Preterm Labor Prevention Using Vaginal Antiseptics Prior to 16 Weeks of Gestation
Condition: Preterm Birth
MeSH terms: Premature Birth
Study type: Observational [Patient Registry]

Summary: 
      The aim of this prospective observational study was to evaluate the efficacy of a universal
      strategy of primary prevention of preterm birth using intravaginal chlorhexidine (CLX)
      applied before 16 weeks.

      The main question is whether universal treatment with vaginal CLX before 16 weeks would
      reduce the incidence of preterm birth, especially before 34 weeks.

      Participants were recruited at the routine first trimester consultation. All patients
      underwent an initial ultrasound examination between 6+0 and 15+6 weeks gestation, including
      assessment of embryo/fetus vitality.

      Antiseptic treatment aimed at reducing possible bacterial overgrowth consisted of 10 days (1
      box) of CLX vaginal ovules (CLX digluconate 0.2%) always starting between 9+0 and 16+0 weeks.

      As this product is widely marketed and frequently indicated in gynaecology, we did not
      deprive the non-treated group of treatment because we wanted to assess whether it could have
      an effect on reducing preterm delivery.

      The pregnant women were then followed up until the end of pregnancy and compared with a
      cohort of patients who had not received any treatment.

      All data related to delivery were collected, as well as any events related to preterm
      delivery, such as onset of contractions, cervical shortening and premature rupture of
      membranes, regardless of final gestational age at delivery.
    

Detailed description: 
      Clinical implications of the study:

      The clinical implications of our project would be to counteract the effect of pathogenic
      bacteria from the beginning of pregnancy (outside the teratogenic period) with the
      administration of the CLX ovules and thus enhance the action of the normal vaginal microbiota
      in the pregnant patient, since the glycogen available due to hormonal action favours the
      growth and development of lactobacillus, responsible for its protective activity against
      pathogens during pregnancy.

      Sample size:

      The approximate number of births per year in Spain is 370,000. The minimum number of patients
      to be recruited would be 400 with a 95% confidence interval.

      Patients were recruited as they attended the consultation where the PI and/or collaborators
      were present.

      Variables:

        -  maternal age,

        -  parity,

        -  Gestational age (GA) at examination in weeks,

        -  GA at delivery in weeks,

        -  Interval between ultrasound and delivery,

        -  Birth weight (BW), BW centile,

        -  fetal gender,

        -  onset of labor (elective cesarean section, induction of labor and spontaneous onset of
           labor),

        -  mode of delivery (cesarean section for abnormal cardiotocography, failure to progress or
           elective, assisted delivery and spontaneous delivery),

        -  Apgar scores at 5 minutes,

        -  neonatal cord arterial hydrogen potential( pH)

        -  Newborn destination: ward, neonatal, neonatal intensive care unit

        -  Type of event triggering preterm birth:Premature rupture of membranes /Uterine dynamics
           + cervical modifications

      Statistical analysis Continuous variables were presented as mean and standard deviations
      (SD), median and interquartile range (IQR), while categorical variables were presented as
      absolute numbers and relative frequencies. Characteristics between both cohorts were compared
      by mean of Mann- Whitney and Fisher tests. Finally, to assess the validity of results and
      ensure consistency an additional multivariable analysis was performed adjusting for clinical
      parameters, to evaluate the odds ratio (OR) of the different determinants in the prediction
      of preterm birth. Finally, preterm birth incidence was calculated for specific groups
      selected according to the multivariable analysis result. Statistical analysis and graphs were
      done using Graph Pad Prism®, Mac version 9.0.1, and Stat Plus® Mac Pro version 8.0.1.s.
      Permissions were obtained from La Fe hospital review board and from the Valencian Autonomic
      Government health authorities (reference: PLUVA, date 4-2-2021). Written informed consent was
      retrieved to participate in the study. The authors report no conflicts of interest.

      Quality control:

      All analyses were performed on a single sample of patients who met the selection criteria and
      who had all the information required for the variables to be analysed.

      In cases where it was not possible to obtain this information, the following were excluded
      from the study
    

Intervention name(s): Clorhexidine
Intervention type(s): Device
Intervention description(s): Antiseptic treatment aimed at reducing potential bacterial overgrowth consisted of 10 days (1 box) of vaginal ovules of CLX (CumLaude CLX ® , CLX digluconate 0.2%) always starting between 10+0 and 16+0 weeks.
Other intervention name(s): Code GMDN (Global Medical Device Nomenclature): 47673 - Vaginal mucosa suppository Code NBOG (Notified Body Operations Group): MD0303- CumLaude CLX ®
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        The population was defined by all pregnant patients previously dated by crown-rump length,
        who attended the initial control or first trimester screening without evident risk of
        preterm birth at the time of consultation at the Hospital Universitari i Politécnic La Fe
        during the year 2021.
      
Keywords: Preterm birth, chlorhexidine, primary prevention