age; Non-invasive prenatal testing; Preeclampsia.