Vaginal, Placental and Neonatal Buccal Mycobiota and Microbiome in Preterm Birth

NCT04165252 | Unknown DMC

• 1 other identifier: 119S463
• Study Type: observational
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

Microbiota contributes to the immunological, hormonal and metabolic homeostasis of the host. As in all natural orifices in the body, there is also a microbiota and mycobiota specific to the vagina. On the other hand, the sonographic short cervix in the second trimester of pregnancy is associated with preterm delivery, which may be an important cause of mortality and morbidity in the neonatal period. American Society of Obstetricians and Gynecologists (ACOG), British Royal Society of Obstetricians and Gynecologists (RCOG) and the American Society of Maternal Fetal Medicine (SMFM) suggest that the measurement of transvaginal sonographic cervical length at 20-24 gestational weeks for the screening of preterm birth. The aforementioned associations also recommend the use of progesterone in the treatment of women who diagnosed with short cervix by transvaginal ultrasonography due to the fact that progesterone is an effective medication in the prevention of preterm birth (Grade B). Previous vaginal microbiota studies have shown that some bacterial species such as Lactobacillus insers cause a predisposition to premature labor in women with a short cervix. However, the prominent lack in these studies is that the eukaryotic fungi in abundant vaginal flora have not been evaluated. On the other hand, it was already shown that progesterone treatment is able to prevent only 45% preterm birth in women with short cervical length. This observational prospective study thus aims to evaluate the variety of microbiota and/or mycobiota in pregnancies resulting in preterm birth and those who give birth at term. Although women with short cervical length receive progesterone regularly from the second trimester, the preterm birth may occur. In this study, the investigators also aim to evaluate the patterns of microbiota and mycobiota from vaginal swabs of women who had preterm birth with short cervical length and postpartum swabs of the placenta and fetal oral cavity.

Conditions

Preterm Birth; Microbial Colonization

Keywords

Preterm birth; Microbiota; Mycobiota; Short Cervix; Progesterone

Outcome Measures

Primary Outcomes (1)

• Characterization of Maternal-Fetal microbiome and mycobiome

  Characterize the maternal(vaginal), placental, and neonatal (buccal) microbiome and mycobiome in a cohort at risk of preterm birth by using the BIO Power Soil DNA Isolation kit. The investigators will able to evaluate whether there is an association between microbiome and mycobiome changes with preterm birth. The V3-V4 regions by the 16s rRNA and ITS regions by 18s rRNA sequencing method will be sequenced. After the "Operational taxonomic units" of the amplicons are configured with the VSEARCH program, the analyzes will be carried out with GENBANK microbiota and micobiota data.

  11 weeks of gestation to date of delivery

Secondary Outcomes (2)

• The effect of progesterone on maternal microbiome (vaginal and placenta) with progesterone

  11 weeks of gestation to date of delivery

• Variety of microbial and mycobial fingerprintings

  11 weeks of gestation to date of delivery

Study Arms (2)

Term Birth

Delivery between 37-41 weeks of gestation

Diagnostic Test: Collection of vaginal, neonatal buccal and placental samples

Preterm birth

Delivery between 24-37 weeks of gestation

Diagnostic Test: Collection of vaginal, neonatal buccal and placental samples

Interventions

Collection of vaginal, neonatal buccal and placental samples DIAGNOSTIC_TEST

Analysis of microbiome and mycobiota of vaginal, neonatal buccal and placental

Preterm birth; Term Birth

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Pregnant women attending prenatal clinics of Koc University Hospital in Istanbul.

You may qualify if:

• Singleton pregnancies
• The subject has voluntarily signed the Informed Consent Form and associated forms after having the contents explained

You may not qualify if:

• Multiple pregnancies
• The presence of a major fetal anomaly or known chromosomal abnormality
• Finding the intrauterine mort de fetus
• Antibiotic and/or antifungal use within two weeks at the collection of samples
• Pregnant women under 18 years of age
• Women with previous cervical surgery
• Women who do not accept to participate to be in the study
• The presence of a uterine anomaly
• Women with vaginal bleeding at the time of cervical swabs taken

Sponsors & Collaborators

• Koç University: lead
• The Scientific and Technological Research Council of Turkey: collaborator

Study Sites (1)

Koc University Hospital

Istanbul, 34010, Turkey (Türkiye)

RECRUITING

Related Publications (10)

• Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med. 2014 May 21;6(237):237ra65. doi: 10.1126/scitranslmed.3008599.

  PMID: 24848255 BACKGROUND

• DiGiulio DB, Romero R, Amogan HP, Kusanovic JP, Bik EM, Gotsch F, Kim CJ, Erez O, Edwin S, Relman DA. Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PLoS One. 2008 Aug 26;3(8):e3056. doi: 10.1371/journal.pone.0003056.

  PMID: 18725970 BACKGROUND

• Gardella C, Riley DE, Hitti J, Agnew K, Krieger JN, Eschenbach D. Identification and sequencing of bacterial rDNAs in culture-negative amniotic fluid from women in premature labor. Am J Perinatol. 2004 Aug;21(6):319-23. doi: 10.1055/s-2004-831884.

  PMID: 15311367 BACKGROUND

• Han YW, Shen T, Chung P, Buhimschi IA, Buhimschi CS. Uncultivated bacteria as etiologic agents of intra-amniotic inflammation leading to preterm birth. J Clin Microbiol. 2009 Jan;47(1):38-47. doi: 10.1128/JCM.01206-08. Epub 2008 Oct 29.

  PMID: 18971361 BACKGROUND

• Iams JD, Goldenberg RL, Meis PJ, Mercer BM, Moawad A, Das A, Thom E, McNellis D, Copper RL, Johnson F, Roberts JM. The length of the cervix and the risk of spontaneous premature delivery. National Institute of Child Health and Human Development Maternal Fetal Medicine Unit Network. N Engl J Med. 1996 Feb 29;334(9):567-72. doi: 10.1056/NEJM199602293340904.

  PMID: 8569824 BACKGROUND

• Kindinger LM, Bennett PR, Lee YS, Marchesi JR, Smith A, Cacciatore S, Holmes E, Nicholson JK, Teoh TG, MacIntyre DA. The interaction between vaginal microbiota, cervical length, and vaginal progesterone treatment for preterm birth risk. Microbiome. 2017 Jan 19;5(1):6. doi: 10.1186/s40168-016-0223-9.

  PMID: 28103952 BACKGROUND

• Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org; McIntosh J, Feltovich H, Berghella V, Manuck T. The role of routine cervical length screening in selected high- and low-risk women for preterm birth prevention. Am J Obstet Gynecol. 2016 Sep;215(3):B2-7. doi: 10.1016/j.ajog.2016.04.027. Epub 2016 Apr 28.

  PMID: 27133011 BACKGROUND

• American College of Obstetricians and Gynecologists' Committee on Practice Bulletins-Obstetrics. Practice Bulletin No. 171: Management of Preterm Labor. Obstet Gynecol. 2016 Oct;128(4):e155-64. doi: 10.1097/AOG.0000000000001711.

  PMID: 27661654 BACKGROUND

• Romero R, Nicolaides KH, Conde-Agudelo A, O'Brien JM, Cetingoz E, Da Fonseca E, Creasy GW, Hassan SS. Vaginal progesterone decreases preterm birth </= 34 weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta-analysis including data from the OPPTIMUM study. Ultrasound Obstet Gynecol. 2016 Sep;48(3):308-17. doi: 10.1002/uog.15953. Epub 2016 Jul 19.

  PMID: 27444208 BACKGROUND

• DiGiulio DB, Romero R, Kusanovic JP, Gomez R, Kim CJ, Seok KS, Gotsch F, Mazaki-Tovi S, Vaisbuch E, Sanders K, Bik EM, Chaiworapongsa T, Oyarzun E, Relman DA. Prevalence and diversity of microbes in the amniotic fluid, the fetal inflammatory response, and pregnancy outcome in women with preterm pre-labor rupture of membranes. Am J Reprod Immunol. 2010 Jul 1;64(1):38-57. doi: 10.1111/j.1600-0897.2010.00830.x. Epub 2010 Mar 21.

  PMID: 20331587 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Maternal (vaginal), neonatal (buccal) and placental specimens will be collected. Genomic DNA will be stored at -80 ℃ until the analysis of microbiota and mycobiota are performed by using BIO PowerSoil DNA isolation kits.

MeSH Terms

Conditions

Premature Birth; Communicable Diseases

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ebru Celik, M.D.

  Koç University

  STUDY DIRECTOR

• Fusun Can, M.D.

  Koc University School of Medicine

  STUDY DIRECTOR

• Mert Turgal, M.D.

  Koc University School of Medicine

  PRINCIPAL INVESTIGATOR

• Ozlem Dogan, M.D.

  Koc University School of Medicine

  PRINCIPAL INVESTIGATOR

• Mehmet Gonen, P.h.D

  Koc University School of Medicine

  PRINCIPAL INVESTIGATOR

• Tugba Gursoy, M.D.

  Koc University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ebru Celik, M.D.

CONTACT

+90 850 250 8 250; ecelik@ku.edu.tr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 41 Weeks
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2019
• First Posted: November 15, 2019
• Study Start: April 1, 2020
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2022
• Last Updated: June 2, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR, ANALYTIC CODE
• Time Frame: The data will be available for 5 years
• Access Criteria: The researchers who are responsible for the recruitment of patients will have access code. The web address will be ready in November 2019 and the researcher will have a personal ID and password to enter the participants' data.

Locations

TU (1)