Cervical Nitric Oxide Release in Women Postterm

OBJECTIVE: Nitric oxide may be a factor in cervical ripening. We compared the nitric oxide metabolite levels in cervical fluid in women going beyond term and in women delivering spontaneously at term. METHODS: We studied a total of 208 women with singleton pregnancies: 108 women who went beyond term (294 days or longer), and 100 women who went spontaneously into labor at term. Cervical fluid samples, collected well before the initiation of labor, were assessed for nitric oxide metabolites using an assay with a detection limit of 3.8 μmol/L. RESULTS: Women going beyond term had detectable levels of nitric oxide metabolites in their cervical fluid (60%) less often (P = .001) than women delivering at term (87%). The nitric oxide metabolite concentration in cervical fluid in women going beyond term (median 23.5 μmol/L; 95% confidence interval less than 3.8, 31.8) was 4.5 times lower (P < .001) than that in women delivering at term (median 106.0 μmol/L; 95% confidence interval 81.8, 135.0). Such a difference (14.0 versus 106.0 μmol/L) also existed when only the 66 women going into spontaneous postterm labor were included in the comparison. Both nulliparous (median less than 3.8 μmol/L) and parous (median 31.3 μmol/L) women going beyond term had lower (P < .01) cervical fluid nitric oxide metabolite levels than nulliparous and parous women delivering at term (medians 76.1 and 101.3 μmol/L, respectively). In the postterm group, women with cervical fluid nitric oxide metabolite concentrations at or below the median failed more often (P < .001) to progress in labor and had longer (P = .02) duration of labor than those with cervical fluid nitric oxide metabolite concentrations above the median. CONCLUSION: Reduced cervical nitric oxide release may contribute to prolonged pregnancy. LEVEL OF EVIDENCE: II-2

[1]  P. Crowley,et al.  Interventions for preventing or improving the outcome of delivery at or beyond term. , 2006, The Cochrane database of systematic reviews.

[2]  V. Hiilesmaa,et al.  Nitric oxide metabolites in cervical fluid during pregnancy: further evidence for the role of cervical nitric oxide in cervical ripening. , 2003, American journal of obstetrics and gynecology.

[3]  G. Saade,et al.  Nitric oxide and its role during pregnancy: from ovulation to delivery. , 2003, Current pharmaceutical design.

[4]  R. Kelly Inflammatory mediators and cervical ripening. , 2002, Journal of reproductive immunology.

[5]  Hong Wang,et al.  Increased Level of Matrix Metalloproteinases 2 and 9 in the Ripening Process of the Human Cervix1 , 2002, Biology of reproduction.

[6]  M. Brännström,et al.  Nitric oxide induced cervical ripening in the human: Involvement of cyclic guanosine monophosphate, prostaglandin F2α, and prostaglandin E2 , 2002 .

[7]  H. Itoh,et al.  Nitric oxide increases matrix metalloproteinase-1 production in human uterine cervical fibroblast cells. , 2001, Molecular human reproduction.

[8]  Shunzhong S Bao,et al.  Brain Nitric Oxide Synthase Expression Is Enhanced in the Human Cervix in Labor , 2001, The Journal of the Society for Gynecologic Investigation: JSGI.

[9]  H. Tsuji,et al.  Nitric Oxide Mediates the Change of Proteoglycan Synthesis in the Human Lumbar Intervertebral Disc in Response to Hydrostatic Pressure , 2001, Spine.

[10]  J. Norman,et al.  Changes in the expression of nitric oxide synthase in the human uterine cervix during pregnancy and parturition. , 2000, Molecular human reproduction.

[11]  M. Brännström,et al.  Nitric oxide synthases in the human cervix at term pregnancy and effects of nitric oxide on cervical smooth muscle contractility. , 2000, American journal of obstetrics and gynecology.

[12]  A. Malmström,et al.  Human cervical ripening, an inflammatory process mediated by cytokines. , 2000, Molecular human reproduction.

[13]  C. Schneeberger,et al.  Human cervical ripening is associated with an increase in cervical inducible nitric oxide synthase expression. , 1999, Biology of reproduction.

[14]  H. Stenlund,et al.  Recurrence of prolonged pregnancy. , 1999, International journal of epidemiology.

[15]  B. Brüne,et al.  Nitric oxide and its role in apoptosis. , 1998, European journal of pharmacology.

[16]  R. Newcombe Two-sided confidence intervals for the single proportion: comparison of seven methods. , 1998, Statistics in medicine.

[17]  H. M. Beier,et al.  Cervical ripening in guinea-pigs after a local application of nitric oxide. , 1997, Human reproduction.

[18]  R. Garfield,et al.  Regulation of the Uterus and Cervix during Pregnancy and Labor Role of Progesterone and Nitric Oxide , 1997, Annals of the New York Academy of Sciences.

[19]  A. Malmström,et al.  Interleukin-8 is a mediator of the final cervical ripening in humans. , 1997, European journal of obstetrics, gynecology, and reproductive biology.

[20]  Truls Østbye,et al.  Post‐Term Birth: Risk Factors and Outcomes in a 10‐Year Cohort of Norwegian Births , 1997, Obstetrics and gynecology.

[21]  P. Ylöstalo,et al.  Ultrasound Screening and Perinatal Mortality: Controlled Trial of Systematic One-stage Screening in Pregnancy The Helsinki Ultrasound Trial , 1991 .

[22]  O. Heinonen,et al.  Ultrasound screening and perinatal mortality: controlled trial of systematic one-stage screening in pregnancy , 1990, The Lancet.

[23]  Jane E Norman,et al.  Leukocyte density and pro-inflammatory cytokine expression in human fetal membranes, decidua, cervix and myometrium before and during labour at term. , 2003, Molecular human reproduction.