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

NCT ID: NCT04017754

Last Updated: 2021-07-30

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 452 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-01-01
• Study Completion Date: 2021-03-29

Brief 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.

Detailed 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.

Conditions

Recurrent Miscarriage; Spontaneous Abortion; Mannose-Binding Lectin Deficiency; Habitual Abortion; Pregnancy Complications; Pregnancy Loss; Recurrent Pregnancy Loss

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Study sample

In total, 267 women with unexplained recurrent pregnancy loss was included.

Only patients with a history of 3 or more consecutive spontaneous pregnancy losses are included. Both biochemical and clinical losses documented in hospital records are accepted. Verified extrauterine pregnancy losses, complete molar pregnancies, and induced abortions of social reasons are not included in the total number of pregnancy losses. Women are excluded from this study, if they have significant uterine malformations, significant parental chromosomal abnormalities, irregular and/or abnormal length of their menstrual cycle length (<22 and >35 days interval), and/or no MBL measurement.

No interventions assigned to this group

Reference Group

The MBL reference group comprised 185 Danish female blood donors of reproductive age (range 21 to 45 years), about whom we have no other information. After informed approval, all controls had an extra blood sample taken, which was analysed for p-MBL.

No interventions assigned to this group

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Aalborg University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Caroline Nørgaard-Pedersen

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Caroline Nørgaard-Pedersen

Role: PRINCIPAL_INVESTIGATOR

Aalborg University Hospital

Locations

Aalborg University Hospital

Aalborg, , Denmark

Countries

Denmark

References

Norgaard-Pedersen C, Rom LH, Steffensen R, Kesmodel US, Christiansen OB. Plasma level of mannose-binding lectin is associated with the risk of recurrent pregnancy loss but not pregnancy outcome after the diagnosis. Hum Reprod Open. 2022 Jun 7;2022(3):hoac024. doi: 10.1093/hropen/hoac024. eCollection 2022.

Reference Type: DERIVED

PMID: 35747402 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

36e19au5

Identifier Type: -

Identifier Source: org_study_id