Consensus protocol for management of early and late twin-twin transfusion syndrome: Delphi study.

OBJECTIVE: Fetoscopic laser photocoagulation (FLP) is a well-established treatment for twin-twin transfusion syndrome (TTTS) between 16 and 26 weeks' gestation. High-quality evidence and guidelines regarding the optimal clinical management of very early (prior to 16 weeks), early (between 16 and 18 weeks) and late (after 26 weeks) TTTS are lacking. The aim of this study was to construct a structured expert-based clinical consensus for the management of early and late TTTS. METHODS: A Delphi procedure was conducted among an international panel of experts. Participants were chosen based on their clinical expertise, affiliation and relevant publications. A four-round Delphi survey was conducted using an online platform and responses were collected anonymously. In the first round, a core group of experts was asked to answer open-ended questions regarding the indications, timing and modes of treatment for early and late TTTS. In the second and third rounds, participants were asked to grade each statement on a Likert scale (1, completely disagree; 5, completely agree) and to add any suggestions or modifications. At the end of each round, the median score for each statement was calculated. Statements with a median grade of 5 without suggestions for change were accepted as the consensus. Statements with a median grade of 3 or less were excluded from the Delphi process. Statements with a median grade of 4 were modified according to suggestions and reconsidered in the next round. In the last round, participants were asked to agree or disagree with the statements, and those with more than 70% agreement without suggestions for change were considered the consensus. RESULTS: A total of 122 experts met the inclusion criteria and were invited to participate, of whom 53 (43.4%) agreed to take part in the study. Of those, 75.5% completed all four rounds. A consensus on the optimal management of early and late TTTS was obtained. FLP can be offered as early as 15 weeks' gestation for selected cases, and can be considered up to 28 weeks. Between 16 and 18 weeks, management should be tailored according to Doppler findings. CONCLUSIONS: A consensus-based treatment protocol for early and late TTTS was agreed upon by a panel of experts. This protocol should be modified at the discretion of the operator, according to their experience and the specific demands of each case. This should advance the quality of future studies, guide clinical practice and improve patient care. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Presurgery motor level assessment for prediction of motor level at birth in fetuses undergoing prenatal repair of open spina bifida: time to abandon anatomical level in counseling.

OBJECTIVES: First, to investigate the correlation between prenatal presurgery anatomical and motor levels of the lesion with motor level at birth in cases undergoing prenatal repair of open spina bifida and, second, to identify factors leading to a loss of two or more motor levels between the presurgery and postnatal assessments. METHODS: This was an observational study of singleton pregnancies undergoing prenatal repair of open spina bifida, conducted between March 2011 and May 2022. All fetuses underwent an ultrasound assessment at 20-24 weeks of gestation to determine the motor and anatomical levels of the lesion before surgery. The anatomical level of the lesion was defined as the highest open posterior vertebral arch. The motor level was determined by systematic observation of the lower limb movements and was defined as the most distal active muscle present. Prenatal repair was performed at 23-26 weeks. At birth, motor level was assessed by a rehabilitation specialist by physical examination. Cases of intrauterine death or termination of pregnancy and those delivered at other sites were excluded from the neonatal assessment. The agreement between presurgery motor level and motor level at birth, and between presurgery anatomical level and motor level at birth, was assessed using the weighted kappa index (wκ). Logistic regression analysis was used to assess factors leading to a loss of two or more motor levels between the presurgery and postnatal assessments. RESULTS: Presurgery motor and anatomical levels were assessed in 61 fetuses at a median gestational age of 22.7 (interquartile range (IQR), 21.6-24.4) weeks. Prenatal repair was performed at a median gestational age of 24.6 (IQR, 23.7-25.7) weeks. Motor level at birth was assessed in 52 neonates after exclusion of nine fetuses due to loss to follow-up or fetal loss. There was moderate agreement between presurgery motor level and motor level at birth (wκ = 0.42; 95% CI, 0.21-0.63), with a median difference of 0 (IQR, -2 to 9) levels. Factors leading to a loss of two or more motor levels between the presurgery ultrasound assessment and postnatal examination were higher presurgery anatomical level (odds ratio (OR), 0.59 (95% CI, 0.35-0.98); P = 0.04) and larger difference between the anatomical and motor levels before surgery (OR, 1.85 (95% CI, 1.12-3.06); P = 0.017). None of the other ultrasound, surgery-related or neonatal variables assessed was associated significantly with a loss of two or more motor levels. There was slight agreement between the presurgery anatomical level of the lesion and motor level at birth (wκ = 0.07; 95% CI, -0.02 to 0.15). CONCLUSIONS: There is moderate agreement between fetal motor level of the lesion before prenatal repair of open spina bifida and motor level at birth, as opposed to only slight agreement between presurgery anatomical level and motor level at birth. A loss of two or more motor levels between the presurgery and postnatal assessments is associated with a higher presurgery anatomical level and with a larger difference between the presurgery anatomical and motor levels. Consequently, motor level, rather than the anatomical level, should be used for prenatal counseling. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Perinatal outcome of monochorionic triamniotic triplet pregnancy: multicenter cohort study.

OBJECTIVE: Monochorionic (MC) triplet pregnancies are extremely rare and information on these pregnancies and their complications is limited. We aimed to investigate the risk of early and late pregnancy complications, perinatal outcome and the timing and methods of fetal intervention in these pregnancies. METHODS: This was a multicenter retrospective cohort study of MC triamniotic (TA) triplet pregnancies managed in 21 participating centers around the world from 2007 onwards. Data on maternal age, mode of conception, diagnosis of major fetal structural anomalies or aneuploidy, gestational age (GA) at diagnosis of anomalies, twin-to-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), twin reversed arterial perfusion (TRAP) sequence and or selective fetal growth restriction (sFGR) were retrieved from patient records. Data on antenatal interventions were collected, including data on selective fetal reduction (three to two or three to one), laser surgery and any other active fetal intervention (including amniodrainage). Data on perinatal outcome were collected, including numbers of live birth, intrauterine demise, neonatal death, perinatal death and termination of fetus or pregnancy (TOP). Neonatal data such as GA at birth, birth weight, admission to neonatal intensive care unit and neonatal morbidity were also collected. Perinatal outcomes were assessed according to whether the pregnancy was managed expectantly or underwent fetal intervention. RESULTS: Of an initial cohort of 174 MCTA triplet pregnancies, 11 underwent early TOP, three had an early miscarriage, six were lost to follow-up and one was ongoing at the time of writing. Thus, the study cohort included 153 pregnancies, of which the majority (92.8%) were managed expectantly. The incidence of pregnancy affected by one or more fetal structural abnormality was 13.7% (21/153) and that of TRAP sequence was 5.2% (8/153). The most common antenatal complication related to chorionicity was TTTS, which affected just over one quarter (27.6%; 42/152, after removing a pregnancy with TOP < 24 weeks for fetal anomalies) of the pregnancies, followed by sFGR (16.4%; 25/152), while TAPS (spontaneous or post TTTS with or without laser treatment) occurred in only 4.6% (7/152) of pregnancies. No monochorionicity-related antenatal complication was recorded in 49.3% (75/152) of pregnancies. Survival was apparently associated largely with the development of these complications: there was at least one survivor beyond the neonatal period in 85.1% (57/67) of pregnancies without antenatal complications, in 100% (25/25) of those complicated by sFGR and in 47.6% (20/42) of those complicated by TTTS. The overall rate of preterm birth prior to 28 weeks was 14.5% (18/124) and that prior to 32 weeks' gestation was 49.2% (61/124). CONCLUSION: Monochorionicity-related complications, which can impact adversely perinatal outcome, occur in almost half of MCTA triplet pregnancies, creating a challenge with regard to counseling, surveillance and management. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

PlanExp: intuitive integration of complex RNA-seq datasets with planarian omics resources.

MOTIVATION: There is an increasing amount of transcriptomic and genomic data available for planarians with the advent of both traditional and single-cell RNA sequencing technologies. Therefore, exploring, visualizing and making sense of all these data in order to understand planarian regeneration and development can be challenging. RESULTS: In this work, we present PlanExp, a web-application to explore and visualize gene expression data from different RNA-seq experiments (both traditional and single-cell RNA-seq) for the planaria Schmidtea mediterranea. PlanExp provides tools for creating different interactive plots, such as heatmaps, scatterplots, etc. and links them with the current sequence annotations both at the genome and the transcript level thanks to its integration with the PlanNET web application. PlanExp also provides a full gene/protein network editor, a prediction of genetic interactions from single-cell RNA-seq data, and a network expression mapper that will help researchers to close the gap between systems biology and planarian regeneration. AVAILABILITY AND IMPLEMENTATION: PlanExp is freely available at https://compgen.bio.ub.edu/PlanNET/planexp. The source code is available at https://compgen.bio.ub.edu/PlanNET/downloads. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Diagnostic accuracy of first-trimester combined screening for early-onset and preterm pre-eclampsia at 8-10 compared with 11-13 weeks' gestation.

OBJECTIVES: To compare the ability of first-trimester combined screening for pre-eclampsia (PE) to predict early-onset and preterm PE when pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) were assessed before vs after 11 weeks' gestation. METHODS: This was a secondary analysis of a prospective cohort study of singleton pregnancies undergoing routine first-trimester screening conducted at Vall d'Hebron University Hospital, Barcelona, Spain, between October 2015 and September 2017. Demographic characteristics, obstetric history, maternal history and biophysical markers (mean uterine artery pulsatility index and mean arterial blood pressure (MAP)) were recorded at the first-trimester scan (at 11 + 0 to 13 + 6 weeks' gestation). Maternal serum concentrations of PAPP-A and PlGF were assessed from the routine first-trimester blood test (at 8 + 0 to 13 + 6 weeks). Women were classified into two groups depending on whether serum biomarkers were assessed at 8 + 0 to 10 + 6 weeks or at 11 + 0 to 13 + 6 weeks. Probability scores for early-onset and preterm PE were calculated by using two different algorithms: the multivariate Gaussian-distribution model and The Fetal Medicine Foundation (FMF) competing-risks model. Receiver-operating-characteristics (ROC) curves were produced and detection rates at fixed 5% and 10% false-positive rates were computed to compare the performance of these algorithms when PAPP-A and PlGF were assessed before vs after 11 weeks. RESULTS: Of the 2641 women included, serum biomarkers were assessed before 11 weeks in 1675 (63.4%) and at or after 11 weeks in 966 (36.6%). Of these, 90 (3.4%) women developed PE, including 11 (0.4%) cases of early-onset PE and 30 (1.1%) of preterm PE. Five (45.5%) cases of early-onset and 16 (53.3%) of preterm PE were identified in the group in which serum biomarkers were assessed at 8 + 0 to 10 + 6 weeks and six (54.5%) cases of early-onset and 14 (46.7%) of preterm PE in the group in which serum biomarkers were assessed at 11 + 0 to 13 + 6 weeks. In the prediction of early-onset and preterm PE using the Gaussian algorithm, no differences were observed between the areas under the ROC curves (AUCs) when PAPP-A and PlGF were measured before or after 11 weeks. In the prediction of early-onset and preterm PE using the FMF algorithm, no differences were observed between AUCs for any of the combinations used for risk calculation when the serum biomarkers were obtained before vs after 11 weeks, except for the combination of PAPP-A and MAP, which showed a greater AUC for the prediction of early-onset PE when PAPP-A was measured at or after 11 weeks. CONCLUSIONS: The prediction of early-onset and preterm PE is similar when serum biomarkers are measured before or after 11 weeks. This allows the use of a two-step approach for PE risk assessment that permits immediate risk calculation at the time of the first-trimester scan. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Pre-eclampsia-like syndrome induced by severe COVID-19: a prospective observational study.

OBJECTIVES: To investigate the incidence of clinical, ultrasonographic and biochemical findings related to pre-eclampsia (PE) in pregnancies with COVID-19, and to assess their accuracy to differentiate between PE and the PE-like features associated with COVID-19. DESIGN: A prospective, observational study. SETTING: Tertiary referral hospital. PARTICIPANTS: Singleton pregnancies with COVID-19 at >20+0  weeks. METHODS: Forty-two consecutive pregnancies were recruited and classified into two groups: severe and non-severe COVID-19, according to the occurrence of severe pneumonia. Uterine artery pulsatility index (UtAPI) and angiogenic factors (soluble fms-like tyrosine kinase-1/placental growth factor [sFlt-1/PlGF]) were assessed in women with suspected PE. MAIN OUTCOME MEASURES: Incidence of signs and symptoms related to PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, abnormal UtAPI and increased sFlt-1/PlGF. RESULTS: Thirty-four cases were classified as non-severe and 8 as severe COVID-19. Five (11.9%) women presented signs and symptoms of PE, all five being among the severe COVID-19 cases (62.5%). However, abnormal sFlt-1/PlGF and UtAPI could only be demonstrated in one case. One case remained pregnant after recovery from severe pneumonia and had a spontaneous resolution of the PE-like syndrome. CONCLUSIONS: Pregnant women with severe COVID-19 can develop a PE-like syndrome that might be distinguished from actual PE by sFlt-1/PlGF, LDH and UtAPI assessment. Healthcare providers should be aware of its existence and monitor pregnancies with suspected pre-eclampsia with caution. TWEETABLE ABSTRACT: This study shows that a pre-eclampsia-like syndrome could be present in some pregnancies with severe COVID-19.

Should phenotype of previous preterm birth influence management of women with short cervix in subsequent pregnancy? Comparison of vaginal progesterone and Arabin pessary.

OBJECTIVE: To investigate whether the classification of a previous spontaneous preterm birth (sPTB) as preterm labor (PTL) with intact membranes (IM) or as preterm prelabor rupture of membranes (PPROM) impacts the efficacy of cervical pessary or vaginal progesterone for prevention of sPTB in pregnant women with short cervix on transvaginal ultrasound. METHODS: This was a retrospective cohort study of asymptomatic high-risk singleton pregnancies with a short cervix and history of sPTB, treated using Arabin pessary or vaginal progesterone for primary PTB prevention, conducted at four European hospitals. A log-rank test on Kaplan-Meier curves was used to assess the difference in performance of pessary and progesterone, according to history of PTL-IM or PPROM. Linear regression analysis was used to evaluate significant predictors of gestational age at delivery. RESULTS: Between 2008 and 2015, 170 women were treated with a pessary and 88 with vaginal progesterone. In women treated with a pessary, rate of sPTB < 34 weeks was 16% in those with a history of PTL-IM and 55% in those with a history of PPROM. In women treated with progesterone, rate of sPTB < 34 weeks was 13% in those with a history of PTL-IM and 21% in those with a history of PPROM. Treatment with a pessary resulted in earlier delivery in women with previous PPROM than in any other subgroup (P < 0.0001). Linear regression analysis showed a clear effect of PPROM history (P < 0.0001), combination of PPROM history and treatment (P = 0.0003) and cervical length (P = 0.0004) on gestational age at birth. CONCLUSIONS: Cervical pessary may be a less efficacious treatment option for women with previous PPROM; however, these results require prospective validation before change in practice is recommended. Phenotype of previous preterm birth may be an important risk predictor and treatment effect modifier; this information should be reported in future clinical trials. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Multicenter prospective clinical study to evaluate children short-term neurodevelopmental outcome in congenital heart disease (children NEURO-HEART): study protocol.

BACKGROUND: Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns. While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. METHODS: Eligible participants are women presenting at 20 to < 37 weeks of gestation carrying a fetus with CHD. Maternal/neonatal recordings are performed at regular intervals, from the fetal period to 24 months of age, and include: placental and fetal hemodynamics, fetal brain magnetic resonance imaging (MRI), functional echocardiography, cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers. Neurodevelopmental assessment is planned at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. Target recruitment is at least 150 cases classified in three groups according to three main severe CHD groups: transposition of great arteries (TGA), Tetralogy of Fallot (TOF) and Left Ventricular Outflow Tract Obstruction (LVOTO). DISCUSSION: The results of NEURO-HEART study will provide the most comprehensive knowledge until date of children's neurologic prognosis in CHD and will have the potential for developing future clinical decisive tools and improving preventive strategies in CHD. TRIAL REGISTRATION: NCT02996630 , on 4th December 2016 (retrospectively registered).

Fetoscopic two-layer closure of open neural tube defects.

OBJECTIVE: Fetoscopy for closure of open neural tube defects (NTD) remains controversial, as the use of patches or single-layer closure is not considered to meet the standards of good neurosurgical reconstruction. In this study, we describe a fetoscopic two-layer (myofascial and skin) closure technique for the treatment of NTD in five patients and report the preliminary anatomical outcome at birth. METHODS: From February to September 2017, five pregnant women with a fetus with a NTD, including three cases of myelomeningocele and two cases of myelocele, were operated on using a fetoscopic two-layer closure technique. In this technique, with the uterus exteriorized and using three 10-Fr ports, the placode is dissected from the surrounding tissue and detethered, removing the cystic tissue. The skin is undermined by blunt dissection and the defect is sutured to the midline in two layers (myofascial and skin) using a running 4/0 resorbable barbed suture. RESULTS: Median gestational age at the procedure was 24 + 3 (range, 23 + 5 to 27 + 3) weeks. Surgery was successful in all cases, without any intraoperative complications. Median time in surgery was 180 (range, 140-180) min and median time for fetoscopy was 105 (range, 65-120) min. In terms of obstetric complications, three cases of premature rupture of membranes and one case of chorioamnionitis were recorded. Median gestational age at delivery was 34 + 1 (range, 25 + 4 to 37 + 2) weeks and two patients delivered vaginally. The closed defect was watertight with good quality tissue in all cases. CONCLUSION: Fetoscopic two-layer closure of NTD may improve the quality of the tissue covering the defect, diminishing the need for postnatal surgical revision, and preserving the well-documented beneficial effects of prenatal closure on the neural tissue and hindbrain herniation. However, this technique may not be appropriate for those cases with wide diastasis of the myofascial layer or with a low quantity of available tissue. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Brain angiogenic gene expression in fetuses with congenital heart disease.

OBJECTIVE: To assess potential differences in the expression of antiangiogenic and angiogenic factors and of genes associated with chronic hypoxia in cerebral tissue of euploid fetuses with congenital heart disease (CHD) vs those without. METHODS: Cerebral tissue was obtained from 15 fetuses with CHD and 12 control fetuses that had undergone termination of pregnancy. Expression profiles of the antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), the angiogenic vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PlGF), and of genes associated with chronic hypoxia were determined by real-time polymerase chain reaction in tissue from the frontal cortex and the basal ganglia of the fetuses. RESULTS: Expression of sFlt-1 was 48% higher in the frontal cortex (P = 0.0431) and 72% higher in the basal ganglia (P = 0.0369) of CHD fetuses compared with controls. The expression of VEGF-A was 60% higher (P = 0.0432) and that of hypoxia-inducible factor 2-alpha was 98% higher (P = 0.0456) in the basal ganglia of CHD fetuses compared with controls. No significant differences were observed between the two groups in the expression of PlGF and hypoxia-inducible factor 1-alpha. CONCLUSION: An overall dysregulation of angiogenesis with a net balance towards an antiangiogenic environment was observed in the cerebral tissue of fetuses with CHD, suggesting that these fetuses may have an intrinsic angiogenic impairment that could contribute to impaired brain perfusion and abnormal neurological development later in life. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Longitudinal changes in fetal biometry and cerebroplacental hemodynamics in fetuses with congenital heart disease.

OBJECTIVES: To determine the longitudinal behavior of fetal biometric measures and cerebroplacental hemodynamics throughout gestation in fetuses with congenital heart disease (CHD). METHODS: Fetal biometry and Doppler hemodynamics (uterine artery (UtA), umbilical artery (UA) and fetal middle cerebral artery (MCA)) were measured serially in a cohort of consecutive fetuses diagnosed with CHD. Evaluations were made at various time points, from diagnosis (20-25 weeks) to delivery, with at least two measurements per fetus that were at least 2 weeks apart. Fetuses were classified into three groups according to the pattern of blood supply to the brain (placental vs systemic) that would be expected on the basis of the type of CHD. All parameters were transformed into Z-scores. A linear mixed model to analyze repeated measurements was constructed for each parameter to assess its behavior throughout gestation. RESULTS: Four hundred and forty-four ultrasound examinations were performed in 119 CHD fetuses, with a median of two measurements per fetus. The fetuses presented a small head at diagnosis (biparietal diameter (BPD) Z-score, -1.32 ± 0.99; head circumference (HC) Z-score, -0.79 ± 1.02), which remained small throughout gestation. UtA and UA pulsatility indices (PI) showed a significant increase towards the end of pregnancy, whereas no significant changes were observed in MCA-PI or cerebroplacental ratio (CPR) with gestational age. Both MCA and CPR presented significant differences in longitudinal behavior between CHD groups, while BPD and HC did not. CONCLUSIONS: CHD fetuses have a relatively small head from the second trimester of pregnancy, regardless of the type of CHD anomaly, and increasing resistance in the UtA and UA as pregnancy progresses, suggestive of increasing degree of placental impairment. Our findings indicate the early onset of mechanisms that could lead to poorer neurodevelopment later in life. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Prenatal ultrasound evaluation of segmental level of neurological lesion in fetuses with myelomeningocele: development of a new technique.

OBJECTIVES: To report our preliminary experience in the use of prenatal ultrasound examination to assess lower-limb movements in fetuses with myelomeningocele. We aimed to determine the accuracy of this method to establish the segmental level of neurological lesion, as this is the best known predictor of the future ability to walk. METHODS: This was a preliminary, observational study including fetuses with myelomeningocele operated on prenatally. The patterns of movements present and absent in the affected fetuses' lower limbs were evaluated systematically by ultrasound examination. According to the known nerve function associated with each muscle group, the segmental level of neurological lesion was established before birth. The agreement for the segmental levels assigned, between the prenatal ultrasound technique and the classical neurological clinical examination after birth (gold standard), was tested using the weighed kappa (wκ) index. RESULTS: Seventy-one fetuses with myelomeningocele were evaluated at the Hospital Universitari Vall d'Hebron. After counseling, the parents opted for prenatal surgery (26 cases), termination of pregnancy (43 cases) or postnatal repair (two cases). Five patients did not fulfil the inclusion criteria for prenatal surgery and three were excluded after birth. In the 18 fetuses that underwent surgery and were analyzed, the agreement between prenatal and postnatal segmental levels assigned was 91.7% for the right limb (wκ = 0.80) and 88.9% for the left limb (wκ = 0.73). CONCLUSIONS: The agreement found between prenatal and postnatal assignment of level of lesion in this preliminary study suggests that neurological sonographic evaluation is feasible before birth. This may provide accurate individualized information about the motor function and future ambulation prognosis of fetuses with myelomeningocele.

Do knowledge of uterine artery resistance in the second trimester and targeted surveillance improve maternal and perinatal outcome? UTOPIA study: a randomized controlled trial.

OBJECTIVES: To ascertain whether screening for pre-eclampsia (PE) and intrauterine growth restriction (IUGR) by uterine artery (UtA) Doppler in the second trimester of pregnancy and targeted surveillance improve maternal and perinatal outcomes in an unselected population. METHODS: This was a multicenter randomized open-label controlled trial. At the routine second-trimester anomaly scan, women were assigned randomly to UtA Doppler or non-Doppler groups. Women with abnormal UtA Doppler were offered intensive surveillance at high-risk clinics of the participating centers with visits every 4 weeks that included measurement of maternal blood pressure, dipstick proteinuria, fetal growth and Doppler examination. The primary outcome was a composite score for perinatal complications, defined as the presence of any of the following: PE, IUGR, spontaneous labor < 37 weeks' gestation, placental abruption, stillbirth, gestational hypertension, admission to neonatal intensive care unit and neonatal complications. Secondary outcomes were a composite score for maternal complications (disseminated intravascular coagulation, maternal mortality, postpartum hemorrhage, pulmonary edema, pulmonary embolism, sepsis), and medical interventions (for example, corticosteroid administration and induction of labor) in patients developing placenta-related complications. RESULTS: In total, 11 667 women were included in the study. Overall, PE occurred in 348 (3.0%) cases, early-onset PE in 48 (0.4%), IUGR in 722 (6.2%), early-onset IUGR in 93 (0.8%) and early-onset PE with IUGR in 32 (0.3%). UtA mean pulsatility index > 90(th) percentile was able to detect 59% of early-onset PE and 60% of early-onset IUGR with a false-positive rate of 11.1%. When perinatal and maternal data according to assigned group (UtA Doppler vs non-Doppler) were compared, no differences were found in perinatal or maternal complications. However, screened patients had more medical interventions, such as corticosteroid administration (relative risk (RR), 1.79 (95% CI, 1.4-2.3)) and induction of labor for IUGR (RR, 1.36 (95% CI, 1.07-1.72)). In women developing PE or IUGR, there was a trend towards fewer maternal complications (RR, 0.46 (95% CI, 0.19-1.11)). CONCLUSIONS: Routine second-trimester UtA Doppler ultrasound in an unselected population identifies approximately 60% of women at risk for placental complications; however, application of this screening test failed to improve short-term maternal and neonatal morbidity and mortality. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Stomach position in prediction of survival in left-sided congenital diaphragmatic hernia with or without fetoscopic endoluminal tracheal occlusion.

OBJECTIVE: To investigate the value of fetal stomach position in predicting postnatal outcome in left-sided congenital diaphragmatic hernia (CDH) with and without fetoscopic endoluminal tracheal occlusion (FETO). METHODS: This was a retrospective review of CDH cases that were expectantly managed or treated with FETO, assessed from May 2008 to October 2013, in which we graded, on a scale of 1-4, stomach position on the four-chamber view of the heart with respect to thoracic structures. Logistic regression analysis was used to investigate the effect of management center (Paris, Brussels, Barcelona, Milan), stomach grading, observed-to-expected lung area-to-head circumference ratio (O/E-LHR), gestational age at delivery, birth weight in expectantly managed CDH, gestational ages at FETO and at removal and period of tracheal occlusion, on postnatal survival in CDH cases treated with FETO. RESULTS: We identified 67 expectantly managed CDH cases and 47 CDH cases that were treated with FETO. In expectantly managed CDH, stomach position and O/E-LHR predicted postnatal survival independently. In CDH treated with FETO, stomach position and gestational age at delivery predicted postnatal survival independently. CONCLUSION: In left-sided CDH with or without FETO, stomach position is predictive of postnatal survival.

Maternal serum placental growth factor at 11-13 weeks' gestation and fetal cardiac defects.

OBJECTIVE: To investigate the relationship between fetal heart defects and maternal serum placental growth factor (PlGF), a marker of placental angiogenesis. METHODS: Maternal serum PlGF, pregnancy-associated plasma protein-A (PAPP-A) and uterine artery pulsatility index (UtA-PI) at 11-13 weeks' gestation were compared in 68 cases of isolated fetal major heart defects and 340 normal controls. Variables were converted into multiples of the median (MoM) after adjustment for gestational age, maternal age, racial origin, weight, parity and method of conception, and then compared between groups. The cardiac defects included 11 cases of obstruction of the left ventricular outflow tract (LVOT), 25 conotruncal abnormalities and 32 valve defects. RESULTS: The median PlGF-MoM in the heart defect group was lower than in controls (0.80 (interquartile range (IQR), 0.57-1.08) vs 1.00 (IQR, 0.79-1.32); P < 0.0001). Low PlGF levels were observed in the presence of conotruncal and valve defects but not in the presence of LVOT defects. There was no significant difference between the group with fetal heart defects and controls in PAPP-A-MoM (0.95 (IQR, 0.68-1.28) vs 1.01 (IQR, 0.70-1.39); P = 0.292) or UtA-PI-MoM (1.01 (IQR, 0.84-1.28) vs 0.99 (IQR, 0.80-1.20); P = 0.396). CONCLUSION: In pregnancies with isolated fetal heart defects there is evidence of impaired placental angiogenesis in the absence of impaired placental perfusion and function.

Early fetoscopic tracheal occlusion for extremely severe pulmonary hypoplasia in isolated congenital diaphragmatic hernia: preliminary results.

OBJECTIVE: To evaluate the effect of early fetoscopic tracheal occlusion (FETO) (22-24 weeks' gestation) on pulmonary response and neonatal survival in cases of extremely severe isolated congenital diaphragmatic hernia (CDH). METHODS: This was a multicenter study involving fetuses with extremely severe CDH (lung-to-head ratio < 0.70, liver herniation into the thoracic cavity and no other detectable anomalies). Between August 2010 and December 2011, eight fetuses underwent early FETO. Data were compared with nine fetuses that underwent standard FETO and 10 without fetoscopic procedure from January 2006 to July 2010. FETO was performed under maternal epidural anesthesia, supplemented with fetal intramuscular anesthesia. Fetal lung size and vascularity were evaluated by ultrasound before and every 2 weeks after FETO. Postnatal therapy was equivalent for both treated fetuses and controls. Primary outcome was infant survival to 180 days and secondary outcome was fetal pulmonary response. RESULTS: Maternal and fetal demographic characteristics and obstetric complications were similar in the three groups (P > 0.05). Infant survival rate was significantly higher in the early FETO group (62.5%) compared with the standard group (11.1%) and with controls (0%) (P < 0.01). Early FETO resulted in a significant improvement in fetal lung size and pulmonary vascularity when compared with standard FETO (P < 0.01). CONCLUSIONS: Early FETO may improve infant survival by further increases of lung size and pulmonary vascularity in cases with extremely severe pulmonary hypoplasia in isolated CDH. This study supports formal testing of the hypothesis with a randomized controlled trial.

Fetoscopic laser ablation of placental anastomoses in twin-twin transfusion syndrome using 'Solomon technique'.

OBJECTIVE: To document perinatal outcomes following use of the 'Solomon technique' in the selective photocoagulation of placental anastomoses for severe twin-twin transfusion syndrome (TTTS). METHODS: Between January 2010 and July 2012, data were collected from 102 consecutive monochorionic twin pregnancies complicated by severe TTTS that underwent fetoscopic laser ablation at four different centers. We compared outcomes between subjects that underwent selective laser coagulation using the Solomon technique (cases) and those that underwent selective laser coagulation without this procedure (controls). RESULTS: Of the 102 pregnancies examined, 26 (25.5%) underwent the Solomon technique and 76 (74.5%) did not. Of the 204 fetuses, 139 (68.1%) survived up to 30 days of age. At least one twin survived in 82 (80.4%) pregnancies and both twins survived in 57 (55.9%) pregnancies. When compared with the control group, the Solomon-technique group had a significantly higher survival rate for both twins (84.6 vs 46.1%; P < 0.01) and a higher overall neonatal survival rate (45/52 (86.5%) vs 94/152 (61.8%); P < 0.01). Use of the Solomon technique remained independently associated with dual twin survival (adjusted odds ratio (aOR), 11.35 (95% CI, 3.11-53.14); P = 0.0007) and overall neonatal survival rate (aOR, 4.65 (95% CI, 1.59-13.62); P = 0.005) on multivariable analysis. There were no cases of recurrent TTTS or twin anemia-polycythemia sequence (TAPS) in the Solomon-technique group. CONCLUSIONS: Use of the Solomon technique following selective laser coagulation of placental anastomoses appears to improve twin survival and may reduce the risk of recurrent TTTS and TAPS. Our data support the idea of performing a randomized controlled trial to evaluate the effectiveness of the Solomon technique.