INTRODUCTION: Low placental growth factor (PlGF) (less than the 5th percentile) is indicative of impaired placentation and predicts preeclampsia and fetal growth restriction (FGR). Off-label prophylactic use of low-molecular-weight heparin (LMWH) may improve endothelial function and enhance PlGF levels. However, prior trials have shown inconsistent results, likely due to the absence of biomarker-based patient selection. The objective was to evaluate whether prophylactic LMWH improves fetal growth and placental pathology in pregnancies with low PlGF. METHODS: Retrospective cohort study comparing outcomes in pregnancies with low PlGF (less than the 5th percentile) who received either daily prophylactic off-label LMWH or standard care (aspirin alone). Primary outcomes were fetal growth categories: FGR (less than 3rd percentile), small for gestational age (SGA) (4th–10th percentile), and normal growth (11th–90th percentile). Secondary outcomes included preeclampsia, neonatal intensive care unit (NICU) admission, and placental pathology. The study was approved by the REB at USASK (#Bio3702). RESULTS: Among 149 low PlGF pregnancies, 57 received LMWH and 92 did not. Low-molecular-weight heparin significantly reduced SGA (5.3% versus 17.4%; odds ratio OR 0.26; 95% CI, 0.08–0.93) and increased the proportion of normally grown infants (52.6% versus 32.6%; OR 2.30; 95% CI, 1.15–4.56). Severe FGR and preeclampsia were more prevalent in low PlGF groups but not significantly improved by LMWH. In treated cases, placentas were often small but lacked widespread maternal vascular malperfusion; nearly half showed only minor lesions. CONCLUSIONS/IMPLICATIONS: In pregnancies identified as low PlGF, prophylactic off-label use of LMWH was associated with improved fetal growth and reduced SGA rates. Placental findings support a potential role in halting disease progression. Biomarker-guided prospective trials are warranted.
Figueiro-Filho et al. (Thu,) studied this question.