Maternal serum placental growth factor concentration in the prediction of growth outcomes and preterm birth in early-onset fetal growth restriction: a retrospective observational study.

OBJECTIVES: To evaluate whether low gestation-specific maternal serum placental growth factor (PlGF; ≤5th centile) is associated with adverse outcomes in early-onset fetal growth restriction (FGR), and to compare these associations with those observed for first-trimester pregnancy-associated plasma protein A (PAPP-A), second-trimester uterine artery Doppler (UtAD) and maternal age. METHODS: This retrospective observational study included a total of 102 pregnancies with early-onset FGR (≤32 weeks) managed at a London tertiary fetal medicine unit between January 2022 and November 2024. Maternal, fetal, and neonatal outcomes were assessed. Univariate logistic regression tested associations between low PlGF concentrations and adverse outcomes, including preterm birth (PTB) ≤32 weeks and birthweight <3rd centile. The predictive value of PlGF was also compared with other associated clinical parameters, including a combined UtAD pulsatility index (PI) >2.5 at 18 to 23 weeks' gestation and a low PAPP-A concentration <0.415 Multiples of the Median (MoM) taken from first trimester combined screening results. RESULTS: The majority of the 102 included pregnancies were diagnosed with FGR <28 weeks' gestation (n = 59, 57.8%), whereas PTB occurred in 39.2% (n = 23). Of the 41 observed preterm births, 40 occurred in the group with PlGF ≤5th centile for gestational age (GA) (Odds Ratio (OR) 35.7, 95% CI 4.6-277.3; p < 0.001), Additionally, 62 of 71 babies with birthweight <3rd centile were in the low PlGF group (OR 12.5, 95% CI 4.5-34.6; p < 0.001). All perinatal deaths (n = 10) occurred in pregnancies with PlGF ≤5th centile. Comparatively, low PAPP-A concentrations <0.415 MoM, combined UtAD PI >2.5 and maternal age >40 were not significantly associated with either PTB <32 weeks or birthweight <3rd centile. CONCLUSION: Though exploratory, these findings support the potential of maternal serum PlGF concentration in routine clinical care for risk stratification and counselling in early-onset FGR; however, further evaluation and validation in larger, prospective studies is warranted.