Predictors of Pregnancy Outcome: Biomarkers in Anti-Phospholipid Antibody Syndrome (APS) and Systemic Lupus Erythematosus (SLE) (PROMISSE)
|Principal Investigator: DavidBranch|
|Keywords: Pregnant , Lupus in Pregnancy , SLE , APL||Department: Maternal-Fetal Medicine|
|IRB Number: 00011097||Co Investigator: BobSilver|
|Specialty: Maternal-Fetal Medicine|
We will utilize a prospective observational study design to determine whether elevations of split products generated by activation of the alternative or classical complement pathways predict poor fetal outcome in women with antiphospholipid antibodies (APL) and/or SLE. The study will involve over 700 pregnant women, enrolled at 9 major clinical centers, and grouped and analyzed according to the presence or absence or aPL and preexisting SLE.
Because SLE flares are often accompanied by alterations in serum complement levels and lupus flares often occur in pregnancy, a four-group study is necessary to distinguish between the contributions of each condition to poor pregnancy outcome and to characterize the specific markers that predict poor pregnancy outcome in each condition.:
Group 1: Patients with aPL antibodies (defined below) and less than 4 criteria for the American College of Rheumatology (ACR) classification of SLE (8).
Group 2: Patients with at least 4 ACR criteria for SLE and the presence of aPL antibodies.
Group 3: Patients with at least 4 ACR criteria for SLE without aPL antibodies.
Group 4: Healthy controls.
At least one of the following aPL criteria* must be present at screening or within 2 visits post-screening in assays run at core lab:
• aCL: IgG ≥ 40 GPL units; IgM ≥ 40 MPL units
• Positive LAC: RVVT, Kaolin, dilute TTI, PTT LA
• Anti-β2GPI: IgG ≥ 40 GPL units; IgM ≥ 40 MPL units
At least one of the following must be present:
• History of positive aPL pre-pregnancy at local or core lab [History of Moderate/High aCL (IgG > 25 GPL units; IgM > 25 MPL units), History of positive LAC (RVVT, Kaolin, dilute TTI, PTT LA, History of Moderate/High anti-β2GPI (IgG > 25 GPL units; IgM > 25 MPL units)], between six weeks and five years prior to the screening visit.
• A second positive aPL during pregnancy (at core lab, meeting the above aPL criteria*)
• A second positive aPL at 3MPP (at core lab, meeting the above aPL criteria*)
Inclusion Criteria for Groups all groups:
1. Patient pregnant with live intrauterine pregnancy, as defined by positive test for elevated β-HCG, but <12 weeks by gestation (for groups 3 and 4) and <18 weeks by gestation (for groups 1 and 2)
2. Age 18-45 years and able to give informed consent
3. Hct > 26%
Inclusion Criteria for Group 4:
1. At least one successful pregnancy
2. No history of fetal death (death of conceptus > 10 weeks’ gestation)
3. No more than 1 miscarriage < 10 weeks’ gestation
4. No history of positive aPL in local lab or positive aPL in core labs at screening
5. Not currently a smoker
6. No medical problems requiring chronic treatment
Inclusion Criteria for Groups 2B and 3B:
(One or more of the following must be present):
1.Prednisone >20 mg/day
2.Renal disease: Proteinuria [urine protein > 1000 mg in 24 hours or protein/creatinine ratio >1000 mg protein/gram creatinine on spot urine (either test performed if dipstick >1+)]; RBC casts; serum creatinine >1.2 mg/dl
3.Hypertension (blood pressure >140/90 mmHg)
For Controls: history of fetal death <10 weeks gestation.
for patients with SLE: Patients on more than 20 mg prednisone, active renal dises (defined as proteinuria >1000mg/24 hr, RBC or WBC casts, unexplained Hematuria, RBC >10 cells/hpf on 2 occasions, or serum creatinine >1.0.
Diabetes Mellitus (type I and type II)
Exclusion Criteria for Groups 1-4:
1. Known or suspected hereditary complement deficiency (defined by CH50 = 0)
2. Prednisone >20 mg/day
3. Active renal disease (proteinuria >1000 mg/24 hr; RBC casts; serum creatinine >1.2 mg/dl)
4. Diabetes mellitus (Type I and Type II) antedating pregnancy
5. Hypertension (blood pressure ≥140/90 mmHg)
6. Multi-fetal pregnancy
Exclusion Criteria for groups 2B and 3B:
1.Known or suspected hereditary complement deficiency (defined by CH50 = 0)
2.Diabetes mellitus (Type I and Type II) antedating pregnancy