Table 1.

Publications investigating the association between cell-free fetal DNA (cff-DNA) and adverse pregnancy outcomes including spontaneous preterm birth (spPTB).

Publication	Total N and (spPTB cases)	Study setup	Methods	Main findings
Leung et al. (1998)	32 (20)	Prospective cohort study to assess association with cff-DNA and spPTB	Quantification of SRY gene in maternal plasma at onset of PTB symptoms	Significantly higher SRY detection in women who deliver preterm (P = 0.042). Lower concentration of cff-DNA associated with successful tocolytic therapy (P = 0.017)
Farina et al. (2005)	71 (50)	Cross-sectional study of women at high risk for spPTB	Quantification of DYS1 gene in maternal serum at onset of PTB symptoms	Higher DYS1 detection in women who deliver preterm, by regression analysis of cff-DNA and gestational age at delivery (P = 0.003), significant maker when using cutoff of 1.82 MoM DYS1 gene
Bauer et al. (2006)	84 (7)	Prospective analysis for Cff-DNA as an indicator for adverse pregnancy outcomes	Quantifying the SRY gene and short tandem sequence from maternal plasma at amniocentesis (average 15 weeks) with blood sample	No significant increase in women who later delivered preterm (gestational age of 15.7 ± 0.5 at time of Cff-DNA quantification)
Illanes et al. (2011)	56 (14)	Case-control study to assess cff-DNA and risk of spPTB	DYS gene quantification from maternal plasma at 22–24 weeks in combination with a cervical length measurement	No correlation between cff-DNA levels and gestational age at delivery (r = −0.23; P = 0.07)
Stein et al. (2013)	611 (76)	Prospective cohort study to assess cff-DNA and adverse pregnancy outcome in low risk pregnancies	RhD gene quantification at 25 weeks (mean gestational age at quantification)	No significant increase in women who delivered preterm
Jakobsen et al. (2012)	876 (19)	Prospective cohort study to assess association with cff-DNA and spPTB	RhD gene quantification at 25 weeks of gestation	Strong association between cff-DNA levels above the 95th centile and subsequent spPTB (odds ratio of 6.3; 95% confidence interval: 1.9–20.9)
Poon et al. (2013)	1949 (20)	Prospective cohort study to assess cff-DNA and adverse pregnancy outcome	Chromosome selective assay at 11–13 weeks of gestation	No significant increase in regression analysis (20 deliveries <34 weeks of gestation P = 0.46)
Quezada et al. (2015)	3169 (103)	Cross-sectional study to assess cff-DNA and prediction of spPTB	Fetal Fraction quantified at 10–14 weeks with chromosome selective assay	No significant increase in women who deliver preterm
Dugoff et al. (2016)	1653 (119)	Retrospective cohort study at increased risk for aneuploidy	Methylation method and regional read depth counts from autosomes generated by whole-genome low coverage massively parallel single-end sequencing at 10–20 weeks	Elevated fetal fraction levels at 14.1–20 weeks were significantly associated with incidence of preterm birth (adjusted odds ratio, 4.59; 95% confidence interval, 1.39–15.2)
Thurik et al. (2016)	527 (49)	Nested case-control study to assess cff-DNA and adverse pregnancy outcome	Quantification of DYS14 gene at 8–14 weeks of gestation	No association with spPTB (49, P = 0.19)