A. Peguero

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 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.

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.

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.

Stroke during pregnancy and pre-eclampsia

Purpose of review Stroke is a life-threatening condition whose frequency is increased during pregnancy, in particular in the two first weeks of the puerperium. Pre-eclampsia/eclampsia is a disorder that enhances this risk. The purpose of this review is to summarize existing data regarding the association, diagnosis as well as management for stroke in pre-eclampsia or eclampsia. Recent findings In about one third of stroke cases during pregnancy or puerperium, pre-eclampsia or eclampsia is concomitantly diagnosed. In these women, hemorrhagic stroke is more common than ischemic stroke, probably as a result of severe hypertension. Clinical presentation may vary but severe headache is the most common symptom. Neuroimaging techniques are warranted to identify affected cases. Prevention is based on blood pressure adjustment and thromboprophylaxis. Summary The risk of stroke should be taken into consideration in women with a diagnosis of pre-eclampsia or eclampsia. In particular, women with neurologic symptoms should be promptly evaluated, blood pressure should be adjusted and thromboprophylaxis should be started.

Chorioamniotic membrane separation after fetoscopy in monochorionic twin pregnancy: incidence and impact on perinatal outcome

To evaluate the incidence of chorioamniotic membrane separation (CMS) after fetoscopy in monochorionic diamniotic (MCDA) twins and its impact on pregnancy outcome.

Chorioamniotic membrane separation after fetoscopy in monochorionic twin pregnancies: incidence and impact on perinatal outcome

To evaluate the incidence of chorioamniotic membrane separation (CMS) after fetoscopy in monochorionic diamniotic (MCDA) twins and its impact on pregnancy outcome.

Diagnosis and surveillance of late-onset fetal growth restriction

&NA; By consensus, late fetal growth restriction is that diagnosed >32 weeks. This condition is mildly associated with a higher risk of perinatal hypoxic events and suboptimal neurodevelopment. Histologically, it is characterized by the presence of uteroplacental vascular lesions (especially infarcts), although the incidence of such lesions is lower than in preterm fetal growth restriction. Screening procedures for fetal growth restriction need to identify small babies and then differentiate between those who are healthy and those who are pathologically small. First‐ or second‐trimester screening strategies provide detection rates for late smallness for gestational age <50% for 10% of false positives. Compared to clinically indicated ultrasonography in the third trimester, universal screening triples the detection rate of late smallness for gestational age. As opposed to early third‐trimester ultrasound, scanning late in pregnancy (around 37 weeks) increases the detection rate for birthweight <3rd centile. Contrary to early fetal growth restriction, umbilical artery Doppler velocimetry alone does not provide good differentiation between late smallness for gestational age and fetal growth restriction. A combination of biometric parameters (with severe smallness usually defined as estimated fetal weight or abdominal circumference <3rd centile) with Doppler criteria of placental insufficiency (either in the maternal [uterine Doppler] or fetal [cerebroplacental ratio] compartments) offers a classification tool that correlates with the risk for adverse perinatal outcome. There is no evidence that induction of late fetal growth restriction at term improves perinatal outcomes nor is it a cost‐effective strategy, and it may increase neonatal admission when performed <38 weeks.

Role of maternal plasma levels of placental growth factor for the prediction of maternal complications in preeclampsia according to the gestational age at onset

This study aimed to describe the distribution of placental growth factor (PlGF) plasma levels in pregnancies complicated by preeclampsia (PE) according to the gestational age at clinical onset and to assess PlGFs predictive role for maternal complications.