Publications by authors named "Giuseppe Rizzo"

117 Publications

Antepartum evaluation of the obstetric conjugate at transabdominal 2D ultrasound: A feasibility study.

Acta Obstet Gynecol Scand 2021 Jul 9. Epub 2021 Jul 9.

Department of Obstetrics and Gynecology, University Hospital of Parma, Parma, Italy.

Introduction: The obstetric conjugate represents the shortest anteroposterior diameter of the birth canal and it reflects the capacity of the pelvic inlet to allow the passage and the engagement of the fetal head. The antepartum evaluation of this parameter may be attempted at digital examination to predict the risk of cephalopelvic disproportion, but the accuracy of clinical pelvimetry is notoriously poor. The aim of our study was to describe the sonographic measurement of the obstetric conjugate at transabdominal 2D-ultrasound and to assess its reproducibility.

Material And Methods: This is a prospective cohort study conducted at a tertiary University hospital. A non-consecutive series of pregnant women with uncomplicated singleton pregnancies attending the antenatal clinic for routine booking from 34 weeks of gestation onward were included. The ultrasound probe was longitudinally placed above the level of the symphysis and the interpubic fibrocartilaginous disk was visualized. Then the promontory was identified as the most prominent segment of the sacral vertebral column. The obstetric conjugate was measured as the distance between the inner edge of the interpubic disk and the promontory. The inter- and intraobserver repeatability of this measurement was calculated using the intraclass correlation coefficient (ICC) and the Bland-Altman method.

Results: In all, 119 women were considered eligible for the study; of these, 111/119 (93.3%) women were included in the analysis with a median gestational age of 36.0 (35.0-37.0) weeks. The mean obstetric conjugate measurement was 11.4 ± 0.93 mm for the first operator and 11.4 ± 0.91 mm for the second operator. The overall interobserver ICC was 0.95 (95% [confidence interval] CI 0.92-0.96) and the overall intraobserver ICC was 0.97 (95% CI 0.96-0.98). Limits of agreement ranged from -0.84 to 0.80 for interobserver measures and from -0.64 to 0.62 for intraobserver measures. The degree of reliability was also analyzed for women with a body mass index ≥30 and for women with a gestational age ≥37 weeks. The inter- and intraobserver ICCs were respectively 0.97 (95% CI 0.90-0.98) and 0.98 (0.95-0.99) in the former group and 0.96 (95% CI 0.93-0.98) and 0.97 (95% CI 0.95-0.98) in the latter group.

Conclusions: Our study demonstrated that among pregnant women at term gestation, sonographic measurement of the obstetric conjugate is feasible and reproducible.
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http://dx.doi.org/10.1111/aogs.14226DOI Listing
July 2021

Comparison between Cerebroplacental Ratio and Umbilicocerebral Ratio in Predicting Adverse Perinatal Outcome in Pregnancies Complicated by Late Fetal Growth Restriction: A Multicenter, Retrospective Study.

Fetal Diagn Ther 2021 06 15:1-9. Epub 2021 Jun 15.

Center for High Risk Pregnancy and Fetal Care, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy.

Introduction: The role of cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) to predict adverse intrapartum and perinatal outcomes in pregnancies complicated by late fetal growth restriction (FGR) remains controversial.

Methods: This was a multicenter, retrospective cohort study involving 5 referral centers in Italy and Spain, including singleton pregnancies complicated by late FGR, as defined by Delphi consensus criteria, with a scan 1 week prior to delivery. The primary objective was to compare the diagnostic accuracy of the CPR and UCR for the prediction of a composite adverse outcome, defined as the presence of either an adverse intrapartum outcome (need for operative delivery/cesarean section for suspected fetal distress) or an adverse perinatal outcome (intrauterine death, Apgar score <7 at 5 min, arterial pH <7.1, base excess of >-11 mEq/mL, or neonatal intensive care unit admission).

Results: Median CPR absolute values (1.11 vs. 1.22, p = 0.018) and centiles (3 vs. 4, p = 0.028) were lower in pregnancies with a composite adverse outcome than in those without it. Median UCR absolute values (0.89 vs. 0.82, p = 0.018) and centiles (97 vs. 96, p = 0.028) were higher. However, the area under the curve, 95% confidence interval for predicting the composite adverse outcome showed a poor predictive value: 0.580 (0.512-0.646) for the raw absolute values of CPR and UCR, and 0.575 (0.507-0.642) for CPR and UCR centiles adjusted for gestational age. The use of dichotomized values (CPR <1, UCR >1 or CPR <5th centile, UCR >95th centile) did not improve the diagnostic accuracy.

Conclusion: The CPR and UCR measured in the week prior delivery are of low predictive value to assess adverse intrapartum and perinatal outcomes in pregnancies with late FGR.
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http://dx.doi.org/10.1159/000516443DOI Listing
June 2021

Prediction of delivery after 40 weeks by antepartum ultrasound in singleton multiparous women: a prospective cohort study.

J Matern Fetal Neonatal Med 2021 Jun 13:1-7. Epub 2021 Jun 13.

Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy.

Objective: Universal elective induction of labor (IOL) in singleton parous pregnancies has been advocated to reduce the rate of cesarean section (CD), without impacting on maternal outcome. However, about 50% of women deliver after 40 weeks; therefore, an accurate estimation of the time of delivery might avoid unnecessary early IOL. The aim of this study was to test the diagnostic accuracy of ultrasound in predicting delivery ≥40 weeks of gestation in singleton parous women.

Methods: Prospective cohort study of singleton parous women undergoing a dedicated ultrasound assessment at 36-38 weeks of gestation. The primary outcome was spontaneous vaginal delivery ≥40 weeks of gestation. Cervical length (CL), posterior cervical angle (PCA), sonoelastographic hardness ratio (HR), angle of progression (AoP) and head perineal distance (HPD) were measured. Multivariate logistic regression and area under the curve (AUC) analyses were used to test the diagnostic accuracy of different maternal and ultrasound characteristics in predicting delivery ≥40 weeks.

Results: 518 singleton pregnancies were included in the analysis and 235 (45.4%) delivered ≥40 weeks. CL (29 vs 19 mm; ≤ .0001) and HPD (50 vs 47 mm;  = .001) were longer, HR higher (38.9 vs 35.5;  = .04), while PCA (98° vs 104°; ≤ .0001) and AOP narrower (93° vs 98°;  = .029) in pregnancies delivered compared to those not delivered after 40 weeks of gestation. At multivariable logistic regression analysis, CL (aOR 1.206; 95% CI 1.164-1.250), HPD (aOR 1.127; 95% CI 1.066-1.191) and HR (aOR 1.022; 95% CI 1.003-1.041 were the only variables independently associated with delivery ≥40 weeks. CL showed had an AUC of 0.863 in predicting delivery ≥40 weeks of gestation, with an optimal cutoff of 23.5 mm. Integration of HPD and HR did not significantly improve the diagnostic performance of CL alone to predict delivery ≥40 weeks (AUC 0.870;  = .472).

Conclusion: Cervical length at 36-38 weeks has a good diagnostic accuracy to predict spontaneous vaginal delivery at ≥40 weeks. Universal assessment of CL in the third trimester of pregnancy may help in identifying those women who may benefit of elective IOL at 39 weeks.
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http://dx.doi.org/10.1080/14767058.2021.1937109DOI Listing
June 2021

Diagnostic performance of cerebroplacental and umbilicocerebral ratio in appropriate for gestational age and late growth restricted fetuses attempting vaginal delivery: a multicenter, retrospective study.

J Matern Fetal Neonatal Med 2021 Jun 8:1-7. Epub 2021 Jun 8.

Fetal Medicine Unit, Maternal and Child Health and Development Network, Department of Obstetrics and Gynecology, University Hospital 12 de Octubre, Complutense University of Madrid, Madrid, Spain.

Background: Cerebroplacental Doppler studies have been advocated to predict the risk of adverse perinatal outcome (APO) irrespective of fetal weight.

Objective: To report the diagnostic performance of cerebroplacental (CPR) and umbilicocerebral (UCR) ratios in predicting APO in appropriate for gestational age (AGA) fetuses and in those affected by late fetal growth restriction (FGR) attempting vaginal delivery.

Study Design: Multicenter, retrospective, nested case-control study between 1 January 2017 and January 2020 involving five referral centers in Italy and Spain. Singleton gestations with a scan between 36 and 40 weeks and within two weeks of attempting vaginal delivery were included. Fetal arterial Doppler and biometry were collected. The AGA group was defined as fetuses with an estimated fetal weight and abdominal circumference >10th and <90th percentile, while the late FGR group was defined by Delphi consensus criteria. The primary outcome was the prediction of a composite of perinatal adverse outcomes including either intrauterine death, Apgar score at 5 min <7, abnormal acid-base status (umbilical artery pH < 7.1 or base excess of more than -11) and neonatal intensive care unit (NICU) admission. Area under the curve (AUC) analysis was performed.

Results: 646 pregnancies (317 in the AGA group and 329 in the late FGR group) were included. APO were present in 12.6% AGA and 24.3% late FGR pregnancies, with an odds ratio of 2.22 (95% CI 1.46-3.37). The performance of CPR and UCR for predicting APO was poor in both AGA [AUC: 0.44 (0.39-0.51)] and late FGR fetuses [AUC: 0.56 (0.49-0.61)].

Conclusions: CPR and UCR on their own are poor prognostic predictors of APO irrespective of fetal weight.
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http://dx.doi.org/10.1080/14767058.2021.1926977DOI Listing
June 2021

Cardiac function in fetal growth restriction: a review.

Minerva Obstet Gynecol 2021 Apr 27. Epub 2021 Apr 27.

Division of Maternal Fetal Medicine, Ospedale Cristo Re, Tor Vergata University of Rome, Rome, Italy -

Fetal growth restriction (FGR) is defined as the inability of the fetus to reach its growth potential. According to the onset of the disease is defined early (< 32 weeks) or late (≥ 32 weeks). FGR is associated with an increased risk of adverse short- and long-term outcomes, including hypoxemic events and neurodevelopmental delay compared to normally grown fetuses and increased risk of complications in the infanthood and adulthood. The underlying cause of FGR is placental insufficiency leading to chronic fetal hypoxia that affects cardiac hemodynamic with different mechanism in early and late onset growth restriction. In early onset FGR adaptive mechanisms involve the diversion of the cardiac output preferentially in favour of the brain and the heart, while abnormal arterial and venous flow manifest in the case of further worsening of fetal hypoxia. In late FGR the fetal heart shows a remodelling of its shape and function mainly related to a reduction of umbilical vein flow. In this review we discuss the modifications occurring at the level of the fetal cardiac hemodynamic in fetuses with early and late FGR.
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http://dx.doi.org/10.23736/S2724-606X.21.04787-0DOI Listing
April 2021

Women perception of SARS-CoV-2 vaccination during pregnancy and subsequent maternal anxiety: a prospective observational study.

J Matern Fetal Neonatal Med 2021 Apr 11:1-4. Epub 2021 Apr 11.

Division of Maternal Fetal Medicine, Ospedale Cristo Re Roma, Università di Roma Tor Vergata, Roma, Italy.

Objective: The use of Coronavirus 2 (SARS-CoV-2) vaccine in pregnant women is controversial and still not performed in Italy. Our objective was to evaluate the propensity of a population of Italian women to receive the vaccine and its psychological impact.

Methods: A prospective, observational study was performed on pregnant women attending Ospedale Cristo Re Università Roma TorVergata. A multi-section questionnaire was sent to each included woman on the first day of available SARS-CoV-2 vaccination. Part-A was finalized to acquire maternal characteristics and to test the women's perception of vaccinations in pregnancy and their fear-induced by vaccines. Part-B included the State-Trait-Anxiety-Inventory (STAI) a validated test for scoring trait anxiety (basal anxiety, STAI-T) and state anxiety (STAI-S). An abnormal value of STAI was considered when ≥40. Comparisons of maternal variables were performed according to their vaccine attitude.

Results: The questionnaire was completed by 161 women (80.5% of the population considered). A positive attitude toward the vaccine was present in 136 (84.5%) women (positive) while the remaining 25.5% considered the vaccine not useful (negative). Among the former group 52.9% were favorable to obtain the vaccine during pregnancy despite the current national limitations, a percentage significantly higher ( = .02) than in the negative groups. Women with a negative attitude to the vaccine had a lower educational ( = .002) and employment level ( = .016) when compared to the positive group. In all the women a significant increase of STAI-S from STAI-T values was evidenced ( < .0001). The incidence of abnormal STAI T values (basal anxiety) was similar between the 2 groups ( = .81), while there was a significant increase of STAI-S values in the negative group (negative 88.0%; vs positive 63.4%;  = .018).

Conclusions: The majority of pregnant women considered have a positive attitude to SARS-CoV-2 vaccine. Vaccine campaign seems to increase the maternal level of anxiety and this increase is more marked with a negative attitude toward the vaccine.
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http://dx.doi.org/10.1080/14767058.2021.1910672DOI Listing
April 2021

Maternal and neonatal outcomes of pregnancies complicated by late fetal growth restriction undergoing induction of labor with dinoprostone compared with cervical balloon: A retrospective, international study.

Acta Obstet Gynecol Scand 2021 07 1;100(7):1313-1321. Epub 2021 Apr 1.

Center for High-Risk Pregnancy and Fetal Care, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy.

Introduction: The aim of this study was to compare vaginal dinoprostone and mechanical methods for induction of labor (IOL) in pregnancies complicated by late fetal growth restriction.

Material And Methods: Multicenter, retrospective, cohort study involving six referral centers in Italy and Spain. Inclusion criteria were pregnancies complicated by late fetal growth restriction as defined by Delphi consensus criteria. The primary outcome was the occurrence of uterine tachysystole; secondary outcomes were either cesarean delivery or operative vaginal delivery for non-reassuring fetal status, a composite score of adverse neonatal outcome and admission to neonatal intensive care unit (NICU). Univariate and multivariate logistic regression analysis was used to analyze the data.

Results: A total of 571 pregnancies complicated by late fetal growth restriction undergoing IOL (391 with dinoprostone and 180 with mechanical methods) were included in the analysis. The incidence of uterine tachysystole (19.2% vs. 5.6%; p = 0.001) was higher in women undergoing IOL with dinoprostone than in those undergoing IOL with mechanical methods. Similarly, the incidence of cesarean delivery or operative delivery for non-reassuring fetal status (25.6% vs. 17.2%; p = 0.027), composite adverse neonatal outcome (26.1% vs. 16.7%; p = 0.013) and NICU admission (16.9% vs. 5.6%; p < 0.001) was higher in women undergoing IOL with dinoprostone than in those undergoing IOL with mechanical methods. At logistic regression analysis, IOL with mechanical methods was associated with a significantly lower risk of uterine tachysystole (odds ratio 0.26, 95% confidence interval 0.13-0.54; p < 0.001).

Conclusions: In pregnancies complicated by late fetal growth restriction, IOL with mechanical methods is associated with a lower risk of uterine tachysystole, cesarean delivery or operative delivery for non-reassuring fetal status, and adverse neonatal outcome compared with pharmacological methods.
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http://dx.doi.org/10.1111/aogs.14135DOI Listing
July 2021

Pregnant women's perspectives on severe acute respiratory syndrome coronavirus 2 vaccine.

Am J Obstet Gynecol MFM 2021 Mar 23;3(4):100352. Epub 2021 Mar 23.

Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy (Drs Carbone, Sirico, Di Girolamo, Saccone, Donadono, Cuomo, Gabrielli, Migliorini, and Prof Maruotti).

Background: Since coronavirus disease 2019 vaccines have been distributed, a debate has raised on whether pregnant women should get the vaccine. No available data exist so far regarding the safety, efficacy, and toxicology of these vaccines when administered during pregnancy. Most of the Obstetrics and Gynecology societies suggested that pregnant could agree to be vaccinated, after a thorough counseling of risks and benefits with their gynecologists, thus leading to an autonomous decision.

Objective: This study aimed to evaluate the attitude to coronavirus disease 2019 vaccination in pregnant and breastfeeding women in Italy.

Study Design: A survey was made at the University of Naples Federico II and the Ospedale Cristo Re, Tor Vergata University of Rome, on pregnant and breastfeeding women asking their perspectives on the available vaccines after reading the recommendations issued by our national Obstetrics, Gynecology, and Neonatology societies. The questionnaire included 12 items finalized to evaluate general features of the women and 6 items specifically correlated to their attitudes toward the severe acute respiratory syndrome coronavirus 2 vaccination. Chi-square or Fisher's exact tests were used to compare group differences of categorical variables and Wilcoxon signed rank or Mann-Whitney U test for continuous variables. The study was approved by the institutional review boards of the University of Naples Federico II (ref. no. 409/2020) and the Ospedale Cristo Re, Tor Vergata University of Rome (ref. #Ost4-2020).

Results: Most of the included women did not agree to eventually receive severe acute respiratory syndrome coronavirus 2 vaccine during pregnancy (40 [28.2%] vs 102 [71.8%]). Being pregnant was considered a determinant factor to refuse the vaccine prophylaxis (99 [69.7%] vs 43 [30.3%]; chi-square test=24.187; P<.001), even if a very large percentage declared to be generally in favor of vaccines (128 [90.1%] vs 14 [9.9%]; chi-square test=6.091; P=.014) and most of them confirmed they received or would receive other recommended vaccines during pregnancy (75 [52.8%] vs 67 [47.2%]; chi-square test=10.996; P=.001).

Conclusion: Urgent data are needed on the safety, efficacy, and toxicology of severe acute respiratory syndrome coronavirus 2 vaccines during pregnancy to modify this trend and to help obstetricians during the counseling. Furthermore, pregnant women should be included in future vaccine development trials to not incur again in such uncertainty.
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http://dx.doi.org/10.1016/j.ajogmf.2021.100352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985679PMC
March 2021

Intrapartum sonographic assessment of the fetal head flexion in protracted active phase of labor and association with labor outcome: a multicenter, prospective study.

Am J Obstet Gynecol 2021 Mar 4. Epub 2021 Mar 4.

Obstetrics and Gynecology Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy. Electronic address:

Background: To date, no research has focused on the sonographic quantification of the degree of flexion of the fetal head in relation to the labor outcome in women with protracted active phase of labor.

Objective: This study aimed to assess the relationship between the transabdominal sonographic indices of fetal head flexion and the mode of delivery in women with protracted active phase of labor.

Study Design: Prospective evaluation of women with protracted active phase of labor recruited across 3 tertiary maternity units. Eligible cases were submitted to transabdominal ultrasound for the evaluation of the fetal head position and flexion, which was measured by means of the occiput-spine angle in fetuses in nonocciput posterior position and by means of the chin-to-chest angle in fetuses in occiput posterior position. The occiput-spine angle and the chin-to-chest angle were compared between women who had vaginal delivery and those who had cesarean delivery. Cases where obstetrical intervention was performed solely based on suspected fetal distress were excluded.

Results: A total of 129 women were included, of whom 43 (33.3%) had occiput posterior position. Spontaneous vaginal delivery, instrumental delivery, and cesarean delivery were recorded in 66 (51.2%), 17 (13.1%), and 46 (35.7%) cases, respectively. A wider occiput-spine angle was measured in women who had vaginal delivery compared with those submitted to cesarean delivery owing to labor dystocia (126±14 vs 115±24; P<.01). At the receiver operating characteristic curve, the area under the curve was 0.675 (95% confidence interval, 0.538-0.812; P<.01), and the optimal occiput-spine angle cutoff value discriminating between cases of vaginal delivery and those delivered by cesarean delivery was 109°. A narrower chin-to-chest angle was measured in cases who had vaginal delivery compared with those undergoing cesarean delivery (27±33 vs 56±28 degrees; P<.01). The area under the curve of the chin-to-chest angle in relation to the mode of delivery was 0.758 (95% confidence interval, 0.612-0.904; P<.01), and the optimal cutoff value discriminating between vaginal delivery and cesarean delivery was 33.0°.

Conclusion: In women with protracted active phase of labor, the sonographic demonstration of fetal head deflexion in occiput posterior and in nonocciput posterior fetuses is associated with an increased incidence of cesarean delivery owing to labor dystocia. Such findings suggest that intrapartum ultrasound may contribute in the categorization of the etiology of labor dystocia.
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http://dx.doi.org/10.1016/j.ajog.2021.02.035DOI Listing
March 2021

Effect of SARS-CoV-2 infection during the second half of pregnancy on fetal growth and hemodynamics: A prospective study.

Acta Obstet Gynecol Scand 2021 06 9;100(6):1034-1039. Epub 2021 Mar 9.

Department of Obstetrics and Gynecology, Università di Chieti, Chieti, Italy.

Introduction: Our objective was to compare the fetal growth velocity and fetal hemodynamics in pregnancies complicated and in those not complicated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Material And Methods: Prospective case-control study of consecutive pregnancies complicated by SARS-CoV-2 infection during the second half of pregnancy matched with unaffected women. The z scores of head circumference, abdominal circumference, femur length, and estimated fetal weight were compared between the two groups. Fetal growth was assessed by analyzing the growth velocity of head circumference, abdominal circumference, femur length, and estimated fetal weight between the second- and third-trimester scans. Similarly, changes in the pulsatility index of uterine, umbilical, and middle cerebral arteries, and their ratios were compared between the two study groups.

Results: Forty-nine consecutive pregnancies complicated, and 98 not complicated, by SARS-CoV-2 infection were included. General baseline and pregnancy characteristics were similar between pregnant women with and those without SARS-CoV-2 infection. There was no difference in head circumference, abdominal circumference, femur length, and estimated fetal weight z scores between pregnancies complicated and those not complicated by SARS-CoV-2 infection at both the second- and third-trimester scans. Likewise, there was no difference in the growth velocity of all these body parameters between the two study groups. Finally, there was no difference in the pulsatility index of both maternal and fetal Doppler scans throughout gestation between the two groups.

Conclusions: Pregnancies complicated by SARS-CoV-2 infection are not at higher risk of developing fetal growth restriction through impaired placental function. The findings from this study do not support a policy of increased fetal surveillance in these women.
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http://dx.doi.org/10.1111/aogs.14130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013660PMC
June 2021

Outcome of fetal Vein Galen aneurysmal malformations: a systematic review and meta-analysis.

J Matern Fetal Neonatal Med 2021 Jan 28:1-6. Epub 2021 Jan 28.

Department of Obstetrics and Gynecology, Center for Fetal Care and High-Risk Pregnancy, University of Chieti, Chieti, Italy.

Objectives: To report the outcome of fetuses with a prenatal diagnosis of Vein of Galen (VOG) malformation.

Methods: PubMed and Embase databases were searched. Random effect meta-analysis of proportions was used to analyze the data. The outcomes explored were prenatal ultrasound findings, mortality, preterm birth (PTB), abnormal neurological outcome, associated findings detected at post-natal brain imaging, need for anticonvulsant therapy, and the rate of children free from neurological impairment. Random effect meta-analysis of proportions were used to analyze the data.

Results: Eleven studies (226 fetuses with a prenatal diagnosis of VOG malformation) were included. All cases were detected during the third trimester of pregnancy. Ventriculomegaly was detected in 31.8% (95% CI 27.6-47.7), cardiomegaly or other ultrasound signs of cardiac compromise in 23.1% (95% CI 14.9-32.5) and hydrops in 7.3% (95% CI 2.8-13.6) of cases. The incidence of IUD, NND, and PND was 1.5% (95% CI 0.2-4.3), 23.8% (95% CI 16.9-31.4), and 24.5% (95% CI 17.6-32.2), respectively, while 12.6% (95% CI 6.0-21.2) of pregnancies were complicated by PTB. Abnormal neurodevelopmental outcome was observed in 36.7% (95% CI 27.9-39.7) of cases, while 60.5% (95% CI 17.0-82.0) of children had abnormal findings on post-natal imaging and only 29.7% (95% CI 23.3-36.5) were free from neurological impairment after birth, although there was a wide heterogeneity in the time at follow-up between the included studies.

Conclusion: VOG malformation diagnoses during fetal life is associated with a high incidence of brain damage, cardiac compromise, and abnormal neurodevelopmental outcome after birth.
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http://dx.doi.org/10.1080/14767058.2021.1878494DOI Listing
January 2021

Intrapartum ultrasound before instrumental vaginal delivery: Clinical benefits are difficult to demonstrate.

Acta Obstet Gynecol Scand 2021 05 5;100(5):988-989. Epub 2021 Feb 5.

Department of Medicine and Surgery, Obstetrics and Gynecology Unit, University of Parma, Parma, Italy.

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http://dx.doi.org/10.1111/aogs.14082DOI Listing
May 2021

Outcome of cesarean scar pregnancy according to gestational age at diagnosis: A systematic review and meta-analysis.

Eur J Obstet Gynecol Reprod Biol 2021 Mar 12;258:53-59. Epub 2020 Nov 12.

Center for Fetal Care and High-Risk Pregnancy, Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy. Electronic address:

Objective: The association between the most severe types of placenta accreta spectrum disorders and caesarean scar pregnancy (CSP) poses the question of whether early diagnosis may impact the clinical outcome of these anomalies. The aim of this study is to report the outcome of cesarean scar pregnancy (CSP) diagnosed in the early (≤9 weeks) versus late (>9 weeks) first trimester of pregnancy.

Study Design: Medline, Embase and Clinicaltrail.gov databases were searched. Studies including cases of CSP with an early (≤9 weeks of gestation) compared to a late (>9 weeks) first trimester diagnosis of CSP, followed by immediate treatment, were included in this systematic review. The primary outcome was a composite measure of severe maternal morbidity including either severe first trimester bleeding, need for blood transfusion, uterine rupture or emergency hysterectomy. The secondary outcomes were the individual components of the primary outcome. Random-effect meta-analyses were used to combine data.

Results: Thirty-six studies (724 women with CSP) were included. Overall, composite adverse outcome complicated 5.9 % (95 % CI 3.5-9.0) of CSP diagnosed ≤9 weeks and 32.4 % (95 % CI 15.7-51.8) of those diagnosed >9 weeks. Massive hemorrhage occurred in 4.3 % (95 % CI 2.3-7.0) of women with early and in 28.0 % (95 % CI 14.1-44.5) of those with late first trimester diagnosis of CSP, while the corresponding figures for the need for blood transfusion were 1.5 % (95 % CI 0.6-2.8) and 15.8 % (95 % CI 5.5-30.2) respectively. Uterine rupture occurred in 2.5 % (95 % CI 1.2-4.1) of women with a prenatal diagnosis of CSP ≤ 9 weeks and in 7.5 % (95 % CI 2.5-14.9) of those with CSP > 9 weeks, while an emergency intervention involving hysterectomy was required in 3.7 % (95 % CI 2.2-5.4) and 16.3 % (95 % CI5.9-30.6) respectively. When computing the risk, early diagnosis of CSP was associated with a significantly lower risk of composite adverse outcome, (OR: 0.14; 95 % CI 0.1-0.4 p < 0.001).

Conclusions: Early first trimester diagnosis of CSP is associated with a significantly lower risk of maternal complications, thus supporting a policy of universal screening for these anomalies in women with a prior cesarean delivery although the cost-effectiveness of such policy should be tested in future studies.
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http://dx.doi.org/10.1016/j.ejogrb.2020.11.036DOI Listing
March 2021

Prediction of delivery after 40 weeks by antepartum ultrasound in singleton nulliparous women: a prospective cohort study.

Am J Obstet Gynecol MFM 2020 11 17;2(4):100193. Epub 2020 Aug 17.

Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy.

Background: Induction of labor at 39 weeks of gestation is associated with better maternal and perinatal outcomes than expectant management. However, a policy of induction of labor implies the identification of women who will deliver after 40 weeks, who are at higher risk of adverse outcome.

Objective: This study primarily aimed to elucidate the role of antepartum ultrasound in predicting the onset of spontaneous labor in a cohort of low-risk singleton pregnancies, and secondarily to compare its diagnostic performance with that of other ultrasonographic and clinical parameters.

Study Design: This was a prospective study including singleton nulliparous women undergoing a dedicated ultrasound assessment at 36 to 38 weeks of gestation. The primary outcome was delivery ≥40 weeks of gestation. The ultrasound parameters explored were cervical length, posterior cervical angle, angle of progression, and head-perineum distance. Multivariate logistic regression, Kaplan-Meier, and area under the curve analyses were used to test the strength of association and diagnostic performance of variables considered in predicting delivery ≥40 weeks.

Results: A total of 457 women were included, and 49.2% delivered ≥40 weeks. Cervical length was longer (30 vs 19 mm; P≤.0001) and posterior cervical angle wider (105° vs 98°, P≤.0001) in women delivering ≥40 weeks than those delivering <40 weeks. Similarly, head-perineum distance was longer (48 vs 40 mm; P=.001) and angle of progression narrower (93° vs 95°; P=.04) in pregnancies delivering after 40 weeks. Conversely, there was no difference in the modified Bishop score between the 2 study groups (P=.689). In multivariable logistic regression analysis, cervical length (adjusted odds ratio, 1.307) and head-perineum distance (adjusted odds ratio, 1.227) were independently associated with delivery ≥40 weeks. Cervical length showed an area under the curve of 0.896 in predicting a delivery after 40 weeks. Integration of head-perineum distance in the diagnostic algorithm did not increase the performance of the model. A cervical length of 24 mm at 36 to 37 weeks of gestation showed the best combination of sensitivity and specificity in predicting delivery ≥40 weeks, with a shorter latency between ultrasound assessment and birth.

Conclusion: Antepartum ultrasound can reliably identify a subset of nulliparous women at higher risk of delivering beyond 40 weeks. A cervical length >24 mm at 36 to 37 weeks of gestation shows the optimal combination of sensitivity and specificity in predicting delivery ≥40 weeks. The findings from this study can help in identifying those women for whom elective induction of labor at 39 weeks of gestation would be beneficial in reducing the risk of adverse pregnancy outcome.
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http://dx.doi.org/10.1016/j.ajogmf.2020.100193DOI Listing
November 2020

Role of ante-partum ultrasound in predicting vaginal birth after cesarean section: A prospective cohort study.

Eur J Obstet Gynecol Reprod Biol 2021 Jan 21;256:385-390. Epub 2020 Nov 21.

Department of Obstetric-Section and Gynecology, University of Chieti, Chieti, Italy.

Introduction: Vaginal birth after caesarean delivery is associated with better outcomes compared to repeat caesarean section. Accurate antenatal risk stratification of women undergoing a trial of labor after caesarean section is crucial in order to maximize perinatal and maternal outcomes. The primary aim of this study was to explore the role of antepartum ultrasound in predicting the probability of vaginal birth in women attempting trial of labor; the secondary aim was to build a multiparametric prediction model including pregnancy and ultrasound characteristics able to predict vaginal birth and compare its diagnostic performance with previously developed models based exclusively upon clinical and pregnancy characteristics.

Methods: Prospective study of consecutive singleton pregnancies scheduled for trial of labor undergoing a dedicated antepartum ultrasound assessment at 36-38 weeks of gestation. Head circumference, estimated fetal weight cervical length, sub-pubic angle were recorded before the onset of labour. The obstetricians and midwives attending the delivery suite were blinded to the ultrasound findings. Multivariate logistic regression and area under the curve analyses were used to explore the strength of association and test the diagnostic accuracy of different maternal and ultrasound characteristics in predicting vaginal birth. Comparison with previously reported clinical models developed by the Maternal-Fetal Medicine Unit Network (Grobman's models) was performed using De Long analysis.

Results: A total of 161women who underwent trial of labor were included in the study. Among them 114 (70.8 %) women had successful vaginal birth. At multivariable logistic regression analysis maternal height (adjusted odds ratio (aOR):1.24;9 5% Confidence Interval (CI)1.17-1.33), previous C-section for arrest labor (aOR:0.77; 95 %CI0.66-0.93), cervical dilation at admission (aOR:1.35 ; 95 %CI1.12-1.74), fetal head circumference (aOR:0.77 ; 5%CI0.43-0.89), subpubic angle (aOR:1.39 95 %CI1.11-1.99) and cervical length (aOR:0.82 95 % CI0.54-0.98) were independently associated with VBAC. A model integrating these variables had an area under curve of 0.839(95 % CI 0.710-0.727) for the prediction of vaginal birth, significantly higher than those achieved with intake (0.694; 95 %CI0.549-0.815; p = 0.01) and admission (0.732: 95 % CI 0.590-0.84; p = 0.04) models reported by Grobman.

Conclusion: Antepartum prediction of vaginal birth after a caesarean section is feasible. Fetal head circumference, subpubic angle and cervical length are independently associated and predictive of vaginal birth. Adding these variables to a multiparametric model including maternal parameters improves the diagnostic accuracy of vaginal birth compared to those based only on maternal characteristic.
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http://dx.doi.org/10.1016/j.ejogrb.2020.11.056DOI Listing
January 2021

Modeling gestational age centiles for fetal umbilicocerebral ratio by quantile regression analysis: a secondary analysis of a prospective cross-sectional study.

J Matern Fetal Neonatal Med 2020 Nov 23:1-5. Epub 2020 Nov 23.

Department of Obstetrics and Gynecology, University Hospital of Chieti, Roma, Italy.

Objective: There is a lack of evidence on whether to favor cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) when assessing pregnancies at risk of fetal growth restriction. The Recent evidences highlight a significant heterogeneity in the methodology of previously published studies reporting reference ranges for Doppler indices, which may affect the clinical applicability of these charts. The aim of this study was to develop charts of UCR based upon a recently proposed standardized methodology and using quantile regression.

Methods: This was a secondary analysis of a prospective cross-sectional study including low-risk singleton pregnancies between 24 and 40 weeks of gestation undergoing Doppler recordings. The UCR centile values were established by quantile regression at different gestational age intervals. Quantile regression analysis was used to build the UCR chart.

Result: 2516 low- risk singleton pregnancies were included in the analysis. UCR decreased with advancing gestational age. The 3rd, 5th 10th, 50th, 90th, 95th, and 97th centiles according to gestational age are provided, as well as equations to allow calculation of any other percentile.

Conclusions: We have established gestational age-specific normative centiles reference limits for UCR.
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http://dx.doi.org/10.1080/14767058.2020.1849123DOI Listing
November 2020

The added value of umbilical vein flow in predicting fetal macrosomia at 36 weeks of gestation: A prospective cohort study.

Acta Obstet Gynecol Scand 2021 05 21;100(5):900-907. Epub 2021 Jan 21.

Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy.

Introduction: Current models based on fetal biometry and maternal characteristics have a poor performance in predicting macrosomia. The primary aim of this study was to elucidate the diagnostic performance of fetal venous and arterial Dopplers in predicting macrosomia in the third trimester of pregnancy; the secondary aim was to build a multiparametric prediction model including pregnancy, ultrasound and Doppler characteristics able to predict macrosomia accurately.

Material And Methods: Prospective cohort study including 2156 singleton pregnancies scheduled for routine ultrasound assessment at 36 weeks of gestation. Fetal biometry, estimated fetal weight (EFW), pulsatility index of the uterine, umbilical, and middle cerebral arteries, cerebroplacental ratio and umbilical vein blood flow (UVBF) normalized for fetal abdominal circumference (UVBF/AC) were recorded. Primary outcome was the prediction of fetal macrosomia, defined as a birthweight >90th percentile; secondary outcome was the prediction of newborns >4000 g. Logistic regression and area under the curve (AUC) analyses were used to analyze the data.

Results: Fetal macrosomia complicated 9.8% of pregnancies, and 7.7% of newborns had a birthweight >4000 g. At multivariate logistic regression analysis, maternal body mass index (adjusted odds ratio [aOR] 1.23), pregestational diabetes (aOR 1.83), a prior newborn with a birthweight >95th centile (aOR 1.49), EFW (aOR 2.23) and UVBF (aOR1.84) were independently associated with macrosomia, whereas gestational diabetes mellitus (P = .07) or any of the other Doppler parameters were not. EFW had an AUC of 0.750 and of 0.801 alone and in association with maternal characteristics for the prediction of macrosomia, respectively. The addition of UVBF to this model significantly improved the prediction of fetal macrosomia provided by maternal and ultrasound parameters with an AUC of 0.892 (De Long P = .044 and P = .0078, respectively). The predictive performance for birthweight >4000 g was similar and significantly improved when UVBF was included in the diagnostic algorithm.

Conclusions: Umbilical vein blood flow evaluation in the third trimester improves the diagnosis of fetal macrosomia. The optimal diagnostic performance for macrosomia is achieved by a multiparametric model including umbilical vein flow, maternal characteristics and EFW.
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http://dx.doi.org/10.1111/aogs.14047DOI Listing
May 2021

Intrapartum Doppler ultrasound: where are we now?

Minerva Obstet Gynecol 2021 Feb 20;73(1):94-102. Epub 2020 Nov 20.

Division of Maternal and Fetal Medicine, Cristo Re Hospital, Tor Vergata University, Rome, Italy.

Intrapartum hypoxic events most commonly occur in low-risk pregnancies with appropriately grown fetuses. Continuous intrapartum monitoring by means of cardiotocography has not demonstrated a reduction in the frequency of adverse perinatal outcome but has been linked with an increase in the caesarean section rate, particularly among women considered at low risk. Available data from the literature suggests that abnormalities in the uterine artery Doppler and in the ratio between fetal cerebral and umbilical Doppler (i.e. cerebroplacental ratio [CPR]) are associated with conditions of subclinical placental function occurring in fetuses who have failed to achieve their growth potential regardless of their actual size. In this review we summarize the available evidence on the use of intrapartum Doppler ultrasound for the fetal surveillance during labor and the identification of the fetuses at risk of intrapartum distress.
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http://dx.doi.org/10.23736/S0026-4784.20.04698-5DOI Listing
February 2021

Diagnostic accuracy of prenatal ultrasound in identifying the level of the lesion in fetuses with open spina bifida: A systematic review and meta-analysis.

Acta Obstet Gynecol Scand 2021 02 11;100(2):210-219. Epub 2020 Oct 11.

Center for Fetal Care and High-risk Pregnancy, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy.

Introduction: The role of prenatal ultrasound in correctly identifying the level of the lesion in fetuses with open spina bifida has yet to be determined. The primary aim of this systematic review was to report the diagnostic accuracy of ultrasound in determining the level of the lesion in fetuses with open spina bifida. The secondary aim was to elucidate whether prenatal magnetic resonance imaging (MRI) improves the diagnostic performance of prenatal imaging in correctly identifying the level of the lesion.

Material And Methods: Inclusion criteria were studies reporting the agreement between ultrasound, MRI and postnatal or postmortem assessment of fetuses with spina bifida. Agreement was defined as: complete (when the upper level of the lesion detected prenatally was the same recorded at postnatal or postmortem evaluation), within one (when the upper level of the lesion recorded prenatally was within one vertebral body higher or lower than that reported postnatally) and within two vertebral bodies (when the upper level of the lesion recorded prenatally was within two vertebral bodies higher or lower than that reported postnatally or postmortem evaluation). Meta-analyses of proportions were used to combine data.

Results: Fourteen studies (655 fetuses) were included. Ultrasound was able to identify the correct level of the lesion in 40.9% (95% confidence interval [CI] 26.9-55.6) of cases. The upper level of the lesion recorded on ultrasound was within one vertebral body in 76.2% (95% CI 65.0-85.9) of cases and within two segments in 92.4% (95% CI 84.3-97.7). Fetal MRI detected the exact level of the lesion in 42.5% (95% CI 35.9-45.2) of cases; the level of the lesion recorded on MRI was higher in 26.4% (95% CI 20.0-33.3) of cases and lower in 32.4% (95% CI 25.5-39.7) than that confirmed postnatally. The upper level of the lesion recorded on MRI was within one vertebral body in 76.2% (95% CI 65.9-85.2) of cases and within two segments in 94.2% (95% CI 90.2-97.2).

Conclusions: Both ultrasound and MRI have a moderate diagnostic accuracy in identify the upper level of the lesion in fetuses with open spina bifida.
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http://dx.doi.org/10.1111/aogs.14001DOI Listing
February 2021

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

J Perinat Med 2020 11;48(9):950-958

Department of Obstetrics and Gynaecology, Ospedale di San Leonardo, Castellammare di Stabia, Italy.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.
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http://dx.doi.org/10.1515/jpm-2020-0355DOI Listing
November 2020

International gestational age-specific centiles for umbilical artery Doppler indices: a longitudinal prospective cohort study of the INTERGROWTH-21st Project.

Am J Obstet Gynecol 2021 02 2;224(2):248-249. Epub 2020 Sep 2.

Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy.

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http://dx.doi.org/10.1016/j.ajog.2020.08.110DOI Listing
February 2021

Sonoelastographic Assessment of the Uterine Cervix in the Prediction of Imminent Delivery in Singleton Nulliparous Women Near Term: A Prospective Cohort Study.

J Ultrasound Med 2021 Mar 25;40(3):559-568. Epub 2020 Aug 25.

Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy.

Objectives: To explore the role of newly developed software to assess cervical sonoelastography in predicting the onset of spontaneous delivery in singleton pregnancies at term and to compare its diagnostic performance with that provided by the cervical length (CL) and posterior cervical angle (PCA).

Methods: This work was a prospective study including nulliparous singleton pregnancies at gestational ages of 37 weeks to 38 weeks 6 days. The CL, PCA, hardness ratio (HR), and mean strain from the internal os and external os were obtained by a transvaginal ultrasound approach using semiautomatic software (E-Cervix; Samsung Medison Co, Ltd, Seoul, Korea). Multivariate logistic regression and area under the curve analyses were used to test the strength of the association and the diagnostic performance of the variables considered in predicting delivery within 7 days.

Results: A total of 398 women were included, and 24.6% delivered within 7 days. The CL was shorter (19.5 versus 2 7 mm; P = .0001), PCA narrower (99° versus 102°; P = .02) HR lower (35.3 versus 40.7; P = .0001), mean strain from the external os higher (0.41 versus 0.35; P = .0001), and mean strain from the internal os higher (0.38 versus 0.33; P = .0001) higher in women who delivered within 7 days from the assessment. At the multivariable logistic regression analysis, the CL (adjusted odds ratio, 1.307) and HR (adjusted odds ratio, 1.227) were the only variables independently associated with delivery within 1 week. A model combining the CL and HR showed an area under the curve of 0.873 in predicting delivery within 7 days, higher than that obtained by using the CL and HR singularly (P ≤ .0001).

Conclusions: The HR assessed by sonoelastography improves the efficacy of the CL in predicting imminent delivery in nulliparous women close to term.
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http://dx.doi.org/10.1002/jum.15434DOI Listing
March 2021

Correlation between estimated fetal weight and weight at birth in infants with gastroschisis and omphalocele.

J Matern Fetal Neonatal Med 2020 Aug 19:1-6. Epub 2020 Aug 19.

Department of Obstetrics, Federal University of São Paulo, Sao Paulo, Brazil.

Background: An accurate estimated fetal weight (EFW) calculated with traditional formulae in cases of abdominal wall defects (AWDs) can be challenging. As a result of reduced abdominal circumference, fetal weight may be underestimated, which could affect prenatal management. Siemer et al. proposed a formula without the use of abdominal circumference, but it is not used in our protocols yet.

Objectives: Our aim was to evaluate the correlation of EFW and birth weight in fetuses with AWD by using Hadlock 1, Hadlock 2, and Siemer et al.'s formulae. Our secondary goal was to evaluate how often fetuses classified as small for gestational age (SGA) were in fact SGA at birth.

Study Design: This was a retrospective cohort study of gestations complicated by gastroschisis and omphalocele at two tertiary-care centers in Brazil and Italy during an 8-year period. Of a total of 114 cases, 85 (44 cases of gastroschisis and 41 cases of omphalocele) met our criteria.

Results: The last prenatal scan was performed 5.2 (±4.1) days before birth. The mean gestational age at birth was 37.2 (±1.8) weeks. Correlation of EFW with birth weight was calculated with the three formulae with and without adjustment for weight gain between scan and birth, with the use of the Spearman coefficient. The correlation between EFW and weight at birth was positive according to all three formulae for the infants with gastroschisis. This finding was not confirmed in the infants with omphalocele. All formulae overestimated the number of SGA cases: although only 17.6% of fetuses were actually SGA at birth, the Hadlock formulae had classified nearly 35% of them as SGA, and Siemer et al.'s formula, 15.3%.

Conclusion: All three formulae yielded a good correlation between EFW in the last scan and birth weight in the infants with gastroschisis but not for those with omphalocele. Cases of SGA were overestimated.
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http://dx.doi.org/10.1080/14767058.2020.1808615DOI Listing
August 2020

Dynamics of Cardiac Neutrophil Diversity in Murine Myocardial Infarction.

Circ Res 2020 10 19;127(9):e232-e249. Epub 2020 Aug 19.

Comprehensive Heart Failure Center Wuerzburg (G.R., L.K., A.-P.A.-L., V.A.N., D.J.J.S., C.C.), University Hospital Wuerzburg, Germany.

Rationale: After myocardial infarction, neutrophils rapidly and massively infiltrate the heart, where they promote both tissue healing and damage.

Objective: To characterize the dynamics of circulating and cardiac neutrophil diversity after infarction.

Methods And Results: We employed single-cell transcriptomics combined with cell surface epitope detection by sequencing to investigate temporal neutrophil diversity in the blood and heart after murine myocardial infarction. At day 1, 3, and 5 after infarction, cardiac Ly6G (lymphocyte antigen 6G) neutrophils could be delineated into 6 distinct clusters with specific time-dependent patterning and proportions. At day 1, neutrophils were characterized by a gene expression profile proximal to bone marrow neutrophils (, , ), and putative activity of transcriptional regulators involved in hypoxic response () and emergency granulopoiesis (). At 3 and 5 days, 2 major subsets of (enriched for eg, and ) and () neutrophils were found. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) analysis in blood and heart revealed that while circulating neutrophils undergo a process of aging characterized by loss of surface CD62L and upregulation of , heart infiltrating neutrophils acquired a unique SiglecF signature. SiglecF neutrophils were absent from the bone marrow and spleen, indicating local acquisition of the SiglecF signature. Reducing the influx of blood neutrophils by anti-Ly6G treatment increased proportions of cardiac SiglecF neutrophils, suggesting accumulation of locally aged neutrophils. Computational analysis of ligand/receptor interactions revealed putative pathways mediating neutrophil to macrophage communication in the myocardium. Finally, SiglecF neutrophils were also found in atherosclerotic vessels, revealing that they arise across distinct contexts of cardiovascular inflammation.

Conclusions: Altogether, our data provide a time-resolved census of neutrophil diversity and gene expression dynamics in the mouse blood and ischemic heart at the single-cell level, and reveal a process of local tissue specification of neutrophils in the ischemic heart characterized by the acquisition of a SiglecF signature.
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http://dx.doi.org/10.1161/CIRCRESAHA.120.317200DOI Listing
October 2020

Comparison between cerebroplacental ratio and umbilicocerebral ratio in predicting adverse perinatal outcome at term.

Eur J Obstet Gynecol Reprod Biol 2020 Sep 24;252:439-443. Epub 2020 Jul 24.

Centre for High Risk Pregnancy and Fetal Care, Department of Obstetrics and Gynecology, University of Chieti, Italy. Electronic address:

Objective: Cerebroplacental ratio (CPR) has been associated with adverse perinatal outcome irrespective of fetal weight. More recently, it has been proposed that the ratio between umbilical and middle cerebral artery pulsatility index, the umbilicocerebral ratio (UCR) had a higher diagnostic accuracy compared to CPR in predicting adverse outcome. The aim of the study was to compare the diagnostic accuracy of CPR and UCR in predicting adverse perinatal outcome in the third trimester of pregnancy.

Study Design: Secondary analysis of prospective study carried out in a dedicated research ultrasound clinic in a single tertiary referral center over a one-year period. Inclusion criteria were consecutive singleton pregnancies between 36 + 0 and 37 + 6 weeks of gestation. Exclusion criteria were multiple gestations, pregnancies affected by structural or chromosomal anomalies, maternal medical complications or drugs intake and abnormal Doppler waveform in the UA, defined as PI>95th or absent/end diastolic flow. All women were pre-screened at 28-32 weeks of gestation in order to rule out signs of early fetal growth restriction. The primary outcome was to compare the diagnostic performance of CPR and UCR in detecting the presence of fetuses affected by a composite adverse outcome.

Results: Mean CPR (1.35 ± 0.39 vs 1.85 ± 0.58, p < 0.001) was significantly lower while mean UCR (0.78 ± 0.25 vs 0.58 ± 0.20, p = 0.001) was significantly higher in pregnancies experiencing compared to those not experiencing composite adverse outcome. There was no difference between CPR and UCR in predicting adverse perinatal outcome in the third trimester of pregnancy and both showed a very low diagnostic accuracy. CPR had an AUC of 0.51 (95 % CI 0.43-0.58) while UCR had an AUC of 0.51 (95 % CI 0.43-0.58) in predicting composite adverse outcome. Likewise, there was no difference in the diagnostic accuracy of CRP (AUC: 0.600, 95 % CI 0.36-0.83) and UCR (AUC: 0.589, 95 % CI 0.35-0.83) when considering only SGA fetuses.

Conclusions: A low CPR and a high UCR are significantly associated with adverse perinatal outcome in singleton pregnancies at term. There was no difference between CPR and UCR in predicting perinatal outcome. Despite this, the diagnostic accuracy of both these parameters is too poor to advocate for their use as a screening tool of perinatal impairment at term, unless specific indications, such as SGA or FGR, have been identified.
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http://dx.doi.org/10.1016/j.ejogrb.2020.07.032DOI Listing
September 2020

Adverse intrapartum outcome in pregnancies complicated by small for gestational age and late fetal growth restriction undergoing induction of labor with Dinoprostone, Misoprostol or mechanical methods: A systematic review and meta-analysis.

Eur J Obstet Gynecol Reprod Biol 2020 Sep 18;252:455-467. Epub 2020 Jul 18.

Department of Obstetrics and Gynecology, Department of Medical and Surgical Sciences, University of Foggia, Italy. Electronic address:

Objective: To investigate the outcome of pregnancies with small baby, including both small for gestational age (SGA) and late fetal growth restriction (FGR) fetuses, undergoing induction of labor (IOL) with Dinoprostone, Misoprostol or mechanical methods.

Study Design: Medline, Embase and Cochrane databases were searched. Inclusion criteria were non-anomalous singleton pregnancies complicated by the presence of a small fetus, defined as a fetus with estimated fetal weight (EFW) or abdominal circumference (AC) <10th centile undergoing IOL from 34 weeks of gestation with vaginal Dinoprostone, vaginal misoprostol, or mechanical methods (including either Foley or Cook balloon catheters). The primary outcome was a composite measure of adverse intrapartum outcome. Secondary outcomes were the individual components of the primary outcome, perinatal mortality and morbidity. All the explored outcomes were reported in three different sub-groups of pregnancies complicated by a small fetus including: all small fetuses (defined as those with an EFW and/or AC <10th centile irrespective of fetal Doppler status), late FGR fetuses (defined as those with EFW and/or AC <3rd centile or AC/EFW <10th centile associated with abnormal cerebroplacental Dopplers) and SGA fetuses (defined as those with EFW and/or AC <10th but >3rd centile with normal cerebroplacental Dopplers). Quality assessment of each included study was performed using the Risk of Bias in Non-randomized Studies-of Interventions tool (ROBINS-I), while the GRADE methodology was used to assess the quality of the body of retrieved evidence. Meta-analyses of proportions and individual data random-effect logistic regression were used to analyze the data.

Results: 12 studies (1711 pregnancies) were included. In the overall population of small fetuses, composite adverse intra-partum outcome occurred in 21.2 % (95 % CI 10.0-34.9) of pregnancies induced with Dinoprostone, 18.0 % (95 % CI 6.9-32.5) of those with Misoprostol and 11.6 % (95 % CI 5.5-19.3) of those undergoing IOL with mechanical methods. Cesarean section (CS) for non-reassuring fetal status (NRFS) was required in 18.1 % (95 % CI 9.9-28.3) of pregnancies induced with Dinoprostone, 9.4 % (95 % CI 1.4-22.0) of those with Misoprostol and 8.1 % (95 % CI 5.0-11.6) of those undergoing mechanical induction. Likewise, uterine tachysystole, was recorded on CTG in 13.8 % (95 % CI 6.9-22.3) of cases induced with Dinoprostone, 7.5 % (95 % CI 2.1-15.4) of those with Misoprostol and 3.8 % (95 % CI 0-4.4) of those induced with mechanical methods. Composite adverse perinatal outcome following delivery complicated 2.9 % (95 % CI 0.5-6.7) newborns after IOL with Dinoprostone, 0.6 % (95 % CI 0-2.5) with Misoprostol and 0.7 % (95 % CI 0-7.1) with mechanical methods. In pregnancies complicated by late FGR, adverse intrapartum outcome occurred in 25.3 % (95 % CI 18.8-32.5) of women undergoing IOL with Dinoprostone, compared to 7.4 % (95 % CI 3.9-11.7) of those with mechanical methods, while CS for NRFS was performed in 23.8 % (95 % CI 17.3-30.9) and 6.2 % (95 % CI 2.8-10.5) of the cases, respectively. Finally, in SGA fetuses, composite adverse intrapartum outcome complicated 8.4 % (95 % CI 4.6-13.0) of pregnancies induced with Dinoprostone, 18.6 % (95 % CI 13.1-25.2) of those with Misoprostol and 8.7 (95 % CI 2.5-17.5) of those undergoing mechanical IOL, while CS for NRF was performed in 8.4 % (95 % CI 4.6-13.0) of women induced with Dinoprostone, 18.6 % (95 % CI 13.1-25.2) of those with Misoprostol and 8.7 % (95 % CI 2.5-17.5) of those undergoing mechanical induction. Overall, the quality of the included studies was low and was downgraded due to considerable clinical and statistical heterogeneity.

Conclusions: There is limited evidence on the optimal type of IOL in pregnancies with small fetuses. Mechanical methods seem to be associated with a lower occurrence of adverse intrapartum outcomes, but a direct comparison between different techniques could not be performed.
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http://dx.doi.org/10.1016/j.ejogrb.2020.07.020DOI Listing
September 2020

Administration of antenatal corticosteroid is associated with reduced fetal growth velocity: a longitudinal study.

J Matern Fetal Neonatal Med 2020 Jul 29:1-6. Epub 2020 Jul 29.

Department of Obstetrics and Gynecology Foggia, Università di Chieti, Chieti, Italy.

Objective: To elucidate whether antenatal administration of corticosteroids in pregnancies with threatened preterm labor affects growth velocity.

Methods: A cohort of 262 pregnancies exposed to antenatal corticosteroids longitudinally studied and delivered from 36 weeks (cases) were compared to an unexposed group of 270 women (controls).

Methods: Fetal growth was assessed analyzing the growth velocity of head circumference (HC), abdominal circumference (AC), femur length (FL) and estimated fetal weight (EFW). Growth velocity (GV) was calculated as the difference in the Z-score between the biometric measurements recorded at the time of steroids administration and at 36 week of gestation, divided by the time interval (expressed in days) between the two scans and multiplied by 100. Similarly, changes in the Pulsatility Index (PI) of uterine, umbilical (UA), middle cerebral (MCA) arteries and cerebroplacental ratio (CPR) during the same time interval were also computed.

Results: Median gestational age at steroid administration (30.2 weeks vs 30.4) and follow-up ultrasound (36.4 weeks vs 36.4) were similar between cases and controls. In pregnancies exposed to antenatal corticosteroids, growth velocity in the HC (-0.61 vs. 0.12;  ≤ 0.001), AC (-0.55 vs. -0.04;  ≤ 0.001) and EFW (-0.89 vs. 0.06;  ≤ 0.001) were lower when compared to pregnancies not exposed to steroid therapy, while there was no difference in the growth velocity of FL (-0.05 vs 0.19;  = .06) or in any of the Doppler parameters explored.

Conclusion: In pregnancies exposed to antenatal steroid therapy, there is a significant reduction in fetal growth velocity not otherwise associated with changes in cerebroplacental Dopplers.
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http://dx.doi.org/10.1080/14767058.2020.1800634DOI Listing
July 2020

Fetal Cardiac Remodeling Is Affected by the Type of Embryo Transfer in Pregnancies Conceived by in vitro Fertilization: A Prospective Cohort Study.

Fetal Diagn Ther 2020 Jul 13:1-7. Epub 2020 Jul 13.

Department of Obstetrics and Gynecology, University Hospital of Chieti, Chieti, Italy.

Objective: Pregnancies conceived via intracytoplasmic sperm injection (ICSI) are associated with a higher risk of fetal cardiac remodeling. The aim of this study was to evaluate whether the type of embryo transfer may affect the magnitude of fetal cardiac remodeling in pregnancies conceived via ICSI.

Methods: Prospective cross-sectional study including 212 pregnancies conceived by ICSI (111 with frozen and 101 with fresh embryos) and 120 spontaneously conceived gestations. All women underwent ultrasound biometric evaluation, Doppler, and echocardiographic assessment, including evaluation of left and right atrial areas and sphericity index (SI), at 20-24 weeks of gestation. The χ2 and Kruskal-Wallis H tests were used to analyze the data.

Results: There was no difference in maternal characteristics, gestational age at ultrasound, Doppler, and fetal weight among the study groups. In pregnancies conceived by ICSI, left and right atrial areas were higher (p < 0.0001) and SI was lower (p < 0.0001) compared to spontaneously conceived pregnancies. Left (p = 0.004) and right (p = 0.023) atrial areas and left (p = 0.036) and right (p = 0.002) SIs were more affected in ICSI pregnancies conceived by fresh embryos.

Conclusion: The risk of fetal cardiac remodeling is higher in pregnancies conceived by ICSI and independent from fetal size and Doppler. The magnitude of these changes is affected by the type of ICSI technique and is higher in pregnancies conceived by fresh embryos.
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http://dx.doi.org/10.1159/000508987DOI Listing
July 2020

Current use and performance of the different fetal growth charts in the Italian population.

Eur J Obstet Gynecol Reprod Biol 2020 Sep 29;252:323-329. Epub 2020 Jun 29.

Department of Medicine and Surgery, Obstetrics and Gynecology Unit, University of Parma, Via Gramsci 14, 43125 Parma, Italy. Electronic address:

Objectives: The choice of growth charts impacts on screening, diagnosis and clinical management of fetal growth abnormalities. The objectives of the study were to evaluate: 1) the clinical practice at a national level among tertiary referral centers in the use of fetal biometric growth charts; and 2) the impact on fetal growth screening of existing national and international growth charts.

Study Design: A questionnaire was sent to 14 Italian tertiary referral centers to explore biometric reference growth charts used in clinical practice. National and international (Intergrowth-21st and World Health Organization) fetal growth charts were tested on a large national cohort of low risk women with singleton uneventful pregnancy derived from a retrospective cross-sectional multicenter study (21 centers). The percentage of fetuses with biometric measurements below and above the 10th and 90th percentile for each biometric parameter and gestational week were calculated for each growth chart. The percentile curves of the study population were calculated by non-linear quantile regressions.

Results: Twelve Italian centers (86 %) answered to the questionnaire showing a wide discrepancy in the use of growth charts for fetal biometry. The cohort included 7347 pregnant women. By applying Intergrowth-21st growth charts the percentage of fetuses with head circumference, abdominal circumference and femur length below the 10th centile was 3.9 %, 3.6 % and 2.3 %, and above the 90th centile 29.9 %, 32.5 % and 46 %, respectively. The percentages for the World Health Organization growth charts for head and abdominal circumferences and femur length were: below the 10th centile 6.3 %, 7.2 % and 5.3 %, and above 90th centile 22.8 %, 21.3 % and 31.9 %, respectively.

Conclusions: The wide discrepancy in clinical use of fetal growth charts in Italian centers warrants the adoption of an uniform set of charts. Our data suggest that immediate application into clinical practice of international growth charts might result into an under-diagnosis of small for gestational age fetuses and, especially, in an over-diagnosis of large for gestational age fetuses with major consequences for clinical practice. On these grounds, there is an urgent need for a nationwide study for the prospective evaluation of international growth charts and, if needed, the construction and adoption of methodologically robust national growth charts.
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http://dx.doi.org/10.1016/j.ejogrb.2020.06.059DOI Listing
September 2020

Role of prenatal magnetic resonance imaging in fetuses with isolated agenesis of corpus callosum in the era of fetal neurosonography: A systematic review and meta-analysis.

Acta Obstet Gynecol Scand 2021 01 24;100(1):7-16. Epub 2020 Aug 24.

Center for Fetal Care and High-risk Pregnancy, Department of Obstetrics and Gynecology, University Hospital of Chieti, Chieti, Italy.

Introduction: Corpus callosum agenesis (ACC) is frequently diagnosed during fetal life; its prognosis depends also on additional anomalies. The additional value of fetal magnetic resonance imaging (MRI) in fetuses with "isolated" complete (cACC) and partial (pACC) agenesis of the corpus callosum on ultrasound is still debated.

Material And Methods: We performed a systematic literature review and meta-analysis including fetuses with a prenatal diagnosis of cACC and pACC without associated structural anomalies on ultrasound, undergoing fetal MRI. The primary outcome was the rate of additional anomalies detected at fetal MRI. Further analyses assessed the effect of type of ultrasound assessment (neurosonography vs standard axial assessment), gestational age at fetal MRI and rate of postnatally detected brain anomalies. Random-effect meta-analyses of proportions were used to analyze the data.

Results: Fourteen studies (798 fetuses) were included. In cases with isolated cACC, 10.9% (95% CI 4.1-20.6) and 4.3% (95% CI 1.4-8.8) additional anomalies were detected by fetal MRI and postnatally, respectively. Stratifying according to the type of ultrasound assessment, the rate of associated anomalies detected only on fetal MRI was 5.7% (95% CI 0.5-16.0) with dedicated neurosonography and 18.5% (95% CI 7.8-32.4) with a standard axial assessment. In fetuses with isolated pACC, 13.4% (95% CI 4.0-27.0) and 16.2% (95% CI 5.9-30.3) additional anomalies were detected by fetal MRI or postnatally, respectively. Stratifying according to the type of ultrasound assessment, the rate of associated anomalies detected only on fetal MRI was 11.4% (95% CI 2.7-25.0) when dedicated neurosonography was performed. Cortical and posterior fossa anomalies represented the most common anomalies missed at ultrasound with both cACC and pACC. Due to the very small number of included cases, stratification according to early (<24 weeks of gestation) and late (>24 weeks) fetal MRI could not be done for either cACC or pACC.

Conclusions: The rate of associated anomalies detected exclusively at fetal MRI in isolated ACC undergoing neurosonography is lower than previously reported. Cortical and posterior fossa anomalies are among the most common anomalies detected exclusively at MRI, thus confirming the crucial role of fetal MRI in determining the prognosis of these fetuses. However, some anomalies still go undetected prenatally and this should be stressed during parental counseling.
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http://dx.doi.org/10.1111/aogs.13958DOI Listing
January 2021
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