Clinical trial NCT04017754: Low Plasma Mannose Binding Lectin (p-MBL) Level is a Risk Factor for Recurrent Pregnancy Loss (RPL)
Official title: Low Plasma MBL Level is a Risk Factor for Recurrent Pregnancy Loss
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Recurrent Miscarriage
Spontaneous Abortion
Mannose-Binding Lectin Deficiency
Habitual Abortion
Pregnancy Complications
Pregnancy Loss
Recurrent Pregnancy Loss
Keywords: Mannose binding lectin
Perinatal outcome
Recurrent pregnancy loss
Lead sponsor: Aalborg University Hospital
Sponsor class: OTHER
First posted: 2019-07-12
Enrollment: 452
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women fulfilling the eligibility criteria will have p-MBL level measured from a blood sample when first admitted to the Centre for Recurrent Pregnancy Loss of Western Denmark and will be followed until delivery of the first child following the consecutive pregnancy losses, if pregnancy is achieved during the study period.

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.

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

Primary outcomes:
measure: Plasma MBL Level (ug/ml)
timeFrame: At first consultation. Results accessible within 3 weeks.
Secondary outcomes:
measure: Participants Giving Birth After Recurrent Pregnancy Loss (RPL) to a Child With Low Birth Weight
timeFrame: at delivery
measure: Participants Giving Birth Before RPL to a Child With Low Birth Weight
timeFrame: At first consultation
measure: Participants Giving Birth After RPL to a Child With Very Low Birth Weight
timeFrame: at delivery
measure: Participants Giving Birth Before RPL to a Child With Very Low Birth Weight
timeFrame: At first consultation
measure: Participants With Preclampsia in Pregnancy After RPL
timeFrame: Developed from 20 weeks gestation and until 6 weeks postpartum. Data collected at delivery.
measure: Participants With Preclampsia in Pregnancy Before RPL
timeFrame: Developed from 20 weeks gestation and until 6 weeks postpartum. Data collected at first consultation.
measure: Patients With Emergency Caesarean Section After RPL
timeFrame: at delivery
measure: Patients With Emergency Caesarean Section Before RPL
timeFrame: At first consultation
measure: Patients With Elective Caesarean Section After RPL
timeFrame: at delivery
measure: Patients With Elective Caesarean Section Before RPL
timeFrame: At first consultation
measure: Patients With Severe Peripartum Hemorrhage in Birth After RPL
timeFrame: During delivery
measure: Patients With Severe Peripartum Hemorrhage in Birth Before RPL
timeFrame: At first consultation
measure: Patients With Moderate Peripartum Hemorrhage in Birth After RPL
timeFrame: During delivery
measure: Patients With Moderate Peripartum Hemorrhage in Birth Before RPL
timeFrame: At first consultation
measure: Patients With a Preterm Birth in Birth After RPL
timeFrame: at delivery
measure: Patients With a Preterm Birth in Birth Before RPL
timeFrame: At first consultation
measure: Patients With a Very Preterm Birth in Birth After RPL
timeFrame: at delivery
measure: Patients With a Very Preterm Birth in Birth Before RPL
timeFrame: At first consultation
measure: Gender Ratio of Children Born After RPL
timeFrame: At delivery
measure: Gender Ratio of Children Born Before RPL
timeFrame: At first consultation
measure: Patients With a Stillbirth After RPL
timeFrame: 1 week after delivery
measure: Patients With a Stillbirth Before RPL
timeFrame: At first consultation
measure: Patients With a Liveborn After RPL
timeFrame: Follow up at study end.
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
Study officials:
affiliation: Aalborg University Hospital
name: Caroline Nørgaard-Pedersen
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.