S100B in maternal circulation of pregnancies complicated by FGR and brain sparing.

OBJECTIVE: To determine whether the presence of brain sparing in fetal growth restricted (FGR) fetuses involves elevation of the cerebral injury biomarker S100B in maternal circulation. METHODS: We included 63 women with suspected small for gestational age (SGA) fetuses between 24 and 35 +6/7 weeks of gestation. Maternal plasma angiogenic factors measurements and sonographic evaluation were performed at recruitment. Next, we subdivided our SGA cohort into three groups: SGA fetuses, FGR fetuses without brain-sparing, and FGR fetuses with brain-sparing (FGR-BS). Serum S100B concentration was calculated as S100B µg/L, S100B MoM, and the ratio S100B/ estimated fetal weight (EFW). We also report one case of S100B concentration surge in maternal serum following the diagnosis of fetal intraventricular hemorrhage (IVH). RESULTS: The FGR-BS group had higher maternal S100B µg/L (p < 0.01, p < 0.05, respectively), S100B MoM (p < 0.001, p < 0.001, respectively), and S100B/EFW (p < 0.001, p < 0.01, respectively), compared to the SGA and FGR groups. In the case report, maternal serum S100B concentrations were 0.0346 µg/L before, and 0.0874 µg/L after IVH occurrence. CONCLUSIONS: S100B concentration in maternal serum increased in pregnancies complicated by FGR and brain sparing. These results may substantiate in-utero cerebral injury and may explain the adverse neurocognitive outcomes reported for this group.

Maternal Blood Angiogenic Factors and the Prediction of Critical Adverse Perinatal Outcomes Among Small-for-Gestational-Age Pregnancies.

OBJECTIVE: Our objective was to determine whether maternal blood angiogenic factors in suspected-small-for-gestational-age (sSGA) fetuses can predict critical adverse perinatal outcomes (CAPO) and improve risk assessment. METHODS: Women with singleton pregnancies diagnosed with sSGA, between 24 and 356/7 weeks' gestation, were included. Clinical and sonographic comprehensive evaluations were performed at enrolment. Plasma angiogenic factors, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), were obtained at diagnosis. In parallel, three attending maternal-fetal-medicine specialists predicted the risk (1-5 scale) of these pregnancies to develop CAPO, based on the clinical presentation. CAPOs were defined as prolonged neonatal intensive care unit hospitalization, fetal or neonatal death, and major neonatal morbidity. Statistical analysis included sensitivity, specificity, positive and negative predictive values, and receiver-operating characteristic (ROC) curve analyses. RESULTS: Of the 79 cases included, 32 were complicated by CAPO (40.5%). In SGA fetuses with CAPO, the sFlt-1/PlGF ratio was higher (p < 0.001) and PlGF was lower (p < 0.001) as compared with uncomplicated pregnancies. The areas under the ROC curves for specialists were 0.913, 0.824, and 0.811 and for PlGF and sFlt-1/PlGF ratio 0.926 and 0.900, respectively. CAPO was more common in pregnancies with absent end-diastolic flow or reversed end-diastolic flow (AEDF or REDF) in the umbilical artery upon enrolment (91.6%). Yet, 65.6% of cases involving CAPO occurred in patients without AEDF or REDF, and 66.6% of these cases were not identified by one or more of the experts. The sFlt-1/PlGF ratio identified 92.9% of the experts' errors in this group and 100% of the errors in cases with AEDF or REDF. CONCLUSIONS: Among sSGA pregnancies prior to 36 weeks' gestation, angiogenic factors testing can identify most cases later complicated with CAPO. Our data demonstrate for the first time that these markers can reduce clinician judgment errors. Incorporation of these measures into decision-making algorithms could potentially improve management, outcomes, and even health care costs. KEY POINTS: · Angiogenic factors at diagnosis of sSGA can be used to predict CAPO.. · The sFlt-1/PlGF ratio can flag sSGA pregnancies at increased risk.. · The sFlt-1/PlGF ratio at admission of sSGA adds to clinical assessment..

Placental growth factor concentration in maternal circulation decreases after fetal death: lessons from a case series study.

PURPOSE: Placental growth factor (PlGF) has been suggested as a possible biomarker for major placenta-related disorders such as preeclampsia and intrauterine growth restriction. However, experimental findings suggest that PlGF concentrations may be influenced by other factors besides the placenta. In the present study, we examined how acute fetal injury affects PlGF concentrations in maternal circulation. We therefore monitored PlGF concentrations in maternal circulation before and after feticide. METHODS: A prospective comparative study was performed. Blood samples were drawn prospectively between January and July 2012, before and after feticide at predetermined time points in relation to the procedure (0, 30, 60, and 120 min). The levels of lactate dehydrogenase (LDH) in the maternal circulation were measured to detect acute tissue damage. PlGF concentrations were measured by standard human ELISA. RESULTS: Following feticide (60 and 120 min), PlGF concentrations decreased significantly compared to the concentrations before feticide. LDH concentrations did not change before and after feticide. CONCLUSIONS: Our finding, along with the detailed review of the literature described in our work, supports a new concept in which primary fetal distress can affect PlGF concentration in maternal circulation. A large-scale study is required to strengthen our finding.

The effects of pravastatin on the normal human placenta: Lessons from ex-vivo models.

INTRODUCTION: Research in animal models and preliminary clinical studies in humans support the use of pravastatin for the prevention of preeclampsia. However, its use during pregnancy is still controversial due to limited data about its effect on the human placenta and fetus. METHODS: In the present study, human placental cotyledons were perfused in the absence or presence of pravastatin in the maternal reservoir (PraM). In addition, placental explants were treated with pravastatin for 5, 24 and 72 h under normoxia and hypoxia. We monitored the secretion of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), endothelial nitric oxide synthase (eNOS) expression and activation and the fetal vasoconstriction response to angiotensin-II. RESULTS: The concentrations of PlGF, sFlt-1 and sEng were not significantly altered by pravastatin in PraM cotyledons and in placental explants compared to control. Under hypoxic conditions, pravastatin decreased sFlt-1 concentrations. eNOS expression was significantly increased in PraM cotyledons but not in pravastatin-treated placental explants cultured under normoxia or hypoxia. eNOS phosphorylation was not significantly affected by pravastatin. The feto-placental vascular tone and the fetal vasoconstriction response to angiotensin-II, did not change following exposure of the maternal circulation to pravastatin. CONCLUSION: We found that pravastatin does not alter the essential physiological functions of the placenta investigated in the study. The relevance of the study lays in the fact that it expands the current knowledge obtained thus far regarding the effect of the drug on the normal human placenta. This data is reassuring and important for clinicians that consider the treatment of high-risk patients with pravastatin, a treatment that exposes some normal pregnancies to the drug.