Prospective Study of BMD and Ca-P Metabolism in RSA Patients: LMWH Use Versus Control

Prospective Cohort Study of Bone Mineral Density and Calcium-phosphorus Metabolism in RSA Patients: Low Molecular Weight Heparin Use Versus Control

The goal of this prospective observational study is to learn about the effect of low molecular weight heparin (LMWH) application on bone mineral density (BMD) and on calcium-phosphorus metabolism in patients with recurrent spontaneous abortion (RSA), and to compare the degree of bone loss and changes in blood calcium and phosphorus in RSA patients and in control groups with normal pregnancy. By monitoring ultrasound BMD and serum indicators related to maternal bone formation and Ca-P metabolism, the association mechanism between long-term use of LMWH, maternal Ca-P regulation and bone loss will be constructed, so as to contribute to clinical treatment and lifestyle guidance during pregnancy in RSA patients.

Study Overview

• Status: Recruiting
• Conditions: Recurrent Spontaneous Abortion
• Intervention / Treatment: Drug: Low molecular weight heparin

Detailed Description

Women who meet the inclusion criteria at the outpatient clinic of Renji Hospital are recruited in this study from November 2022 to December 2023. Basic information of all subjects is recorded, including number of miscarriages, duration of breastfeeding, comorbidities, and intake of nutritional supplements. Subjects' medication use during the study is recorded as well. Subjects will undergo ultrasound BMD at six time points: before and after medication during pregnancy preparation, at 10, 24, 32 weeks of pregnancy, and at 42 days postpartum. Peripheral blood will also be collected at the time points above to measure serum osteocalcin, blood calcium, blood phosphorus, 25(OH) D, thyroid hormone, and parathyroid hormone levels. Subjects will be followed up to 42 days postpartum to observe pregnancy outcomes and health conditions of the newborn.

• Study Type: Observational
• Enrollment (Estimated): 344

Contacts and Locations

• Study Contact: Name: Daier Yu; Phone Number: 0086+15000732499; Email: sylviatender@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Recruiting
      • Renji Hospital, Shanghai Jiaotong University School of Medicine
      • Contact: Daier Yu; Phone Number: 0086+15000732499; Email: sylviatender@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

All women with a need for pregnancy preparation or a confirmed pregnancy who meet the inclusion criteria from November 2022 to December 2023 at the outpatient clinic of Renji Hospital.

Description

Inclusion Criteria:

• Age between 18 to 45 years.
• Female who needs to prepare for pregnancy or have a confirmed pregnancy
• normal karyotype of chromosomes.
• normal uterine anatomy under pelvic ultrasound examination.
• Cooperation in completing blood sample collection, testing and ultrasound examination.
• no serious medical or surgical comorbidities.
• Sign the informed consent form.

Exclusion Criteria:

• Presence of diseases affecting calcium metabolism, including primary hyperparathyroidism, Cushing's disease, chronic liver, kidney and gastrointestinal (e.g., celiac disease) disorders and rheumatoid arthritis.
• Known HIV positive and / or screening visit, HBsAg or HCV antibody positive.
• The malignant tumors occurred in the past 5 years (except for the skin squamous basal cell carcinoma which has been resected and considered cured). Subjects who developed malignancies five years ago should provide evidence of remission or cure. Subjects with a history of cervical cancer who had undergone conization or cure in the past 3 years were eligible.
• Patients with a history of chronic infection such as Mycoplasma, chlamydia, Cryptococcus and invasive fungal infection should be discussed with the main researchers.
• History of active tuberculosis (TB) or evidence of previous TB infection. Subjects with a history of potential TB infection should also be excluded, unless there is a documented evidence that they have completed appropriate anti TB treatment in accordance with CDC guidelines or local regulations before screening. In addition, subjects were strictly forbidden to have any clinical symptoms / signs of active TB.
• Presence of pregnancy contraindications.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
LMWH group; Continuous use of low molecular weight heparin for more than 3 months during pregnancy preparation and during pregnancy with a history of more than 2 consecutive miscarriages before 28 weeks of gestation	Drug: Low molecular weight heparin; Continuous use of LMWH for more than 3 months during pregnancy preparation and through pregnancy; Other Names: LMWH
control group; No use of low molecular weight heparin during pregnancy preparation and throughout pregnancy and history of more than 2 consecutive miscarriages before 28 weeks of gestation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ultrasound BMD before medication during pregnancy preparation	use ultrasound to test heel bone mineral density before medication during pregnancy preparation	4 weeks
ultrasound BMD after medication during pregnancy preparation	use ultrasound to test heel bone mineral density after medication during pregnancy preparation	up to 16 weeks
ultrasound BMD at 10th weeks of pregnancy	use ultrasound to test heel bone mineral density at 10th weeks of pregnancy	up to 26 weeks
ultrasound BMD at 24th weeks of pregnancy	use ultrasound to test heel bone mineral density at 24th weeks of pregnancy	40 weeks
ultrasound BMD at 32nd weeks of pregnancy	use ultrasound to test heel bone mineral density at 32nd weeks of pregnancy	1 year
ultrasound BMD at postpartum	use ultrasound to test heel bone mineral density at postpartum	up to 1 year and 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
osteocalcin before medication during pregnancy preparation	use peripheral blood test to detect N-terminal mid-molecular fragment of serum osteocalcin before medication during pregnancy preparation	4 weeks
osteocalcin after medication during pregnancy preparation	use peripheral blood test to detect N-terminal mid-molecular fragment of serum osteocalcin after medication during pregnancy preparation	up to 16 weeks
osteocalcin at 10th weeks of pregnancy	use peripheral blood test to detect N-terminal mid-molecular fragment of serum osteocalcin at 10th weeks of pregnancy	up to 26 weeks
osteocalcin at 24th weeks of pregnancy	use peripheral blood test to detect N-terminal mid-molecular fragment of serum osteocalcin at 24th weeks of pregnancy	40 weeks
osteocalcin at 32nd weeks of pregnancy	use peripheral blood test to detect N-terminal mid-molecular fragment of serum osteocalcin at 32nd weeks of pregnancy	1 year
osteocalcin at postpartum	use peripheral blood test to detect N-terminal mid-molecular fragment of serum osteocalcin at postpartum	up to 1 year and 2 months
calcium before medication during pregnancy preparation	use peripheral blood test to detect calcium level before medication during pregnancy preparation	4 weeks
calcium after medication during pregnancy preparation	use peripheral blood test to detect calcium level after medication during pregnancy preparation	up to 16 weeks
calcium at 10th weeks of pregnancy	use peripheral blood test to detect calcium level at 10th weeks of pregnancy	up to 26 weeks
calcium at 24th weeks of pregnancy	use peripheral blood test to detect calcium level at 24th weeks of pregnancy	40 weeks
calcium at 32nd weeks of pregnancy	use peripheral blood test to detect calcium level at 32nd weeks of pregnancy	1 year
calcium at postpartum	use peripheral blood test to detect calcium level at postpartum	up to 1 year and 2 months
PTH before medication during pregnancy preparation	use peripheral blood test to detect parathyroid hormone level before medication during pregnancy preparation	4 weeks
PTH after medication during pregnancy preparation	use peripheral blood test to detect parathyroid hormone level after medication during pregnancy preparation	up to 16 weeks
PTH at 10th weeks of pregnancy	use peripheral blood test to detect parathyroid hormone level at 10th weeks of pregnancy	up to 26 weeks
PTH at 24th weeks of pregnancy	use peripheral blood test to detect parathyroid hormone level at 24th weeks of pregnancy	40 weeks
PTH at 32nd weeks of pregnancy	use peripheral blood test to detect parathyroid hormone level at 32nd weeks of pregnancy	1 year
PTH at postpartum	use peripheral blood test to detect parathyroid hormone level at postpartum	up to 1 year and 2 months
live bitrh	A live baby born after 23 weeks of gestation	1 year

Collaborators and Investigators

• Sponsor: Aimin Zhao
• Investigators: Principal Investigator: Aimin Zhao, MD, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): March 1, 2024

Study Registration Dates

• First Submitted: May 7, 2023
• First Submitted That Met QC Criteria: May 18, 2023
• First Posted (Actual): May 26, 2023

Study Record Updates

• Last Update Posted (Actual): May 26, 2023
• Last Update Submitted That Met QC Criteria: May 18, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Abortion, Spontaneous; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin
• Other Study ID Numbers: IIT-2023-0010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No