Stefania Triunfo

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.

Evaluation of an optimal gestational age cut-off for the definition of early- and late-onset fetal growth restriction.

Objective: The terms early- and late-onset fetal growth restriction (FGR) are commonly used to distinguish two phenotypes characterized by differences in onset, fetoplacental Doppler, association with preeclampsia (PE) and severity. We evaluated the optimal gestational age (GA) cut-off maximizing differences among these two forms. Patients and Methods: A cohort of 656 consecutive singleton pregnancies with FGR was created. We used the decision tree analysis to evaluate the GA cut-off that best discriminated perinatal mortality, association with PE and adverse perinatal outcome (fetal demise, early neonatal death, neonatal acidosis at birth, and 5-min Apgar score <7). Results: We identified 32 weeks at diagnosis as the optimal cut-off, resulting in two groups with 7.1 and 0%, p < 0.001 perinatal mortality, 35.1 and 12.1%, p < 0.001 association with PE, and 13.4 and 4.6%, p < 0.001 composite adverse perinatal outcome. Abnormal versus normal umbilical artery (UA) Doppler classified two groups with 10.6 and 0.2%, p < 0.001 perinatal mortality, 50.0 and 11.8%, p < 0.001 association with PE, and 18.2 and 4.2%, p < 0.001 composite adverse perinatal outcome. Conclusions: UA Doppler discriminated better the two forms of FGR with average early- and late-onset presentation, higher association with PE and poorer outcome. In the absence of UA information, a GA cut-off of 32 weeks at diagnosis maximizes differences between early- and late-onset FGR.

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.

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.

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.

Impact of maternal under nutrition on obstetric outcomes

Maternal malnutrition, ranging from under nutrition to over dietary intake before and in the pregnant state, is worldwide problem with significant consequences, not only for survival and increased risk for acute and chronic diseases both in mother and child, but also for economic productivity of individuals in the societies and additional costs on health system. Inter alia, pre-pregnancy underweight and insufficient gestational weight gain are considered as individual risk factors for the occurrence of spontaneous interruption, preterm birth, fetal growth restriction, and hypertensive disorders, strongly associated with poorer perinatal outcome. In a portion of this population, major eating disorders (anorexia and bulimia nervosa), once thought to be rare, but nowadays enlarged due to cultural pressure on the drive for thinness, have been identified as the etiology of an abnormal nutritional condition in developed countries, in contrast to long standing food deprivation in developing countries. Actually, even if without a complete weight management guidance for these selected pregnant women, an appropriate weight gain is recommended during pregnancy. Mainly, therapeutic approach is prevention using specific programs of improving weight before pregnant status. In this article, a review of the literature on selected obstetrical risks associated with maternal underweight has been performed and both the target prevention and management strategies have been described.

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.

Conservative Management of Placenta Previa-Accreta by Prophylactic Uterine Arteries Ligation and Uterine Tamponade

Background: Placenta previa-accreta is associated with severe hemorrhage occurring while separating the placenta during cesarean delivery and hysterectomy is considered the treatment of choice. Conservative management has recently been proposed. Case: A 26-year-old woman had pregnancy complicated by placenta previa with suspected accreta. During elective cesarean section a prophylactic double bilateral ligation of uterine arteries was performed before removal of the placenta; subsequently, the continuous small bleeding from the placental bed was stopped by tamponade with a balloon catheter filled with saline solution. The patient was discharged 5 days later. An ultrasonographic color Doppler follow-up demonstrated a renewed uterine vascularization. Conclusion: Double bilateral ligation of uterine arteries can be used as a prophylactic surgical treatment when a severe bleeding because of placenta previa-accreta is expected, in order to avoid hysterectomy.

First‐trimester screening with specific algorithms for early‐ and late‐onset fetal growth restriction

To develop optimal first‐trimester algorithms for the prediction of early and late fetal growth restriction (FGR).