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Changes in Cervical Nitric Oxide Concentration Correlate With Bishop Score and Cervical Length Modifications in Prostaglandin E2-Mediated Induction of Labor

Gianluca Verocchi, MD

Paolo Venturini, MD

Mother-Infant Department, Section of Obstetrics, Modena Policlinico Hospital, University of Modena and Reggio Emilia, Modena, Italy

Fabio Facchinetti, MD

Mother-Infant Department, Section of Obstetrics, Modena Policlinico Hospital, University of Modena and Reggio Emilia, Modena, Italy; Mother-Infant Department, Section of Obstetrics, Modena Policlinico Hospital, University of Modena and Reggio Emilia, via del Pozzo 71, 41100, Modena, Italy; facchinetti.fabio{at}unimore.it

Objective: Nitric oxide (NO) plays a fundamental role in cervical ripening and it is synthesized in the human cervix. We studied the effect of the dinoprostone on cervical NO release in pregnant women, and we investigated the relationship between cervical NO metabolites, cervical length, and Bishop score.

Methods: Seventy-seven women underwent induction of labor at 37 weeks of gestation, due to post-term pregnancy (23.8%), oligohydraminos (36.3) or preeclampsia (29.9%). Cervical fluid samples for NO metabolites (NOx), Bishop score, and cervical length assessed immediately before (time 0 [T0]) and 6 hours after (T6) the local application of dinoprostone, a commercially available prostaglandin E2 (PGE2) analog.

Results: The mean patients' age was 34 ± 3.2 years, mean gestational age at enrollment was 284 ± 9.2 days, and nulliparous represented 31.2% of the study population. At time 0, Bishop score was less than 4 in 74% (57/77) of the subjects, mean cervical length was 28.6 ± 5.8 mm, mean NOx concentration was 208.6 ± 10.3 µM/mL; 6 hours later, at T6, the mean cervical length decreased to 19.5 ± 8.8 mm, and the mean NOx concentration increased up to 316.7 ± 240.9 µM/mL. Data were unaffected by parity or by regular uterine contraction patterns. A statistically significant positive correlation was found between changes in cervical NOx levels and Bishop score modification (P <.01; r = .494), as well as between the modification of NO metabolites concentration and cervical shortening (P <.01; r = .307).

Conclusions: Prostaglandin (PG)-induced cervical ripening is associated with local NO release. NO plays an active role in cervical remodeling since it positively correlates with both cervical shortening and Bishop score increase. NO oxide and PG are the two pathways that, cross activating other, trigger the cascade of events responsible of cervical ripening.

Key Words: Induction of labor • dinoprostone • prostaglandin E2 • nitric oxide • nitric oxide • metabolites • cervical ripening

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