The Clinical Features and Pregnancy Outcomes of CTD Patients

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Connective Tissue Diseases, Pregnancy Related

Intervention / Treatment
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* Drug: Prednisone
* Drug: Hydroxychloroquine
* Drug: Aspirin
* Drug: low molecular weight heparin Enoxaparin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| The Antiphospholipid syndrome (APS)<br>The cohort includes that patients who meet the proposed Sydney criteria. | Drug: Prednisone<br>* 5-30mg, po, once per day(Qd) prescribed if needed and adjusted due to patient response<br>* Other names: Pred;Drug: Hydroxychloroquine<br>* 100-200mg, po, twice per day (Bid) prescribed if needed and adjusted due to patient response.<br>* Other names: HCQ;Drug: Aspirin<br>* 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.<br>* Other names: Asp;Drug: low molecular weight heparin Enoxaparin<br>* 40-60mg, ih, Subcutaneous injection, once per day (Qd) or twice per day (Bid) if needed and adjusted due to patient response.<br>* Other names: LMWH;|
| Undifferentiated connective tissue disease (UCTD)<br>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<br>* 5-30mg, po, once per day(Qd) prescribed if needed and adjusted due to patient response<br>* Other names: Pred;Drug: Hydroxychloroquine<br>* 100-200mg, po, twice per day (Bid) prescribed if needed and adjusted due to patient response.<br>* Other names: HCQ;Drug: Aspirin<br>* 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.<br>* Other names: Asp;Drug: low molecular weight heparin Enoxaparin<br>* 40-60mg, ih, Subcutaneous injection, once per day (Qd) or twice per day (Bid) if needed and adjusted due to patient response.<br>* Other names: LMWH;|

What is the study measuring?
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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 | 
| 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 | 
| Low-weight birth | newborns with low weight (<2500g) | after 28 weeks of gestation | 
| Premature rupture of membranes | the number of participants complicated with premature rupture of membranes | 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Connective tissue disease, Pregnancy outcomes, Clinical features, Risk factors