Recurrent MiscarriageNCT04017754
Low Plasma Mannose Binding Lectin (p-MBL) Level is a Risk Factor for Recurrent Pregnancy Loss (RPL)
An observational study of Recurrent Miscarriage and Spontaneous Abortion, run by Aalborg University Hospital at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Recurrent Miscarriage, Spontaneous Abortion, Mannose-Binding Lectin Deficiency
- How many people
- 452 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Jan 2016to 29 Mar 2021
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
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.
Who may be able to join
- Women admitted to the Centre for Recurrent Pregnancy Loss of Western Denmark January 2016 to March 2020
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Low Plasma MBL Level is a Risk Factor for Recurrent Pregnancy Loss
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.
Read the 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
- Keywords
- Mannose binding lectin, Perinatal outcome, Recurrent pregnancy loss
- Medical subject headings
- Abortion, Habitual, Abortion, Spontaneous, Mannose-Binding Protein Deficiency, Pregnancy Complications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. | |
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma MBL Level (ug/ml)
Manose Binding Lectin level in a blood sample
Measured: At first consultation. Results accessible within 3 weeks.
Secondary outcomes (23)
Participants Giving Birth After Recurrent Pregnancy Loss (RPL) to a Child With Low Birth Weight
<2500g
Measured: at delivery
Participants Giving Birth Before RPL to a Child With Low Birth Weight
<2500g
Measured: At first consultation
Participants Giving Birth After RPL to a Child With Very Low Birth Weight
<1500g
Measured: at delivery
Participants Giving Birth Before RPL to a Child With Very Low Birth Weight
<1500g
Measured: At first consultation
Participants With Preclampsia in Pregnancy After RPL
High blood pressure and proteinuria
Measured: Developed from 20 weeks gestation and until 6 weeks postpartum. Data collected at delivery.
Participants With Preclampsia in Pregnancy Before RPL
High blood pressure and proteinuria
Measured: Developed from 20 weeks gestation and until 6 weeks postpartum. Data collected at first consultation.
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.
Measured: at delivery
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
Measured: At first consultation
Patients With Elective Caesarean Section After RPL
A surgical delivery in women who were planned for caesarean delivery
Measured: at delivery
Patients With Elective Caesarean Section Before RPL
A surgical delivery in women who were planned for caesarean delivery
Measured: At first consultation
Patients With Severe Peripartum Hemorrhage in Birth After RPL
Hemorrhage of >999 ml
Measured: During delivery
Patients With Severe Peripartum Hemorrhage in Birth Before RPL
Hemorrhage of >999 ml in minimum one previous birth befor RPL
Measured: At first consultation
Patients With Moderate Peripartum Hemorrhage in Birth After RPL
Hemorrhage of 500-1000 ml
Measured: During delivery
Patients With Moderate Peripartum Hemorrhage in Birth Before RPL
Hemorrhage of 500-1000 ml in minumum one previous birth before RPL
Measured: At first consultation
Patients With a Preterm Birth in Birth After RPL
<37 weeks of gestation
Measured: at delivery
Patients With a Preterm Birth in Birth Before RPL
<37 weeks of gestation
Measured: At first consultation
Patients With a Very Preterm Birth in Birth After RPL
<32 weeks of gestation
Measured: at delivery
Patients With a Very Preterm Birth in Birth Before RPL
<32 weeks of gestation
Measured: At first consultation
Gender Ratio of Children Born After RPL
Gender ratio in births before RPL
Measured: At delivery
Gender Ratio of Children Born Before RPL
Gender ratio in births after RPL
Measured: At first consultation
Patients With a Stillbirth After RPL
Stillbirth are defined as fetal death >22 weeks of gestation and within 1 week after delivery
Measured: 1 week after delivery
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.
Measured: At first consultation
Patients With a Liveborn After RPL
Number of women who give birth to a healthy liveborn child after RPL
Measured: Follow up at study end.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2019
- Study start1 Jan 2016
- Primary completion29 Mar 2021
- Study completion29 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent MiscarriageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 452 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aalborg University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Caroline Nørgaard-Pedersen, Aalborg University Hospital
- Investigators
- Caroline Nørgaard-Pedersen, Principal investigator, Aalborg University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04017754
- Sponsor's protocol ID
- 36e19au5
- Status last verified
- Jul 2021
- First submitted
- 9 Jul 2019
- Last updated
- 30 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 35747402
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low Plasma MBL Level is a Risk Factor for Recurrent Pregnancy Loss
- ClinicalTrials.gov ID
- NCT04017754
- Acronym / sponsor ID
- 36e19au5
- Conditions
- Recurrent Miscarriage, Spontaneous Abortion, Mannose-Binding Lectin Deficiency, Habitual Abortion, Pregnancy Complications, Pregnancy Loss
- Keywords
- Mannose binding lectin, Perinatal outcome, Recurrent pregnancy loss
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 452 participants (actual)
- Lead sponsor
- Aalborg University HospitalUniversity, hospital or other
- Study start
- 1 Jan 2016 (actual)
- Primary completion
- 29 Mar 2021 (actual)
- Study completion
- 29 Mar 2021 (actual)
- First posted
- 12 Jul 2019 (actual)
- Results
- Posted 24 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
| 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- 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.
Key inclusion criteria (1 listed)
- Women admitted to the Centre for Recurrent Pregnancy Loss of Western Denmark January 2016 to March 2020
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Plasma MBL Level (ug/ml)
Time frame: At first consultation. Results accessible within 3 weeks.
Manose Binding Lectin level in a blood sample
23 secondary outcomes
Participants Giving Birth After Recurrent Pregnancy Loss (RPL) to a Child With Low Birth Weight
Time frame: at delivery
Participants Giving Birth Before RPL to a Child With Low Birth Weight
Time frame: At first consultation
Participants Giving Birth After RPL to a Child With Very Low Birth Weight
Time frame: at delivery
Participants Giving Birth Before RPL to a Child With Very Low Birth Weight
Time frame: At first consultation
Participants With Preclampsia in Pregnancy After RPL
Time frame: Developed from 20 weeks gestation and until 6 weeks postpartum. Data collected at delivery.
Participants With Preclampsia in Pregnancy Before RPL
Time frame: Developed from 20 weeks gestation and until 6 weeks postpartum. Data collected at first consultation.
Patients With Emergency Caesarean Section After RPL
Time frame: at delivery
Patients With Emergency Caesarean Section Before RPL
Time frame: At first consultation
Patients With Elective Caesarean Section After RPL
Time frame: at delivery
Patients With Elective Caesarean Section Before RPL
Time frame: At first consultation
Patients With Severe Peripartum Hemorrhage in Birth After RPL
Time frame: During delivery
Patients With Severe Peripartum Hemorrhage in Birth Before RPL
Time frame: At first consultation
Patients With Moderate Peripartum Hemorrhage in Birth After RPL
Time frame: During delivery
Patients With Moderate Peripartum Hemorrhage in Birth Before RPL
Time frame: At first consultation
Patients With a Preterm Birth in Birth After RPL
Time frame: at delivery
Patients With a Preterm Birth in Birth Before RPL
Time frame: At first consultation
Patients With a Very Preterm Birth in Birth After RPL
Time frame: at delivery
Patients With a Very Preterm Birth in Birth Before RPL
Time frame: At first consultation
Gender Ratio of Children Born After RPL
Time frame: At delivery
Gender Ratio of Children Born Before RPL
Time frame: At first consultation
Patients With a Stillbirth After RPL
Time frame: 1 week after delivery
Patients With a Stillbirth Before RPL
Time frame: At first consultation
Patients With a Liveborn After RPL
Time frame: Follow up at study end.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35747402Norgaard-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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Caroline Nørgaard-Pedersen principal investigator
Aalborg University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Recurrent Miscarriage and Spontaneous Abortion, run by Aalborg University Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma MBL Level (ug/ml) (time frame: At first consultation. Results accessible within 3 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04017754, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2021.