The Clinical Features and Pregnancy Outcomes of CTD Patients

The Clinical Features and Pregnancy Outcomes of Patients With Connective Tissue Disease :a Prospective Cohort Study

Connective tissue disease (CTD) is a common group of autoimmune diseases, mainly including systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS) , and so on. APS is caused by autoimmune disorders that cause recurrent miscarriage, thrombosis, and thrombocytopenia, and often secondary to connective tissue diseases such as SLE. Undifferentiated connective tissue disease (UCTD) is currently considered to be an independent disease in the classification of CTD. And women of childbearing age who suffer UCTD is more common than that in other definite CTDs. Therefore, the impact of the disease flare and the influence of medicine on pregnancy and lactation are important for these patients who may suffer high-risk of abnormal pregnance.

Study Overview

• Status: Recruiting
• Conditions: Connective Tissue Diseases; Pregnancy Related
• Intervention / Treatment: Drug: Prednisone; Drug: Hydroxychloroquine; Drug: Aspirin; Drug: low molecular weight heparin Enoxaparin

Detailed Description

Objective: To study the risk factors of poor pregnancy outcomes in CTD patients, and evaluate impact of different therapies on the maternal and fetal health.

Methods: Our department and Shanghai Gothic Network Technology Co.Ltd. jointly established the chronic disease management of CTD patients during pregnancy and lactation by using Smart System of Disease Management (SSDM). With this platform, patients in pregnancy can consult with rheumatologists face to face and follow-up regularly.

Follow-up: Consultation and followup will be scheduled every 4 weeks from confirmed pregnancy until delivery.

• Study Type: Observational
• Enrollment (Estimated): 126

Contacts and Locations

• Study Contact: Name: Shuting Li; Phone Number: 0086-0531-82169654; Email: leeshuting1994@163.com
• Study Contact Backup: Name: Qiang Shu, Dr.; Phone Number: 0086-0531-82169654; Email: shuqiang@sdu.edu.cn

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250012
      • Recruiting
      • Qilu hospital
      • Contact: Xiaoyun Yang, Dr; Phone Number: 0086-0531-82169166; Email: qlyykyc@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

female with pregnance in accordance with the diagnostic criteria of connective tissue disease

Description

Inclusion Criteria:

• Women who meet the following inclusion criteria will be eligible to participate in the study:

  1. Age between 20-45 years;
  2. Diagnosed with APS: patients meet the Sydney classification criteria;
  3. Diagnosed with UCTD: at least one presence of auto-antibodies, including antinuclear antibody (ANA), anti-extractable nuclear antigen (ENA) antibodies, anti-doublestranded DNA (ds-DNA) antibody, antiphospholipid antibody(aPL), and non-criteria aPL (NC-aPL), with at least one symptoms or signs suggesting connective tissue disease(CTD) , while not fulfilling any classification criteria of a defined CTD.
  4. Participate voluntarily in this study, willing to use medication and follow-up according to treatment plan, and sign informed consent.

Exclusion Criteria:

• Women who meet any of the following criteria will be excluded from the study:

  1.Any known etiology of previous pregnancy loss:

  1. Known paternal, maternal or embryo chromosome abnormality.
  2. Maternal endocrine dysfunction: corpus luteal insufficiency; polycystic ovarian syndrome; premature ovarian failure (follicle stimulating hormone, FSH ≥20uU/L in follicular phase);
  3. hyperprolactinemia; diabetes mellitus; other hypothalamic pituitary-adrenal axis abnormality
  4. Maternal anatomical abnormality: uterine malformation; Asherman syndrome; cervical incompetence; uterine fibrosis more than 5 cm.Vaginal infection.
  5. Any known severe cardiac, hepatic, renal, hematological or endocrinal diseases:

  2. Any active infection: Active infection including V aricella zostervirus(VZV), human immunodeficiency virus (HIV), Human papillomavirus (HPV),syphilis or tuberculosis.

  3. Allergic to prednisone, hydroxychloroquine, low-molecular-weight heparin or aspirin.

  4.Disease history as follows:

  1. Past history of digestive ulcers or upper gastrointestinal hemorrhage.
  2. Past history of malignancy.
  3. Past history of epilepsia or psychotic disorders.

  5.Women have been diagnosed with Systemic lupus erythematosus

  6. Women who disagree or cannot complete pregnancy and follow-up after delivery.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
The Antiphospholipid syndrome (APS); The cohort includes that patients who meet the proposed Sydney criteria.	Drug: Prednisone; 5-30mg, po, once per day(Qd) prescribed if needed and adjusted due to patient response; Other Names: Pred; Drug: Hydroxychloroquine; 100-200mg, po, twice per day (Bid) prescribed if needed and adjusted due to patient response.; Other Names: HCQ; Drug: Aspirin; 100mg, po, once per day (Qd) prescribed if needed and adjusted due to patient response to 32 weeks of pregnancy. 75mg po, once per day (Qd) to 34 weeks of pregnancy. 50mg po, once per day (Qd) to 36 weeks of pregnancy.; Other Names: Asp; Drug: low molecular weight heparin Enoxaparin; 40-60mg, ih, Subcutaneous injection, once per day (Qd) or twice per day (Bid) if needed and adjusted due to patient response.; Other Names: LMWH
Undifferentiated connective tissue disease (UCTD); The cohort includes the patients who are diagnosed with UCTD: at least one presence of auto-antibodies, including antinuclear antibody (ANA), anti-extractable nuclear antigen (ENA) antibodies, anti-doublestranded DNA (ds-DNA) antibody, antiphospholipid antibodies (aPL), and non-criteria aPL (NC-aPL), with at least one symptoms or signs suggesting CTD ,while not fulfilling any classification criteria of a defined CTD.	Drug: Prednisone; 5-30mg, po, once per day(Qd) prescribed if needed and adjusted due to patient response; Other Names: Pred; Drug: Hydroxychloroquine; 100-200mg, po, twice per day (Bid) prescribed if needed and adjusted due to patient response.; Other Names: HCQ; Drug: Aspirin; 100mg, po, once per day (Qd) prescribed if needed and adjusted due to patient response to 32 weeks of pregnancy. 75mg po, once per day (Qd) to 34 weeks of pregnancy. 50mg po, once per day (Qd) to 36 weeks of pregnancy.; Other Names: Asp; Drug: low molecular weight heparin Enoxaparin; 40-60mg, ih, Subcutaneous injection, once per day (Qd) or twice per day (Bid) if needed and adjusted due to patient response.; Other Names: LMWH

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth rate	Percentage of all patients that lead to live birth after 28 weeks of gestation	After 28 weeks of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early fetal loss	Spontaneous pregnancy loss within 10 weeks of gestation	within 10 weeks of gestation
Late fetal loss	Spontaneous pregnancy loss after 10 weeks of gestation	after 10 weeks of gestation
Low-weight birth	newborns with low weight (<2500g)	after 28 weeks of gestation
Placental abruption	the number of participants complicated with placental abruption	after 28 weeks of gestation
Fetal growth retardation (FGR)	weight below the 10th percentile for the gestational age	after 12 weeks of gestation
Number of participants with low amniotic fluid during pregnancy	the number of participants whose B-ultrasound indicates low amniotic fluid during pregnancy	after 12 weeks of gestation
Number of participants with abnormal S / D values during pregnancy	the number of participants whose B-ultrasound indicates abnormal S / D values during pregnancy	after 12 weeks of gestation
Eclampsia	New-onset hypertension after 20 weeks of gestation, with or without proteinuria > 300mg/24h, with or without any organ damage with seizures	after 20 weeks of gestation
Gestational diabetes	the number of participants who were diagnosed with gestational diabetes	through study completion, an average of 10 months
Gestational hypertension	the number of participants who were diagnosed with gestational hypertension	through study completion, an average of 10 months
Number of participants with placental infarction	the number of participants whose placenta with infarction.	at delivery
Stillbirth	Spontaneous pregnancy loss after 20 weeks of gestation	after 20 weeks of gestation
Preterm delivery	Live birth before 37 weeks of gestation	between 28 and 37 weeks of gestation
Premature rupture of membranes	the number of participants complicated with premature rupture of membranes	after 28 weeks of gestation
Number of participants with placental hematoma during pregnancy	the number of participants whose B-ultrasound indicates placental hematoma during pregnancy	during pregnancy, an average of 10 months

Collaborators and Investigators

• Sponsor: Qilu Hospital of Shandong University
• Investigators: Study Director: Xiaoyun Yang, Dr., Qilu Hospital of Shandong University

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2018
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: June 2, 2021
• First Submitted That Met QC Criteria: June 2, 2021
• First Posted (Actual): June 9, 2021

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Risk factors; Pregnancy outcomes; Connective tissue disease; Clinical features
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Anticoagulants; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Aspirin; Heparin; Prednisone; Enoxaparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin; Hydroxychloroquine
• Other Study ID Numbers: CTD with Pregnancy QiluH

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