Predictors of Pregnancy Outcomes in Patients With Lupus: A Cohort Study

Abstract

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.

Primary funding source: National Institutes of Health.

Appendix Figure 1. Patient enrollment and classification for the PROMISSE Study

Pregnant women at <12 weeks' gestation with antiphospholipid antibody (aPL) positivity and systemic lupus erythematosus (SLE) and healthy controls were screened. Exclusion criteria included: multifetal pregnancy, prednisone >20 mg/day, blood pressure ≥140/90 mm Hgurine protein (mg)/creatinine (gram) ratio ≥1,000 mg protein/gm creatinine on 24-hour urine or spot urine collection, serum creatinine >1.2 mg/dl, screened too late in pregnancy, and previously enrolled in PROMISSE. Healthy pregnant women were enrolled if they had ≥ one successful pregnancy, no history of fetal death, and no more than 1 miscarriage <10 weeks' gestation and no antiphospholipid antibodies. The current study included all PROMISSE patients who met American College of Rheumatology criteria for systemic lupus erythematosus (SLE). Number of subjects is shown in parenthesis. *Four patients whose pregnancy ended at <23 weeks did not meet study criteria for primary study outcome: elective termination (1), incompetent cervix (2), PPROM (1).See Table 1. **Twenty patients whose pregnancy ended at <35 weeks did not meet study criteria for primary study outcome: indicated delivery for poor obstetric history (1), for SLE flare (1), for bleeding placental abruption (1); termination for complete heart block (1); fetal death due to trisomy 18 (1); PPROM and/or premature labor (15).See Table 1. APO = adverse pregnancy outcome; aPL = antiphospholipid antibodies; PPROM = premature preterm rupture of membranes

Figure 1. Frequency of Adverse Pregnancy Outcomes in Patients and Healthy Controls

Error bars represent 95% confidence bounds. *SLE patients with no risk factors are non-Hispanic White, LAC negative, PGA ≤1, platelet count >100,000 and not treated with antihypertensive medications at baseline. They constitute a subset of “All SLE”. † Because women enrolled in the PROMISSE control group had at least one successful pregnancy, no history of fetal death, no more than 1 miscarriage <10 weeks' gestation, and no underlying medical problems requiring treatment, it was anticipated that their pregnancy outcomes would be better than those in unselected healthy patients, particularly nulliparous women. In addition to the APOs in the bar graph, the healthy control patients had 10 (5.1%) adverse outcomes that did not meet the study primary outcome definition: ≤ 23 weeks: 2 genetic terminations; >23 to ≤ 35 weeks: 3 premature preterm rupture of membranes and/or spontaneous preterm births, 2 placental abruptions, 1 delivery for fetal indications (supraventricular tachycardia and hydrops); >35 weeks: 3 premature preterm rupture of membranes and/or spontaneous preterm births (event numbers may add to more than total because some women had more than one adverse outcome). ‡ When available, pregnancy outcomes in the general population are represented by the broken line (27, 28). No general population norm line is available for the study definition used for pre-term birth (see below). § Pre-term birth is defined as delivery at <36 weeks and indicated by gestational hypertension, preeclampsia, or placental insufficiency. SGA = small for gestational age