title: Efficacy of midtrimester short cervix interventions is conditional on intraamniotic inflammation.
abstract: BACKGROUND
  Midtrimester ultrasound is a valuable method for identifying asymptomatic women at risk for spontaneous preterm delivery (PTD). However, response to various treatments (cerclage, progestogen) has been variable in the clinical setting. It remains unclear how other biomarkers may be used to guide intervention strategies.
  
  
  OBJECTIVE
  We applied an amniotic fluid inflammatory scoring system to determine if the degree of inflammation is associated with intervention efficacy in patients with midtrimester short cervix.
  
  
  METHODS
  Women carrying a singleton fetus between 16-24 weeks' gestation with a short cervix (≤25 mm) on transvaginal ultrasound underwent amniocentesis and were assigned to McDonald cerclage, no cerclage, or weekly 17-alpha hydroxyprogesterone caproate (17OHP-C). Our previously described inflammatory risk score (comprised of 14 inflammatory markers) was used to classify patients as high (score ≥8) or low (score <8) risk for inflammation. Gestational age at delivery was compared for each intervention and risk score status. Risk of delivering as a function of the remaining gestation was evaluated using modified Cox proportional hazards models with incorporation of methods to account for both left and right truncation bias.
  
  
  RESULTS
  Ninety patients were included: 24 were in the nonintervention control group, 51 received cerclage, and 15 received 17OHP-C. Inflammation status at time of sampling influenced the efficacy of the treatment (P < .001). Compared to the nonintervention control group, in patients with low inflammation (score < 8), both cerclage (adjusted hazard ratio [HR], 2.86; 95% confidence interval [CI], 1.28-6.37) and 17OHP-C (HR, 3.11; 95% CI, 1.04-9.30) were associated with increased hazard of PTD. In contrast, in patients with high inflammation (score ≥8) both cerclage (HR, 0.22; 95% CI, 0.08-0.65) and 17OHP-C (HR, 0.20; 95% CI, 0.05-0.81) were associated with lower hazard of delivering preterm.
  
  
  CONCLUSIONS
  Cerclage placement or administration of 17OHP-C therapy for midtrimester short cervix for PTD prevention appears beneficial only in the subset of patients with high inflammation. Knowledge of the amniotic fluid inflammatory status may aid in guiding the appropriate therapy for women presenting with midtrimester short cervix who are at increased risk of PTD.
authors.affiliation: Department Obstetrics and Gynecology, Lehigh Valley Health Network, Allentown, PA.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Kiefer
authors.affiliation: Women and Children Research Laboratory, Winthrop University Hospital, Mineola, NY; Department of Obstetrics and Gynecology, Winthrop University Hospital, Mineola, NY.
authors.forename: Morgan R
authors.initials: MR
authors.lastname: Peltier
authors.affiliation: Desert Perinatal Associates, Las Vegas, NV.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Keeler
authors.affiliation: Department Obstetrics and Gynecology, Lehigh Valley Health Network, Allentown, PA.
authors.forename: Orion
authors.initials: O
authors.lastname: Rust
authors.affiliation: Department Obstetrics and Gynecology, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY.
authors.forename: Cande V
authors.initials: CV
authors.lastname: Ananth
authors.affiliation: Department of Obstetrics and Gynecology, Winthrop University Hospital, Mineola, NY.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Vintzileos
authors.affiliation: Women and Children Research Laboratory, Winthrop University Hospital, Mineola, NY; Department of Pediatrics, Winthrop University Hospital, Mineola, NY. Electronic address: nazeehhanna@gmail.com.
authors.forename: Nazeeh
authors.initials: N
authors.lastname: Hanna
mesh_terms: D000077713:17 alpha-Hydroxyprogesterone Caproate; D000328:Adult; D000649:Amniocentesis; D000653:Amniotic Fluid / Q000276:immunology*; D023802:Cerclage, Cervical / Q000379:methods*; D054791:Cervical Length Measurement; D002584:Cervix Uteri / Q000000981:diagnostic imaging*; D018932:Chemokine CCL2 / Q000276:immunology; D054405:Chemokine CCL3 / Q000276:immunology; D054407:Chemokine CCL4 / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D006908:Hydroxyprogesterones / Q000627:therapeutic use*; D007249:Inflammation; D007378:Interleukins / Q000276:immunology; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D047928:Premature Birth / Q000276:immunology / Q000517:prevention & control*; D011372:Progestins; D016016:Proportional Hazards Models; D018570:Risk Assessment; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D055815:Young Adult
chemical_list: D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines; D006908:Hydroxyprogesterones; D007378:Interleukins; D011372:Progestins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D000077713:17 alpha-Hydroxyprogesterone Caproate
keywords: amniotic fluid; cerclage; inflammation; prematurity; progesterone; sonographic short cervix