Francesca Crovetto

First trimester screening for early and late preeclampsia based on maternal characteristics, biophysical parameters, and angiogenic factors.

The aim of this article is to develop the best first‐trimester screening model for preeclampsia (PE) based on maternal characteristics, biophysical parameters, and angiogenic factors in a low‐risk population.

Association of Doppler parameters with placental signs of underperfusion in late-onset small-for-gestational-age pregnancies

To elucidate the association between Doppler parameters and histological signs of placental underperfusion in late‐onset small‐for‐gestational‐age (SGA) babies.

Usefulness of circulating microRNAs for the prediction of early preeclampsia at first-trimester of pregnancy.

To assess the usefulness of circulating microRNAs (miRNAs) as non-invasive molecular biomarkers for early prediction of preeclampsia, a differential miRNA profiling analysis was performed in first-trimester pooled sera from 31 early preeclampsia patients, requiring delivery before 34 weeks of gestation, and 44 uncomplicated pregnancies using microfluidic arrays. Among a total of 754 miRNAs analyzed, the presence of 63 miRNAs (8%) was consistently documented in the sera from preeclampsia and control samples. Nevertheless, only 15 amplified miRNAs (2%) seemed to be differentially, although modestly, represented (fold change range: 0.4–1.4). After stem loop RT-qPCR from individual samples, the statistical analysis confirmed that none of the most consistent and differentially represented miRNAs (3 overrepresented and 4 underrepresented) were differentially abundant in serum from preeclamptic pregnancies compared with serum from normal pregnancies. Therefore, maternal serum miRNA assessment at first-trimester of pregnancy does not appear to have any predictive value for early preeclampsia.

Angiogenic factors vs Doppler surveillance in the prediction of adverse outcome among late-pregnancy small-for- gestational-age fetuses.

To compare the value of Doppler surveillance with maternal blood angiogenic factors at diagnosis for the prediction of adverse outcome in late‐pregnancy small‐for‐gestational‐age (SGA) fetuses.

Angiogenic factors at diagnosis of late-onset small-for-gestational age and histological placental underperfusion

OBJECTIVE This study was designed to explore the association between angiogenic factors levels at diagnosis of small-for-gestational age (SGA) and placental underperfusion (PUP). METHODS In a cohort of SGA singleton pregnancies, each delivered at >34 weeks, uterine (UtA), umbilical (UA), and middle cerebral (MCA) arteries were evaluated by Doppler upon diagnosis of SGA status. In addition, maternal circulating concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were assayed by ELISA, and each placenta was evaluated for histologic signs of PUP using a hierarchical and standardized classification system. Logistic regression was applied to analyze independent relationships (at diagnosis) between angiogenic factors and Doppler parameters. RESULTS A total of 122 suspected SGA pregnancies were studied, 70 (57.4%) of which ultimately met PUP criteria. In this group, 85 placental findings qualified as PUP. Both mean UtA pulsatility index z-values (1.26 vs. 0.84; p = 0.038) and PlGF multiples of normal median (0.21 vs. 0.55; p = 0.002) differed significantly in pregnancies with and without PUP, respectively. By logistic regression, PlGF alone was independently predictive of PUP (OR = 0.11 [95% CI 0.025-0.57]; p = 0.008). DISCUSSION Histologic placental abnormalities in term SGA neonates reflect latent insufficiency in uteroplacental blood supply. The heightened risk of adverse perinatal outcomes in this context underscores a need for new Doppler or biochemical prenatal markers of placental disease. Angiogenic factors may be pivotal identifying SGA neonates. CONCLUSIONS Diminished circulating levels of placental growth factor, determined upon discovery of SGA status, are associated with histologic evidence of PUP.

First-trimester screening for early and late small-for-gestational-age neonates using maternal serum biochemistry, blood pressure and uterine artery Doppler.

To assess the effectiveness of first‐trimester screening for early and late small‐for‐gestational‐age (SGA) neonates using maternal serum biochemistry, blood pressure and uterine artery Doppler.

Confined placental mosaicism at chorionic villous sampling: risk factors and pregnancy outcome

This study aims to investigate the clinical relevance of confined placental mosaicism (CPM) detected at chorionic villous sampling (CVS) and to identify risk factors for this condition.

Added value of angiogenic factors for the prediction of early and late preeclampsia in the first trimester of pregnancy.

Objective: To explore the predictive role of angiogenic factors for the prediction of early and late preeclampsia (PE) in the first trimester. Methods: A nested case-control study, within a cohort of 5,759 pregnancies, including 28 cases of early, 84 of late PE (cut-off 34 weeks) and 84 controls. Maternal characteristics, mean blood pressure (MAP), uterine artery (UtA) Doppler (11-13 weeks), vascular endothelial growth factor, placental growth factor (PlGF), soluble Fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (8-11 weeks) were measured/recorded. All parameters were normalized by logarithmic transformation; logistic regression analysis was used to predict PE. Results: For early PE, significant contributions were chronic hypertension, previous PE, MAP, UtA Doppler, PlGF and sFlt-1. A model including these predictors achieved detection rates (DR) of 77.8 and 88.9% for 5 and 10% false-positive rates (FPR), respectively (AUC 0.958; 95% CI 0.920-0.996). For late PE, significant contributions were provided by body mass index, previous PE, UtA Doppler, PlGF and sFlt-1. The model including these factors achieved DR of 51.2 and 69% at 5 and 10% FPR, respectively (AUC 0.888; 95% CI 0.840-0.936). Conclusions: Among angiogenic factors, not only PlGF but also sFlt-1 substantially improve the prediction for early and late PE. The data need confirmation in larger studies.

Correlation between histological signs of placental underperfusion and perinatal morbidity in late-onset small-for-gestational-age fetuses

To investigate whether signs of placental underperfusion (PUP), defined as any maternal and/or fetal vascular pathology, confer an increased risk of neonatal morbidity in late‐onset small‐for‐gestational‐age (SGA) fetuses with normal umbilical artery (UA) Doppler indices.

Neurodevelopmental outcomes of near-term small-for-gestational-age infants with and without signs of placental underperfusion.

OBJECTIVE To evaluate 2-year neurodevelopmental outcomes of near-term, small-for-gestational-age (SGA) newborns segregated by presence or absence of histopathology reflecting placental underperfusion (PUP). PATIENTS AND METHODS A cohort of consecutive near-term (≥ 34.0 weeks) SGA newborns with normal prenatal umbilical artery Doppler studies was selected. All placentas were inspected for evidence of underperfusion and classified in accordance with established histologic criteria. Neurodevelopmental outcomes at 24 months (age-corrected) were then evaluated, applying the Bayley Scale for Infant and Toddler Development, Third Edition (Bayley-III) to assess cognitive, language, and motor competencies. The impact of PUP on each domain was measured via analysis of covariance, logistic and ordinal regression, with adjustment for smoking, socioeconomic status, gestational age at birth, gender, and breastfeeding. RESULTS A total of 83 near-term SGA deliveries were studied, 46 (55.4%) of which showed signs of PUP. At 2 years, adjusted neurodevelopmental outcomes were significantly poorer in births involving PUP (relative to SGA infants without PUP) for all three domains of the Bayley scale: cognitive (105.5 vs 96.3, adjusted-p = 0.03), language (98.6 vs 87.8, adjusted-p<0.001), and motor (102.7 vs 94.5, adjusted-p = 0.007). Similarly, the adjusted likelihood of abnormal cognitive, language, and motor competencies in instances of underperfusion was 9.3-, 17.5-, and 1.44-fold higher, respectively, differing significantly for the former two domains. CONCLUSIONS In a substantial fraction of near-term SGA babies without Doppler evidence of placental insufficiency, histologic changes compatible with PUP are still identifiable. These infants are at greater risk of abnormal neurodevelopmental outcomes at 2 years.