Comparison between trans-vaginal and trans-abdominal ultrasound examination of the cervix in the second trimester of pregnancy: a prospective study.

OBJECTIVES: To compare transvaginal (TV) and trans-abdominal (TA) ultrasound assessment of cervical length (CL) at the time of the second-trimester scan for fetal anomalies. METHODS: This was a prospective study including consecutive pregnant women attending the low-risk ultrasound clinic of two fetal medicine centres in Italy. The inclusion criteria were women between 19 + 0 and 22 + 0 weeks of gestation, attending the prenatal ultrasound clinic for the routine second trimester screening for fetal anomalies. The primary outcome was to compare the CL measurement obtained at TV compared to TA ultrasound; the secondary outcome was to report the inter and intra-observer variability of CL measured with the two different approaches. All women underwent TV and TA assessment of the cervix performed by two experienced certified operators, blinded to each other. Intra-class correlation coefficients (ICC) and Bland-Altman analyses were used to analyse the data. RESULTS: Two hundred and fifty women were included in the analysis. All women had anteverted uterus. The mean gestational age at ultrasound was 20.7 ± 0.7 weeks; 1.2 % (3/250) scans were performed at 19 weeks, 49.2 % (123/250) at 20 weeks, 44.8 % (112/250) at 21 weeks and 4.8 % (12/250) at 22 weeks of gestations. Identification of the major landmarks of CL at TA ultrasound was achieved in all the included cases. There was good reliability between CL measured at TA (ICC 0.95, 95 % CI 0.93-0.97 for observer 1 and 0.92 %, 95 % CI 0.89-0.94 for observer 2) and TV ultrasound 0.97, 95 % CI 0.96-0.98 for observer 1 and 0.96, 95 % CI 0.95-0.97 for observer 2). There was also good reliability between the two observers for both the TA and TV assessment of the CL. Mean TA CL was 41.4 ± 5.5 for observer 1 and 40.5 ± 4.8 for observer 2 with no significant differences between the two measurements (mean difference 0.92 mm, 95 % CI -9.7 to 11.2). Likewise, there was no difference between the CL measured at TV ultrasound between the two observers (mean difference -0.83 mm, 95 % CI -5.97 to 4.30). Finally, there was no difference in the mean CL measured at TA compared to TV, either considering the overall population of women (mean difference: -0.43, 955 CI -8.65 to 7.79), or when stratifying the analysis according to the parity status and the operator. CONCLUSIONS: Among experienced operators, there was no difference between TV and TA ultrasound assessment of the CL at the time of the routine anomaly scan for fetal anomaly.

Extracellular vesicles during the three trimesters of pregnancy.

OBJECTIVES: Extracellular vesicles (EVs) are cell-derived particles released during different pathophysiological processes and emerging as relevant players in inter-cellular crosstalk. Previous studies have highlighted the role of EVs as potential biomarkers for several pregnancy complications, including miscarriage, pre-eclampsia and gestational diabetes. Despite that, the actual distribution of EVs through gestation has not been reported yet. The aim of this study was to report the concentration of different sub-types of EVs in the first, second and third trimester of pregnancy and to correlate them with different pregnancy and ultrasound characteristics. STUDY DESIGNS: Prospective observational study including uncomplicated pregnancies in the first, second and third trimester of pregnancy. The first aim of the study was to report the concentration of the EVs derived from endothelial, epithelial, platelet and leukocyte cells of maternal peripheral blood samples in the first, second and third trimester pregnancy using polychromatic flow cytometry. The secondary aim was to correlate EVs with neonatal birthweight and fetal Dopplers, including uterine and umbilical arteries. Un and multivariate analyses were used to compute the data. RESULTS: 64 women (20 in the first, 22 in the second and 22 in the third trimester of pregnancies) were included in the analysis. There was no difference in the median concentration of either platelet, leukocyte and endothelial EVs between the first, second and third trimester of pregnancy. The concentration of epithelial derived EVs was higher in the third compared to first and second trimester of pregnancy. When analyzing the percentage of EV vesicles through gestation, there was no difference in the percentage of either leukocyte or endothelial EVs through gestation. Conversely, the median percentage of platelet derived vesicles was higher in the first (48.7 %, IQR 34.1-58.5) compared to second (34.0 %, IQR 22.7-44.9) and third (9.13 %, IQR 5.01-12.1) trimester of pregnancy, while the median percentage of third trimester (6.01, IQR 2.42-7.34) epithelial derived vesicles was higher than that of the second (1.53 %, IQR 0.65-2.98), but not of the first (4.45 %, IQR 1.44-6.07) trimester. Finally, we found no association between the median concentration or percentage of endothelial, epithelial, leukocyte vesicles, neonatal birthweight and fetal or maternal Dopplers. CONCLUSIONS: Distribution of EVs examined does not change during the three trimesters of pregnancy and is not influenced by neonatal birthweight or maternal and fetal Dopplers. The findings from this study allows a more objective interpretation of studies comparing EVs in pregnancies with compared to those without obstetric complication. EVs in future can be used for "liquid biopsy" for the early diagnosis of pathological pregnancies up to the development of possible screening protocols.

Placenta accreta spectrum disorders clinical practice guidelines: A systematic review.

OBJECTIVES: To objectively assess the quality of the published clinical practice guidelines (CPGs) on the management of pregnancies complicated by placenta accreta spectrum (PAS)disorders. METHODS: MEDLINE, Embase, Scopus, and ISI Web of Science databases were searched. The following aspects related to the management of pregnancies with suspected PAS disorders were evaluated: risk factors for PAS, prenatal diagnosis, role of interventional radiology and ureteral stenting, and optimal surgical management. The assessment of risk of bias and quality assessment of the CPGs were performed using the (AGREE II) tool (Brouwers et al., 2010). To define a CPG as of good quality we adopted a cut-off score >60%. RESULTS: Nine CPGs were included. Specific risk factors for referral were assessed by 44.4% (4/9) of CPGs, mainly consisting in the presence of placenta previa and a prior cesarean delivery or uterine surgery. About 55.6% of CPGs (5/9) suggested ultrasound assessment of women with risk factors for PAS in the second and third trimester of pregnancy and 33.3% (3/9) recommended magnetic resonance imaging (MRI); 88.9% (8/9) of CPGs recommended cesarean delivery at 34-37 weeks of gestation. There was not generally consensus on the use of interventional radiology and ureteral stenting before surgery for PAS. Finally, hysterectomy was the recommend surgical approach by 77.8% (7/9) of the included CPGs. CONCLUSION: Most of the published CPGs on PAS are generally of good quality. There was general agreement among the different CPGs on PAS as a regard as risk stratification, timing at diagnosis and delivery but not on the indication for MRI, use of interventional radiology and ureteral stenting.

Monkeypox infection in pregnancy: a systematic review and metaanalysis.

OBJECTIVE: The World Health Organization has recently declared a monkeypox outbreak as a public health emergency of global concern. The main aim of this systematic review was to ascertain the maternal and perinatal outcomes of pregnancies complicated by monkeypox infection. DATA SOURCES: The Medline, Embase, and Cochrane databases were searched on June 25, 2022 utilizing combinations of the relevant medical subject heading terms, key words, and word variants for "monkeypox" and "pregnancy." STUDY ELIGIBILITY CRITERIA: The search and selection criteria were restricted to the English language. METHODS: The outcomes observed were miscarriage; intrauterine, neonatal, and perinatal death; preterm birth, vertical transmission, and maternal symptoms. A metaanalysis of proportions was used to analyze the data. RESULTS: Four studies were included. All the cases in the present systematic review presented with symptoms and signs of monkeypox infection. There was no case of maternal death. Miscarriage occurred in 39% of cases (95% confidence interval, 0-89.0), whereas intrauterine fetal death occurred in 23.0% (95% confidence interval, 0-74.0) of cases. The overall incidence of late fetal and perinatal loss was 77.0% (95% confidence interval, 26.0-100), whereas only 23% (95% confidence interval, 0-74.0) of the included fetuses survived to birth. The incidence of preterm birth before 37 weeks of gestation was 8.0% (95% confidence interval, 0-62.0). Vertical transmission occurred in 62.0% (95% confidence interval, 3.0-100) of cases. When stratifying the analysis according to gestational age at infection, fetal loss was found to occur in 67.0% (95% confidence interval, 9.0-99.0) of cases with first-trimester infection and in 82.0% (95% confidence interval, 17.0-100) of those with second-trimester infection. CONCLUSION: Monkeypox infection in pregnancy is associated with a high risk of perinatal loss and vertical transmission. The preliminary results from this systematic review affected by a very small number of included cases highlight the need for thorough maternal and fetal surveillance in pregnancies complicated by monkeypox infection.

Role of lactoferrin in preventing preterm birth and pregnancy complications: a systematic review and meta-analysis.

INTRODUCTION: The aim of this systematic review was to report the role of lactoferrin supplementation for the prevention of preterm birth (PTB) in women at risk. EVIDENCE ACQUISITION: PubMed and Embase databases were searched. Inclusion criteria were studies exploring maternal and perinatal outcomes in women at high-risk for preterm birth receiving compared to those not receiving lactoferrin during pregnancy. The primary outcome was preterm PTB<37 weeks; the secondary outcomes were gestational age at birth, PTB<34 and 28 weeks, preterm premature rupture of the membranes (PPROM), chorioamnionitis and admission to Neonatal Intensive Care Unit. Random effect meta-analyses were used to analyze the data. EVIDENCE SYNTHESIS: Six studies (333 pregnancies) were included. Overall, women taking lactoferrin had a lower risk of PTB<37 weeks of gestation with an OR of 0.43 (95% CI: 0.2-0.9). Likewise, gestational age at delivery was higher in women-taking compared to those not-taking lactoferrin (MD=0.46 weeks, SD=0.17, P=0.006). The other included studies explored the role of lactoferrin in affecting the inflammatory profile in the amniotic fluid of women undergoing invasive test, without reporting its actual role in preventing PTB. CONCLUSIONS: Prophylactic administration of lactoferrin can reduce the risk of PTB in women at risk. Further large and adequately powered randomized trial are needed in order to elucidate the actual role of lactoferrin in reducing the risk of preterm birth and in affecting perinatal outcomes in women at risk.

Systematic review and meta-analysis on placenta accreta spectrum disorders in twin pregnancies: risk factors, detection rate and histopathology.

INTRODUCTION: The occurrence of PAS has been recently associated with the presence of twin pregnancy. Aim of this review is to report the risk factors, histopathological correlation, diagnostic accuracy of prenatal ultrasound and clinical outcome of twin pregnancies complicated by placenta accreta spectrum (PAS) disorders. EVIDENCE ACQUISITION: PubMed, Embase, Cinahl, Clinical Trial.Gov and Google Scholar databases were searched. Inclusion criteria were studies on twin pregnancies complicated by PAS. The outcomes explored were risk factors for PAS (including placenta previa, prior uterine surgery or assisted reproductive technology, ART), histopathology (placenta accreta and increta/percreta), detection rate of prenatal ultrasound and clinical outcome, including need for blood transfusion, hysterectomy, emergency or scheduled Cesarean delivery (CD), and maternal death. Random effect meta-analyses of proportions were sued to combine the data. EVIDENCE SYNTHESIS: Two studies considering 103 pregnancies were included in this systematic review: 41.86% (95% CI 27.0-57.9) of twin pregnancies complicated by PAS disorders had a prior CD, 28.22% (95% CI 13.4-46.0) presented placenta previa and 58.14% (95% CI 42.1-73.0) of twin pregnancies were conceived by ART. 74.49% (95% CI 41.6-96.5) of PAS in twin pregnancies were placenta accreta, while 25.51% (95% CI 3.5-58.4) were placenta increta or percreta. Prenatal diagnosis of PAS in twin pregnancies was accomplished only in 27.91% (95% CI 15.3-43.7) of cases. Finally, only one study consistently reported the clinical outcome of PAS in twins. 31.67% (95% CI 20.3-45.0) of women required blood transfusion, 26.67% (95% CI 16.1-39.7) had hysterectomy, while there was no case of maternal death. 44.19% of women had an emergency CD. CONCLUSIONS: There is still limited evidence on the clinical course of PAS disorders in twin pregnancies. Placenta previa, prior uterine surgery (mainly CD), and ART are the most commonly risk factors for PAS disorders in twins. Prenatal diagnosis of PAS in twins is lower compared to what reported in singleton. Finally, about 30% of women with a twin pregnancy complicated by PAS required blood transfusion and hysterectomy.

Aspirin for prevention of preeclampsia and adverse perinatal outcome in twin pregnancies: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate the potential role of aspirin in reducing the risk of preeclampsia and adverse maternal and perinatal outcomes in twin pregnancies. DATA SOURCES: Medline, Embase, Google Scholar, Cochrane, and ClinicalTrial.gov databases were searched. STUDY ELIGIBILITY CRITERIA: The search and selection criteria were restricted to the English language. METHODS: The primary outcome was the incidence of preeclampsia. The secondary outcomes included gestational hypertension; fetal growth restriction; preterm birth, either spontaneous or iatrogenic, before 34 weeks of gestation; gestational age at birth; neonatal birthweight; and adverse events secondary to the administration of aspirin, including antepartum and postpartum hemorrhage. In addition, subgroup analyses according to chorionicity (dichorionic vs monochorionic), aspirin dose, and gestational age at administration of aspirin (<16 vs ≥16 weeks of gestation) and considering only studies with a daily aspirin dose of ≥100 mg/d were performed. Head-to-head meta-analyses reporting results as summary odds ratios and mean differences were used to analyze categorical and continuous variables, respectively. Quality assessment for randomized controlled trials was independently performed by 2 researchers based on the risk of bias that was assessed using the revised Cochrane risk-of-bias tool for randomized trials. The conclusion of the meta-analysis on the primary outcome was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation. RESULTS: Overall, 9 studies (2273 twin pregnancies) were included. When considering all studies, the risk of preeclampsia was lower in twin pregnancies treated with aspirin than in those not treated with aspirin (odds ratio, 0.64; 95% confidence interval, 0.48-0.85; P=.003), although there was no significant difference in the risk of gestational hypertension (P=.987), fetal growth restriction (P=.9), or adverse maternal and perinatal events (P=.9) in twin pregnancies treated with aspirin compared with those not treated with aspirin. There was no significant difference in the gestational age at birth (P=.2) and neonatal birthweight (P=.06) between women receiving aspirin and those not receiving aspirin. When considering only studies with an aspirin dose of >100 mg/d, the risk of preeclampsia (odds ratio, 0.45; 95% confidence interval, 0.23-0.86; P=.02) was significantly lower in pregnancies receiving aspirin than in those not receiving aspirin, Conversely, there was no significant difference in the risk of gestational hypertension (P=.20), fetal growth restriction (P=.1), gestational age at birth (P=.06), and neonatal weight (P=.05) between the 2 groups. Furthermore, there was no significant difference in the risk of preeclampsia when considering only studies with an aspirin dose of >80 mg/d (P=.611). The association between the administration of aspirin and preeclampsia persisted when considering an aspirin dose of >100 mg/day or when the medication was started before 16 weeks of gestation. The overall quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation assessment was low. CONCLUSION: The administration of aspirin in women with twin pregnancies reduced the risk of preeclampsia. The findings from this study highlighted the need for randomized controlled trials elucidating the actual role of aspirin in affecting maternal and perinatal outcomes in twin pregnancies.

Extracellular Vesicles in pregnancy: Their potential role as a liquid biopsy.

OBJECTIVE: Extracellular Vesicles (EVs) are cell-derived particles released during different pathophysiological processes, circulating in many body fluids and mediating the inter-cellular crosstalk. We have analyzed, for the first time, different EV phenotypes and concentrations in the peripheral blood of uncomplicated pregnant women. STUDY DESIGN: In this prospective case-control study, uncomplicated singleton pregnant women at term (N = 59) and aged matched non-pregnant women (N = 21) were enrolled. Freshly drowned peripheral blood samples were stained for flow cytometry analyses of EVs. RESULTS: EVs derived from platelets, leukocytes, endothelial and epithelial cells were identified and counted. Platelet-derived EVs were higher in pregnant compared to non-pregnant women, both in terms of absolute counts (2064.4 ± 1156.3 vs 701.1 ± 378.8; p < 0.0001) and percentages (27.6 ± 17.2 vs 10.7 ± 5.9; p < 0.0001). The opposite pattern was observed both for concentrations of endothelial-EV counts (525.8 ± 499.6 vs 844.7 ± 652.9; p = 0.007) and percentages (6.1 ± 5.5 vs 11.8 ± 8.0; p < 0.0001) and leukocyte-derived EV percentages (10.2 ± 7.4 vs 17.9 ± 11.2; p = 0.002) EVs. CONCLUSIONS: Uncomplicated pregnancies are characterized by a specific EV signature. These cell-derived particles may therefore represent promising biomarkers of different pathological conditions complicating pregnancies, such as preeclampsia or preterm birth.

Systematic review and critical evaluation of quality of clinical practice guidelines on the management of SARS-CoV-2 infection in pregnancy.

OBJECTIVE: To systematically identify and critically assess the quality of clinical practice guidelines for the management of SARS-CoV-2 infection in pregnancy. DATA SOURCES: Medline, Scopus, and ISI Web of Science databases were searched until February 15, 2022. STUDY ELIGIBILITY CRITERIA: Inclusion criteria were clinical practice guidelines on the management of SARS-CoV-2 infection in pregnancy. The risk of bias and quality assessments of the included clinical practice guidelines were performed using the Appraisal of Guidelines for REsearch and Evaluation II tool, which is considered the gold standard for quality assessment of clinical practice guidelines. To define a clinical practice guideline as of good quality, we adopted the cutoff score proposed by Amer et al: if the overall clinical practice guideline score was >60%, it was recommended. METHODS: The following clinical points related to the management of pregnant women with SARS-CoV-2 infection were addressed: criteria for maternal hospitalization, recommendations for follow-up fetal growth scan, specific recommendations against invasive procedures, management of labor, timing of delivery, postpartum care, and vaccination strategy. RESULTS: A total of 28 clinical practice guidelines were included. All recommended hospitalization only for severe disease; 46.1% (6/13) suggested a fetal growth scan after SARS-CoV-2 infection, whereas 23.1% (3/13) did not support this practice. Thromboprophylaxis with low-molecular-weight heparin was recommended in symptomatic women by 77.1% (7/9) of the clinical practice guidelines. None of the guidelines recommended administering corticosteroids only for the presence of SARS-CoV-2 infection in preterm gestation, unless specific obstetrical indication exists. Elective induction of labor from 39 weeks of gestation was suggested by 18.1% (2/11) of the clinical practice guidelines included in the present review, whereas 45.4% (5/11) did not recommend elective induction unless other obstetrical indications coexisted. There were 27% (3/11) of clinical practice guidelines that suggested shortening of the second stage of labor, and active pushing was supported by 18.1% (2/11). There was general agreement among the clinical practice guidelines in not recommending cesarean delivery only for the presence of maternal infection and in recommending vaccine boosters at least 6 months after the primary series of vaccination. The Appraisal of Guidelines for REsearch and Evaluation II standardized domain scores for the first overall assessment of clinical practice guidelines had a mean of 50% (standard deviation±21.82%), and 9 clinical practice guidelines scored >60%. CONCLUSION: A significant heterogeneity was found in some of the main aspects of the management of SARS-CoV-2 infection in pregnancy, as reported by the published clinical practice guidelines.

Reproductive and pregnancy outcomes of fertility-sparing treatments for early-stage endometrial cancer or atypical hyperplasia: A systematic review and meta-analysis.

OBJECTIVE: To report the pregnancy outcomes of women with prior endometrial cancer and endometrial hyperplasia managed with fertility-sparing treatments. METHODS: Medline and Embase databases were searched. Inclusion criteria were studies reporting the pregnancy outcomes of women who had undergone fertility-sparing treatments for endometrial hyperplasia or early endometrioid endometrial cancer. Outcomes explored were pregnancy, miscarriage and livebirth rates according to the type of progestin treatment used. Subgroup analyses according to the type of diagnostic follow-up were also performed. Meta-analyses of proportions using a random effects model were used to combine data. RESULTS: Twenty-nine studies (1036 women) were included, and 82.8% [95% confidence interval (CI) 72.3-91.2] of women achieved complete remission. Pregnancy rates were 56.3% (95% CI 41.6-70.5) with megestrol (MA) or medroxyprogesterone acetate (MPA), 63.1% (95% CI 37.0-85.6) with levonorgestrel-releasing intrauterine device (LNG-IUD), 57.9% (95% CI 37.7-76.8) with MA or MPA and metformin, 59.8% (95% CI 48.3-70.7) with MPA and LNG-IUD, 15.4% (95% CI 4.3-42.2) with gonadotropin-releasing hormone analogue (GnRHa) combined with LNG-IUD or letrozole, and 40.7% (95% CI 24.5-59.3) with LNG-IUD and GnRHa. Miscarriage rates were 17.4% (95% CI 12.2-23.4), 14.3% (95% CI 6.4-24.7), 57.9% (95% CI 37.7-76.8), 26.9% (95% CI 14.6-39.3), 100% (95% CI 34.0-100) and 18.2% (95% CI 5.1-47.7), respectively, and livebirth rates were 68.8% (95% CI 56.0-80.3), 80.8% (95% CI 69.5-90.0), 69.9% (95% CI 56.1-82.0), 25.97 (95% CI 14.6-39.3), 0% (95% CI 0-66.0) and 81.8% (95% CI 52.3-94.8), respectively. Finally, stratifying the analysis considering the endometrial sampling method alone, the pregnancy rate was 68.6% (95% CI 51.2-83.6; 10 studies, I2 = 83.5%) in women who underwent hysteroscopy and 60.5% (95% CI 53.4-67.5; 13 studies, I2 = 39.8%) in women managed with dilatation and curettage biopsy; the miscarriage and livebirth rates were 13.2% (95% CI 8.0-19.5; I2 = 0%) and 81.2% (95% CI 67.4-91.8; I2 = 67.3%), respectively, for hysteroscopy, and 25.2% (95% CI 17.8-33.3; I2 = 15.5%) and 67.5% (95% CI 58.8-75.5; I2 = 0%), respectively, for dilatation and curettage biopsy. CONCLUSION: Fertility-sparing treatment in women with endometrial cancer or hyperplasia is associated with an overall good response to therapy, good chance of achieving pregnancy and a good livebirth rate. Diagnostic follow-up with hysteroscopy was associated with a higher pregnancy rate, although this requires confirmation in adequately powered randomized trials.

Methodological Quality of Fetal Brain Structure Charts for Screening Examination and Targeted Neurosonography: A Systematic Review.

INTRODUCTION: Several fetal brain charts have been published in the literature and are commonly used in the daily clinical practice. However, the methodological quality of these charts has not been critically appraised. MATERIAL AND METHODS: MEDLINE, EMBASE, CINAHL, and the Web of Science databases were searched electronically up to December 31, 2020. The primary outcome was to evaluate the methodology of the studies assessing the growth of fetal brain structures throughout gestation. A list of 28 methodological quality criteria divided into three domains according to "study design," "statistical and reporting methods," and "specific relevant neurosonography aspects" was developed in order to assess the methodological appropriateness of the included studies. The overall quality score was defined as the sum of low risk of bias marks, with the range of possible scores being 0-28. This quality assessment was applied to each individual study reporting reference ranges for fetal brain structures. Furthermore, we performed a subgroup analysis according to the different brain structures (ventricular and periventricular, fore-brain and midbrain cerebral and posterior fossa). RESULTS: Sixty studies were included in the systematic review. The overall mean quality score of the studies included in this review was 51.3%. When focusing on each of the assessed domains, the mean quality score was 53.7% for "study design," 54.2% for "statistical and reporting methods," and 38.6% for "specific relevant neurosonography aspects." The sample size calculation, the correlation with a postnatal imaging evaluation, and the whole fetal brain assessment were the items at the highest risk of bias for each domain assessed, respectively. The subgroup analysis according to different anatomical location showed the lowest quality score for ventricular and periventricular structures and the highest for cortical structures. CONCLUSIONS: Most previously published studies reporting fetal brain charts suffer from poor methodology and are at high risk of biases, mostly when focusing on neurosonography issues. Further prospective longitudinal studies aiming at constructing specific growth charts for fetal brain structures should follow rigorous methodology to minimize the risk of biases, guarantee higher levels of reproducibility, and improve the standard of care.

Placenta accreta spectrum disorders in twin pregnancies as an under reported clinical entity: a case series and systematic review.

Recent reports suggested a potential association between twin pregnancy and the occurrence of placenta accreta spectrum (PAS) disorders. Despite this, scarce data on PAS disorders in twins has been reported in the published literature. We present a series of twelve twin pregnancies complicated by PAS from two large institutions over 5 years. A systematic review of the literature was also conducted in order to find studies reporting on the risk factors, prenatal diagnosis using ultrasound and clinical outcomes of PAS in twin pregnancies.

Prenatal risk factors for urgent atrial septostomy at birth in fetuses with transposition of the great arteries: a systematic review and meta-analysis.

MATERIAL AND METHODS: Medline, Embase, and Cochrane databases were searched. The primary aim was to explore the differences in prenatal echocardiographic parameters among fetuses diagnosed with TGA that required urgent BAS within 24 h of birth due to life-threatening cyanosis compared to those who did not require such procedure. Random-effect meta-analyses were used to compute the data. RESULTS: Six studies (292 fetuses) were included. Restrictive appearance of the FO was present in 64.5% (95% CI = 39.8-85.7) of fetuses with TGA requiring BAS at birth compared to 7.9% (95% CI = 2.1-16.8) not requiring such procedure (OR = 71.1; 95% CI = 8.3-608.5, p < .0001). Hypermobile appearance of the atrial septum was present in 39.1% (95% CI = 26.4-56.5) of fetuses requiring BAS at birth compared to 9.8% (95% CI = 1.4-24.3) of those which did (OR 3.6; 95% CI = 1.4-9.0, p = .05). There was no difference in the prevalence of redundant (p = .374) or fixed (p = .051) atrial septum, bidirectional flow in the DA (p = .26) or an abnormal size of the DA (p = .06) in fetuses requiring urgent BAS at birth compared to those which did not. Mean (±SD) size of the right atrium was smaller in the fetuses with TGA undergoing urgent BAS at birth (23.4 ± 6.7) compared to those which did not (29.2 ± 6.2, p = .01). The mean (±SD) ratio between the FO and the aortic valve diameters (1.01 ± 0.41 versus 1.41 ± 0.43, p = .009) and the mean (±SD) ratio between the FO diameter and the septal length (0.36 ± 0.13 versus 0.51 ± 0.14, p = .001) were significantly smaller in fetuses requiring compared to those not undergoing urgent BAS at birth. The diagnostic accuracy of each independent ultrasound marker of the need for urgent BAS showed an overall good specificity but a low sensitivity. CONCLUSION: Fetal echocardiography prior to birth can stratify the risk of BAS in fetuses with TGA. Further studies are needed to validate these findings and build individualized multiparametric predictive models in order to more accurately identify those fetuses with TGA at a higher risk of urgent BAS after birth.

Neonatal Morbidity of Monoamniotic Twin Pregnancies: A Systematic Review and Meta-analysis.

OBJECTIVE: This study was aimed to report the incidence of neonatal morbidity in monochorionic monoamniotic (MCMA) twin pregnancies according to gestational age at birth and type of management adopted (inpatient or outpatient). STUDY DESIGN: Medline and Embase databases were searched. Inclusion criteria were nonanomalous MCMA twins. The primary outcome was a composite score of neonatal morbidity, defined as the occurrence of at least one of the following outcomes: respiratory morbidity, overall neurological morbidity, severe neurological morbidity, and infectious morbidity, necrotizing enterocolitis at different gestational age windows (24-30, 31-32, 33-34, and 35-36 weeks). Secondary outcomes were the individual components of the primary outcome and admission to neonatal intensive care unit (NICU). Subanalysis according to the type of surveillance strategy (inpatient compared with outpatient) was also performed. Random effect meta-analyses were used to analyze the data. RESULTS: A total of 14 studies including 685 MCMA twin pregnancies without fetal anomalies were included. At 24 to 30, 31 to 32, 33 to 34, and 35 to 36 weeks of gestation, the rate of composite morbidity was 75.4, 65.5, 37.6, and 18.5%, respectively, the rate of respiratory morbidity was 74.2, 59.1, 35.5, and 12.2%, respectively, while overall neurological morbidity occurred in 15.3, 10.2, 4.3, and 0% of the cases, respectively. Infectious morbidity complicated 13, 4.2, 3.1, and 0% of newborns while 92.1, 81.6, 58.7, and 0% of cases required admission to NICU. Morbidity in pregnancies delivered between 35 and 36 weeks of gestation was affected by the very small sample size of cases included. When comparing the occurrence of overall morbidity according to the type of management (inpatient or outpatient), there was no difference between the two surveillance strategies (p = 0.114). CONCLUSION: MCMA pregnancies are at high risk of composite neonatal morbidity, mainly respiratory morbidity that gradually decreases with increasing gestational age at delivery with a significant reduction for pregnancies delivered between 33 and 34 weeks. We found no difference in the occurrence of neonatal morbidity between pregnancies managed as inpatient or outpatient. KEY POINTS: · MCMA pregnancies are at high risk of composite neonatal morbidity, mainly respiratory morbidity.. · Neonatal morbidity gradually decreases with increasing GA at delivery, mostly between 33 and 34 weeks.. · There is no difference in the occurrence of neonatal morbidity between in- or outpatient management..

Pre- and postnatal brain hemodynamics in pregnancies at term: correlation with Doppler ultrasound, birthweight, and adverse perinatal outcome.

PURPOSE: To elucidate the correlation between pre- and postnatal cerebral Doppler in pregnancies close to term and to explore whether they are associated with perinatal outcome. MATERIALS AND METHODS: Prospective study on singleton pregnancies at 36-37 weeks of gestation. The primary outcome was a composite score of perinatal morbidity, while secondary outcomes were adverse intra-partum outcome and abnormal acid-base status. All pregnancies underwent ultrasound assessment of umbilical artery (UA), middle cerebral artery (MCA), uterine arteries (UtAs) pulsatility index (PI), and cerebroplacental ratio (CPR). At birth, neonatal MCA PI was measured 72 h from delivery and correlated with prenatal Doppler, primary and secondary outcomes. Fisher's test and multivariate logistic regression analysis were used to analyze the data. RESULTS: One hundred and sixty-six fetuses with both pre- and postnatal Doppler assessment of the MCA were included in the study. The risk of composite perinatal morbidity was higher in fetuses (OR: 5.7, 95% CI 2.2-14.6) and newborns (OR: 4.1, 95% CI 1.8-9.6) with fetal MCA PI < 10th centile. Likewise, the incidence of abnormal acid-base status was higher both in fetuses (20 versus 4.2%, p = .026) and newborns (17.1 versus 3.2%, p = .001) with a low MCA PI before and at birth, respectively. At logistic regression analysis, fetal and neonatal MCAPI were independently associated with composite perinatal morbidity and abnormal acid-base status, but not with adverse intra-partum outcome. In small for gestational age (SGA) fetuses, the incidence of composite perinatal morbidity was higher in fetuses and new-borns presenting compared to those not presenting with an MCA PI < 10th centile (61.5 versus 20%, p = .003 and 52.6% versus 7.1%, p = .008, respectively), while such association was lost when considering non-SGA fetuses. CONCLUSION: A low MCA PI is associated with adverse perinatal outcome in pregnancies at term and tends to persist after birth.

Ovarian hyperstimulation syndrome and adverse pregnancy outcome.

INTRODUCTION: The aim of this study was to investigate the association between ovarian hyperstimulation syndrome (OHSS) and adverse pregnancy outcome. EVIDENCE ACQUISITION: Medline, Embase and Cochrane databases were searched. The primary outcome was a composite score of adverse maternal outcome including either preterm birth (PTB), gestational diabetes mellitus (GDM), pre-eclampsia (PE) or pregnancy induced hypertension, intrahepatic cholestasis of pregnancy, thromboembolic events or need for caesarean section (CS). Secondary outcomes were a composite score of adverse fetal outcome including either miscarriage, low birthweight, fetal anomalies or intrauterine fetal death (IUD) and the individual components of both primary and secondary outcomes. EVIDENCE SYNTHESIS: Thirteen studies (3303 ART pregnancies with and 89,720 without OHSS) were included. The risk of composite adverse maternal outcome (RR: 8.8, 95% CI: 8.1-9.5) was higher in women with compared to those without OHSS. The association between OHSS and adverse pregnancy outcome was mainly due to the higher risk of PTB (RR: 11.4, 95% CI: 10.5-12.4), while there was no difference in the risk of others primary outcome. Likewise, the risk of composite fetal outcome was higher in pregnancies with a prior OHSS (RR: 1.5, 95% CI: 1.1-2.0). The strength of association between OHSS and composite adverse maternal outcome persisted when considering singleton pregnancies or those with severe disease. CONCLUSIONS: Pregnancies complicated by OHSS are at high risk of adverse pregnancy outcome, especially PTB.

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

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.