Publications by authors named "Maddalena Morlando"

42 Publications

Reproductive and pregnancy outcomes following embryo transfer in women with previous cesarean section: A systematic review and meta-analysis.

Acta Obstet Gynecol Scand 2021 Aug 19. Epub 2021 Aug 19.

Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.

Introduction: Cesarean section affects subsequent spontaneous pregnancies because of implantation issues. However, its impact on post-embryo transfer pregnancies is still debated. This review aimed to evaluate the impact of a previous cesarean section on fertility and pregnancy outcomes of women undergoing fresh or frozen embryo transfer.

Material And Methods: MEDLINE, Scopus, ClinicalTrials.gov, Scielo, EMBASE, Cochrane Library at the CENTRAL, and LILACS were searched from inception to February 2021. Studies were included if they evaluated reproductive or pregnancy outcomes after fresh or frozen embryo transfer in infertile women with a previous cesarean section relative to women with a previous vaginal delivery. Random-effect meta-analyses to calculate risk ratio (RR) or mean differences with 95% confidence intervals (CI) followed by subgroup analysis for fresh and frozen embryo transfer were performed. Risk of bias and quality assessment were conducted using Newcastle-Ottawa scale and GRADE criteria. The review was registered in the International Prospective Register of Systematic Reviews (CRD42021226297).

Results: Ten studies, with data provided for 13 696 participants, were eligible. For embryo transfers after cesarean section, compared with vaginal delivery, there was a significant reduction of the live birth rate (RR 0.88, 95% CI 0.79-0.99) and biochemical pregnancy rate (RR 0.89, 95% CI 0.82-0.96). No statistically significant differences were found for clinical pregnancy rate (RR 0.92, 95% CI 0.84-1.02), ectopic pregnancies (RR 1.00, 95% CI 0.68-1.46), pregnancy loss (RR 1.05, 95% CI 0.94-1.18), multiple pregnancies (RR 0.80, 95% CI 0.63-1.02), stillbirths (RR 0.86, 95% CI 0.27-2.69), birth defects (RR 1.71, 95% CI 0.49-5.96) or birthweight (mean difference 46.82, 95% CI -40.16 to 133.80). Subgroup analysis revealed an increased risk for preterm birth in post-cesarean section fresh embryo transfer pregnancies (RR 1.59, 95% CI 1.16-2.19).

Conclusions: Low-grade evidence shows that post-embryo transfer pregnancies in infertile women who had a previous cesarean delivery result in reduced biochemical pregnancy and live birth rates relative to women with a previous vaginal delivery. An increased risk for preterm birth is notable in post-fresh embryo transfer pregnancies.
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http://dx.doi.org/10.1111/aogs.14239DOI Listing
August 2021

Impact of Braxton-Hicks contractions on fetal wellbeing; a prospective analysis through computerised cardiotocography.

J Obstet Gynaecol 2021 Aug 14:1-5. Epub 2021 Aug 14.

Department of Woman, Child and General and Specialized Surgery, Obstetrics and Gynecology Unit, University of Campania "Luigi Vanvitelli", Naples, Italy.

To estimate the correlation between the maternal perception of Braxton-Hicks contractions (BHC) and foetal wellbeing throughout antepartum computerised cardiotocography (cCTG) parameters, we performed a prospective observational study between April 2019 and March 2020. Non-labouring women with a term pregnancy were recruited. We collected data regarding maternal perception of BHC in the last two weeks before delivery. For each patient, an external computerised cardiotocography (cCTG) was registered. Women were subdivided in accordance with perception or non-perception of BHC. Fifty women were recruited. Women who felt BHC showed higher foetal heart rate (135 bpm vs 128 bpm,  = .008), lower long-term variability (47.2 ms vs 57.7 ms,  = .02) and reduced number of accelerations (7.8 vs 11.4,  = .04). In conclusion, the absence of mother's perception of BHC showed lower baseline foetal heart rate, increased number of accelerations and higher long-term variability related to mothers who perceived BHC.IMPACT STATEMENT BHC are common painful contractions that start in the third trimester. They are random spots of uterine action that happen in the absence of sufficient gap-junction connectivity. BHC have a significant impact on foetal wellbeing. BHC are associated with reduced long-term variability during cCTG examination. Moreover, baseline foetal heart rate seems lower, and accelerations are less frequent when BHC are felt by pregnant women. These findings could be related to a cumulative effect on the uterine flow mediated by BHC. Further researches are needed to state the impact of BHC on the foetal wellbeing.
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http://dx.doi.org/10.1080/01443615.2021.1929115DOI Listing
August 2021

Timing of delivery and blood pressure cut-off in chronic hypertension during pregnancy: State of art and new proposals.

Int J Gynaecol Obstet 2021 Jun 23. Epub 2021 Jun 23.

Department of Obstetrics and Gynecology, New York Health and Hospitals/Lincoln, Bronx, NY, USA.

Objective: Pregnant women with chronic hypertension are recommended to deliver at 36-39  weeks. The American College of Cardiology and American Heart Association in 2017 lowered the blood pressure cut-off for stage I hypertension to 130/80 mm Hg.

Methods: We performed a literature review on studies comparing elective induction of labor versus expectant management in pregnant women with chronic hypertension. In addition, we reviewed fetal and maternal outcomes in pregnant women with blood pressure of 120-139/80-89 or 130-139/80-89 mm Hg.

Results: We found two randomized clinical trials and one retrospective observational study comparing elective delivery of pregnant women with chronic hypertension versus expectant management. The randomized trials favored expectant management and the observational study favored induction of labor. We found 15 retrospective cohort studies analyzing maternal and fetal outcomes in pregnant women with blood pressure cut-off lower than 140/90 mm Hg. There was a consistent finding of increased risk of any hypertensive disorder of pregnancy, gestational diabetes mellitus, and small-for-gestational-age neonate.

Conclusion: Randomized clinical trials are needed to assess the appropriate timing of delivery for women with stage I hypertension with a blood pressure cut-off of 130/80 mm Hg.
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http://dx.doi.org/10.1002/ijgo.13794DOI Listing
June 2021

Efficacy of phloroglucinol in shortening the first stage of labor: systematic review and meta-analysis of randomized controlled trials.

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

Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.

Background: Protracted labor is associated with an elevated risk of maternal and fetal complications. Results of randomized controlled trials on the efficacy in labor of phloroglucinol (PHL), a pure antispasmodic drug, are uncertain.

Objectives: To evaluate whether PHL is effective in shortening the first stage of labor.

Search Strategy: MEDLINE, EMBASE, LILACS, Scopus, ClinicalTrials.gov, and the Cochrane Library were searched from inception to July 2020.

Selection Criteria: Randomized controlled trials (RCTs) concerning women with a singleton vertex pregnancy at term who were treated with PHL.

Data Collection And Analysis: Relevant data were extracted and tabulated. Review Manager 5.3 was used for data analysis. Primary outcome evaluated was the mean reduction of the first stage of labor.

Main Results: Five RCTs, including 487 pregnant women, were analyzed. The first stage of labor duration was significantly shorter in the treatment arm compared to the control group [MD-113.21 min (95% CI-119.63,-106.79)]. A significant shortening of the second stage was achieved in the PHL group [MD-11.12 min (95% CI-12.64,-9.75)] while no differences were reported for the third stage.

Conclusions: PHL might represent an effective treatment to shorten the duration of the first and second stage of labor.

Synopsis: A meta-analysis of 5 trials found that Phloroglucinol favorably impacts on the total duration of the labor in primiparae and multiparae women with a singleton pregnancy.
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http://dx.doi.org/10.1080/14767058.2021.1936488DOI Listing
June 2021

Aberrant right subclavian artery: the association with chromosomal defects and the related post-natal outcomes in a third level referral centre.

J Obstet Gynaecol 2021 May 27:1-5. Epub 2021 May 27.

Pediatric Cardiology Unit, Monaldi Hospital, University "Luigi Vanvitelli", Naples, Italy.

Aberrant right subclavian artery (ARSA) is the most common embryologic abnormality of the aortic arch. The presence of ARSA has been previously associated with an increased risk of Down syndrome. ARSA at birth may be associated with dysphagia, respiratory distress and stridor and there is no clear evidence-based management. The aim of this study was to describe the associations with chromosomal abnormalities and the postnatal outcome of fetuses diagnosed with ARSA. We analysed fetuses diagnosed antenatally with ARSA between January 2013 and September 2019 in the fetal echocardiography unit of the Hospital Monaldi, University 'Vanvitelli' of Naples, Italy. The results showed fifty fetuses diagnosed with ARSA, all confirmed after birth. The ARSA was an isolated finding in 46 fetuses (92%), while in 4 fetuses the ARSA was associated with other cardiac and/or extra-cardiac anomalies. Only one fetus was diagnosed with trisomy 21 (2%). In this fetus the ARSA was the only ultrasound anomaly identified. There were no cases necessitating referral due to the presence of compression symptoms at birth. The presence of ARSA was associated with trisomy 21 in the 2% of cases in our series and there were no neonatal complications due to airway compression at birth.IMPACT STATEMENT Aberrant right subclavian artery (ARSA) is the most common embryologic abnormality of the aortich arch. ARSA at birth could be associated with dysphagia, respiratory distress and stridor and no evidence-based management of these fetuses has been described yet. The presence of ARSA has been previously associated with an increased risk of Down syndrome. This study confirms known data on association with chromosomal defects and provides some original data on the absence of symptomatology due to tracheal compression with a postnatal follow-up up to three years of age. Our findings suggest that in cases with adequate prenatal assessment performed by experienced clinicians, delivery can safely take place at local hospitals, with no need of referral soon after birth. The use of transthoracic echocardiography to confirm the diagnoses of ARSA after birth and to plan the next follow-up appointments can be supported.
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http://dx.doi.org/10.1080/01443615.2021.1904228DOI Listing
May 2021

Maternal death related to COVID-19: A systematic review and meta-analysis focused on maternal co-morbidities and clinical characteristics.

Int J Gynaecol Obstet 2021 Aug 18;154(2):212-219. Epub 2021 May 18.

Department of Woman, Child and General and Specialized Surgery, Obstetrics and Gynecology Unit, University of Campania "Luigi Vanvitelli", Naples, Italy.

Background: Besides reducing the quality of obstetric care, the direct impact of COVID-19 on pregnancy and postpartum is uncertain.

Objective: To evaluate the characteristics of pregnant women who died due to COVID-19.

Search Strategy: Cochrane Library, Embase, MEDLINE, Scopus, and Google Scholar were searched from inception to February 2021.

Selection Criteria: Studies that compared deceased and survived pregnant women with COVID-19.

Data Collection And Analysis: Relevant data were extracted and tabulated. The primary outcome was maternal co-morbidity.

Main Results: Thirteen studies with 154 deceased patients were included. Obesity doubled the risk of death (relative risk [RR] 2.48, 95% confidence interval [CI] 1.41-4.36, I  = 0%). No differences were found for gestational diabetes (RR 5.71; 95% CI 0.77-42.44, I  = 94%) or asthma (RR 2.05, 95% CI 0.81-5.15, I  = 0%). Overall, at least one severe co-morbidity showed a twofold increased risk of death (RR 2.26, 95% CI 1.77-2.89, I  = 76%). Admission to intensive care was related to a fivefold increased risk of death (RR 5.09, 95% CI 2.00-12.98, I  = 56%), with no difference in need for respiratory support (RR 0.53, 95% CI 0.23-1.48, I  = 95%) or mechanical ventilation (RR 4.34, 95% CI 0.96-19.60, I  = 58%).

Conclusion: COVID-19 with at least one co-morbidity increases risk of intensive care and mortality.
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http://dx.doi.org/10.1002/ijgo.13726DOI Listing
August 2021

The Impact of a Plant-Based Diet on Gestational Diabetes: A Review.

Antioxidants (Basel) 2021 Apr 2;10(4). Epub 2021 Apr 2.

Independent Researcher, Via Venezuela 66, 98121 Messina, Italy.

Gestational diabetes mellitus (GDM) represents a challenging pregnancy complication in which women present a state of glucose intolerance. GDM has been associated with various obstetric complications, such as polyhydramnios, preterm delivery, and increased cesarean delivery rate. Moreover, the fetus could suffer from congenital malformation, macrosomia, neonatal respiratory distress syndrome, and intrauterine death. It has been speculated that inflammatory markers such as tumor necrosis factor-alpha (TNF-α), interleukin (IL) 6, and C-reactive protein (CRP) impact on endothelium dysfunction and insulin resistance and contribute to the pathogenesis of GDM. Nutritional patterns enriched with plant-derived foods, such as a low glycemic or Mediterranean diet, might favorably impact on the incidence of GDM. A high intake of vegetables, fibers, and fruits seems to decrease inflammation by enhancing antioxidant compounds. This aspect contributes to improving insulin efficacy and metabolic control and could provide maternal and neonatal health benefits. Our review aims to deepen the understanding of the impact of a plant-based diet on oxidative stress in GDM.
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http://dx.doi.org/10.3390/antiox10040557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065523PMC
April 2021

Developing a database for multicenter evaluation of placenta accreta spectrum.

Acta Obstet Gynecol Scand 2021 03;100 Suppl 1:7-11

Department of Obstetrics and Gynecology, Fetomaternal Medical Center, Helsinki University Hospital and University of Helsinki, Finland.

Studies of rare, but complex clinical conditions require multicenter cooperation. The International Society for Placenta accreta spectrum (IS-PAS) have established a secure web-based database to analyze pregnancies complicated by PAS. By repeated in-person meetings of the IS-PAS, a core dataset was established. Then, a custom-made, secure online database, capable of receiving strictly anonymized patient-related textual and imaging data and allowing statistical queries was designed, tested, amended and implemented. Between 2008 and 2019, 14 IS-PAS centers across Europe and one center in the USA contributed data for all their PAS cases, containing pregnancy data for a total of 442 pregnant women. Data were analyzed by a designated data analysis sub-group of the IS-PAS. Center characteristics are presented. Based on experiences with previous versions, our new online database now allows an all-encompassing data collection. It has shown its usefulness in the current analysis project.
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http://dx.doi.org/10.1111/aogs.14085DOI Listing
March 2021

Maternal and neonatal outcomes in planned versus emergency cesarean delivery for placenta accreta spectrum: A multinational database study.

Acta Obstet Gynecol Scand 2021 03 12;100 Suppl 1:41-49. Epub 2021 Mar 12.

Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK.

Introduction: Placenta accreta spectrum (PAS) is a condition often resulting in severe maternal morbidity. Scheduled delivery by an experienced team has been shown to improve maternal outcomes; however, the benefits must be weighed against the risk of iatrogenic prematurity. The aim of this study is to investigate the rates of emergency delivery seen for antenatally suspected PAS and compare the resulting outcomes in the 15 referral centers of the International Society for PAS (IS-PAS).

Material And Methods: Fifteen centers provided cases between 2008 and 2019. The women included were divided into two groups according to whether they had a planned or an emergency cesarean delivery. Delivery was defined as "planned" when performed at a time and date to suit the team. All the remaining cases were classified as "emergency". Maternal characteristics and neonatal outcomes were compared between the two groups according to gestation at delivery.

Results: In all, 356 women were included. Of these, 239 (67%) underwent a planned delivery and 117 (33%) an emergency delivery. Vaginal bleeding was the indication for emergency delivery in 41 of the 117 women (41%). There were no significant differences in terms of blood loss, transfusion rates or major maternal morbidity between planned and emergency deliveries. However, the rate of maternal intensive therapy unit admission was increased with emergency delivery (45% vs 33%, P = .02). Antepartum hemorrhage was the only independent predictor of emergency delivery (aOR: 4.3, 95% confidence interval 2.4-7.7). Emergency delivery due to vaginal bleeding was more frequent with false-positive cases (antenatally suspected but not confirmed as PAS at delivery) and the milder grades of PAS (accreta/increta). The rate of infants experiencing any major neonatal morbidity was 25% at 34 to 36  weeks and 19% at >36  weeks.

Conclusions: Emergency delivery in centers of excellence did not increase blood loss, transfusion rates or maternal morbidity. The single greatest risk factor for emergency delivery was antenatal hemorrhage. When adequate expertise and resources are available, to defer delivery in women with no significant antenatal bleeding and no risk factors for pre-term birth until >36  weeks can be considered to improve fetal outcomes. Further studies are needed to investigate this fully.
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http://dx.doi.org/10.1111/aogs.14120DOI Listing
March 2021

Maternal and perinatal outcomes in high compared to low risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection (phase 2): the World Association of Perinatal Medicine working group on coronavirus disease 2019.

Am J Obstet Gynecol MFM 2021 07 20;3(4):100329. Epub 2021 Feb 20.

Department of Obstetrics and Gynecology, Centre for High-Risk Pregnancy and Fetal Care, University of Chieti, Chieti, Italy (Dr Liberati, Dr Sebastiano, Dr Oronzi, Dr Cerra, and Dr Buca).

Background: It has still to be ascertained whether severe acute respiratory syndrome coronavirus 2 infection in pregnancy is associated with worse maternal and fetal outcomes compared to low risk gestations.

Objective: This study aimed to evaluate maternal and perinatal outcomes in high- and low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection.

Study Design: This was a multinational retrospective cohort study involving women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection from 76 centers from 25 countries in Europe, the United States, South America, Asia, and Australia from April 4, 2020, to October 28, 2020. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit, use of mechanical ventilation, or death. The secondary outcome was a composite measure of adverse perinatal outcome, including miscarriage, fetal loss, neonatal and perinatal death, and admission to the neonatal intensive care unit. All outcomes were assessed in high- and low-risk pregnancies. Pregnancies were considered high risk in case of either preexisting chronic medical conditions in pregnancy or obstetrical disorders occurring in pregnancy. The Fisher exact test and logistic regression analysis were used to analyze the data.

Results: A total of 887 singleton pregnancies who tested positive for severe acute respiratory syndrome coronavirus 2 infection using reverse transcription-polymerase chain reaction of nasal and pharyngeal swab specimens were included in the study. The risk of composite adverse maternal outcomes was higher in high-risk pregnancies than in low-risk pregnancies (odds ratio, 1.52; 95% confidence interval, 1.03-2.24; P=.035). In addition, women carrying high-risk pregnancies were at higher risk of hospital admission (odds ratio, 1.48; 95% confidence interval, 1.07-2.04; P=.002), presence of severe respiratory symptoms (odds ratio, 2.13; 95% confidence interval, 0.41-3.21; P=.001), admission to the intensive care unit (odds ratio, 2.63; 95% confidence interval, 1.42-4.88), and invasive mechanical ventilation (odds ratio, 2.65; 95% confidence interval, 1.19-5.94; P=.002). When exploring perinatal outcomes, high-risk pregnancies were at high risk of adverse perinatal outcomes (odds ratio, 1.78; 95% confidence interval, 0.15-2.72; P=.009). However, such association was mainly because of the higher incidence of miscarriage in high-risk pregnancies compared with that in low-risk pregnancies (5.3% vs 1.6%, P=.008); furthermore, there was no difference in other explored outcomes between the 2 study groups. At logistic regression analysis, maternal age (odds ratio, 1.12; 95% confidence interval, 1.02-1.22; P=.023) and high-risk pregnancy (odds ratio, 4.21; 95% confidence interval, 3.90-5.11; P<.001) were independently associated with adverse maternal outcomes.

Conclusion: High-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection were at higher risk of adverse maternal outcomes than low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection.
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http://dx.doi.org/10.1016/j.ajogmf.2021.100329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896113PMC
July 2021

Mediterranean Diet for the Prevention of Gestational Diabetes in the Covid-19 Era: Implications of Il-6 In Diabesity.

Int J Mol Sci 2021 Jan 26;22(3). Epub 2021 Jan 26.

Research Centre for Food and Nutrition, Council for Agricultural Research and Economics (CREA-AN), 00178 Rome, Italy.

The aim of this review is to highlight the influence of the Mediterranean Diet (MedDiet) on Gestational Diabetes Mellitus (GDM) and Gestational Weight Gain (GWG) during the COVID-19 pandemic era and the specific role of interleukin (IL)-6 in diabesity. It is known that diabetes, high body mass index, high glycated hemoglobin and raised serum IL-6 levels are predictive of poor outcomes in coronavirus disease 2019 (COVID-19). The immunopathological mechanisms of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection include rising levels of several cytokines and in particular IL-6. The latter is associated with hyperglycemia and insulin resistance and could be useful for predicting the development of GDM. Rich in omega-3 polyunsaturated fatty acids, vitamins, and minerals, MedDiet improves the immune system and could modulate IL-6, C reactive protein and Nuclear Factor (NF)-κB. Moreover, polyphenols could modulate microbiota composition, inhibit the NF-κB pathway, lower IL-6, and upregulate antioxidant enzymes. Finally, adhering to the MedDiet prior to and during pregnancy could have a protective effect, reducing GWG and the risk of GDM, as well as improving the immune response to viral infections such as COVID-19.
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http://dx.doi.org/10.3390/ijms22031213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866163PMC
January 2021

Usefulness of atosiban for tocolysis during external cephalic version: Systematic review and meta-analysis.

Eur J Obstet Gynecol Reprod Biol 2021 Mar 31;258:86-92. Epub 2020 Dec 31.

Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.

Introduction: Breech/transverse presentation is responsible for about 30-50 % of cesarean sections in the world. Cesarean section carries a five-fold greater morbidity than vaginal delivery, deeply impacting on women's health. External Cephalic Version (ECV) is an external manipulation used to convert a non-cephalic to a cephalic presentation. The use of tocolysis might facilitate this procedure; however, it is still controversial which drug should be considered as first choice.

Objective: To assess the effectiveness of tocolysis with atosiban, a competitive oxytocin receptor antagonist, in order to increase the rate of successful ECV.

Study Design: Nine databases (including MEDLINE, CINAHL, LILACS, EMBASE, Scopus, ClinicalTrials.gov, Scielo, PROSPERO, Cochrane at CENTRAL) were searched from the inception to August 2020 using a combination of MeSH terms and keywords regarding "atosiban" and "external cephalic version". We included trials of women with a singleton pregnancy who reached at least 36 weeks of gestation and were scheduled to ECV and tocolysis with atosiban (intervention group) compared to beta-agonists or other drugs (control group). The primary outcome was the incidence of successful ECV. Summary measures were reported as relative risk (RR) with 95 % confidence interval (CI).

Data Collection And Analysis: Four studies (1534 women) were eligible for analysis. ECV success rate was significantly lower in women randomized to atosiban (36.7 % vs 45.3 %; RR 0.78 [95 % CI 0.6 to 0.98]). Cesarean section and vaginal delivery rates did not differ between intervention and control group ((59.8 % vs 52.6 %; RR 1.17 [0.98-1.38] and (38.6 % vs 45.0 %; RR 0.83 [95 % CI 0.69-1.01] respectively). Cephalic (36.9 % vs 44.6 %; RR 0.81 [95 % CI 0.65 to 1.01], or breech/transverse presentation at labor (63.4 % vs 55.1 %; RR 1.18 [95 % CI 0.99-1.40]), APGAR score less than 7 at 5 min (1.6 % vs 2.0 %; RR 1.14 [95 % CI 0.27-4.73], NICU admissions (44.2 % vs 48.1 %; RR 0.92 [95 % CI 0.58-1.46] and Umbilical cord pH were similar in both groups. Drug-related side effects were lower in women randomized to atosiban, compared with control group (16.0 % vs 42.9 %; RR 0.38 [95 % CI 0.31 to 0.47].

Conclusion: The use of atosiban for tocolysis does not improve the rate of successful ECVs when compared to beta-agonists. However, atosiban was associated with a significantly lower incidence of side effects and comparable cesarean section rates.
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http://dx.doi.org/10.1016/j.ejogrb.2020.12.053DOI Listing
March 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

Transversus abdominis plane block versus wound infiltration for post-cesarean section analgesia: A systematic review and meta-analysis of randomized controlled trials.

Int J Gynaecol Obstet 2021 Jun 11;153(3):383-392. Epub 2021 Feb 11.

Obstetrics and Gynecology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.

Background: Transversus abdominis plane (TAP) block and wound infiltration (WI) with local anesthetics are used for postoperative analgesia after cesarean section (CS), reducing the need for administration of opioids.

Objective: To compare the analgesic effect of TAP block related to WI.

Search Strategy: MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Cochrane Library, and CINAHL were searched from inception until April 2020.

Selection Criteria: Randomized controlled trials (RCTs) about women who underwent TAP block or WI after CS.

Data Collection And Analysis: Relevant data were extracted and tabulated. Review Manager 5.3 was used for data analysis. Primary outcome was cumulative opioid consumption (COC) 24 and 48 h after CS.

Main Results: Five RCTs, enrolling 268 women, were included. There were no significant differences between the interventions regarding COC at 24 (mean difference [MD] -1.68, 95% confidence interval [CI] -6.29 to 2.93) and 48 hours (MD 1.28, 95% CI -10.44 to 13.00). Adverse effects (relative risk [RR] 0.93, 95% CI 0.75-1.16), gastrointestinal reactions (RR 1.30, 95% CI 0.46-3.68), or mild-moderate sedation (RR 1.12, 95% CI 0.72-1.74), pain scores, satisfaction of women, and withdrawals were similar between groups.

Conclusions: There might be no significant advantages selecting TAP block over WI for post-CS analgesia.
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http://dx.doi.org/10.1002/ijgo.13563DOI Listing
June 2021

Placenta Accreta Spectrum Disorders: Challenges, Risks, and Management Strategies.

Int J Womens Health 2020 10;12:1033-1045. Epub 2020 Nov 10.

Nuffield Department of Women's and Reproductive Health, University of Oxford, Fetal Medicine Unit, John Radcliffe Hospital, Oxford, UK.

The worldwide incidence of placenta accreta spectrum (PAS) is rapidly increasing, following the trend of rising cesarean delivery. PAS is an heterogeneous condition associated with a high maternal morbidity and mortality rate, presenting unique challenges in its diagnosis and management. So far, the rarity of this condition, together with the absence of high quality evidence and the lack of a standardized approach in reporting PAS cases for the ultrasound, clinical, and pathologic diagnosis, represented the main challenges for a deep understanding of this condition. The study of the available management strategies of PAS has been hampered by the heterogeneity of the available epidemiological data on this condition. The aim of this review is to provide a critical view of the current available evidence on the screening, the diagnosis, and the management options for PAS disorders, with a special focus on the challenges we foresee for the near future.
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http://dx.doi.org/10.2147/IJWH.S224191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667500PMC
November 2020

Is Uterine Myomectomy a Real Contraindication to Vaginal Delivery? Results from a Prospective Study.

J Invest Surg 2020 Oct 26:1-6. Epub 2020 Oct 26.

Obstetrics and Gynecology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.

Objectives: The main goal of our research was to explore correlations between a history of uterine myomectomy and maternal-fetal outcomes, throughout a comparison between vaginal deliveries in patients with or without a history of uterine myoma excision.

Materials And Methods: A prospective study was carried out at two tertiary care hospitals between January 2019 and January 2020. Women were assigned into two groups according to the history of laparoscopic or laparotomic myomectomy (Group 1) or without myomectomy (Group 2).

Results: 80 women successfully delivered after myomectomy. Pregnancies with previous laparoscopic or laparotomic myomectomy were associated with a minor rate of spontaneous labor onset (RR 1.17; 95% CI 1.04 - 1.31) and with an increased rate of emergency cesarean section (RR 1.22; 95% CI 1.09 - 1.36). Moreover, myomectomy group had a significant number of indications to emergency cesarean section correlated to suspected uterine rupture (RR 1.19; 95% CI 1.02-1.39). There were no uterine ruptures or neonatal deaths recorded. First stage of labor was longer in the myomectomy group (316 vs 204 mins, p = 0.01). No differences in the rates of the prolonged first and second stage of labor, postpartum hemorrhage and vaginal laceration, and no neonatal adverse outcomes were found between groups.

Conclusions: Pregnancies after myomectomy might be associated with an elevated rate of emergency cesarean section only due to a higher percentage of suspected uterine rupture, without a real hazard of adverse obstetric or neonatal outcomes.
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http://dx.doi.org/10.1080/08941939.2020.1836289DOI Listing
October 2020

The impact of obesity on haemodynamic profiles of pregnant women beyond 34 weeks' gestation.

Pregnancy Hypertens 2020 Oct 7;22:191-195. Epub 2020 Oct 7.

Department of Neurosciences, Reproductive Science and Dentistry, University of Naples Federico II, Via Pansini 5, 80131 Naples, Italy.

Objective: We aimed to compare the haemodynamic profiles of obese and non-obese pregnant women, alongside describing the haemodynamic changes that occur in hypertensive disorders of pregnancies with an Appropriate for Gestational Age Fetus (HDP-AGA) beyond 34 weeks' gestation.

Study Design: In this prospective case-control study, maternal haemodynamic assessment was carried out by a trained operator using an UltraSonic Cardiac Output Monitor during a routine clinical assessment after 34 weeks of gestation. Indexed and non-indexed parameters were evaluated.

Main Outcome Measures: Maternal hemodynamic parameters.

Results: Obese and non-obese women did not differ for non-indexed parameters (Cardiac Output, Stroke Volume, Systemic Vascular Resistance). Using indexed parameters, corrected for Body Surface Area, obese women presented significantly lower Cardiac Index z-score (-0.23 ± 0.5 vs 0.26 ± 1.2; p = 0.004), Stroke Volume Index z-score (-0.27 ± 0.8 vs 0.31 ± 1.0; p < 0.0001) and significantly higher Systemic Vascular Resistance Index (0.16 ± 0.8 vs -0.36 ± 0.7; p < 0.0001). In obese women, HDP-AGA (n = 19) had significantly higher Systemic Vascular Resistance Index z-score (1.26 ± 1.7 vs 0.16 ± 0.8; P = 0.009) and significantly lower Stroke Volume Index (-0.68 ± 0.8 vs -0.27 ± 0.8; 0.049).

Conclusion: Using indexed parameters, differences in haemodynamic profiles between obese and non obese women can be highlighted. Obese women seem to present a cardiac maladapation to the pregnancy (reduced cardiac index and stroke volume and increased vascular resistance) that could explain the increased risk of complications in this subgroup.
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http://dx.doi.org/10.1016/j.preghy.2020.10.001DOI Listing
October 2020

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

Efficacy of hyoscine butyl-bromide in shortening the active phase of labor: Systematic review and meta-analysis of randomized trials.

Eur J Obstet Gynecol Reprod Biol 2020 Sep 23;252:218-224. Epub 2020 Jun 23.

Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.

Introduction: Prolonged labor increases the risk of maternal and fetal complications. The active management of labor has been proven effective in lowering neonatal and maternal morbidity by shortening the duration of labor. Several pharmaceutical and non-pharmaceutical approaches are currently being used in the active management of labor. Hyoscine Butyl-bromide (HBB) is an antispasmodic and anticholinergic drug that acts as a cervical spasmolytic agent. It has been widely used in everyday practice for shortening the active phase of labor. Nonetheless, only a few trials have been conducted on the topic.

Objective: This review aimed to evaluate whether HBB is effective in decreasing the mean duration of the active phase of labor.

Study Design: An electronic search was conducted on Medline (through PubMed), Scopus, ClinicalTrials.gov, EMBASE, PROSPERO, and Cochrane Library from the beginning of all databases to December 2019. Results were limited to randomized trials. Restriction for English language was applied. Inclusion criteria were: randomized clinical trials regarding primiparae or multiparae women with a singleton vertex pregnancy at term who were randomized to HBB versus placebo or other drugs. Primary outcome evaluated was the mean reduction of the active phase of labor.

Data Collection And Analysis: Eight randomized clinical trials, including 1159 pregnant women, were analyzed. Significant heterogeneity (I = 99 %) between studies was noted for the primary outcome. The active phase of labor duration was significantly reduced in the treatment arm compared to controls [mean difference (MD) -83.93 min (95 % confidence interval (CI) -163.61, -4.25)]. Achieved reduction in primiparae women was -55.09 min [95 % CI -68.83, -41.35; I = 37 %].

Conclusion: HBB is an effective treatment to shorten the duration of the active phase of labor in primiparae and multiparae women.
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http://dx.doi.org/10.1016/j.ejogrb.2020.06.042DOI Listing
September 2020

Reproductive outcome after cesarean scar pregnancy: A systematic review and meta-analysis.

Acta Obstet Gynecol Scand 2020 10 19;99(10):1278-1289. Epub 2020 Jun 19.

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

Introduction: To evaluate subsequent reproductive among women with a prior cesarean scar pregnancy (CSP).

Material And Methods: MEDLINE, Embase and ClinicalTrials.gov databases were searched. Inclusion criteria were women with a prior CSP, defined as the gestational sac or trophoblast within the dehiscence/niche of the previous cesarean section scar or implanted on top of it. The primary outcome was the recurrence of CSP; secondary outcomes were the chance of achieving a pregnancy after CSP, miscarriage, preterm birth, uterine rupture and the occurrence of placenta accreta spectrum disorders. Subgroup analysis according to the management of CSP (surgical vs non-surgical) was also performed. Random effect meta-analyses of proportions were used to analyze the data.

Results: Forty-four studies (3598 women with CSP) were included. CSP recurred in 17.6% of women. Miscarriage, preterm birth and placenta accreta spectrum disorders complicated 19.1% (65/341), 10.3% (25/243) and 4.0% of pregnancies, and 67.0% were uncomplicated. When stratifying the analysis according to the type of management, CSP recurred in 21% of women undergoing surgical and in 15.2% of those undergoing non-surgical management. Placenta accreta spectrum disorders complicated 4.0% and 12.0% of cases, respectively.

Conclusions: Women with a prior CSP are at high risk of recurrence, miscarriage, preterm birth and placenta accreta spectrum. There is still insufficient evidence to elucidate whether the type of management adopted (surgical vs non-surgical) can impact reproductive outcome after CSP. Further large, prospective studies sharing an objective protocol of prenatal management and long-term follow up are needed to establish the optimal management of CSP and to elucidate whether it may affect its risk of recurrence and pregnancy outcome in subsequent gestations.
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http://dx.doi.org/10.1111/aogs.13918DOI Listing
October 2020

Use of routine ureteral stents in cesarean hysterectomy for placenta accreta.

J Matern Fetal Neonatal Med 2021 Feb 2;34(3):386-389. Epub 2019 May 2.

Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples "Federico II", Naples, Italy.

To evaluate benefits of use of ureteral stents in association with cesarean hysterectomy in case of placenta accreta. This was a single center, cohort study. Clinical records of singleton pregnancies with placenta accreta who underwent cesarean hysterectomy were included in the study. For this study, pregnancies with diagnoses of placenta accreta, increta, or percreta were considered under the umbrella term of placenta accreta. For all women with placenta accreta, delivery was planned via cesarean hysterectomy at 34-35 weeks, without any attempt to remove the placenta. Reasons for earlier delivery included vaginal bleeding and spontaneous onset of labor. The primary outcome was the incidence of unintentional urinary tract injury. Outcomes were compared in a cohort of women who had planned the placement of ureteral stents and in those who did not. Forty-four singleton gestations with confirmed placenta accreta at the time of cesarean hysterectomy were included in the study. Twenty-four (54.5%) of the included women had the placing of ureteral stents prior to cesarean, while 20 (45.5%) did not. At histological confirmation, most of them had placenta accreta (17/44, 38.6%), 14 placenta increta (31.8%), and 13 placenta percreta (29.6%). Urinary tract injuries occurred in eight cases (18.2%), six in the ureteral stents and two in the non-ureteral stents group (25 versus 10%;  = .21). All the injuries were bladder injuries, while no cases of ureteral injury were recorded. All injuries were recognized intraoperatively. In case of placenta accreta, the use of ureteral stents in association with cesarean hysterectomy does not reduce the risk of urinary tract injury.
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http://dx.doi.org/10.1080/14767058.2019.1609935DOI Listing
February 2021

Evidence-based guidelines for the management of abnormally invasive placenta: recommendations from the International Society for Abnormally Invasive Placenta.

Am J Obstet Gynecol 2019 06 5;220(6):511-526. Epub 2019 Mar 5.

Departments of Obstetrics and Division of Experimental Obstetrics, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany.

The worldwide incidence of abnormally invasive placenta is rapidly rising, following the trend of increasing cesarean delivery. It is a heterogeneous condition and has a high maternal morbidity and mortality rate, presenting specific intrapartum challenges. Its rarity makes developing individual expertise difficult for the majority of clinicians. The International Society for Abnormally Invasive Placenta aims to improve clinicians' understanding and skills in managing this difficult condition. By pooling knowledge, experience, and expertise gained within a variety of different healthcare systems, the Society seeks to improve the outcomes for women with abnormally invasive placenta globally. The recommendations presented herewith were reached using a modified Delphi technique and are based on the best available evidence. The evidence base for each is presented using a formal grading system. The topics chosen address the most pertinent questions regarding intrapartum management of abnormally invasive placenta with respect to clinically relevant outcomes, including the following: definition of a center of excellence; requirement for antenatal hospitalization; antenatal optimization of hemoglobin; gestational age for delivery; antenatal corticosteroid administration; use of preoperative cystoscopy, ureteric stents, and prophylactic pelvic arterial balloon catheters; maternal position for surgery; type of skin incision; position of the uterine incision; use of interoperative ultrasound; prophylactic administration of oxytocin; optimal method for intraoperative diagnosis; use of expectant management; adjuvant therapies for expectant management; use of local surgical resection; type of hysterectomy; use of delayed hysterectomy; intraoperative measures to treat life-threatening hemorrhage; and fertility after conservative management.
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http://dx.doi.org/10.1016/j.ajog.2019.02.054DOI Listing
June 2019

Clinical and Ultrasound Predictors of Placenta Accreta in Pregnant Women with Antepartum Diagnosis of Placenta Previa: A Multicenter Study.

Gynecol Obstet Invest 2019 16;84(3):242-247. Epub 2018 Nov 16.

Department of Obstetrics and Gynecology, Obstetrical-Gynecological Ultrasound Unit, "Sant'Anna Hospital", Turin, Italy.

Background/aims: Abnormally invasive placenta (AIP) includes placenta accreta, increta, and percreta and represents major complications of pregnancy. This study was designed to assess the role of ultrasonography in the identification of AIP among pregnant women with antepartum diagnosis of placenta previa.

Methods: A cross-sectional study was performed between May 2015 and April 2016 in 11 centers, including 242 women with antepartum diagnosis of placenta previa.

Results: Ninety-eight out of 242 (40.49%) women had a histological diagnosis of placenta accreta. A higher number of caesarean deliveries (p = 0.001) and curettages (p = 0.027) and older age of the woman at the delivery (p = 0.031) were identified as risk factors for placenta accreta. The presence of irregularly shaped placental lacunae (vascular spaces) within the placenta (p = 0.008), protrusion of the placenta into the bladder (p < 0.0001), and turbulent blood flow through the lacunae on Doppler ultrasonography (p = 0.008) were predictors of placenta accreta.

Conclusions: Women with a prior delivery by caesarean section have a high incidence of placenta accreta among women with antepartum diagnosis of placenta previa.
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http://dx.doi.org/10.1159/000494492DOI Listing
August 2019

[Diagnostic accuracy of endocervicoscopy as preoperative tool to improve the excisional treatment of cervical preneoplastic lesions].

Minerva Ginecol 2018 Aug 31;70(4):364-370. Epub 2018 Jan 31.

Obstetric and Ginecological Center, Department of Woman and Child, University of Campania "Luigi Vanvitelli", Naples, Italy -

Background: The aim of this study was to evaluate the diagnostic accuracy of endocervicoscopy as a preoperative examination to improve the outcome of the excisional treatment (LEEP) of high-grade cervical preneoplastic lesions.

Methods: Patients with histologic diagnosis of CIN II-CIN III undergoing LEEP divided in two groups: in group A (85 women) a preoperative endocervicoscopy was performed, in group B (85 women) no additional examination was performed before LEEP. The size of the surgical specimen (H, D, W) and the margins of the lesion were evaluated.

Results: Seventy-four women in group A and 80 in group B completed the follow-up. group A showed significant correlation between colposcopic examination and endocervicoscopic examination (P=0.001, k=0.30) and between endocervicoscopic and definitive histological examination (P<0.05, k=0.16). The depth of the operative sample was significantly lower (P<0.0001) in group A (0.91±0.4) than in group B (1.58±0.2), group A showed fewer patients B with positive endocervical margins than group B (3 vs. 17, P<002). Colposcopic, cytological and virological follow-up did not show significant differences between the two groups.

Conclusions: Endocervicoscopy as preoperative tool for excisional treatment of cervical lesions showed high diagnostic effectiveness and allows to perform a conservative surgery.
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http://dx.doi.org/10.23736/S0026-4784.18.04196-5DOI Listing
August 2018

Response to Letter Regarding Article, "Risk Factors for Coarctation of the Aorta on Prenatal Ultrasound: A Systematic Review and Meta-Analysis".

Circulation 2017 07;136(3):338-339

From Department of Maternal-Fetal Medicine, Catholic University of the Sacred Heart Rome, Italy (A.F.); Department of Neuroscience, Reproductive Sciences, and Dentistry, School of Medicine, University of Naples Federico II, Italy (M.-M.); Pediatric Cardiology Unit Department of Women's and Children's Health Karolinska Institute, Stockholm, Sweden (S.-E.S.); Department of Obstetrics and Gynaecology, University of TorVergata, Rome, Italy (G.R.); Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden (G.-A.); Department of Medical Sciences, University of Ferrara, Italy (L.M.); and Department of Clinical Medicine-The Arctic University of Norway Department of Obstetrics and Gynecology University Hospital of Northern Norway, Tromsø (F.D.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.117.029014DOI Listing
July 2017

Fetal Tricuspid Regurgitation in the First Trimester as a Screening Marker for Congenital Heart Defects: Systematic Review and Meta-Analysis.

Fetal Diagn Ther 2017 9;42(1):1-8. Epub 2017 May 9.

Academic Unit of Obstetrics and Gynaecology, IRCCS AOU San Martino - IST, University of Genoa, Genoa, Italy.

Background: Assessment of tricuspid flow has been reported to improve the performance of screening for aneuploidies and congenital heart defects (CHD). However, the performance of tricuspid regurgitation (TR) as a screening marker for CHD in euploid fetuses is yet to be established. The main aim of this meta-analysis was to establish the predictive accuracy of TR for CHD.

Methods: MEDLINE, Embase, and the Cochrane Library were searched electronically utilizing combinations of the relevant medical subject heading for "fetus," "tricuspid regurgitation," and "first trimester." The outcomes explored were prevalence of TR in an euploid population, strength of association between TR and CHD, and predictive accuracy of TR for CHD in euploid fetuses. Summary estimates of sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio for the overall predictive accuracy of TR for the detection of CHD were computed using the hierarchical summary receiver-operating characteristics model.

Results: A total of 452 articles were identified; 60 were assessed with respect to their eligibility for inclusion and a total of 4 studies were included in the study. TR was associated with an increased risk of CHD (RR: 9.6, 95% CI 2.8-33.5; I2: 92.7%). The strength of association between TR and CHD persisted when considering fetuses at risk for CHD, such as those with increased nuchal translucency (RR: 7.2, 95% CI 5.2-9.8; I2: 0%), while TR did not show any association with CHD when detected in a population at low risk for cardiac defects (RR: 9.3, 95% CI 0.8-111.8; I2: 93%). The overall diagnostic performance of TR in detecting CHD was poor in detecting CHD (sROC: 0.684, SE: 0.61) with a sensitivity of 35.2% (95% CI 26.9-44.1) and a specificity of 98.6% (95% CI 98.5-98.7). Detection of TR at the 11-14 weeks' scan showed a positive likelihood ratio of 7.2 (95% CI 5.3-9.8) in detecting CHD when applied to a population at risk for CHD such as fetuses with an increased nuchal translucency.

Conclusion: The detection of TR in the first trimester increases the risk of CHD. However, isolated TR in the first trimester does not seem to be a strong predictor for CHD.
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http://dx.doi.org/10.1159/000455947DOI Listing
May 2018

Risk Factors for Coarctation of the Aorta on Prenatal Ultrasound: A Systematic Review and Meta-Analysis.

Circulation 2017 Feb 29;135(8):772-785. Epub 2016 Dec 29.

From Department of Maternal-Fetal Medicine, Catholic University of the Sacred Heart, Rome, Italy (A.F., G.D.S., C.V., A.L., G.S.); Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Italy (M.M.); Fetal Medicine Unit, Saint George's Hospital, London, United Kingdom (A.K.); Pediatric Cardiology Unit, Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden (S.S.-E.); Department of Obstetrics and Gynecology, IRCCS San Martino Hospital University of Genoa, Italy (C.S.); Department of Obstetrics and Gynaecology, University of TorVergata, Rome, Italy (G.R.); Department of Medicine and Aging Sciences, University of Chieti-Pescara, Italy (M.E.F.); Department of Medical Sciences, University of Ferrara, Italy (L.M.); Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden (G.A.); and Department of Clinical Medicine, UiT- The Arctic University of Norway and Department of Obstetrics and Gynecology, University Hospital of Northern Norway, Tromsø (F.D.A.).

Background: Prenatal diagnosis of coarctation of the aorta (CoA) is still challenging and affected by high rates of false-positive diagnoses. The aim of this study was to ascertain the strength of association and to quantify the diagnostic accuracy of different ultrasound signs in predicting CoA prenatally.

Methods: Medline, Embase, CINAHL, and Cochrane databases were searched. Random-effects and hierarchical summary receiver operating characteristic model meta-analyses were used to analyze the data.

Results: Seven hundred ninety-four articles were identified, and 12 (922 fetuses at risk for CoA) articles were included. Mean mitral valve diameter score was lower (<0.001) and the mean tricuspid valve diameter score was higher in fetuses with CoA than in those without CoA (=0.01). Mean aortic valve diameter score was lower in fetuses with CoA than in healthy fetuses (≤0.001), but the ascending aorta diameter, expressed as score or millimeters, was similar between groups (=0.07 and 0.47, respectively). Mean aortic isthmus diameter scores measured either in sagittal (=0.02) or in 3-vessel trachea view (<0.001) were lower in fetuses with CoA. Conversely, the mean pulmonary artery diameter score, the right/left ventricular and pulmonary artery/ascending aorta diameter ratios were higher (<0.001, =0.02, and =0.02, respectively) in fetuses with CoA in comparison with controls, although aortic isthmus/arterial duct diameter ratio was lower in fetuses with CoA than in those without CoA (<0.001). The presence of coarctation shelf and aortic arch hypoplasia were more common in fetuses with CoA than in controls (odds ratio, 26.0; 95% confidence interval, 4.42-153; <0.001 and odds ratio, 38.2; 95% confidence interval, 3.01-486; =0.005), whereas persistent left superior vena cava (=0.85), ventricular septal defect (=0.12), and bicuspid aortic valve (=0.14) did not carry an increased risk for this anomaly. Multiparametric diagnostic models integrating different ultrasound signs for the detection of CoA were associated with an increased detection rate.

Conclusions: The detection rate of CoA may improve when a multiple-criteria prediction model is adopted. Further large multicenter studies sharing the same imaging protocols are needed to develop objective models for risk assessment in these fetuses.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.116.024068DOI Listing
February 2017

The association between prenatal atrioventricular septal defects and chromosomal abnormalities.

Eur J Obstet Gynecol Reprod Biol 2017 Jan 29;208:31-35. Epub 2016 Oct 29.

Fetal Medicine Unit, Academic Department of Obstetrics and Gynaecology, St George's University of London, London, United Kingdom; Royal Brompton Hospital, London, United Kingdom.

Objective: Atrioventricular septal defect is associated with a high risk of a chromosomal abnormality, particularly trisomy 21. The aim of this study is to assess the rate of trisomy 21 in fetuses diagnosed with an atrioventricular septal defect and to examine the influence of prior screening on the rate of trisomy 21.

Methods: Electronic ultrasound database was searched to identify fetuses diagnoses with an atrioventricular septal defect from 2002 to 2014. Rate of trisomy 21 and other aneuploidies was calculated among fetuses with normal situs. The prevalence of trisomy 21 and other aneuploidies was assessed in women with low and high first trimester risk for trisomy 21, using a cut-off value of 1:150 and 1:250.

Results: A total 110 fetuses with a diagnosis of atrioventricular septal defect were identified. Among the 98 fetuses with normal situs, the prevalence of trisomy 21 was 46% (95% CI: 36-56%). Using a 1:150 threshold, the rate of trisomy 21 within the low-risk group was 41% (95% CI: 27-57%) while in the high-risk group it was 70% (95% CI: 52-83%), significantly higher than in the low risk group (p=0.028). Similar results were obtained when the 1:250 threshold was applied (66% versus 41%, p=0.055).

Conclusions: The rate of trisomy 21 among fetuses identified with an atrioventricular septal defect in the second trimester is high even in those that undergo first trimester combined screening. Some fetuses with a high-risk screening result show a normal karyotype. Therefore, an offer of an invasive procedure to check fetal karyotyping is indicated. Knowledge of these rates may be helpful for parents in the decision making process.
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http://dx.doi.org/10.1016/j.ejogrb.2016.10.039DOI Listing
January 2017

Mid-pregnancy fetal growth, uteroplacental Doppler indices and maternal demographic characteristics: role in prediction of stillbirth.

Acta Obstet Gynecol Scand 2016 Nov;95(11):1313-1318

Fetal Medicine Unit, Academic Department of Obstetrics and Gynecology, St George's University of London, London, UK.

Introduction: To evaluate the relative value of mid trimester fetal growth, uterine artery Doppler indices and maternal demographics in prediction of stillbirth.

Material And Methods: Retrospective cohort study; 23 894 singleton pregnancies routinely scanned between 19 and 24 weeks' gestation. Maternal characteristics included age, body mass index, ethnicity and medical history. Fetal biometry indices, birthweight and uterine artery pulsatility index values were converted to percentiles and multivariable logistic regression analysis was performed. The predictive accuracy was assessed using receiver operating characteristic curves analysis. The main outcome was prediction of preterm and term stillbirths.

Results: Non-Caucasian ethnicity, femur length centile and uterine artery pulsatility index were significantly associated with the risk of stillbirth (all p < 0.01). The detection rate of screening by maternal factors alone was 19% for all stillbirths, and 12 and 14% for term and preterm stillbirth at a 10% false positive rate, respectively. Using femur length centile alone, the detection rates were 27 and 23%, respectively. Uterine artery pulsatility index alone was able to predict 24 and 31% of term and preterm stillbirths. Screening by combining maternal factors, femur length centile and uterine artery Doppler detected 27 and 35% of term and preterm stillbirths at a 10% false positive rate.

Conclusions: Second trimester ultrasound assessment offers an opportunity to identify pregnancies at the highest risk of stillbirth occurring as a consequence of placental dysfunction. This information may be useful to improve pregnancy outcome by identifying women who may benefit from increased ultrasound surveillance and/or timely intervention.
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http://dx.doi.org/10.1111/aogs.13012DOI Listing
November 2016

Diagnostic accuracy of intracranial translucency in detecting spina bifida: a systematic review and meta-analysis.

Prenat Diagn 2016 Nov 23;36(11):991-996. Epub 2016 Aug 23.

Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy.

Objective: To evaluate the diagnostic accuracy of intracranial translucency (IT) in the detection of spina bifida (SB) in the first trimester of pregnancy.

Methods: We included study assessing the accuracy of sonographic measurements of IT in a mid-sagittal view of the fetal face in prediction of SB in the first trimester of pregnancy. The primary outcome was the accuracy of IT in prediction of spina bifida. Summary estimates of sensitivity, specificity, positive and negative likelihood ratios (LR), and diagnostic odds ratio for the overall predictive accuracy of IT were computed.

Results: Nine studies (21 070 fetuses) were included in the analysis. IT was successfully assessed in the majority of fetuses 97.8% (95% CI 97.6-98.0). The diagnostic performance of IT in detecting SB was as follows: sensitivity: 53.5% (95% CI 42.4-64.3), specificity: 99.7% (95% CI 99.6-99.8), positive LR: 62.1 (95% CI 12.2-317), negative LR:0.55 (95% CI 0.45-0.68), and diagnostic odds ratio: 223 (95% CI 25-2039).

Conclusions: Intracranial translucency had low diagnostic accuracy in prediction of open spina bifida, thus questioning its role as a screening marker for open SB in an unselected population. When looking at the individual study data, it appears that IT assessment for open SB prediction can be affected by a high rate of false positive results potentially leading to unnecessary parental anxiety. © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/pd.4883DOI Listing
November 2016
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