Clinical trial NCT05878574: Prospective Study of BMD and Ca-P Metabolism in RSA Patients: LMWH Use Versus Control
Official title: Prospective Cohort Study of Bone Mineral Density and Calcium-phosphorus Metabolism in RSA Patients: Low Molecular Weight Heparin Use Versus Control
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Recurrent Spontaneous Abortion
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
First posted: 2023-05-26
Enrollment: 344
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: ultrasound BMD before medication during pregnancy preparation
timeFrame: 4 weeks
measure: ultrasound BMD after medication during pregnancy preparation
timeFrame: up to 16 weeks
measure: ultrasound BMD at 10th weeks of pregnancy
timeFrame: up to 26 weeks
measure: ultrasound BMD at 24th weeks of pregnancy
timeFrame: 40 weeks
measure: ultrasound BMD at 32nd weeks of pregnancy
timeFrame: 1 year
measure: ultrasound BMD at postpartum
timeFrame: up to 1 year and 2 months
Secondary outcomes:
measure: osteocalcin before medication during pregnancy preparation
timeFrame: 4 weeks
measure: osteocalcin after medication during pregnancy preparation
timeFrame: up to 16 weeks
measure: osteocalcin at 10th weeks of pregnancy
timeFrame: up to 26 weeks
measure: osteocalcin at 24th weeks of pregnancy
timeFrame: 40 weeks
measure: osteocalcin at 32nd weeks of pregnancy
timeFrame: 1 year
measure: osteocalcin at postpartum
timeFrame: up to 1 year and 2 months
measure: calcium before medication during pregnancy preparation
timeFrame: 4 weeks
measure: calcium after medication during pregnancy preparation
timeFrame: up to 16 weeks
measure: calcium at 10th weeks of pregnancy
timeFrame: up to 26 weeks
measure: calcium at 24th weeks of pregnancy
timeFrame: 40 weeks
measure: calcium at 32nd weeks of pregnancy
timeFrame: 1 year
measure: calcium at postpartum
timeFrame: up to 1 year and 2 months
measure: PTH before medication during pregnancy preparation
timeFrame: 4 weeks
measure: PTH after medication during pregnancy preparation
timeFrame: up to 16 weeks
measure: PTH at 10th weeks of pregnancy
timeFrame: up to 26 weeks
measure: PTH at 24th weeks of pregnancy
timeFrame: 40 weeks
measure: PTH at 32nd weeks of pregnancy
timeFrame: 1 year
measure: PTH at postpartum
timeFrame: up to 1 year and 2 months
measure: live bitrh
timeFrame: 1 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
Study officials:
affiliation: Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
name: Aimin Zhao, MD
role: PRINCIPAL_INVESTIGATOR
References: