Recurrent fetal loss is a manifestation of several autoimmune diseases, including systemic lupus erythematosus. The lupus anticoagulant, an inhibitor of in vitro coagulation, and several other autoantibodies have been detected in otherwise healthy women with a history of recurrent fetal loss. The mechanism of spontaneous abortion in these patients is not known. Moderate to high doses of prednisone and aspirin have been recommended as therapy on the rationale that most of these women have a subtle autoimmune disorder that is manifested by recurrent fetal loss. Laskin and associates evaluated the use of aspirin and prednisone in women with autoantibodies and a history of unexplained fetal loss with respect to maternal morbidity and fetal mortality.
Patients included in the study were 18 to 39 years of age with a history of at least two consecutive fetal losses before 32 weeks' gestation, and at least one of the following laboratory findings on two of three occasions: antinuclear antibodies, anti-DNA antibodies (double- or single-stranded), antilymphocyte IgM, anticardiolipin IgG or lupus anticoagulant. Exclusion criteria included diabetes mellitus, systemic lupus erythematosus, luteal phase defect, chromosomal abnormality, diastolic blood pressure greater than 90 mm Hg and previous prednisone therapy. Those selected for the study were randomized to receive placebo or 100 mg per day of aspirin until 36 weeks' gestation, plus prednisone, 0.8 mg per kg daily (maximum: 60 mg) for four weeks, followed by 0.5 mg per kg per day (maximum: 40 mg) until delivery.
A total of 202 women were enrolled in the study, and 101 were randomized into each group. Each woman was followed throughout her pregnancy and for at least two years post-partum, regardless of the outcome of the pregnancy. There were no baseline differences between the groups in age, number of prior fetal losses, number of live births, percentages with a specific type of autoantibody or lupus anticoagulant, and smoking history.
There were a total of 66 live births in the treatment group and 57 live births in the placebo group. However, after adjusting for maternal age and the week of gestation at which the previous fetal losses occurred, the aspirin and prednisone had no beneficial effect. Preterm delivery, premature labor and premature rupture of the membranes all occurred significantly more often in the treatment group. The majority of these births occurred between 32 and 38 weeks of gestation. However, the birth weights of all infants, including those in the placebo group, were appropriate for gestational age (between the 10th and 90th percentiles). There was no difference between the two groups with respect to congenital anomalies or incidence of infection.
Hypertension occurred in 13 percent of patients in the treatment group compared with 5 percent of patients in the placebo group. Gestational diabetes was also more common in patients in the treatment group (15 percent versus 5 percent in the placebo group). Two women in the treatment group developed cataracts, compared with none in the placebo group.
The authors conclude that in women with a history of recurrent fetal loss and the presence of autoantibodies, aspirin and prednisone are no more effective than placebo in preventing fetal loss during a subsequent pregnancy. They also found a higher incidence of preterm delivery in patients treated with aspirin and prednisone compared with those treated with placebo. Had this therapy been effective in improving pregnancy outcome in women with recurrent fetal loss, the few instances of hypertension and gestational diabetes would not be sufficient to warrant withholding treatment.