Maternal nutritional depletion and inflammatory stress in late-onset fetal growth restriction: Rethinking...

Fetal growth restriction (FGR) is a multifactorial condition involving placental dysfunction and maternal systemic stress. While diagnosis depends on biometry and Doppler ultrasound, maternal nutritional depletion and inflammation may provide complementary clinical insight after diagnosis. To evaluate maternal nutritional (prognostic nutritional index [PNI], hemoglobin-albumin-lymphocyte-platelet [HALP]) and inflammatory (SII, AISI, SIRI) index differences in pregnancies with late-onset FGR, and explore whether these systemic markers are further altered in the presence of Doppler abnormalities. We conducted a retrospective cohort analysis of anonymized pregnancies followed at Acibadem Atakent Hospital and a private obstetrics clinic in Ankara, Turkey. Women with abdominal circumference and/or estimated fetal weight < 3rd percentile between 34 to 37 weeks were included as late-onset FGR. Two FGR subgroups were defined based on Doppler status (normal vs abnormal uterine, umbilical, or middle cerebral artery Doppler). Controls consisted of healthy singleton pregnancies with normal biometry (>10th percentile) and third-trimester hemogram/biochemical tests. Maternal indices were calculated from routine complete blood count and albumin values, and their association with Doppler abnormalities was assessed using univariate and multinomial logistic regression models. Normality was tested using Kolmogorov-Smirnov; group comparisons used ANOVA or Kruskal-Wallis and χ2 tests. FGR pregnancies showed marked maternal systemic shifts. Nutritional indices (PNI, HALP) progressively declined from controls to Doppler-normal and Doppler-abnormal FGR, indicating maternal protein reserve depletion. Inflammatory indices (SII, AISI, SIRI) were higher in FGR and further increased in Doppler-abnormal cases, suggesting a maternal inflammatory-dominant stress response that may mirror uteroplacental vascular resistance. These markers did not demonstrate value for FGR prediction prior to clinical diagnosis, but highlight maternal systemic status once FGR is established. Maternal nutritional and inflammatory indices are not diagnostic or predictive tools for FGR, but may support individualized, sustainable nutritional counseling and protein-focused dietary planning after FGR diagnosis. Prospective studies with quantitative dietary assessment are needed to validate mechanistic links and clinical impact.