A prospective, multicenter, observational study found low-dose aspirin and/or unfractionated heparin treatment significantly improved pregnancy outcomes in women with recurrent pregnancy loss who tested positive for anti-β2-glycoprotein I/human leukocyte antigen-DR antibodies. The research demonstrates increased live birth rates and reduced pregnancy complications in this patient population.
The study, conducted between August 2019 and December 2023 and published in Frontiers in Immunology, included 47 pregnancies in women with recurrent pregnancy loss (RPL) and anti-β2-glycoprotein I (β2GPI)/human leukocyte antigen (HLA)-DR antibody positivity. Participants were divided into two groups consisting of 39 women treated with low-dose aspirin (LDA) and/or unfractionated heparin (UFH) and 8 women who received neither.
The outcomes showed promise for the use of LDA and or UFH with an 87.2% live birth rate for the LDA/UFH group and a 50.0% live birth rate for the cohort of women who did not receive any combination of those medications. Additionally, the LDA/UFH group had a pregnancy complication rate of just 5.9% compared with a rate of 50% in the non-LDA/non-UFH group.
The 12 women who received LDA alone had a 100% live birth rate and a 0% complication rate. The 19 women who received both LDA and UFH had an 89.5% live birth rate and an 11.8% complication rate. The 4 women who received LDA, UFH along with prednisone (PSL) exhibited a 75% live birth rate and a 0% complication rate. The 6 women group receiving no treatment had a 66.7 live birth rate and a 50% complication rate. The 2 women who only received PSL did not have any live births during the study.
The study also finds that PSL therapy alone may not be effective for women with RPL and anti-β2GPI/HLA-DR antibody positivity, as all women in this category had miscarriages.
The study enrolled women with RPL who visited one of five medical centers between August 2019 and December 2021. RPL was defined as two or more pregnancy losses. Participants underwent measurements of serum anti-β2GPI/HLA-DR antibody levels and conventional assessments to identify causes and risk factors for RPL.
Anti-β2GPI/HLA-DR antibody levels were measured using a standardized method at HuLA Immune Inc. (Tokyo, Japan). The normal range was established as <73.3 U using sera from 374 healthy controls at the 99th percentile.
Treatment modalities were decided by attending physicians based on individual risk factors. The LDA/UFH group received various combinations of treatments, including LDA alone, LDA + UFH, LDA + UFH + PSL, and LDA + UFH + intravenous immunoglobulin (IVIG). The non-LDA/non-UFH group either received no treatment or 5 mg/day of PSL.
Pregnancy outcomes were followed until December 2023. The primary outcomes were live birth rates and pregnancy complication rates, including preeclampsia and preterm delivery before 34 gestational weeks due to placental insufficiency.
The women included in the study ranged in age between 27 and 48 years with a median age of 34 years. The LDA/UFH group had a median BMI of 20.8 kg/m2, while the non LDA/non-UFH group had a median BMI of 22.3 kg/m2. Additional risk factors for RPL in the study population included thyroid dysfunction,low protein S activity, low protein C activity, low factor XII activity, and uterine malformation.
Limitations of the study include its relatively small sample size, heterogeneity among treatment subgroups, and its observational nature. The authors noted that randomized controlled trials with larger sample sizes are needed to confirm these findings.
The authors declared that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
