Antiphospholipid Syndrome and Recurrent Abortion by Trimester
Antiphospholipid syndrome (APS) most commonly causes recurrent pregnancy loss in the first trimester, though it can affect all trimesters and is particularly associated with losses occurring after 10 weeks gestation.
Timing of Pregnancy Loss in APS
First Trimester Predominance
- The majority of APS-related pregnancy losses occur in the first trimester, with studies showing that 7-25% of recurrent spontaneous abortions are attributable to APS as the main risk factor 1.
- Women with three or more consecutive first trimester spontaneous abortions and antiphospholipid antibodies represent a significant clinical population, with treatment studies specifically targeting this group demonstrating 89.4% of pregnancies proceeding beyond the first trimester with appropriate therapy 2.
- Unexplained miscarriages, especially those occurring after 10 weeks gestation, should raise particular suspicion for APS, as this timing pattern is characteristic of the syndrome 3.
Clinical Pattern Across Trimesters
- While first trimester losses are most common, APS is characterized by recurrent fetal loss across all gestational ages, distinguishing it from other causes of miscarriage 4.
- The syndrome manifests not only as early pregnancy loss but also as severe complications in later pregnancy including preeclampsia, fetal growth retardation, and placental insufficiency, with these complications occurring in approximately 50% of treated patients 4.
- Fetal death can occur in the second and third trimesters as part of the APS clinical spectrum, though early losses remain more frequent 5.
Diagnostic Considerations
Key Clinical Indicators
- Women presenting with recurrent miscarriages (particularly after 10 weeks), unexplained single miscarriage in the first trimester, history of thrombosis, intrauterine growth restriction, or preeclampsia are candidates for APS evaluation 3.
- The most clinically important serologic markers are lupus anticoagulant, anticardiolipin antibodies, and anti-beta-2-glycoprotein 1 antibodies 4.
Important Caveat
- Association does not equal causation: the exact proportion of abortions directly caused by APS is difficult to estimate due to variable definitions of recurrent abortion, lack of standardized antibody assays, and author-dependent inclusion criteria based on antibody titers 1.
Treatment Implications by Trimester
- Treatment with low molecular weight heparin and low-dose aspirin initiated as soon as pregnancy is confirmed represents the evidence-based standard, with continuation throughout pregnancy 4, 3.
- The general failure rate of heparin/aspirin treatment is approximately 30%, with intravenous immunoglobulin reserved for refractory cases 4.
- Treatment should begin immediately upon pregnancy confirmation and continue through all trimesters, as the risk extends beyond the first trimester despite the higher frequency of early losses 2, 5.