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

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.

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