A systematic review and meta-analysis published in the American Journal of Obstetrics & Gynecology assessed maternal serum concentrations of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and the sFlt-1/PlGF ratio in women with and without placental abruption.1
Placental abruption, defined as the premature separation of the placenta from the uterine wall, remains a leading cause of maternal and fetal morbidity, affecting approximately 0.6% to 1.4% of pregnancies worldwide.2 It is frequently unrecognized until clinical signs such as vaginal bleeding or abdominal pain appear, by which point fetal compromise may already be present.1
Key takeaways:
- Maternal serum PlGF concentrations were not significantly associated with placental abruption.
- Elevated maternal serum sFlt-1 was linked to placental abruption, particularly when measured after 21 weeks of gestation.
- The sFlt-1/PlGF ratio showed the strongest and most consistent association with placental abruption across studies and gestational ages.
- Among women with preeclampsia, the sFlt-1/PlGF ratio was not predictive, likely due to preexisting angiogenic imbalance.
- Monitoring sFlt-1 and the sFlt-1/PlGF ratio may support early risk stratification and guide prenatal care in singleton pregnancies, especially in normotensive women.
Placental abruption is part of a spectrum of placental disorders that includes preeclampsia (PE) and fetal growth restriction (FGR). These conditions share underlying mechanisms related to impaired placentation, trophoblast stress, and angiogenic imbalance.
PlGF and placental abruption
The study aimed to clarify inconsistencies in previous research regarding these angiogenic biomarkers. It followed PRISMA guidelines and included 6 studies conducted from 1992 to 2022 in Egypt, Spain, India, the United States, and Finland. These studies analyzed 124 cases of placental abruption and 827 controls, with maternal blood samples collected at gestational ages ranging from 7 to 36 weeks. Biomarker measurements were performed using enzyme-linked immunosorbent assays.
- Maternal serum PlGF concentrations were not significantly associated with placental abruption. Subgroup analyses by gestational age at sample collection (≤21 weeks vs >21 weeks) similarly showed no significant differences. Sensitivity analyses suggested that individual studies, particularly that by Signore et al, could influence pooled estimates, but the overall result remained nonsignificant.
- Maternal serum sFlt-1 levels were higher in women with placental abruption. The pooled standardized mean difference (SMD) was 0.96 (95% CI, 0.07–1.85). Subgroup analysis revealed that elevated sFlt-1 was significant only when measured beyond 21 weeks of gestation (SMD, 1.89; 95% CI, 1.29–2.50), while measurements earlier in pregnancy showed no association. Sensitivity analyses indicated that individual studies, especially those by Signore et al and Tikkanen et al, had a notable impact on overall results.
sFlt-1/PlGF ratio and placental abruption
The sFlt-1/PlGF ratio demonstrated the strongest and most consistent association with placental abruption. Five studies assessed this ratio in 96 cases and 827 controls, yielding a pooled SMD of 3.05 (95% CI, 0.69–5.41). Subgroup analyses confirmed significant associations both at or below 21 weeks (SMD, 1.92; 95% CI, 1.14–2.69) and beyond 21 weeks of gestation (SMD, 2.45; 95% CI, 1.13–3.77). Among women with PE, no significant association was observed, likely reflecting the angiogenic imbalance already present in preeclampsia.
"The risk of placental abruption is associated with serum sFlt-1 concentration and the sFlt-1/PlGF ratio," wrote the authors.
While PlGF alone was not predictive, sFlt-1 and the sFlt-1/PlGF ratio may support early risk stratification, particularly in the second half of pregnancy. These biomarkers may provide insight into the pathophysiology of placental abruption and could inform monitoring strategies for women considered at elevated risk. Investigators concluded prospective trials are needed to confirm predictive thresholds and clinical utility, especially among normotensive women.
References
- Kosińska-Kaczyńska K, Szymusik I, Brawura Biskupski Samaha R, Sys D. The association between serum soluble fms-like tyrosine kinase-1, placental growth factor, and soluble fms-like tyrosine kinase-1/placental growth factor ratio in singleton pregnancy and placental abruption: a systematic review and meta-analysis. American Journal of Obstetrics & Gynecology. 2025;233(4):263.E1-263.E18. doi:10.1016/j.ajog.2025.04.020
- Brandt JS, Ananth CV. Placental abruption at near-term and term gestations: pathophysiology, epidemiology, diagnosis, and management. Am J Obstet Gynecol. 2023;228(5S):S1313-S1329. doi:10.1016/j.ajog.2022.06.059
