Characterization of Neonatal Clinical Risk Profiles in Relation to Prenatal Obstetric Characteristics in Infants With Early-FGR Secondary to Doppler Flowmetry Alterations

This study, titled "Characterization of clinical neonatal risk profiles in relation to prenatal obstetric characteristics in infants with Early Fetal Growth Restriction (FGR) secondary to Doppler flowmetry alterations," is designed as a multicenter, spontaneous, observational investigation combining both retrospective and prospective data collection to analyze the complex interplay between maternal-fetal hemodynamics and neonatal outcomes. The primary objective is to evaluate the association between specific maternal and obstetric factors-including preeclampsia, gestational diabetes, the timing of onset, and the longitudinal progression of Doppler alterations-and the resulting clinical neonatal outcomes. A key focus of the research is to determine how these relationships fluctuate according to the specific prenatal flowmetric profile, categorized by umbilical artery (UA) end-diastolic flow status (UA bs-, UA bs+, or UA combined with ductus venosus [DV] alterations), in comparison to a control group of preterm infants who did not experience FGR. The study population consists of mothers and their preterm neonates, specifically targeting those with a gestational age of 32 weeks or less and/or a birth weight under 1500 grams. The case group includes neonates with a documented prenatal history of FGR, defined by a fetal weight or abdominal circumference-to-fetal weight ratio below the 10th percentile, accompanied by abnormal fetal or utero-placental Doppler flowmetry. Conversely, the control group comprises neonates of similar gestational age or weight who showed no prenatal evidence of growth restriction or Doppler abnormalities. To maintain the integrity of the data regarding vascular-driven growth restriction, the study excludes pregnancies involving fetal malformations, known or suspected genetic anomalies, maternal substance abuse, and multiple gestations. Conducted over a total duration of 30 months, the timeline allocates 12 months for patient enrollment and selection and 6 months for comprehensive data analysis. The targeted sample size is 850 subjects, consisting of 600 neonates without an FGR diagnosis and 200 with a confirmed FGR diagnosis. The statistical methodology is rigorous and tailored to the multicenter nature of the study, synthesizing continuous variables as mean with standard deviation or median with interquartile range, while categorical variables will be presented as absolute frequencies and percentages. Exploratory comparisons between groups will utilize parametric or non-parametric tests based on data distribution. The primary analysis will employ logistic regression models for binary outcomes and linear regression models for continuous outcomes, utilizing clustered standard errors by center to account for intra-center correlation. Candidate covariates for these models include gestational age, sex, and significant maternal or obstetric conditions such as preeclampsia, diabetes, pathological cardiotocography (CTG), and the specific timing and progression of Doppler changes. In instances where the number of predictors is high relative to the statistical units, penalization techniques such as lasso or elastic net will be applied for automatic covariate reduction and estimate stabilization, ensuring that subsequent analyses and interaction studies focus on the most statistically relevant predictors. Informed consent is a mandatory prerequisite for participation, ensuring ethical standards are maintained throughout the retrospective and prospective phases of the study.