The Clinical Features and Pregnancy Outcomes of CTD Patients

Official title

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

Overview

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.

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.

Interventions

• Drug Prednisone
  5-30mg, po, once per day(Qd) prescribed if needed and adjusted due to patient response
• Drug Hydroxychloroquine
  100-200mg, po, twice per day (Bid) prescribed if needed and adjusted due to patient response.
• 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.
• 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.

Primary outcome measures

• Live birth rate [Time frame: After 28 weeks of gestation]

Secondary outcome measures (12)

• Early fetal loss [Time frame: within 10 weeks of gestation]
• Late fetal loss [Time frame: after 10 weeks of gestation]
• Stillbirth [Time frame: after 20 weeks of gestation]
• Preterm delivery [Time frame: between 28 and 37 weeks of gestation]
• Low-weight birth [Time frame: after 28 weeks of gestation]
• Premature rupture of membranes [Time frame: after 28 weeks of gestation]
• Placental abruption [Time frame: after 28 weeks of gestation]
• Fetal growth retardation (FGR) [Time frame: after 12 weeks of gestation]
• Number of participants with low amniotic fluid during pregnancy [Time frame: after 12 weeks of gestation]
• Number of participants with abnormal S / D values during pregnancy [Time frame: after 12 weeks of gestation]
• Number of participants with placental hematoma during pregnancy [Time frame: during pregnancy, an average of 10 months]
• Eclampsia [Time frame: after 20 weeks of gestation]

Eligibility criteria

Inclusion criteria

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

• Age between 20-45 years;
• Diagnosed with APS: patients meet the Sydney classification criteria;
• 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.
• 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:

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

• Past history of digestive ulcers or upper gastrointestinal hemorrhage.
• Past history of malignancy.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• Qilu Hospital — Jinan

Identifiers

NCT: NCT04918524 · CTD with Pregnancy QiluH

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗