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Introduction: Preeclampsia (PE) is a pregnancy disease which represents a leading cause of maternal and perinatal mortality and morbidity. Accurate prediction of PE risk could provide an increase in health benefits and better patient management., Objective: To estimate the economic impact of introducing Elecsys sFlt-1/PlGF ratio test, in addition to standard practice, for the prediction of PE in women with suspected PE in the Italian National Health Service (INHS)., Methods: A decision tree model has been developed to simulate the progression of a cohort of pregnant women from the first presentation of clinical suspicion of PE in the second and third trimesters until delivery. The model provides an estimation of the financial impact of introducing sFlt-1/PlGF versus standard practice. Clinical inputs have been derived from PROGNOSIS study and from literature review, and validated by National Clinical Experts. Resources and unit costs have been obtained from Italian-specific sources., Results: Healthcare costs associated with the management of a pregnant woman with clinical suspicion of PE equal €2384 when following standard practice versus €1714 using sFlt-1/PlGF ratio test., Conclusions: Introduction of sFlt-1/PlGF into hospital practice is cost-saving. Savings are generated primarily through improvement in diagnostic accuracy and reduction in unnecessary hospitalization for women before PE's onset.

Objective: To evaluate pregnancy, delivery and neonatal outcome in singleton primiparous versus multiparous women with/without endometriosis., Methods: Multicentric, observational and cohort study on a group of Caucasian pregnant women (n = 2239) interviewed during their hospitalization for delivery in five Italian Gynecologic and Obstetric Units (Siena, Rome, Padua, Varese and Florence)., Results: Primiparous women with endometriosis (n = 219) showed significantly higher risk of small for gestational age fetuses (OR: 2.72, 95% CI 1.46-5.06), gestational diabetes (OR: 2.13, 95% CI 1.32-3.44), preterm premature rupture of membranes (OR: 2.93, 95% CI 1.24-6.87) and preterm birth (OR: 2.24, 95% CI 1.46-3.44), and were hospitalized for a longer period of time (p < 0.0001) comparing with control group (n = 1331). Multiparous women with endometriosis (n = 97) delivered significantly more often small for gestational age fetuses (OR: 2.93, 95% CI 1.28-6.67) than control group (n = 592). Newborns of primiparous women with endometriosis needed more frequently intensive care (p = 0.05) and were hospitalized for a longer period of time (p < 0.0001)., Conclusions: Women with endometriosis at first pregnancy have an increased risk of impaired obstetric outcome, while a reduced number of complications occur in the successive gestation. Therefore, it is worthy for obstetricians to increase the surveillance in nulliparous women with endometriosis during pregnancy.

Aim: To search a specific gene expression profile in women with intrahepatic cholestasis of pregnancy (ICP) and to evaluate the maternal and foetal outcome., Methods: We consecutively enrolled 12 women with ICP and 12 healthy pregnant controls. The gene expression profile was assayed with the microarray technique including a panel of 5541 human genes. Microarray data were validated by real-time PCR technique., Results: Caesarean delivery was performed in eight patients with ICP versus three controls (p = 0.05). ICP women delivered at earlier gestational age than control (p < 0.001). Foetal distress was recorded in two babies, but we failed to find any correlation between bile salt concentration and foetal distress. Twenty genes potentially correlated with ICP were found differentially expressed (p < 0.05). Among these, three belong to genetic classes involved in pathogenic mechanisms of ICP: (1) pathophysiology of pruritus (GABRA2, cases versus controls = 2, upregulated gene); (2) lipid metabolism and bile composition (HLPT, cases versus controls = 0.6, down-regulated gene) and (3) protein trafficking and cytoskeleton arrangement (KIFC3, cases versus controls = 0.5, down-regulated gene)., Conclusions: Different gene expression may contribute to the complex pathogenesis of ICP. An upregulation of GABRA2 receptor may indicate that GABA may play a role in the pathogenesis of pruritus in this condition.

Introduction: The prevalence of viral infections in the amniotic fluid (AF) has not yet been ascertained. The aim of this study was to determine the prevalence of specific viral nucleic acids in the AF and its relationship to pregnancy outcome., Study Design: From a cohort of 847 consecutive women undergoing midtrimester amniocentesis, 729 cases were included in this study after exclusion of documented fetal anomalies, chromosomal abnormalities, unavailability of AF specimens and clinical outcomes. AF specimens were tested by quantitative real-time PCR for the presence of genome sequences of the following viruses: adenoviruses, herpes simplex virus (HSV), varicella zoster virus (VZV), human herpesvirus 6 (HHV6), human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), parvovirus B19 and enteroviruses. Viral nucleic acid testing was also performed in maternal blood and cord blood in the population of women in whom AF was positive for viruses and in a control group of 29 women with AF negative for viral nucleic acids. The relationship between the presence of viruses and pregnancy and neonatal outcome was examined. The correlation between the presence of nucleic acids of viruses in the AF and the concentration of the cytokine interleukin-6 (IL-6) and the T cell chemokine CXCL-10 (or IP-10) in AF and maternal blood were analyzed., Results: Viral genome sequences were found in 16 of 729 (2.2%) AF samples. HHV6 was the most commonly detected virus (7 cases, 1.0%), followed by HCMV (6 cases, 0.8%), parvovirus B19 (2 cases, 0.3%) and EBV (1 case, 0.1%), while HSV, VZV, enteroviruses and adenoviruses were not found in this cohort. Corresponding viral DNA was also detected in maternal blood of six out of seven women with HHV6-positive AF and in the umbilical cord plasma, which was available in one case. In contrast, viral DNA was not detected in maternal blood of women with AF positive for parvovirus B19, HCMV, EBV or of women with AF negative for viruses. HHV6 genome copy number in AF and maternal blood was consistent with genomic integration of viral DNA and genetic infection in all women. There was no significant difference in the AF concentration of IL-6 and IP-10 between patients with and without VIAC. However, for HCMV, there was a significant relationship between viral copy number and IP-10 concentration in maternal blood and AF. The group of women with AF positive for viral DNA delivered at term healthy neonates without complications in 14 out of 16 cases. In one case of HHV6 infection in the AF, the patient developed gestational hypertension at term, and in another case of HHV6 infection in the AF, the patient delivered at 33 weeks after preterm premature rupture of membranes (PPROM)., Conclusion: Viral nucleic acids are detectable in 2.2% of AF samples obtained from asymptomatic women in the midtrimester. HHV6 was the most frequently detected virus in AF. Adenoviruses were not detected. Vertical transmission of HHV6 was demonstrated in one case.

Congenital pulmonary airway malformations (CPAM) are a family of hamartomatous disorders due to the uncontrolled overgrowth of the terminal bronchioles. Congenital pulmonary airway malformations can co-exist with cardiovascular and/or urogenital malformations, but their association with thoracopulmonary malformations is extremely rare. We report the first case of CPAM type I, co-existing with tracheo-esophageal fistula and corpus callosum agenesis.

Objective: Women with a fetal death at the time of diagnosis have higher maternal plasma concentrations of the anti-angiogenic factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, than women with a normal pregnancy. An important question is whether these changes are the cause or consequence of fetal death. To address this issue, we conducted a longitudinal study and measured the maternal plasma concentrations of selective angiogenic and anti-angiogenic factors before the diagnosis of a fetal death. The anti-angiogenic factors studied were sVEGFR-1 and soluble endoglin (sEng), and the angiogenic factor, placental growth factor (PlGF)., Methods: This retrospective longitudinal nested case-control study included 143 singleton pregnancies in the following groups: (1) patients with uncomplicated pregnancies who delivered a term infant with an appropriate weight for gestational age (n=124); and (2) patients who had a fetal death (n=19). Blood samples were collected at each prenatal visit, scheduled at 4-week intervals from the first trimester until delivery. Plasma concentrations of sVEGFR-1, sEng, and PlGF were determined by specific and sensitive ELISA. A linear mixed-effects model was used for analysis., Results: (1) The average profiles of analyte concentrations as a function of gestational age for sVEGFR-1, sEng and PlGF were different between women destined to have a fetal death and those with a normal pregnancy after adjusting for covariates (p<0.05); (2) Plasma sVEGFR-1 concentrations in patients destined to have a fetal death were significantly lower between 7 and 11 weeks of gestation and became significantly higher than those of women with a normal pregnancy between 20 and 37 weeks of gestation (p<0.05); (3) Similarly, plasma sEng concentrations of women destined to have a fetal death were lower at 7 weeks of gestation (p=0.04) and became higher than those of controls between 20 and 40 weeks of gestation (p<0.05); (4) In contrast, plasma PlGF concentrations were higher among patients destined to develop a fetal death between 7 and 14 weeks of gestation and became significantly lower than those in the control group between 22 and 39 weeks of gestation (p<0.05); (5) The ratio of PlGF/(sVEGFR-1 × sEng) was significantly higher in women destined to have a fetal death between 7 and 13 weeks of gestation (94-781%) and significantly lower (44-75%) than those in normal pregnant women between 20 and 40 weeks of gestation (p<0.05); (6) Similar results were obtained when patients with a fetal death were stratified into those who were diagnosed before or after 37 weeks of gestation., Conclusions: Fetal death is characterised by higher maternal plasma concentrations of PlGF during the first trimester compared to normal pregnancy. This profile changes into an anti-angiogenic one during the second and third trimesters.

Objective: Preeclampsia and pregnancies complicated by small-for-gestational age (SGA) neonates share several underlying mechanisms of disease. However, while an exaggerated systemic maternal inflammatory response is regarded as one of the hallmarks of the pathogenesis of preeclampsia, the presence of a similar systemic intra-vascular inflammation in mothers of SGA neonates without hypertension is controversial. The aim of this study was to determine phenotypic and metabolic changes in granulocytes and monocytes of women who develop preeclampsia and those who deliver an SGA neonate, compared to normal pregnant women., Methods: This cross-sectional study included patients with a normal pregnancy (n = 33), preeclampsia (n = 33), and an SGA without preeclampsia (n = 33), matched for gestational age at blood sample collection. Granulocyte and monocyte phenotypes were determined by flow cytometry, using monoclonal antibodies against selective cluster of differentiation (CD) antigens. The panel of antibodies included the following: CD11b, CD14, CD16, CD18, CD49d, CD62L, CD64, CD66b, and HLA-DR. Intracellular reactive oxygen species (iROS) were assessed at the basal state and after stimulation (oxidative burst). Results were reported as mean channel brightness (MCB) or intensity of detected fluorescence. Analysis was conducted with non-parametric statistics. A p-value < 0.01 was considered statistically significant., Results: (1) Women who delivered an SGA neonate had a higher MCB of CD11b in granulocytes and monocytes than those with a normal pregnancy (p < 0.001 for both); (2) patients with preeclampsia had a lower median MCB of CD62L in granulocytes (p = 0.006) and a higher median basal iROS and oxidative burst in monocytes than women with an SGA neonate (p = 0.003 and p = 0.002, respectively)., Conclusion: Pregnancies complicated by the delivery of an SGA neonate are characterized by a higher activation of maternal peripheral leukocytes than in normal pregnancies, but lower than in pregnancies complicated by preeclampsia.