@article {10446, title = {Non-invasive biomarkers of fetal brain development reflecting prenatal stress: An integrative multi-scale multi-species perspective on data collection and analysis.}, journal = {Neurosci Biobehav Rev}, year = {2018}, month = {2018 May 30}, abstract = {

Prenatal stress (PS) impacts early postnatal behavioural and cognitive development. This process of {\textquoteright}fetal programming{\textquoteright} is mediated by the effects of the prenatal experience on the developing hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). We derive a multi-scale multi-species approach to devising preclinical and clinical studies to identify early non-invasively available pre- and postnatal biomarkers of PS. The multiple scales include brain epigenome, metabolome, microbiome and the ANS activity gauged via an array of advanced non-invasively obtainable properties of fetal heart rate fluctuations. The proposed framework has the potential to reveal mechanistic links between maternal stress during pregnancy and changes across these physiological scales. Such biomarkers may hence be useful as early and non-invasive predictors of neurodevelopmental trajectories influenced by the PS as well as follow-up indicators of success of therapeutic interventions to correct such altered neurodevelopmental trajectories. PS studies must be conducted on multiple scales derived from concerted observations in multiple animal models and human cohorts performed in an interactive and iterative manner and deploying machine learning for data synthesis, identification and validation of the best non-invasive detection and follow-up biomarkers, a prerequisite for designing effective therapeutic interventions.

}, issn = {1873-7528}, doi = {10.1016/j.neubiorev.2018.05.026}, author = {Frasch, Martin G and Lobmaier, Silvia M and Stampalija, Tamara and Desplats, Paula and Pallar{\'e}s, Mar{\'\i}a Eugenia and Pastor, Ver{\'o}nica and Brocco, Marcela A and Wu, Hau-Tieng and Schulkin, Jay and Herry, Christophe L and Seely, Andrew J E and Metz, Gerlinde A S and Louzoun, Yoram and Antonelli, Marta C} } @article {10837, title = {Pre-eclampsia affects procalcitonin production in placental tissue.}, journal = {Am J Reprod Immunol}, volume = {79}, year = {2018}, month = {2018 04}, pages = {e12823}, abstract = {

PROBLEM: Procalcitonin (PCT) is the prohormone of calcitonin which is usually released from neuroendocrine cells of the thyroid gland (parafollicular) and the lungs (K cells). PCT is synthesized by almost all cell types and tissues, including monocytes and parenchymal tissue, upon LPS stimulation. To date, there is no evidence for PCT expression in the placenta both in physiological and pathological conditions.

METHOD: Circulating and placental PCT levels were analysed in pre-eclamptic (PE) and control patients. Placental cells and macrophages (PBDM), stimulated with PE sera, were analysed for PCT expression. The effect of anti-TNF-α antibody was analysed.

RESULTS: Higher PCT levels were detected in PE sera and in PE placentae compared to healthy women. PE trophoblasts showed increased PCT expression compared to those isolated from healthy placentae. PE sera induced an upregulation of PCT production in macrophages and placental cells. The treatment of PBDM with PE sera in the presence of anti-TNF-α completely abrogated the effect induced by pathologic sera.

CONCLUSION: Trophoblast cells are the main producer of PCT in PE placentae. TNF-α, in association with other circulating factors present in PE sera, upregulates PCT production in macrophages and normal placental cells, thus contributing to the observed increased in circulating PCT in PE sera.

}, keywords = {Adult, Calcitonin, Cohort Studies, Female, Humans, Macrophages, Placenta, Pre-Eclampsia, Pregnancy, Trophoblasts, Tumor Necrosis Factor-alpha, Up-Regulation, Young Adult}, issn = {1600-0897}, doi = {10.1111/aji.12823}, author = {Agostinis, Chiara and Rami, Damiano and Zacchi, Paola and Bossi, Fleur and Stampalija, Tamara and Mangogna, Alessandro and Amadio, Leonardo and Vidergar, Romana and Vecchi Brumatti, Liza and Ricci, Giuseppe and Celeghini, Claudio and Radillo, Oriano and Sargent, Ian and Bulla, Roberta} } @article {10517, title = {Cervical stitch (cerclage) for preventing preterm birth in singleton pregnancy.}, journal = {Cochrane Database Syst Rev}, volume = {6}, year = {2017}, month = {2017 06 06}, pages = {CD008991}, abstract = {

BACKGROUND: Cervical cerclage is a well-known surgical procedure carried out during pregnancy. It involves positioning of a suture (stitch) around the neck of the womb (cervix), aiming to give mechanical support to the cervix and thereby reduce risk of preterm birth. The effectiveness and safety of this procedure remains controversial. This is an update of a review last published in 2012.

OBJECTIVES: To assess whether the use of cervical stitch in singleton pregnancy at high risk of pregnancy loss based on woman{\textquoteright}s history and/or ultrasound finding of {\textquoteright}short cervix{\textquoteright} and/or physical exam improves subsequent obstetric care and fetal outcome.

SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth{\textquoteright}s Trials Register (30 June 2016) and reference lists of identified studies.

SELECTION CRITERIA: We included all randomised trials of cervical suturing in singleton pregnancies. Cervical stitch was carried out when the pregnancy was considered to be of sufficiently high risk due to a woman{\textquoteright}s history, a finding of short cervix on ultrasound or other indication determined by physical exam. We included any study that compared cerclage with either no treatment or any alternative intervention. We planned to include cluster-randomised studies but not cross-over trials. We excluded quasi-randomised studies. We included studies reported in abstract form only.

DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for inclusion. Two review authors independently assessed risk of bias and extracted data. We resolved discrepancies by discussion. Data were checked for accuracy. The quality of the evidence was assessed using the GRADE approach.

MAIN RESULTS: This updated review includes a total of 15 trials (3490 women); three trials were added for this update (152 women). Cerclage versus no cerclageOverall, cerclage probably leads to a reduced risk of perinatal death when compared with no cerclage, although the confidence interval (CI) crosses the line of no effect (RR 0.82, 95\% CI 0.65 to 1.04; 10 studies, 2927 women; moderate quality evidence). Considering stillbirths and neonatal deaths separately reduced the numbers of events and sample size. Although the relative effect of cerclage is similar, estimates were less reliable with fewer data and assessed as of low quality (stillbirths RR 0.89, 95\% CI 0.45 to 1.75; 5 studies, 1803 women; low quality evidence; neonatal deaths before discharge RR 0.85, 95\% CI 0.53 to 1.39; 6 studies, 1714 women; low quality evidence). Serious neonatal morbidity was similar with and without cerclage (RR 0.80, 95\% CI 0.55 to 1.18; 6 studies, 883 women; low-quality evidence). Pregnant women with and without cerclage were equally likely to have a baby discharged home healthy (RR 1.02, 95\% CI 0.97 to 1.06; 4 studies, 657 women; moderate quality evidence).Pregnant women with cerclage were less likely to have preterm births compared to controls before 37, 34 (average RR 0.77, 95\% CI 0.66 to 0.89; 9 studies, 2415 women; high quality evidence) and 28 completed weeks of gestation.Five subgroups based on clinical indication provided data for analysis (history-indicated; short cervix based on one-off ultrasound in high risk women; short cervix found by serial scans in high risk women; physical exam-indicated; and short cervix found on scan in low risk or mixed populations). There were too few trials in these clinical subgroups to make meaningful conclusions and no evidence of differential effects. Cerclage versus progesteroneTwo trials (129 women) compared cerclage to prevention with vaginal progesterone in high risk women with short cervix on ultrasound; these trials were too small to detect reliable, clinically important differences for any review outcome. One included trial compared cerclage with intramuscular progesterone (75 women) which lacked power to detect group differences. History indicated cerclage versus ultrasound indicated cerclageEvidence from two trials (344 women) was too limited to establish differences for clinically important outcomes.

AUTHORS{\textquoteright} CONCLUSIONS: Cervical cerclage reduces the risk of preterm birth in women at high-risk of preterm birth and probably reduces risk of perinatal deaths. There was no evidence of any differential effect of cerclage based on previous obstetric history or short cervix indications, but data were limited for all clinical groups. The question of whether cerclage is more or less effective than other preventative treatments, particularly vaginal progesterone, remains unanswered.

}, keywords = {Administration, Intravaginal, Cerclage, Cervical, Cesarean Section, Female, Humans, Injections, Intramuscular, Perinatal Death, Pregnancy, Premature Birth, Progesterone, Randomized Controlled Trials as Topic, Stillbirth, Suture Techniques}, issn = {1469-493X}, doi = {10.1002/14651858.CD008991.pub3}, author = {Alfirevic, Zarko and Stampalija, Tamara and Medley, Nancy} } @article {10583, title = {Fetal and umbilical Doppler ultrasound in high-risk pregnancies.}, journal = {Cochrane Database Syst Rev}, volume = {6}, year = {2017}, month = {2017 06 13}, pages = {CD007529}, abstract = {

BACKGROUND: Abnormal blood flow patterns in fetal circulation detected by Doppler ultrasound may indicate poor fetal prognosis. It is also possible that false positive Doppler ultrasound findings could lead to adverse outcomes from unnecessary interventions, including preterm delivery.

OBJECTIVES: The objective of this review was to assess the effects of Doppler ultrasound used to assess fetal well-being in high-risk pregnancies on obstetric care and fetal outcomes.

SEARCH METHODS: We updated the search of Cochrane Pregnancy and Childbirth{\textquoteright}s Trials Register on 31 March 2017 and checked reference lists of retrieved studies.

SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of Doppler ultrasound for the investigation of umbilical and fetal vessels waveforms in high-risk pregnancies compared with no Doppler ultrasound. Cluster-randomised trials were eligible for inclusion but none were identified.

DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. Data entry was checked. We assessed the quality of evidence using the GRADE approach.

MAIN RESULTS: Nineteen trials involving 10,667 women were included. Risk of bias in trials was difficult to assess accurately due to incomplete reporting. None of the evidence relating to our main outcomes was graded as high quality. The quality of evidence was downgraded due to missing information on trial methods, imprecision in risk estimates and heterogeneity. Eighteen of these studies compared the use of Doppler ultrasound of the umbilical artery of the unborn baby with no Doppler or with cardiotocography (CTG). One more recent trial compared Doppler examination of other fetal blood vessels (ductus venosus) with computerised CTG.The use of Doppler ultrasound of the umbilical artery in high-risk pregnancy was associated with fewer perinatal deaths (risk ratio (RR) 0.71, 95\% confidence interval (CI) 0.52 to 0.98, 16 studies, 10,225 babies, 1.2\% versus 1.7 \%, number needed to treat (NNT) = 203; 95\% CI 103 to 4352, evidence graded moderate). The results for stillbirths were consistent with the overall rate of perinatal deaths, although there was no clear difference between groups for this outcome (RR 0.65, 95\% CI 0.41 to 1.04; 15 studies, 9560 babies, evidence graded low). Where Doppler ultrasound was used, there were fewer inductions of labour (average RR 0.89, 95\% CI 0.80 to 0.99, 10 studies, 5633 women, random-effects, evidence graded moderate) and fewer caesarean sections (RR 0.90, 95\% CI 0.84 to 0.97, 14 studies, 7918 women, evidence graded moderate). There was no comparative long-term follow-up of babies exposed to Doppler ultrasound in pregnancy in women at increased risk of complications.No difference was found in operative vaginal births (RR 0.95, 95\% CI 0.80 to 1.14, four studies, 2813 women), nor in Apgar scores less than seven at five minutes (RR 0.92, 95\% CI 0.69 to 1.24, seven studies, 6321 babies, evidence graded low). Data for serious neonatal morbidity were not pooled due to high heterogeneity between the three studies that reported it (1098 babies) (evidence graded very low).The use of Doppler to evaluate early and late changes in ductus venosus in early fetal growth restriction was not associated with significant differences in any perinatal death after randomisation. However, there was an improvement in long-term neurological outcome in the cohort of babies in whom the trigger for delivery was either late changes in ductus venosus or abnormalities seen on computerised CTG.

AUTHORS{\textquoteright} CONCLUSIONS: Current evidence suggests that the use of Doppler ultrasound on the umbilical artery in high-risk pregnancies reduces the risk of perinatal deaths and may result in fewer obstetric interventions. The results should be interpreted with caution, as the evidence is not of high quality. Serial monitoring of Doppler changes in ductus venosus may be beneficial, but more studies of high quality with follow-up including neurological development are needed for evidence to be conclusive.

}, keywords = {Cardiotocography, Cesarean Section, Female, Fetal Monitoring, Humans, Labor, Induced, Perinatal Mortality, Pregnancy, Pregnancy, High-Risk, Randomized Controlled Trials as Topic, Stillbirth, Ultrasonography, Prenatal, Umbilical Arteries, Umbilical Cord}, issn = {1469-493X}, doi = {10.1002/14651858.CD007529.pub4}, author = {Alfirevic, Zarko and Stampalija, Tamara and Dowswell, Therese} } @article {10462, title = {Is middle cerebral artery Doppler related to neonatal and 2-year infant outcome in early fetal growth restriction?}, journal = {Am J Obstet Gynecol}, volume = {216}, year = {2017}, month = {2017 05}, pages = {521.e1-521.e13}, abstract = {

BACKGROUND: Reduced fetal middle cerebral artery Doppler impedance is associated with hypoxemia in fetal growth restriction. It remains unclear as to whether this finding could be useful in timing delivery, especially in the third trimester. In this regard there is a paucity of evidence from prospective studies.

OBJECTIVES: The aim of this study was to determine whether there is an association between middle cerebral artery Doppler impedance and its ratio with the umbilical artery in relation to neonatal and 2 year infant outcome in early fetal growth restriction (26-31 weeks of gestation). Additionally we sought to explore which ratio is more informative for clinical use.

STUDY DESIGN: This is a secondary analysis from the Trial of Randomized Umbilical and Fetal Flow in Europe, a prospective, multicenter, randomized management study on different antenatal monitoring strategies (ductus venosus Doppler changes and computerized cardiotocography short-term variation) in fetal growth restriction diagnosed between 26 and 31 weeks. We analyzed women with middle cerebral artery Doppler measurement at study entry and within 1 week before delivery and with complete postnatal follow-up (374 of 503). The primary outcome was survival without neurodevelopmental impairment at 2 years corrected for prematurity. Neonatal outcome was defined as survival until first discharge home without severe neonatal morbidity. Z-scores were calculated for~middle cerebral artery pulsatility index and both umbilicocerebral and cerebroplacental ratios. Odds ratios of Doppler parameter Z-scores for neonatal and 2 year infant outcome were calculated by multivariable logistic~regression analysis adjusted for gestational age and birthweight p50~ratio.

RESULTS: Higher middle cerebral artery pulsatility index at inclusion but not within 1 week before delivery was associated with neonatal survival without severe morbidity (odds ratio, 1.24; 95\% confidence interval, 1.02-1.52). Middle cerebral artery pulsatility index Z-score and umbilicocerebral ratio Z-score at inclusion were associated with~2~year survival with normal neurodevelopmental outcome (odds ratio, 1.33; 95\% confidence interval, 1.03-1.72, and odds ratio, 0.88; 95\% confidence interval, 0.78-0.99, respectively) as were gestation at delivery and birthweight p50 ratio (odds ratio, 1.41; 95\% confidence interval, 1.20-1.66, and odds ratio, 1.86; 95\% confidence interval, 1.33-2.60, respectively). When comparing cerebroplacental ratio against umbilicocerebral ratio, the incremental range of the cerebroplacental ratio tended toward zero, whereas the umbilicocerebral ratio tended toward infinity as the values became more abnormal.

CONCLUSION: In a monitoring protocol based on ductus venosus and cardiotocography in early fetal growth restriction (26-31 weeks of gestation), the impact of middle cerebral artery Doppler and its ratios on outcome is modest and less marked than birthweight and delivery gestation. It is unlikely that middle cerebral artery Doppler and its ratios are informative in optimizing the timing of delivery in fetal growth restriction before 32 weeks of gestation. The umbilicocerebral ratio allows for a better differentiation in the abnormal range than the cerebroplacental ratio.

}, keywords = {Birth Weight, Child Development, Child, Preschool, Delivery, Obstetric, Female, Fetal Growth Retardation, Gestational Age, Humans, Middle Cerebral Artery, Pregnancy, Prospective Studies, Pulsatile Flow, Ultrasonography, Doppler, Ultrasonography, Prenatal, Umbilical Arteries}, issn = {1097-6868}, doi = {10.1016/j.ajog.2017.01.001}, author = {Stampalija, Tamara and Arabin, Birgit and Wolf, Hans and Bilardo, Caterina M and Lees, Christoph} } @article {8482, title = {A Case of Prenatal Neurocytoma Associated With ATR-16 Syndrome.}, journal = {J Ultrasound Med}, volume = {35}, year = {2016}, month = {2016 Jun}, pages = {1359-61}, issn = {1550-9613}, doi = {10.7863/ultra.15.07045}, author = {Quadrifoglio, Mariachiara and Faletra, Flavio and Bussani, Rossana and Pecile, Vanna and Zennaro, Floriana and Grasso, Alessandra and Zandon{\`a}, Lorenzo and Alberico, Salvatore and Stampalija, Tamara} } @article {7716, title = {More than (Double) Bubble.}, journal = {J Pediatr}, volume = {167}, year = {2015}, month = {2015 Oct}, pages = {942-942.e1}, keywords = {Amniotic Fluid, Duodenum, Female, Humans, Infant, Infant, Newborn, Polyhydramnios, Pregnancy, Pregnancy Trimester, Third, Prenatal Diagnosis, Ultrasonography, Prenatal}, issn = {1097-6833}, doi = {10.1016/j.jpeds.2015.06.066}, author = {Ferrara, Giovanna and Stampalija, Tamara and Codrich, Daniela and Simionato, Cristina and Taddio, Andrea and Travan, Laura} } @article {8081, title = {New lenses to look at preeclampsia.}, journal = {Gynecol Endocrinol}, year = {2015}, month = {2015 Nov 25}, pages = {1-4}, issn = {1473-0766}, doi = {10.3109/09513590.2015.1115833}, author = {Zullino, Sara and Di Martino, Daniela and Stampalija, Tamara and Ferrazzi, Enrico} } @article {3545, title = {Assessment of coupling between trans-abdominally acquired fetal ECG and uterine activity by bivariate phase-rectified signal averaging analysis.}, journal = {PLoS One}, volume = {9}, year = {2014}, month = {2014}, pages = {e94557}, abstract = {

UNLABELLED: Couplings between uterine contractions (UC) and fetal heart rate (fHR) provide important information on fetal condition during labor. At present, couplings between UC and fHR are assessed by visual analysis and interpretation of cardiotocography. The application of computerized approaches is restricted due to the non-stationarity of the signal, missing data and noise, typical for fHR. Herein, we propose a novel approach to assess couplings between UC and fHR, based on a signal-processing algorithm termed bivariate phase-rectified signal averaging (BPRSA).

METHODS: Electrohysterogram (EHG) and fetal electrocardiogram (fECG) were recorded non-invasively by a trans-abdominal device in 73 women at term with uneventful singleton pregnancy during the first stage of labor. Coupling between UC and fHR was analyzed by BPRSA and by conventional cross power spectral density analysis (CPSD). For both methods, degree of coupling was assessed by the maximum coefficient of coherence (CPRSA and CRAW, respectively) in the UC frequency domain. Coherence values greater than 0.50 were consider significant. CPRSA and CRAW were compared by Wilcoxon test.

RESULTS: At visual inspection BPRSA analysis identified coupled periodicities in 86.3\% (63/73) of the cases. 11/73 (15\%) cases were excluded from further analysis because no 30 minutes of fECG recording without signal loss was available for spectral analysis. Significant coupling was found in 90.3\% (56/62) of the cases analyzed by BPRSA, and in 24.2\% (15/62) of the cases analyzed by CPSD, respectively. The difference between median value of CPRSA and CRAW was highly significant (0.79 [IQR 0.69-0.90] and 0.29 [IQR 0.17-0.47], respectively; p<0.0001).

CONCLUSION: BPRSA is a novel computer-based approach that can be reliably applied to trans-abdominally acquired EHG-fECG. It allows the assessment of correlations between UC and fHR patterns in the majority of labors, overcoming the limitations of non-stationarity and artifacts. Compared to standard techniques of cross-correlations, such as CPSD, BPRSA is significantly superior.

}, keywords = {Electrocardiography, Female, Heart Rate, Fetal, Humans, Labor, Obstetric, Pregnancy, Uterine Contraction}, issn = {1932-6203}, doi = {10.1371/journal.pone.0094557}, author = {Casati, Daniela and Stampalija, Tamara and Rizas, Konstantinos and Ferrazzi, Enrico and Mastroianni, Cristina and Rosti, Eleonora and Quadrifoglio, Mariachiara and Bauer, Axel} }