H- 02 : classification of lupus nephritis
C- 06 : Pregnancy and the kidney
Jill P. Buyon, MD; Mimi Y. Kim, ScD; Marta M. Guerra, MS; Carl A. Laskin, MD; Michelle Petri, MD,
MPH; Michael D. Lockshin, MD; Lisa Sammaritano, MD; D. Ware Branch, MD; T. Flint Porter, MD,
MPH; Allen Sawitzke, MD; Joan T. Merrill, MD; Mary D. Stephenson, MD, MSc; Elisabeth Cohn, BA;
Lamya Garabet, MD; and Jane E. Salmon, MD
Journal : Ann Intern Med.
Year : 2015 / Month : August
Volume : 163
Pages :153-163. doi:10.7326/M14-2235
Background
Because systemic lupus erythematosus (SLE) affects women of reproductive age, pregnancy is a major concern.
Objective
To identify predictors of adverse pregnancy outcomes (APOs) in patients with inactive or stable active
SLE.
Design
Prospective cohort.
Setting
Multicenter.
Patients
385 patients (49% non-Hispanic white; 31% with prior nephritis) with SLE in the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus
Erythematosus) study. Exclusion criteria were urinary protein –creatinine ratio greater than 1000 mg/g, creatinine level greater than 1.2 mg/dL, prednisone use greater than 20 mg/d, and multifetal pregnancy.
Measurements
APOs included fetal or neonatal death; birth before 36 weeks due to placental insufficiency, hypertension, or preeclampsia; and small-for-gestational-age (SGA) neonate (birthweight below the fifth percentile). Disease activity was assessed with the Systemic Lupus Erythematosus Pregnancy
Disease Activity Index and the Physician's Global Assessment (PGA).
Results
APOs occurred in 19.0% (95% CI, 15.2% to 23.2%) of pregnancies; fetal death occurred in 4%, neonatal death occurred in 1%, preterm delivery occurred in 9%, and SGA neonate occurred in 10%.

Severe flares in the second and third trimesters occurred in 2.5% and 3.0%, respectively. Baseline predictors of APOs included presence of lupus anticoagulant (LAC) (odds ratio [OR], 8.32 [CI, 3.59 to
19.26]), antihypertensive use (OR, 7.05 [CI, 3.05 to 16.31]), PGA score greater than 1 (OR, 4.02 [CI,
1.84 to 8.82]), and low platelet count (OR, 1.33 [CI, 1.09 to 1.63] per decrease of 50 × 109 cells/L).
Non-Hispanic white race was protective (OR, 0.45 [CI, 0.24 to 0.84]). Maternal flares, higher disease activity, and smaller increases in C3 level later in pregnancy also predicted APOs. Among women without baseline risk factors, the APO rate was 7.8%. For those who either were LAC-positive or were
LAC-negative but nonwhite or Hispanic and using antihypertensives, the APO rate was 58.0% and fetal or neonatal mortality was 22.0%.
Limitation
Patients with high disease activity were excluded.
Conclusion
In pregnant patients with inactive or stable mild/moderate SLE, severe flares are infrequent and, absent specific risk factors, outcomes are favorable.
COMMENTS
Most pregnant patients with SLE had favorable pregnancy outcomes —few experienced severe flares.
Without treatment with cytotoxic agents, SLE does not adversely affect fertility . Certain clinical and laboratory variables can identify patients at high risk for adverse pregnancy outcomes.
It has been suggested that pregnancies in women with SLE result in higher rates of preterm birth, preeclampsia, and fetal loss than in healthy women .Previous studies have identified active disease, hypocomplementemia, presence of anti –double-stranded DNA (dsDNA) antibodies, prior nephritis, and presence of antiphospholipid antibodies (aPLs) as risk factors for adverse pregnancy outcomes
(APOs). The effects of pregnancy on SLE activity and the contribution of disease activity to APOs are unclear. Currently, patients with SLE are advised to consider pregnancy during periods of minimal and stable disease.
This longitudinal study enrolled and followed a multiethnic group of pregnant women with inactive or stable mild/moderate SLE at conception. Clinical and disease activity assessments and laboratory and serologic studies were performed at baseline and in each trimester.
The study recruited a large multiethnic, multiracial group of pregnant women with SLE from 8 clinical centers in the United States and 1 in Canada. Women aged 18 to 45 years with inactive or stable mild/moderate. SLE were entered into the study during the first trimester of pregnancy.
Most (81%) of the pregnancies were uncomplicated. About 1 in 5 women had 1 or more of the bad pregnancy outcomes; fetal or infant death was very rare. Few women (<5%) had severe flares in the second or third trimester of pregnancy. Some of the risk factors for bad pregnancy outcomes were more active lupus disease, high blood pressure requiring medications, and a positive lupus anticoagulant test result during the first trimester. More active lupus disease and lupus flares during the second and third trimesters were also risk factors for bad pregnancy outcomes. The chance of a bad pregnancy outcome was less than 8% for women who did not have any risk factors during the first trimester.
This study has several limitations:
Women with very active lupus (for example, active kidney disease with protein in the urine) and women who were taking more than 20 milligrams of prednisone per day were not allowed to participate in the study. The study also excluded women who had diabetes or high blood pressure. The timing of patient enrollment precluded ascertainment of first-trimester losses.
Pr. Jacques CHANARD

Professor of Nephrology