Clinical trial NCT02284867: Are Uterine Natural Killer Cells Involved in the Initiation of Preterm Labor ?
Official title: Comparison Between Uterine Natural Killer Cells In Preterm Labor And Term Labor
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Preterm Labour
Keywords: uterine natural killer cells
CD16
CD56
Preterm labour
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2014-11-06
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: The patients will be recruited from women attending casualty at Ain Shams University Maternity Hospital.

Brief summary: Research question:

Population of study: women diagnosed as term pregnancy in labor (control) and the other group diagnosed as preterm labor (cases).

Intervention: measuring uterine natural killer cells . Outcome: uterine natural killer cells has a role in initiation of preterm labor.

Research hypothesis:

• Are uterine Natural Killer cells involved in the initiation of preterm labor ?

Medical Application:

• Possibility of prediction of preterm labor by assessment of Natural killer cells as well as preventing preterm labor by suppressing their activity .

Detailed description: Type of the Study:

This is a case control study .

Study Settings:

This clinical trial will be conducted at Ain Shams University Maternity Hospital and the laboratory work will be done at Ain Shams University histopathology Laboratory , in the period between August 2012 to August 2014 .

Study Population:

The patients will be recruited from women attending casualty at Ain Shams University Maternity Hospital.

The included patients will be

Divided into two groups:

* Group 1: Patients who has threatened preterm labor and will receive tocolysis and these patients will either not respond to tocolysis and delivered preterm or will respond to tocolysis and will deliver at term .
* Group 2: Patient delivered vaginally at term with no history of having tocolysis for preterm labor at the current pregnancy .

Intervention:

After taking informed written consent, the recruited patients will be subjected to the following:

- History taking, with particular emphasis on: Past medical history (no diabetes mellitus, no hypertension, etc..) Past obstetric history (history of preterm labor). Menstrual history(to be sure of her LMP( last menstrual period) and this date is reliable).

* Having earlier ultrasound to document gestational age.
* History of labor pains which is becoming regular and frequent.
* No suggestive history of preterm prelabor rupture of membranes
* General examination with particular emphasis on blood pressure, weight and height.
* Abdominal examination with particular emphasis on uterine activity.
* Obstetric ultrasound (transabdominal) to document viability of pregnancy and to ensure the gestational age.
* Included patients will receive tocolysis (according to Ain Shams University Maternity hospital protocol which is recommending usage of calcium channel blocker (Nifedipine) Initially 10mg orally every 15 minutes, up to 4 doses of Nifedipine to stop contractions. After this slow release nifedipine. It has been found that an 8 hourly dosage of 40mg - 20mg - 40mg calcium channel blocker is suitable for most women. This is in addition to use of steroids to enhance lung maturity (dexamethasone, 6 mg intramuscular /12 hrs for 48 hrs)
* Patients will be traced by fetal monitor and uterine tocodynamometer (Oxford Sonicaid Team ®)to monitor uterine contractions and if the treatment was successful or not.
* After delivery a placental sample will be taken either the patient delivered preterm or at term (term patients will be either control term group or patients with successful treatment of preterm labor). The placental sample taken should have part of the decidua and then the sample will be fixed in 10% neutral-buffered formalin for 24-48 h, routinely processed, embedded in paraffin wax, sectioned at 3 μm thickness, and mounted on 3-aminopropyl-triethoxysilane -coated slides. Serial sections will be immunostained for CD 16 and CD56 . immunohistochemistry study will be done at Ain Shams Maternity Hospital Histopathology department.

Eligibility criteria: Inclusion Criteria:

1. Maternal age: 18-35 years old (to decrease the incidence of preterm labor related to age factor).
2. Women who present with viable pregnancy (between 28 and 37 weeks' gestation), and having a threatened preterm labor (which is defined as ≥ 2 uterine contractions at 28-37 weeks' gestation, The onset of labor may be determined by documented uterine contractions (at least one every 10 minutes) and ruptured fetal membranes or documented cervical change with an estimated length of less than 1cm or cervical dilation of more than 2 cm. Threatened preterm labor may be diagnosed when there are documented uterine contractions but no evidence of cervical change.

Exclusion Criteria:

1. Multiple pregnancy.
2. Documented uterine anomalies.
3. Oligohydramnios and polyhydramnios .
4. Medical disorders as Diabetes mellitus and hypertension.
5. Preterm premature rupture of membranes.
6. Conditions that may have an influence on immune reaction e.g. history of chorioamnionitis.
7. Smoking as a risk factor for preterm labor.
8. Patients having Autoimmune disorder as it may affect Uterine NK( natural killer ) cells level .

Primary outcomes:
measure: Uterine Natural Killer Cells In Preterm Labor
timeFrame: 2 years
Secondary outcomes:
measure: Comparison of CD16+ CD56 Dim Uterine Natural Killer Cells (uNK) Prevalence in Decidua vs. Villi in Placenta of Both Study Groups
timeFrame: 2 years
Other outcomes:
Locations:
Study officials:
affiliation: +02-01223165820
name: Murad Elsaed, proffesor
role: STUDY_CHAIR
References:
citation: Koga K, Cardenas I, Aldo P, Abrahams VM, Peng B, Fill S, Romero R, Mor G. Activation of TLR3 in the trophoblast is associated with preterm delivery. Am J Reprod Immunol. 2009 Mar;61(3):196-212. doi: 10.1111/j.1600-0897.2008.00682.x.
citation: Murphy SP, Hanna NN, Fast LD, Shaw SK, Berg G, Padbury JF, Romero R, Sharma S. Evidence for participation of uterine natural killer cells in the mechanisms responsible for spontaneous preterm labor and delivery. Am J Obstet Gynecol. 2009 Mar;200(3):308.e1-9. doi: 10.1016/j.ajog.2008.10.043. Epub 2008 Dec 27.