Recurrent miscarriage and antiphospholipid antibodies: prognosis of subsequent pregnancy

Abstract

Background: Although women with antiphospholipid antibodies (APLAs) are at increased risk of recurrent miscarriage, the outcome of a subsequent pregnancy is not clearly elucidated.

Objectives: To assess the pregnancy outcome of a subsequent pregnancy in women with APLAs and compare this outcome with women with unexplained recurrent miscarriage.

Methods: We performed a cohort study among all women who attended the Miscarriage Clinic at Liverpool Women's Hospital between 1987 and 2006 after being referred due to recurrent miscarriage (≥2 consecutive pregnancy losses). All women underwent a standardized investigation sequence. Women with other reasons for recurrent miscarriage were excluded.

Results: A total of 693 women fulfilled the selection criteria, of whom 176 (25%) had APLAs. One hundred and twenty-two (69%) women with APLAs had a subsequent live birth compared with 324 (63%) women with unexplained recurrent miscarriage (OR 1.3, 95% CI 0.9-1.9). No differences were found for birth weight, gestational age, and intra-uterine growth restriction. When treatment was analyzed, 53/67 (79%) of women with APLAs who had received aspirin and heparin during their pregnancy had a live birth, compared with 64/104 (62%) of women with APLAs who received aspirin only (adjusted OR 2.7, 95% CI 1.3-5.8). In unexplained recurrent miscarriage, stratification for treatment showed no differences in outcome.

Conclusion: The prognosis of a subsequent pregnancy in women with APLAs is good. Although this was not a randomized clinical trial, combined treatment of aspirin and heparin seemed associated with a better outcome in women with APLAs, but not in women with unexplained recurrent miscarriage.

Fig. 1

FVIIa activity and antigen in tissues following rFVIIa administration. Mouse rFVIIa (120 μg/kg body weight in 100 μl) or saline was administered i.v. to C57BL/6 mice. Mice were exsanguinated at 30 min, 6 h, and 24 h following the administration of rFVIIa. Various tissues were collected and homogenized (500 μl/100 mg tissue) using tissue homogenizer. Tissue homogenates were centrifuged (after adding EDTA, 20 mM) and the supernatants were collected and assayed for FVIIa levels in FVIIa-specific clotting activity assay using soluble TF (A) or FVII/FVIIa antigen in ELISA using antibodies specific to mouse FVII/FVIIa (B). For the clotting assay, the samples were diluted at least 10 times in TBS supplemented with 1 mg/ml bovine serum albumin before they were used in the assay. Under these conditions, EDTA will not affect the assay. Protein concentrations in tissue supernatants were measured using Bio-Rad protein assay kit. FVIIa activity and antigen levels were normalized to the protein concentration. The four bars in each group in panels A and B represent FVIIa levels in mice at 30 min following saline administration or 30 min, 6 h, 1 d following rFVIIa administration, respectively. *indicates statistically significant increase in FVIIa activity or antigen compared to the value obtained in the corresponding tissue of mice administered with saline. Panel C depicts the amount of rFVIIa (in %) in plasma and various organs following rFVIIa administration. To determine FVIIa levels specific to rFVIIa administration, FVIIa activity levels measured in saline-administered mice were deducted from FVIIa activity levels measured following rFVIIa administration. rFVIIa associated in each organ was determined by taking into consideration of organ weight and the amount of protein in the organ. rFVIIa activity found in plasma, liver, kidney, brain, lung, heart and spleen at specific time periods were added together and the combined value was taken as 100% to determine fraction of FVIIa associated with each tissue at a specific time point.