Low Plasma Mannose Binding Lectin (p-MBL) Level is a Risk Factor for Recurrent Pregnancy Loss (RPL)

Pregnancy Complications Clinical Trial

Official title:

Low Plasma MBL Level is a Risk Factor for Recurrent Pregnancy Loss

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04017754
• Other study ID #: 36e19au5
• Status: Completed
• Start date: January 1, 2016
• Est. completion date: March 29, 2021

Study information

• Verified date: July 2021
• Source: Aalborg University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The present study is based on the hypothesis, that recurrent pregnancy loss (RPL) is associated with abnormal plasma mannose binding lectin (p-MBL) level. Secondarily, p-MBL level may affect the reproductive and the perinatal outcome in the first pregnancy following RPL. Thus, the present study aim to examine whether MBL should be a biomarker for women at risk for RPL and, secondarily, affect the reproductive and perinatal outcome, and thereby help clinicians identify fragile women who need intensified perinatal care.

Description:

Recurrent pregnancy loss (RPL), defined as 3 or more consecutive pregnancy losses before 22 weeks of gestation, is a multifactorial disorder affecting 1-3% of all females of reproductive age. The underlying cause of RPL remain unknown in up to 50% of patients. Some of these patients may be affected by an aberrant immune system.

Low p-MBL levels have been associated with RPL, while relations to high p-MBL levels have been poorly studied. Reports concerning association between maternal p-MBL levels and perinatal outcomes including birth weight and gestational age are conflicting. Low p-MBL level may possess a negative effect by promoting an unfavorable immune response against foreign cells such as fetal/trophoblast cells.

This study is a single center a combined cross-sectional and prospective cohort study, that aims to investigate wether high and/or low p-MBL levels are associated with RPL (primary outcome) and whether it affects reproductive outcome in the first pregnancy following admission and the perinatal outcome in the first birth before and after admission (secondary outcome). If such associations exist, p-MBL could become an biomarker for the early identification of women with need for intensified perinatal care.

The study sample consists of Danish women admitted to the Centre for Recurrent Pregnancy Loss of Western Denmark. The study group includes 267 women with RPL. P-MBL levels in patients are compared to those of 185 female blood donors of fertile age with unknown reproductive history. The association between low p-MBL level and successful reproductive outcomes is analyzed with logistic regression adjusted for confounding variables (age, BMI and smoking). The perinatal outcomes in first birth (>22 weeks of gestation) before and after admission are compared between RPL subgroups according to their p-MBL level; low (≤500 ug/l), intermediate (501-3000 ug/l), and high (>3000 ug/l) p-MBL levels.

Female patients in the study group will have a blood sample taken at their first meeting in the the Centre for Recurrent Pregnancy Loss of Western Denmark before they become pregnant, and they will be followed until delivery of the first child after RPL, if pregnancy after RPL is achieved, or until end of study March 2021. Data on perinatal outcomes of pregnancies before and after RPL were collected at the first consultation, from hospital records, and, when needed, completed by telephone or e-mail correspondence.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 452
• Est. completion date: March 29, 2021
• Est. primary completion date: March 29, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Women admitted to the Centre for Recurrent Pregnancy Loss of Western Denmark January 2016 to March 2020

Exclusion Criteria:

• Less than 3 consecutive pregnancy losses

• Significant uterine malformation on hydrosonography or hysteroscopy

• Significant chromosomal abnormalities

• Abnormal menstrual cycle length (<22 or >35 days) or irregular cycle

• Pregnancy at first meeting in the Recurrent Miscarriage Clinic

• Age <18 and >45 years

Related Conditions & MeSH terms

• Abortion, Habitual
• Abortion, Spontaneous
• Fetal Death
• Habitual Abortion
• Mannose-Binding Lectin Deficiency
• Pregnancy Complications
• Pregnancy Loss
• Recurrent Miscarriage
• Recurrent Pregnancy Loss
• Spontaneous Abortion

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital	Aalborg

Sponsors (1)

Lead Sponsor	Collaborator
Aalborg University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma MBL Level (ug/ml)	Manose Binding Lectin level in a blood sample	At first consultation. Results accessible within 3 weeks.
Secondary	Participants Giving Birth After Recurrent Pregnancy Loss (RPL) to a Child With Low Birth Weight	<2500g	at delivery
Secondary	Participants Giving Birth Before RPL to a Child With Low Birth Weight	<2500g	At first consultation
Secondary	Participants Giving Birth After RPL to a Child With Very Low Birth Weight	<1500g	at delivery
Secondary	Participants Giving Birth Before RPL to a Child With Very Low Birth Weight	<1500g	At first consultation
Secondary	Participants With Preclampsia in Pregnancy After RPL	High blood pressure and proteinuria	Developed from 20 weeks gestation and until 6 weeks postpartum. Data collected at delivery.
Secondary	Participants With Preclampsia in Pregnancy Before RPL	High blood pressure and proteinuria	Developed from 20 weeks gestation and until 6 weeks postpartum. Data collected at first consultation.
Secondary	Patients With Emergency Caesarean Section After RPL	A surgical delivery in women who were planned for vaginal delivery initially, but an acute indication for caesarean delivery has since developed.	at delivery
Secondary	Patients With Emergency Caesarean Section Before RPL	A surgical delivery in women who were planned for vaginal delivery initially, but an acute indication for caesarean delivery has since developed	At first consultation
Secondary	Patients With Elective Caesarean Section After RPL	A surgical delivery in women who were planned for caesarean delivery	at delivery
Secondary	Patients With Elective Caesarean Section Before RPL	A surgical delivery in women who were planned for caesarean delivery	At first consultation
Secondary	Patients With Severe Peripartum Hemorrhage in Birth After RPL	Hemorrhage of >999 ml	During delivery
Secondary	Patients With Severe Peripartum Hemorrhage in Birth Before RPL	Hemorrhage of >999 ml in minimum one previous birth befor RPL	At first consultation
Secondary	Patients With Moderate Peripartum Hemorrhage in Birth After RPL	Hemorrhage of 500-1000 ml	During delivery
Secondary	Patients With Moderate Peripartum Hemorrhage in Birth Before RPL	Hemorrhage of 500-1000 ml in minumum one previous birth before RPL	At first consultation
Secondary	Patients With a Preterm Birth in Birth After RPL	<37 weeks of gestation	at delivery
Secondary	Patients With a Preterm Birth in Birth Before RPL	<37 weeks of gestation	At first consultation
Secondary	Patients With a Very Preterm Birth in Birth After RPL	<32 weeks of gestation	at delivery
Secondary	Patients With a Very Preterm Birth in Birth Before RPL	<32 weeks of gestation	At first consultation
Secondary	Gender Ratio of Children Born After RPL	Gender ratio in births before RPL	At delivery
Secondary	Gender Ratio of Children Born Before RPL	Gender ratio in births after RPL	At first consultation
Secondary	Patients With a Stillbirth After RPL	Stillbirth are defined as fetal death >22 weeks of gestation and within 1 week after delivery	1 week after delivery
Secondary	Patients With a Stillbirth Before RPL	Stillbirth are defined as fetal death >22 weeks of gestation and within 1 week after delivery - all women with min one previous birth are included in this analysis.	At first consultation
Secondary	Patients With a Liveborn After RPL	Number of women who give birth to a healthy liveborn child after RPL	Follow up at study end.