Prediction of Labor Induction Outcome in Nulliparous Women

Официальное название

Evaluation of Biomarkers in Term Labor Induction in Low-Risk Nulliparous Patients: Toward Better Prediction of Induction Outcomes

Обзор

Labor induction rates are increasing worldwide, yet nulliparous patients remain at high risk of failed induction and intrapartum cesarean delivery as well as prolonged labor which are associated with increased maternal morbidity, adverse outcomes in future pregnancies, increased neonatal morbidity and negative childbirth experience. This study aims to evaluate whether macrophage activation biomarkers in cervicovaginal secretions can predict successful labor induction in low-risk nulliparous women at term with an unfavorable cervix (Bishop score \<6). The study focuses on three patented biomarkers of "imminence of delivery" (MCP1, CD14, and CD163), previously shown to be markedly elevated during spontaneous labor. We hypothesize that higher biomarker concentrations reflect biological readiness for labor and are associated with successful induction, defined as entry into the active phase of labor (cervical dilation ≥6 cm). Secondary objectives include evaluating the association between biomarker concentrations and labor progression. Identifying reliable predictive biomarkers could improve patient selection for induction and optimize obstetrical management in nulliparous women.

Подробное описание

The aim of labor induction is to reduce maternal and/or fetal complications associated with continuation of pregnancy while enabling vaginal delivery.

The investigators hypothesize that, at the time of induction, some key biological changes may already have occurred, thereby facilitating the initiation and progression of labor.

Our objective is to evaluate the association between the concentration of three macrophage activation biomarkers (referred to as "imminence of delivery" biomarkers) in cervicovaginal secretions (MCP1, CD14, and CD163) and successful labor induction among low-risk nulliparous women with an unfavorable cervix (Bishop score \<6) at ≥39 weeks of gestation. We hypothesize that high biomarker concentrations will predict successful induction.

Pregnant women ≥ 39 weeks of gestation admitted to the maternity unit for labor induction who are eligible for the study will be approached to participate. The study procedures will be explained by the clinician (obstetrician-gynaecologist or midwife) in charge of the patient. In the absence of objection, the clinician who provided the information will complete the non-opposition form required for the patient's inclusion in the study. A cervicovaginal swab for biomarker measurement will be collected prior to labor induction.

A non-parametric Kruskal-Wallis test will be used to compare biomarker concentrations between patients who underwent caesarean delivery before 6 cm of cervical dilation and those whose labor progressed beyond 6 cm. The predictive value of biomarkers for induction success will be assessed using receiver operating characteristic (ROC) curves. The area under the curve (AUC) will be calculated with its 95% confidence interval, and the optimal threshold for each biomarker will be determined.

The predictive value of the three biomarkers will be assessed in the same manner for the following secondary outcomes: the rate of vaginal delivery within 24 hours of induction onset, the time from induction onset to delivery, and the time from induction onset to reaching 6 cm of cervical dilation.

In addition, patients will be offered the option of donating a sample of the placenta and fetal membranes (amniotic sac) following delivery. These tissues, which are not routinely preserved, will be analyzed with the aim of identifying potential new biomarkers of interest. The collection of a placental sample at delivery is not a prerequisite for participation in the study. Patients will be free to participate in the study (i.e. biomarker measurement in vaginal secretions) while objecting to the collection of a placental sample at delivery.

Вмешательства

• Биопрепарат Vaginal sample
  A vaginal sample will be collected from 39 weeks of gestation onward, prior to labor induction. The vaginal swab for biomarker testing will be collected at the same time as the vaginal swab for Group B streptococcus screening (which is routinely performed as part of standard care, in accordance with clinical practice guidelines). Therefore, no additional procedure is required for this research.

Первичные конечные точки

• The primary outcome is successful labor induction, defined as entry into the active phase of labor (cervical dilation ≥6 cm). [Срок оценки: Up to 7 days]

Вторичные конечные точки (3)

• The rate of vaginal delivery within 24 hours of the start of induction [Срок оценки: Within 24hours of the start of induction]
• The time from the beginning of labour induction to vaginal delivery (in hours) [Срок оценки: From the beginning of labour induction to vaginal delivery (in hours)]
• The time from the beginning of labour induction to 6 cm of dilation (entry into the active phase) (in hours) [Срок оценки: From the beginning of labour induction to 6 cm of dilation]

Критерии участия

Критерии включения

• Age ≥ 18 years
• Singleton pregnancy
• Gestational age ≥ 39 weeks
• Nulliparous
• Live foetus
• Cephalic presentation
• Intact membranes
• Bishop score < 6
• Willing to participate in the study

Критерии исключения

• A minor or a protected adult (under guardianship or conservatorship)
• Individuals who don't speak French or are not accompanied by a third party who speaks French
• Suspected intrauterine fetal growth restriction (estimated fetal weight < 3rd percentile or < 10th percentile with abnormal fetal Doppler)
• Presence of fetal malformations and/or genetic or chromosomal abnormalities

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Франция · 1 центр

• AP-HP - Hôpital Cochin - Maternité Port-Royal — Paris

Публикации

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• Norwitz ER, Bonney EA, Snegovskikh VV, Williams MA, Phillippe M, Park JS, Abrahams VM. Molecular Regulation of Parturition: The Role of the Decidual Clock. Cold Spring Harb Perspect Med. 2015 Apr 27;5(11):10.1101/cshperspect.a023143 a023143. doi: 10.1101/cshperspect.a023143. PMID 25918180
• Stelzer IA, Ghaemi MS, Han X, Ando K, Hedou JJ, Feyaerts D, Peterson LS, Rumer KK, Tsai ES, Ganio EA, Gaudilliere DK, Tsai AS, Choisy B, Gaigne LP, Verdonk F, Jacobsen D, Gavasso S, Traber GM, Ellenberger M, Stanley N, Becker M, Culos A, Fallahzadeh R, Wong RJ, Darmstadt GL, Druzin ML, Winn VD, Gibbs RS, Ling XB, Sylvester K, Carvalho B, Snyder MP, Shaw GM, Stevenson DK, Contrepois K, Angst MS, Ag PMID 33952678
• Socha MW, Flis W, Pietrus M, Wartega M, Stankiewicz M. Signaling Pathways Regulating Human Cervical Ripening in Preterm and Term Delivery. Cells. 2022 Nov 21;11(22):3690. doi: 10.3390/cells11223690. PMID 36429118
• Osterman MJK, Hamilton BE, Martin JA, Driscoll AK, Valenzuela CP. Births: Final Data for 2021. Natl Vital Stat Rep. 2023 Jan;72(1):1-53. PMID 36723449
• Grobman WA, Rice MM, Reddy UM, Tita ATN, Silver RM, Mallett G, Hill K, Thom EA, El-Sayed YY, Perez-Delboy A, Rouse DJ, Saade GR, Boggess KA, Chauhan SP, Iams JD, Chien EK, Casey BM, Gibbs RS, Srinivas SK, Swamy GK, Simhan HN, Macones GA; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Labor Induction versus Expectant Management PMID 30089070
• Le Ray C, Blondel B, Prunet C, Khireddine I, Deneux-Tharaux C, Goffinet F. Stabilising the caesarean rate: which target population? BJOG. 2015 Apr;122(5):690-9. doi: 10.1111/1471-0528.13199. Epub 2014 Nov 21. PMID 25412695
• Johnson DP, Davis NR, Brown AJ. Risk of cesarean delivery after induction at term in nulliparous women with an unfavorable cervix. Am J Obstet Gynecol. 2003 Jun;188(6):1565-9; discussion 1569-72. doi: 10.1067/mob.2003.458. PMID 12824994

Идентификаторы

NCT: NCT07637318 · APHP251724 · IDRCB

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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