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High levels of fetal cell-free DNA in maternal serum: a risk factor for spontaneous preterm delivery.

Abstract

OBJECTIVE

This study was conducted to determine whether there is a relationship between the concentration of fetal cell-free DNA in maternal serum and the duration of pregnancy in women who are at high risk for preterm delivery because of either preterm labor or preterm premature rupture of the membranes.

STUDY DESIGN

Sera were collected and frozen from 71 women with a male fetus. Maternal serum fetal cell-free DNA concentration was measured with the use of real-time polymerase chain reaction amplification of DYS1. Fetal cell-free DNA concentrations were converted to multiples of the median. The following groups were studied: group 1: women with preterm labor and intact membranes who were delivered at > or = 36 weeks of gestation (n = 21); group 2: women with preterm labor who were delivered at <36 weeks of gestation (n = 29); and group 3: women with preterm premature rupture of the membranes in labor (n = 20) or not in labor (n = 1) who were delivered prematurely (<36 weeks of gestation). Kaplan-Meier and Cox regression analyses were used to analyze the relationship between fetal cell-free DNA concentrations and the likelihood of preterm delivery.

RESULTS

A cut-off value for fetal cell-free DNA of 1.82 multiples of the median was chosen for analysis. The cumulative rate of early preterm delivery (<30 weeks of gestation) was significantly higher for women with fetal cell-free DNA concentrations of > or = 1.82 multiples of the median than those with fetal cell-free DNA concentrations below this cut-off (45% [95% CI, 36%-74%] vs 18% [95% CI, 11%-25%]; P = .008]. The cumulative rate of preterm delivery (<36 weeks of gestation) was also significantly higher at > or = 1.82 multiples of the median (73% [95% CI, 52%-93%] vs 66% [95% CI, 54%-79%]; P = .02). After adjustment for covariates, Cox analysis showed that fetal cell-free DNA at > or = 1.82 multiples of the mechanisms of disease that are associated with a mean hazard rate of delivery of 1.57 (P = .005).

CONCLUSION

High concentrations of fetal cell-free DNA in maternal serum are associated with an increased risk of spontaneous preterm delivery. This observation may have implications for the understanding of the mechanisms of disease that is associated with preterm labor.

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  • Authors+Show Affiliations

    ,

    Department of Embryology, Obstetrics and Gynecology, Prenatal Medicine Unit, University of Bologna, Bologna, Italy.

    , , , , ,

    Source

    MeSH

    Cross-Sectional Studies
    DNA
    Female
    Fetal Membranes, Premature Rupture
    Fetus
    Gestational Age
    Humans
    Obstetric Labor, Premature
    Pregnancy
    Proportional Hazards Models
    Risk Factors

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    16098864

    Citation

    Farina, Antonio, et al. "High Levels of Fetal Cell-free DNA in Maternal Serum: a Risk Factor for Spontaneous Preterm Delivery." American Journal of Obstetrics and Gynecology, vol. 193, no. 2, 2005, pp. 421-5.
    Farina A, LeShane ES, Romero R, et al. High levels of fetal cell-free DNA in maternal serum: a risk factor for spontaneous preterm delivery. Am J Obstet Gynecol. 2005;193(2):421-5.
    Farina, A., LeShane, E. S., Romero, R., Gomez, R., Chaiworapongsa, T., Rizzo, N., & Bianchi, D. W. (2005). High levels of fetal cell-free DNA in maternal serum: a risk factor for spontaneous preterm delivery. American Journal of Obstetrics and Gynecology, 193(2), pp. 421-5.
    Farina A, et al. High Levels of Fetal Cell-free DNA in Maternal Serum: a Risk Factor for Spontaneous Preterm Delivery. Am J Obstet Gynecol. 2005;193(2):421-5. PubMed PMID: 16098864.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - High levels of fetal cell-free DNA in maternal serum: a risk factor for spontaneous preterm delivery. AU - Farina,Antonio, AU - LeShane,Erik S, AU - Romero,Roberto, AU - Gomez,Ricardo, AU - Chaiworapongsa,Tinnakorn, AU - Rizzo,Nicola, AU - Bianchi,Diana W, PY - 2003/04/17/received PY - 2004/12/10/revised PY - 2004/12/14/accepted PY - 2005/8/16/pubmed PY - 2005/9/16/medline PY - 2005/8/16/entrez SP - 421 EP - 5 JF - American journal of obstetrics and gynecology JO - Am. J. Obstet. Gynecol. VL - 193 IS - 2 N2 - OBJECTIVE: This study was conducted to determine whether there is a relationship between the concentration of fetal cell-free DNA in maternal serum and the duration of pregnancy in women who are at high risk for preterm delivery because of either preterm labor or preterm premature rupture of the membranes. STUDY DESIGN: Sera were collected and frozen from 71 women with a male fetus. Maternal serum fetal cell-free DNA concentration was measured with the use of real-time polymerase chain reaction amplification of DYS1. Fetal cell-free DNA concentrations were converted to multiples of the median. The following groups were studied: group 1: women with preterm labor and intact membranes who were delivered at > or = 36 weeks of gestation (n = 21); group 2: women with preterm labor who were delivered at <36 weeks of gestation (n = 29); and group 3: women with preterm premature rupture of the membranes in labor (n = 20) or not in labor (n = 1) who were delivered prematurely (<36 weeks of gestation). Kaplan-Meier and Cox regression analyses were used to analyze the relationship between fetal cell-free DNA concentrations and the likelihood of preterm delivery. RESULTS: A cut-off value for fetal cell-free DNA of 1.82 multiples of the median was chosen for analysis. The cumulative rate of early preterm delivery (<30 weeks of gestation) was significantly higher for women with fetal cell-free DNA concentrations of > or = 1.82 multiples of the median than those with fetal cell-free DNA concentrations below this cut-off (45% [95% CI, 36%-74%] vs 18% [95% CI, 11%-25%]; P = .008]. The cumulative rate of preterm delivery (<36 weeks of gestation) was also significantly higher at > or = 1.82 multiples of the median (73% [95% CI, 52%-93%] vs 66% [95% CI, 54%-79%]; P = .02). After adjustment for covariates, Cox analysis showed that fetal cell-free DNA at > or = 1.82 multiples of the mechanisms of disease that are associated with a mean hazard rate of delivery of 1.57 (P = .005). CONCLUSION: High concentrations of fetal cell-free DNA in maternal serum are associated with an increased risk of spontaneous preterm delivery. This observation may have implications for the understanding of the mechanisms of disease that is associated with preterm labor. SN - 0002-9378 UR - https://www.unboundmedicine.com/medline/citation/16098864/High_levels_of_fetal_cell_free_DNA_in_maternal_serum:_a_risk_factor_for_spontaneous_preterm_delivery_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9378(04)02106-4 DB - PRIME DP - Unbound Medicine ER -