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

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

Status
Completed
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT04017754
Enrollment
452
Registered
2019-07-12
Start date
2016-01-01
Completion date
2021-03-29
Last updated
2021-07-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Keywords

Mannose binding lectin, Perinatal outcome, Recurrent pregnancy loss

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.

Interventions

None listed

Sponsors

Aalborg University Hospital
Lead SponsorOTHER

Study design

Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL

Eligibility

Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No

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

Design outcomes

Primary

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

Secondary

MeasureTime frameDescription
Participants Giving Birth After RPL to a Child With Very Low Birth Weightat delivery\<1500g
Participants Giving Birth Before RPL to a Child With Very Low Birth WeightAt first consultation\<1500g
Participants Giving Birth After Recurrent Pregnancy Loss (RPL) to a Child With Low Birth Weightat delivery\<2500g
Participants With Preclampsia in Pregnancy After RPLDeveloped from 20 weeks gestation and until 6 weeks postpartum. Data collected at delivery.High blood pressure and proteinuria
Participants With Preclampsia in Pregnancy Before RPLDeveloped from 20 weeks gestation and until 6 weeks postpartum. Data collected at first consultation.High blood pressure and proteinuria
Patients With Emergency Caesarean Section After RPLat deliveryA 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 RPLAt first consultationA 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 RPLat deliveryA surgical delivery in women who were planned for caesarean delivery
Patients With Elective Caesarean Section Before RPLAt first consultationA surgical delivery in women who were planned for caesarean delivery
Patients With Severe Peripartum Hemorrhage in Birth After RPLDuring deliveryHemorrhage of \>999 ml
Patients With Severe Peripartum Hemorrhage in Birth Before RPLAt first consultationHemorrhage of \>999 ml in minimum one previous birth befor RPL
Participants Giving Birth Before RPL to a Child With Low Birth WeightAt first consultation\<2500g
Patients With Moderate Peripartum Hemorrhage in Birth Before RPLAt first consultationHemorrhage of 500-1000 ml in minumum one previous birth before RPL
Patients With a Preterm Birth in Birth After RPLat delivery\<37 weeks of gestation
Patients With a Preterm Birth in Birth Before RPLAt first consultation\<37 weeks of gestation
Patients With a Very Preterm Birth in Birth After RPLat delivery\<32 weeks of gestation
Patients With a Very Preterm Birth in Birth Before RPLAt first consultation\<32 weeks of gestation
Gender Ratio of Children Born After RPLAt deliveryGender ratio in births before RPL
Gender Ratio of Children Born Before RPLAt first consultationGender ratio in births after RPL
Patients With a Stillbirth After RPL1 week after deliveryStillbirth are defined as fetal death \>22 weeks of gestation and within 1 week after delivery
Patients With a Stillbirth Before RPLAt first consultationStillbirth 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 RPLFollow up at study end.Number of women who give birth to a healthy liveborn child after RPL
Patients With Moderate Peripartum Hemorrhage in Birth After RPLDuring deliveryHemorrhage of 500-1000 ml

Countries

Denmark

Participant flow

Pre-assignment details

The study sample consisted of 267 female patients with RPL fulfilling the inclusion criterias.

Participants by arm

ArmCount
Study Sample
Women with unexplained recurrent pregnancy loss. Only patients with a history of 3 or more consecutive spontaneous pregnancy losses were included. Both biochemical and clinical losses documented in hospital records were accepted. Verified extrauterine pregnancy losses, complete molar pregnancies, and induced abortions of social and genetic reasons were 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. At the first consultation in The Centre for Recurrent Pregnancy Loss of Western Denmark, all women have a diagnostic work-up, including collection of an obstetric and gynaecologic history, a routine blood analysis, a uterine hydrosonography, hysteroscopy, or hysterosalpingography, and a parental chromosomal analysis in most cases.
267
Total267

Baseline characteristics

CharacteristicStudy Sample
Age, Categorical
<=18 years
0 Participants
Age, Categorical
>=65 years
0 Participants
Age, Categorical
Between 18 and 65 years
267 Participants
Age, Continuous33.2 years
STANDARD_DEVIATION 5.3
Body mass index25.4 kg/m²
Number of consecutive pregnancy losses3 consecutive pregnancy losses
Percentage with primary Recurrent pregnancy loss (RPL)53.9 Percentage of all RPL patients
Race/Ethnicity, Customized
Caucasian
267 participants
Race/Ethnicity, Customized
Unknown
0 participants
Region of Enrollment
Denmark
267 participants
Sex: Female, Male
Female
267 Participants
Sex: Female, Male
Male
0 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
0 / 267
other
Total, other adverse events
0 / 267
serious
Total, serious adverse events
0 / 267

Outcome results

Primary

Plasma MBL Level (ug/ml)

Manose Binding Lectin level in a blood sample

Time frame: At first consultation. Results accessible within 3 weeks.

Population: 18 women were pregnant \<12 weeks when blood sample was collected.

ArmMeasureValue (MEDIAN)
Study SamplePlasma MBL Level (ug/ml)717 ug/l
MBL Reference GroupPlasma MBL Level (ug/ml)1717 ug/l
Comparison: Comparing the risk of low p-MBL level between RPL patients and MBL reference group. We hypothesized that more RPL patients had a low p-MBL level; thus, the null hypothesis was that no difference existed.p-value: <0.00195% CI: [1.34, 2.38]Chi-squared
Secondary

Gender Ratio of Children Born After RPL

Gender ratio in births before RPL

Time frame: At delivery

Population: male:female ratio

ArmMeasureValue (NUMBER)
Study SampleGender Ratio of Children Born After RPL1.08 male:female ratio
MBL Reference GroupGender Ratio of Children Born After RPL2.29 male:female ratio
Secondary

Gender Ratio of Children Born Before RPL

Gender ratio in births after RPL

Time frame: At first consultation

ArmMeasureValue (NUMBER)
Study SampleGender Ratio of Children Born Before RPL3.27 male:female ratio
MBL Reference GroupGender Ratio of Children Born Before RPL1.88 male:female ratio
Secondary

Participants Giving Birth After Recurrent Pregnancy Loss (RPL) to a Child With Low Birth Weight

\<2500g

Time frame: at delivery

Population: Patients who have given birth after admission within each p-MBL level subgroup

ArmMeasureValue (NUMBER)
Study SampleParticipants Giving Birth After Recurrent Pregnancy Loss (RPL) to a Child With Low Birth Weight3 participants
MBL Reference GroupParticipants Giving Birth After Recurrent Pregnancy Loss (RPL) to a Child With Low Birth Weight1 participants
Secondary

Participants Giving Birth After RPL to a Child With Very Low Birth Weight

\<1500g

Time frame: at delivery

ArmMeasureValue (NUMBER)
Study SampleParticipants Giving Birth After RPL to a Child With Very Low Birth Weight0 participants
MBL Reference GroupParticipants Giving Birth After RPL to a Child With Very Low Birth Weight0 participants
Secondary

Participants Giving Birth Before RPL to a Child With Low Birth Weight

\<2500g

Time frame: At first consultation

Population: participants who had sRPL; thus, who had given birth before admission to at least one child. Data concerns first delivery.

ArmMeasureValue (NUMBER)
Study SampleParticipants Giving Birth Before RPL to a Child With Low Birth Weight4 participants
MBL Reference GroupParticipants Giving Birth Before RPL to a Child With Low Birth Weight2 participants
Secondary

Participants Giving Birth Before RPL to a Child With Very Low Birth Weight

\<1500g

Time frame: At first consultation

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Study SampleParticipants Giving Birth Before RPL to a Child With Very Low Birth Weight0 Participants
MBL Reference GroupParticipants Giving Birth Before RPL to a Child With Very Low Birth Weight0 Participants
Secondary

Participants With Preclampsia in Pregnancy After RPL

High blood pressure and proteinuria

Time frame: Developed from 20 weeks gestation and until 6 weeks postpartum. Data collected at delivery.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Study SampleParticipants With Preclampsia in Pregnancy After RPL7 Participants
MBL Reference GroupParticipants With Preclampsia in Pregnancy After RPL0 Participants
Secondary

Participants With Preclampsia in Pregnancy Before RPL

High blood pressure and proteinuria

Time frame: Developed from 20 weeks gestation and until 6 weeks postpartum. Data collected at first consultation.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Study SampleParticipants With Preclampsia in Pregnancy Before RPL6 Participants
MBL Reference GroupParticipants With Preclampsia in Pregnancy Before RPL2 Participants
Secondary

Patients With a Liveborn After RPL

Number of women who give birth to a healthy liveborn child after RPL

Time frame: Follow up at study end.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Study SamplePatients With a Liveborn After RPL79 Participants
MBL Reference GroupPatients With a Liveborn After RPL23 Participants
Secondary

Patients With a Preterm Birth in Birth After RPL

\<37 weeks of gestation

Time frame: at delivery

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Study SamplePatients With a Preterm Birth in Birth After RPL8 Participants
MBL Reference GroupPatients With a Preterm Birth in Birth After RPL3 Participants
Secondary

Patients With a Preterm Birth in Birth Before RPL

\<37 weeks of gestation

Time frame: At first consultation

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Study SamplePatients With a Preterm Birth in Birth Before RPL4 Participants
MBL Reference GroupPatients With a Preterm Birth in Birth Before RPL1 Participants
Secondary

Patients With a Stillbirth After RPL

Stillbirth are defined as fetal death \>22 weeks of gestation and within 1 week after delivery

Time frame: 1 week after delivery

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Study SamplePatients With a Stillbirth After RPL0 Participants
MBL Reference GroupPatients With a Stillbirth After RPL0 Participants
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.

Time frame: At first consultation

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Study SamplePatients With a Stillbirth Before RPL4 Participants
MBL Reference GroupPatients With a Stillbirth Before RPL3 Participants
Secondary

Patients With a Very Preterm Birth in Birth After RPL

\<32 weeks of gestation

Time frame: at delivery

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Study SamplePatients With a Very Preterm Birth in Birth After RPL2 Participants
MBL Reference GroupPatients With a Very Preterm Birth in Birth After RPL0 Participants
Secondary

Patients With a Very Preterm Birth in Birth Before RPL

\<32 weeks of gestation

Time frame: At first consultation

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Study SamplePatients With a Very Preterm Birth in Birth Before RPL0 Participants
MBL Reference GroupPatients With a Very Preterm Birth in Birth Before RPL0 Participants
Secondary

Patients With Elective Caesarean Section After RPL

A surgical delivery in women who were planned for caesarean delivery

Time frame: at delivery

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Study SamplePatients With Elective Caesarean Section After RPL13 Participants
MBL Reference GroupPatients With Elective Caesarean Section After RPL3 Participants
Secondary

Patients With Elective Caesarean Section Before RPL

A surgical delivery in women who were planned for caesarean delivery

Time frame: At first consultation

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Study SamplePatients With Elective Caesarean Section Before RPL6 Participants
MBL Reference GroupPatients With Elective Caesarean Section Before RPL0 Participants
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.

Time frame: at delivery

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Study SamplePatients With Emergency Caesarean Section After RPL10 Participants
MBL Reference GroupPatients With Emergency Caesarean Section After RPL4 Participants
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

Time frame: At first consultation

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Study SamplePatients With Emergency Caesarean Section Before RPL12 Participants
MBL Reference GroupPatients With Emergency Caesarean Section Before RPL6 Participants
Secondary

Patients With Moderate Peripartum Hemorrhage in Birth After RPL

Hemorrhage of 500-1000 ml

Time frame: During delivery

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Study SamplePatients With Moderate Peripartum Hemorrhage in Birth After RPL21 Participants
MBL Reference GroupPatients With Moderate Peripartum Hemorrhage in Birth After RPL2 Participants
Secondary

Patients With Moderate Peripartum Hemorrhage in Birth Before RPL

Hemorrhage of 500-1000 ml in minumum one previous birth before RPL

Time frame: At first consultation

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Study SamplePatients With Moderate Peripartum Hemorrhage in Birth Before RPL6 Participants
MBL Reference GroupPatients With Moderate Peripartum Hemorrhage in Birth Before RPL6 Participants
Secondary

Patients With Severe Peripartum Hemorrhage in Birth After RPL

Hemorrhage of \>999 ml

Time frame: During delivery

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Study SamplePatients With Severe Peripartum Hemorrhage in Birth After RPL6 Participants
MBL Reference GroupPatients With Severe Peripartum Hemorrhage in Birth After RPL3 Participants
Secondary

Patients With Severe Peripartum Hemorrhage in Birth Before RPL

Hemorrhage of \>999 ml in minimum one previous birth befor RPL

Time frame: At first consultation

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Study SamplePatients With Severe Peripartum Hemorrhage in Birth Before RPL8 Participants
MBL Reference GroupPatients With Severe Peripartum Hemorrhage in Birth Before RPL0 Participants

Source: ClinicalTrials.gov · Data processed: Feb 13, 2026