Melatonin, Soluble Urokinase-type Plasminogen Activator Receptor, and Orosomucoid 2 Levels in PPROM (melatonin&PROM)

Umbilical Cord and Maternal Blood Concentrations of Melatonin, Soluble Urokinase-type Plasminogen Activator Receptor, and Orosomucoid 2 in Pregnancy Complicated by Preterm Premature Rupture of the Membranes and Histological Chorioamnionitis

Introduction: To evaluate the maternal blood serum melatonin, soluble urokinase-type plasminogen activator receptor, and orosomucoid 2 levels in pregnant women complicated by preterm premature rupture of membranes (PPROM) and to compare the results with healthy pregnancies. In addition, to determine whether maternal/umbilical cord blood concentrations of melatonin, soluble urokinase-type plasminogen activator receptor, and orosomucoid 2 are of value in the diagnosis of histological chorioamnionitis in patients with preterm premature rupture of membranes (PPROM).

Methods: This cohort study will be included 44 pregnant women with PPROM and 44 gestational age-matched healthy subjects in 24-32 weeks of pregnancy. The blood for analysis will be firstly obtained in maternal blood on the day of diagnosis at the study group. Healthy subjects who have a normal pregnancy and outcomes without any fetal-neonatal complications will be accepted into the control group. Forty-four gestational age-matched healthy pregnant women who will be delivered at term will be included in the study as the control group. In the control group, the pregnant women will be taken the maternal blood at the admission day. The women in both groups will be observed until the delivery and perinatal data will be noted. Then, the blood for analysis will be secondly obtained in maternal blood during termination of the pregnancy (or spontaneous labor) at the study group. Lastly, the blood for analysis will be also obtained in umbilical cord blood at the study group. These three markers levels will be measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. The placenta will be sent to histological examination in the study group. These three markers levels in women with PPROM will be compared to those of volunteer healthy pregnant women. In the study group, these three markers levels at maternal serum and cord serum will be evaluated for histological chorioamnionitis and maternal/neonatal outcomes.

Study Overview

• Status: Unknown
• Conditions: Preterm Premature Rupture of Membranes
• Intervention / Treatment: Other: Obstetric ultrasound and fetal-maternal assessment

Detailed Description

This observational case-control study will be conducted at the Department of Obstetrics and Gynecology, Cengiz Gokcek Public Hospital, Gaziantep, Turkey, between October 2020 and October 2021. The protocol was approved by the Ethics Committee for Clinical Research of Gaziantep University (reference no: 2020/276). The study strictly will be adhered to the principles of the Declaration of Helsinki. All subjects will be included in the study gave oral and written informed consent. Membrane rupture before labor and before 37 weeks of gestation is referred to as preterm premature rupture of membranes (PPROM). Every woman in the study population will be undergone obstetric ultrasound examination and fetal-maternal assessment will be carried out. The blood for analysis will be firstly obtained in maternal blood on the day of diagnosis at the study group. Healthy subjects who had a normal pregnancy and outcomes without any fetal-neonatal complications will be accepted into the control group. Forty-four gestational age-matched healthy pregnant women who will be delivered at term will be included in the study as the control group. In the control group, the pregnant women will be taken the maternal blood at the admission day. The women in both groups will be observed until the delivery and perinatal data will be noted. All The participants with PPROM will be also hospitalized. Then, the protocols for pregnant women with PPROM in our hospital are as follows: All patients with PPROM are hospitalized and expectant protocol is applied. After hospitalization until the delivery of baby, all pregnant women with PPROM receive prophylactic antibiotics for 1 week and betamethasone injection. The non-stress test and fetal movement determined by the mother are used for the detection of fetal well-being. The signs for clinical chorioamnionitis such as uterine tenderness, fever, purulent discharges from the cervical canal and inflammatory markers like white blood cell count (WBC) and C-reactive protein (CRP) levels are monitored carefully during the hospitalization. After a latency period, PPROM pregnancy will gone to spontaneous delivery or will be applied termination procedure. In the study group, the placenta will be stained with hematoxylin-eosin and will be examined under a light microscope for histological signs of neutrophil infiltration and chorioamnionitis. Then, this study will be determined maternal serum melatonin, soluble urokinase-type plasminogen activator receptor, and orosomucoid 2 levels in women with PPROM(n=44) compared to those of volunteer healthy pregnant women (n=44). Then, these three markers levels at maternal serum and cord serum will be evaluated for histological chorioamnionitis and maternal/neonatal outcomes in the study group.

• Study Type: Observational
• Enrollment (Anticipated): 88

Contacts and Locations

Study Locations

• Turkey
  • Gaziantep, Turkey
    • Cengiz Gokcek Women's and Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

The investigators consecutively will be recruited 44 subjects with PPROM, and 44 healthy pregnancies will be selected for the control group.

Description

Inclusion Criteria:

• Pregnant women complicated with PPROM
• Healthy pregnant women who will be delivered at term
• Singleton pregnancy

Exclusion Criteria:

1. pregnant women with any systemic condition (such as chronic hypertension, renal disease and )
2. women who have dyed their hair in the last 9 months
3. history of using any medication
4. presence of gestational hypertension or gestational diabetes
5. drug user
6. patients who had fetal congenital abnormalities or genetic syndromes
7. multiple-gestation pregnancies
8. intrauterine fetal death
9. women who had any other infection or fever
10. fetal distress at admission
11. cord prolapse
12. active labor
13. antenatal bleeding
14. cervical or uterine anomaly

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
preterm premature rupture of membranes; Preterm premature rupture of membranes is the rupture of membranes during pregnancy before 37 weeks' gestation.	Other: Obstetric ultrasound and fetal-maternal assessment; melatonin, soluble urokinase-type plasminogen activator receptor, and orosomucoid 2 measurements; Other Names: melatonin, soluble urokinase-type plasminogen activator receptor, and orosomucoid 2 measurements
Control group; Healthy subjects who had a normal pregnancy and outcomes without any fetal-neonatal complications will be accepted into the control group. Forty-four gestational age-matched healthy pregnant women who will be delivered at term will be included in the study as the control group.	Other: Obstetric ultrasound and fetal-maternal assessment; melatonin, soluble urokinase-type plasminogen activator receptor, and orosomucoid 2 measurements; Other Names: melatonin, soluble urokinase-type plasminogen activator receptor, and orosomucoid 2 measurements

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
melatonin levels in PPROM	The primary outcome in these analyses will compare maternal serum melatonin concentrations in PPROM group and control group.	1 week
soluble urokinase-type plasminogen activator receptor levels in PPROM	The other primary outcome in these analyses will compare maternal serum soluble urokinase-type plasminogen activator receptor concentrations in PPROM group and control group.	1 week
orosomucoid 2 levels in PPROM	The primary outcome in these analyses will compare maternal serum orosomucoid 2 concentrations in PPROM group and control group.	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
markers levels for histological chorioamnionitis in PPROM	The secondary result in these analyzes will compare whether there is a difference at the levels of these three markers in maternal serum and cord serum for the presence of histological chorioamnionitis in the study group.	1 week

Collaborators and Investigators

• Sponsor: Cengiz Gokcek Women's and Children's Hospital

Publications and helpful links

General Publications

• Ekstrom B, Berggard I. Human alpha1-microglobulin. Purification procedure, chemical and physiochemical properties. J Biol Chem. 1977 Nov 25;252(22):8048-57. No abstract available.
• Wilkinson D, Shepherd E, Wallace EM. Melatonin for women in pregnancy for neuroprotection of the fetus. Cochrane Database Syst Rev. 2016 Mar 29;3(3):CD010527. doi: 10.1002/14651858.CD010527.pub2.
• Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 188: Prelabor Rupture of Membranes. Obstet Gynecol. 2018 Jan;131(1):e1-e14. doi: 10.1097/AOG.0000000000002455.
• Desdicioglu R, Yildirim M, Kocaoglu G, Demir Cendek B, Avcioglu G, Tas EE, Sengul O, Erel O, Yavuz AF. Soluble urokinase-type plasminogen activator receptor (suPAR) and interleukin-6 levels in hyperemesis gravidarum. J Chin Med Assoc. 2018 Sep;81(9):825-829. doi: 10.1016/j.jcma.2017.08.013. Epub 2017 Oct 9.

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2020
• Primary Completion (Anticipated): October 30, 2021
• Study Completion (Anticipated): December 30, 2021

Study Registration Dates

• First Submitted: October 8, 2020
• First Submitted That Met QC Criteria: October 8, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 8, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Rupture; Premature Birth; Fetal Membranes, Premature Rupture; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Fibrinolytic Agents; Fibrin Modulating Agents; Protective Agents; Antioxidants; Melatonin; Plasminogen
• Other Study ID Numbers: CengizGWCH10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No