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

Completed

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

Registration Number: NCT04017754

Lead Sponsor: Aalborg University Hospital

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 452

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

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Plasma MBL Level (ug/ml)	At first consultation. Results accessible within 3 weeks.	Manose Binding Lectin level in a blood sample

Secondary Outcome Measures

Name	Time	Method
Participants Giving Birth After Recurrent Pregnancy Loss (RPL) to a Child With Low Birth Weight	at delivery	\<2500g
Participants Giving Birth Before RPL to a Child With Low Birth Weight	At first consultation	\<2500g
Participants Giving Birth After RPL to a Child With Very Low Birth Weight	at delivery	\<1500g
Participants Giving Birth Before RPL to a Child With Very Low Birth Weight	At first consultation	\<1500g
Patients With Emergency Caesarean Section After RPL	at delivery	A surgical delivery in women who were planned for vaginal delivery initially, but an acute indication for caesarean delivery has since developed.
Patients With Emergency Caesarean Section Before RPL	At first consultation	A surgical delivery in women who were planned for vaginal delivery initially, but an acute indication for caesarean delivery has since developed
Patients With Elective Caesarean Section After RPL	at delivery	A surgical delivery in women who were planned for caesarean delivery
Participants With Preclampsia in Pregnancy After RPL	Developed from 20 weeks gestation and until 6 weeks postpartum. Data collected at delivery.	High blood pressure and proteinuria
Participants With Preclampsia in Pregnancy Before RPL	Developed from 20 weeks gestation and until 6 weeks postpartum. Data collected at first consultation.	High blood pressure and proteinuria
Patients With Elective Caesarean Section Before RPL	At first consultation	A surgical delivery in women who were planned for caesarean delivery
Patients With Severe Peripartum Hemorrhage in Birth After RPL	During delivery	Hemorrhage of \>999 ml
Patients With Severe Peripartum Hemorrhage in Birth Before RPL	At first consultation	Hemorrhage of \>999 ml in minimum one previous birth befor RPL
Patients With Moderate Peripartum Hemorrhage in Birth After RPL	During delivery	Hemorrhage of 500-1000 ml
Patients With Moderate Peripartum Hemorrhage in Birth Before RPL	At first consultation	Hemorrhage of 500-1000 ml in minumum one previous birth before RPL
Patients With a Preterm Birth in Birth After RPL	at delivery	\<37 weeks of gestation
Patients With a Very Preterm Birth in Birth After RPL	at delivery	\<32 weeks of gestation
Gender Ratio of Children Born After RPL	At delivery	Gender ratio in births before RPL
Patients With a Stillbirth After RPL	1 week after delivery	Stillbirth are defined as fetal death \>22 weeks of gestation and within 1 week after delivery
Patients With a Preterm Birth in Birth Before RPL	At first consultation	\<37 weeks of gestation
Gender Ratio of Children Born Before RPL	At first consultation	Gender ratio in births after RPL
Patients With a Very Preterm Birth in Birth Before RPL	At first consultation	\<32 weeks of gestation
Patients With a Stillbirth Before RPL	At first consultation	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.
Patients With a Liveborn After RPL	Follow up at study end.	Number of women who give birth to a healthy liveborn child after RPL