Predictors of fetal death, neonatal survival and neurological outcomes in severe twin-twin transfusion syndrome treated by laser ablation of placental vessels.

OBJECTIVES: To identify predictors of outcomes in severe twin oligo-polyhydramnios sequence (TOPS) with or without twin anemia-polycythemia sequence (TAPS) and/or selective fetal growth restriction (SFGR) treated by laser ablation of placental vessels (LAPV). METHODS: Analysis of cases treated from 2011 to 2022. Variables evaluated Prenatal predictors: stages of TOPS, presence of TAPS and/or SFGR; pre-LAPV fetal ultrasound parameters; peri-LAPV variables. Perinatal predictors: GA at birth; birthweight; Apgar scores; transfontanellar ultrasonography (TFUS). OUTCOME VARIABLES: fetal death, neonatal survival, infant's neurodevelopment. Binary logistic regression analyses were performed to detect predictors of outcomes. RESULTS: 265 cases were included. Predictors of post-LAPV donor fetus' death were delta EFW (p:0.045) and absent/reverse end-diastolic flow in the umbilical artery (AREDF-UA) (p < 0.001). The predictor of post-LAPV recipient fetus' death was hydrops (p:0.009). Predictors of neonatal survival were GA at birth and Apgar scores. Predictors of infant's neurodevelopment were TFUS and pre-LAPV middle cerebral artery Doppler (MCAD) for the donor twin; and pre-LAPV ductus venosus' flow and MCAD for the recipient twin. CONCLUSIONS: Prediction of fetal death, neonatal survival and infant's neurodevelopment is possible in cases of TOPS associated or not with SFGR and/or TAPS that were treated by LAPV.

Learning-based keypoint registration for fetoscopic mosaicking.

PURPOSE: In twin-to-twin transfusion syndrome (TTTS), abnormal vascular anastomoses in the monochorionic placenta can produce uneven blood flow between the two fetuses. In the current practice, TTTS is treated surgically by closing abnormal anastomoses using laser ablation. This surgery is minimally invasive and relies on fetoscopy. Limited field of view makes anastomosis identification a challenging task for the surgeon. METHODS: To tackle this challenge, we propose a learning-based framework for in vivo fetoscopy frame registration for field-of-view expansion. The novelties of this framework rely on a learning-based keypoint proposal network and an encoding strategy to filter (i) irrelevant keypoints based on fetoscopic semantic image segmentation and (ii) inconsistent homographies. RESULTS: We validate our framework on a dataset of six intraoperative sequences from six TTTS surgeries from six different women against the most recent state-of-the-art algorithm, which relies on the segmentation of placenta vessels. CONCLUSION: The proposed framework achieves higher performance compared to the state of the art, paving the way for robust mosaicking to provide surgeons with context awareness during TTTS surgery.

Topographical Systematization of Human Placenta Model for Training in Microneurosurgery.

BACKGROUND: Neurosurgical training continuously seeks innovative methods to enhance the acquisition of essential technical skills for neurosurgeons worldwide. While various training models have been employed, few truly replicate real-life conditions optimally. Human placenta is a good model for neurosurgical microsurgery training due to its anatomic similarities to neurovascular structures. Placental vessels exhibit a branching pattern and caliber comparable with intracranial vessels, making them suitable for practicing microsurgical techniques. The study aims to delineate the anatomic zones of the placenta and propose a segmented training model, resulting in a reproducible, cost-effective, and realistic neurosurgical microsurgery training environment. METHODS: Twenty human placentas were meticulously prepared, injected with dyes, and categorized into zones on the basis of anatomic features. Measurements of placental vessels were recorded and compared with cerebral vessels. The placenta was divided into 4 quadrants to facilitate specific training techniques. RESULTS: Our results revealed varying vessel diameters across placental zones, closely resembling cerebral vessels. Different microsurgical techniques were applied to specific placental zones, thereby optimizing training scenarios. The applicability section described exercises such as membrane dissection, vessel skeletonization, aneurysm creation, vascular bypass, and tumor dissection within the placental model, providing detailed guidance on the zones suitable for each exercise. CONCLUSIONS: Human placenta serves as an effective microsurgical training model for neurosurgery, enhancing neurosurgeons' skills through anatomic segmentation. Integrating this model into training programs can significantly contribute to skill acquisition and improved surgical outcomes. Further research is warranted to refine and expand its utilization, complemented by clinical experiences and other simulation tools.

Placental Findings in Infants Gestational Age < 34 Weeks and Impact on Short-Term Outcomes.

AIM: To analyse placental changes in infants' gestational age < 34 weeks and its correlation to short-term respiratory outcomes or death until hospital discharge. MATERIAL AND METHODS: Information regarding all in-house born preterm infants born before 34 weeks gestation and born from January 2009 until December 2014 were collected and included among others, placental pathology and relevant data on demographics and outcomes of infants. RESULTS: Placental abnormalities was found in 157/253 (65.05%) cases. Acute placental inflammation was found to be the most common in both groups of premature neonates, followed by maternal vascular underperfusion. Maternal vascular underperfusion was significantly more common in GA ≤ 27 weeks compared to infants GA 28-33 weeks (35.2% vs. 13.7%; p = 0.018). Similarly, chronic placental inflammation was more common in infants GA ≤ 27 weeks compared to infants GA 28-33 weeks (14.3% vs. 3.3%; p = 0.014). Infants with placental pathology had a lower median birth weight (1460g vs. 1754g; p = 0.001, and were of shorter median GA at birth (31 vs. 32; p = 0.001). Infants with any placental disease had higher rates of death until hospital discharge (10.2% vs. 3.1%; p = 0.039) and higher rates of any stage of bronchopulmonary dysplasia (41.4% vs. 26.0%; p = 0.013). There were no significant differences in mechanical ventilation rates, duration of mechanical ventilation and duration of supplemental oxygen therapy. CONCLUSION: Identifiable placental abnormalities were found in most infants born < 34 weeks gestation. Placental pathology is associated with increased rates of bronchopulmonary dysplasia and death until hospital discharge.

How we do it: the Zurich Microsurgery Lab technique for placenta preparation.

BACKGROUND: Perfused placentas provide an excellent and accessible model for microvascular dissection, microsuturing and microanastomosis training - particularly in the early microsurgical learning curve. This way, a significant amount of live animals can be spared. METHOD: We present the Zurich Microsurgery Lab protocol, detailing steps for obtaining, selecting, cleaning, flushing, cannulating, and preserving human placentas - as well as microsurgical training examples - in a tried-and-true, safe, cost-effective, and high-yield fashion. CONCLUSION: Our technique enables highly realistic microsurgical training (microdissection, microvascular repair, microanastomosis) based on readily available materials. Proper handling, preparation, and preservation of the perfused placenta models is key.

B-Flow/Spatiotemporal Image Correlation M-Mode and Contrast-Enhanced/Microbubble Ultrasonography Quantification of Spiral Artery Distensibility and Placental Intervillous Perfusion in the First Trimester in a Primate Model of Impaired Spiral Artery Remodeling.

OBJECTIVE: During early human pregnancy, placental trophoblasts remodel spiral arteries into distensible low-resistance vessels to promote placental perfusion. We have established a model of impaired spiral artery remodeling (SAR) by elevating estradiol levels in the first trimester of baboon pregnancy. In the present study, B-flow/spatiotemporal image correlation (STIC) M-mode ultrasonography, a non-Doppler technology for sharp rendering of vessel dimensions, was used to determine whether spiral artery distensibility was altered in SAR-suppressed baboons. Contrast-enhanced ultrasound/microbubble imaging was also performed to determine whether it detected changes in placenta intervillous space perfusion in SAR-suppressed baboons. METHODS: The two imaging procedures were performed in the first trimester in baboons not treated or treated with estradiol to suppress SAR. RESULTS: Spiral artery distensibility, that is, luminal diameter at systole minus diameter at diastole, and volume flow as quantified by B-flow/STIC M-mode were 26% (p = 0.03) and 55% (p = 0.059) lower, respectively, in SAR-suppressed baboons. However, placental intervillous space flow rate and video intensity plateau levels reflecting blood perfusion, quantified by contrast-enhanced ultrasound/microbubble imaging, were unaltered in SAR-suppressed baboons. CONCLUSION: The results indicate that B-flow/STIC M-mode ultrasonography provides a non-invasive method to detect reduced distensibility and, thus, function of spiral arteries across the cardiac cycle in the first trimester in a primate model of impaired SAR. This study represents a first step in determining whether B-flow/STIC M-mode detects a similar defect in SAR early in adverse human pregnancy. This would provide an avenue to develop therapeutic modalities to prevent the devastating consequences of impaired SAR.

Deficiency of HtrA4 in BeWo cells downregulates angiogenesis through IL-6/JAK/STAT3 signaling.

In a previous study, we investigated the effects of high-temperature requirement factor A4 (HtrA4) deficiency on trophoblasts using the BeWo KO cell line. However, the effects of this deficiency on angiogenesis remain unclear. To explore the role of HtrA4 in angiogenesis, HUVECs were co-cultured with wild-type BeWo cells (BeWo WT), BeWo KO, and HtrA4-rescued BeWo KO (BeWo KO-HtrA4 rescue) cells. Dil staining and dextran analysis revealed that HUVECs co-cultured with BeWo KO formed tubes, but they were often disjointed compared to those co-cultured with BeWo WT, BeWo KO-HtrA4 rescue, and HUVECs controls. RT-PCR, ELISA, and western blot analysis were performed to assess angiogenesis-related factors at the mRNA and protein levels. HtrA4 deficiency inhibited IL-6 expression in trophoblasts, and the reduced secretion of IL-6 decreases VEGFA expression in HUVECs by modulating the JAK2/STAT3 signaling pathway to prevent tube formation. Moreover, rescuing HtrA4 expression restored the HUVEC tube formation ability. Interestingly, IL-6 expression was lower in supernatants with only cultured HUVECs than in co-cultured HUVECs with BeWo WT cells, but the HUVEC tube formation ability was similar. These findings suggest that the promoting angiogenesis-related signaling pathway differs between only HUVECs and co-cultured HUVECs, and that the deficiency of HtrA4 weakens the activation of the IL-6/JAK/STAT3/VEGFA signaling pathway, reducing the ability of tube formation in HUVECs. HtrA4 deficiency in trophoblasts hinders angiogenesis and may contribute to placental dysfunction.

Timing and duration of nutrient restriction and its impacts on placental development and umbilical blood flow in adolescent sheep.

We hypothesized that nutrient restriction from day 50-90 of gestation decreases umbilical blood flow and that umbilical blood flow would recover to control values upon realimentation during late gestation (d 90 to 130) or remain reduced in ewes that continued to be nutrient restricted. On d 50 of gestation, young nulliparous whiteface ewes (6-8 mo; n = 41) carrying singletons were randomly assigned to two dietary treatments: 100% of NRC recommendations (CON) or 60% of CON (RES). On d 90 of gestation, ewes either remained on CON or RES until d 130, or CON ewes were RES from d 90 to 130, or RES ewes were realimented to CON from d 90 to 130. This resulted in 4 treatment groups on day 130: CON-CON, CON-RES, RES-RES, RES-CON. Umbilical blood flow and fetal and placental measurements were obtained via ultrasonography every 10 days from day 50-110. Non-survival surgeries were performed on days 50, 90, and 130 (n = 6-7 ewes/group) where uterine artery and umbilical blood flows were measured during surgery via ultrasonography. Conceptus weights were recorded and placentomes collected to determine binucleate cell numbers. The study was conducted as a completely randomized design arrangement with repeated measures. Data were analyzed using the MIXED procedure of SAS. There was a nutritional treatment by day interaction (P < 0.01) with CON ewes having greater umbilical blood flow compared with RES by d 90. Fetal biparietal distance, abdominal width, and kidney area increased (P < 0.05) in CON-RES with all these measurements increasing during late gestation. We partially accept our hypothesis as nutrient restriction during mid gestation decreased umbilical blood flow. However, blood flow did not return to control levels upon realimentation. By d 130, fetal and placental weights were similar between RES-RES and CON-CON. Binucleate cell numbers in the fetal trophoblast were not influenced by nutritional treatments. Our findings suggest that refeeding previously nutrient restricted pregnant adolescent ewes to control levels does not reestablish umbilical blood flow. Adequate placental development during mid gestation could protect the fetus from a decreased umbilical blood flow later in gestation when nutrients were limited by 40%.

Development and validation of a flexible fetoscope for fetoscopic laser coagulation.

PURPOSE: Fetoscopic laser coagulation for twin-to-twin transfusion syndrome is challenging for anterior placenta due to the rigidity of current tools. The capacity to keep entry port forces minimal is critical for this procedure, as is optimal coagulation distance and orientation. This work introduces technological tools to this end. METHODS: A novel fetoscope is presented with a rigid shaft and a flexible steerable segment at the distal end. The steerable segment can bend up to 90[Formula: see text] even when loaded with a laser fiber. An artificial pneumatic muscle makes such acute bending possible while allowing for a low-weight and disposable device. RESULTS: The flexible fetoscope was validated in a custom-made phantom model to measure visual range and coagulation efficacy. The flexible fetoscope shows promising results when compared to a clinical rigid curved fetoscope to reach anterior targets. The new fetoscope was then evaluated in vivo (pregnant ewe) where it successfully coagulated placental vasculature. CONCLUSION: The flexible fetoscope improved the ability to achieve optimal coagulation angle and distance on anteriorly located targets. The fetoscope also showed the potential to lead fetoscopic laser coagulation and other fetal surgical procedures toward safer and more effective interventions.

Preliminary Study of Iron Concentration in the Human Placenta in Twin Pregnancies.

BACKGROUND: Pregnancy significantly increases the demand for iron (Fe) in the female body to facilitate maternal blood volume expansion, placental development, and fetal growth. As Fe flux in pregnancy is significantly influenced by the placenta, the aim of this study was to determine the dependencies between the Fe concentration in the placenta, the infant's morphometric parameters and the woman's morphological blood parameters in the last trimester. METHODS: The study was conducted on 33 women with multiple (dichorionic-diamniotic) pregnancies from whom the placentas were drawn, and their 66 infants, including pairs of monozygotic (n = 23) and mixed-sex twins (n = 10). Fe concentrations were determined based on inductively coupled plasma atomic emission spectroscopy (ICP-OES) using ICAP 7400 Duo, Thermo Scientific. RESULTS: The results of the analysis showed that lower placental Fe concentrations were associated with deteriorated morphometric parameters of infants, including weight and head circumference. Although we found no statistically significant dependencies between Fe concentration in the placenta and the women's morphological blood parameters, higher Fe concentration in the placenta of mothers supplemented with Fe correlated with better morphometric parameters in infants compared to those whose mothers received no Fe supplementation. CONCLUSIONS: The research adds additional knowledge for placental iron-related processes during multiple pregnancies. However, many limitations of the study do not allow detailed conclusions to be assessed, and statistical data should be assessed conservatively.

Development of placental lesions after recovery from COVID-19 during pregnancy: case-control study.

OBJECTIVE: To study whether the occurrence and type of placental lesions vary according to the time of onset of COVID-19 in pregnant women. DESIGN: Case-control study. SETTING: Departments of Gynaecology-Obstetrics and Pathology, Strasbourg University Hospital, France. POPULATION: Cases were 49 placentas of women with COVID-19. Controls were 50 placentas from women who had a past history of molar pregnancy. COVID-19 placentas were categorised based on whether birth occurred at more or less than 14 days post-infection. METHODS: Comparison between case and controls. MAIN OUTCOME MEASURES: Maternal and neonatal outcomes were recorded. Macroscopic and microscopic examination of the placentas was performed. RESULTS: The rate of vascular complications was higher in the COVID groups than in the controls (8 [16.3%] versus 1 [2%], p = 0.02). Signs of fetal (22[44.9%] versus 13 [26%], p = 0.05) and maternal (44 [89.8%] versus 36 [72.0%], p = 0.02) vascular malperfusion and signs of inflammation (11 [22.4%] versus 3 [6.0%], p = 0.019) were significantly more common in the COVID-19 groups than in the control group. Fetal malperfusion lesions (9 [39.1%] versus 13 [50.0%], p = 0.45) and placental inflammation (4 [17.4%] versus 7 [26.9%], p = 0.42) rates were not significantly different between the two COVID-19 groups. Chronic villitis was significantly more common when the delivery occurred >14 days after infection than in the group that delivered <14 days after infection (7 [26.9%] versus 1 [4.4%], p = 0.05). CONCLUSIONS: Our study suggests that SARS-COV-2 induces placental lesions that evolve after disease recovery, especially with the development of inflammatory lesions, such as chronic villitis.

Functional Photoacoustic Imaging for Placental Monitoring: A Mini Review.

The placenta, a highly vascularized interface between the mother and fetus, undergoes dramatic anatomical and functional changes during pregnancy. These changes occur both during healthy development and adverse pathologies of pregnancy, such as preeclampsia (PE). Abnormal placental development can lead to life-long health impacts on both the mother and child. Photoacoustic (PA) imaging, extensively developed for preclinical imaging applications in oncology and cardiovascular disease, uses optical energy to generate acoustic waves through thermoelastic expansion of light-absorbing chromophores within tissue. Recently, PA imaging has been used to study preclinical placental anatomy and function. If clinical translation of PA imaging of the placenta is achieved, the impact on maternal-fetal health could be expansive. This perspective highlights the recent progress in PA imaging for placental monitoring and discusses the progress needed for human clinical translation.

Specific HIF-2α (Hypoxia-Inducible Factor-2) Inhibitor PT2385 Mitigates Placental Dysfunction In Vitro and in a Rat Model of Preeclampsia (RUPP).

BACKGROUND: Preeclampsia is one of the leading causes of maternal mortality worldwide and is strongly associated with long-term morbidity in mothers and newborns. Referred to as one of the deep placentation disorders, insufficient remodeling of the spiral arteries during the first trimester remains a major cause of placental dysfunction. Persisting pulsatile uterine blood flow causes abnormal ischemia/reoxygenation phenomenon in the placenta and stabilizes the HIF-2α (hypoxia-inducible factor-2α) in the cytotrophoblasts. HIF-2α signaling impairs trophoblast differentiation and increases sFLT-1 (soluble fms-like tyrosine kinase-1) secretion, which reduces fetal growth and causes maternal symptoms. This study aims to evaluate the benefits of using PT2385-an oral specific HIF-2α inhibitor-to treat severe placental dysfunction. METHODS: To evaluate its therapeutic potential, PT2385 was first studied in primary human cytotrophoblasts isolated from term placenta and exposed to 2.5% O2 to stabilize HIF-2α. Viability and luciferase assays, RNA sequencing, and immunostaining were used to analyze differentiation and angiogenic factor balance. The ability of PT2385 to mitigate maternal manifestations of preeclampsia was studied in the selective reduced uterine perfusion pressure model performed in Sprague-Dawley rats. RESULTS: In vitro, RNA sequencing analysis and conventional techniques showed that treated cytotrophoblast displayed an enhanced differentiation into syncytiotrophoblasts and normalized angiogenic factor secretion compared with vehicle-treated cells. In the selective reduced uterine perfusion pressure model, PT2385 efficiently decreased sFLT-1 production, thus preventing the onset of hypertension and proteinuria in pregnant dams. CONCLUSIONS: These results highlight HIF-2α as a new player in our understanding of placental dysfunction and support the use of PT2385 to treat severe preeclampsia in humans.

Estrogen Actions in Placental Vascular Morphogenesis and Spiral Artery Remodeling: A Comparative View between Humans and Mice.

Estrogens, mainly 17ß-estradiol (E2), play a critical role in reproductive organogenesis, ovulation, and fertility via estrogen receptors. E2 is also a well-known regulator of utero-placental vascular development and blood-flow dynamics throughout gestation. Mouse and human placentas possess strikingly different morphological configurations that confer important reproductive advantages. However, the functional interplay between fetal and maternal vasculature remains similar in both species. In this review, we briefly describe the structural and functional characteristics, as well as the development, of mouse and human placentas. In addition, we summarize the current knowledge regarding estrogen actions during utero-placental vascular morphogenesis, which includes uterine angiogenesis, the control of trophoblast behavior, spiral artery remodeling, and hemodynamic adaptation throughout pregnancy, in both mice and humans. Finally, the estrogens that are present in abnormal placentation are also mentioned. Overall, this review highlights the importance of the actions of estrogens in the physiology and pathophysiology of placental vascular development.

Flexible Video Fetoscopy: Feasibility and Outcomes of a Novel Modality for Laser Therapy in Twin-to-Twin Transfusion Syndrome Presenting with Inaccessible Anterior Placenta.

INTRODUCTION: Identification of intertwin anastomosis may be challenging during fetoscopy in cases with complete anterior placenta. The aim of this study was to describe the technique, feasibility, and outcomes of flexible video fetoscopy for laser coagulation in monochorionic (MC) twin pregnancies with twin-to-twin transfusion syndrome (TTTS) presenting with inaccessible anterior placenta. METHODS: From April 2021 to March 2022, a prospective cohort of consecutive MC twin pregnancies complicated with TTTS presenting with anterior placenta after 20 weeks was recruited. Cases with inaccessible anterior placenta during standard technique were converted into flexible video fetoscopy for completion of laser coagulation of placental anastomoses using a 270° flexible video endoscope through the same uterine port. Descriptive analysis includes feasibility, remaining anastomoses requiring laser photocoagulation, and perinatal outcomes. RESULTS: A total of 45 pregnancies with TTTS were treated with fetoscopic laser therapy during the 1-year study period. Twenty-one pregnancies presented with anterior placenta after 20 weeks, in which an inaccessible vascular equator was observed in 33.3% (7/21). Flexible video fetoscopy was successfully performed in all 7 cases at a median gestational age of 22+2 (20+0-27+1) weeks+days. Visualization of the entire placental surface, coagulation of selected vessels, and exploration of the entire vascular equator were achieved in all cases. Six cases (85.7%) required additional laser coagulation due to either vascular patency despite initial coagulation with conventional fetoscopy (1/6, 16.7%) and/or remaining noncoagulated anastomoses (5/6, 83.3%). Perinatal survival of at least one twin and both twins was achieved in 85.7% and 57.1%, respectively. DISCUSSION: Flexible video fetoscopy for completion of laser coagulation of placental anastomoses is feasible and represents a good option for TTTS cases presenting after 20 weeks with inaccessible anterior placenta.

Ca2+-Activated K+ Channels and the Regulation of the Uteroplacental Circulation.

Adequate uteroplacental blood supply is essential for the development and growth of the placenta and fetus during pregnancy. Aberrant uteroplacental perfusion is associated with pregnancy complications such as preeclampsia, fetal growth restriction (FGR), and gestational diabetes. The regulation of uteroplacental blood flow is thus vital to the well-being of the mother and fetus. Ca2+-activated K+ (KCa) channels of small, intermediate, and large conductance participate in setting and regulating the resting membrane potential of vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) and play a critical role in controlling vascular tone and blood pressure. KCa channels are important mediators of estrogen/pregnancy-induced adaptive changes in the uteroplacental circulation. Activation of the channels hyperpolarizes uteroplacental VSMCs/ECs, leading to attenuated vascular tone, blunted vasopressor responses, and increased uteroplacental blood flow. However, the regulation of uteroplacental vascular function by KCa channels is compromised in pregnancy complications. This review intends to provide a comprehensive overview of roles of KCa channels in the regulation of the uteroplacental circulation under physiological and pathophysiological conditions.

Abnormal umbilical artery pulsatility index in appropriately grown fetuses in the early third trimester: an observational cohort study.

OBJECTIVE: The aim of this study was to determine if appropriately grown fetuses (those that are not small-for-gestational-age) with a raised umbilical artery pulsatility index (>95th centile) in the mid third trimester are at increased risk of placental dysfunction and adverse outcome. METHODS: This is a 5-year retrospective cohort study using routinely collected data. Inclusion criteria were singleton, non-anomalous pregnancies having a growth scan with umbilical artery Doppler velocimetry between 28 + 0 and 33 + 6 weeks' gestation. Small-for-gestational-age fetuses were excluded. Cases were classified as group 1 (those with an umbilical artery pulsatility index >95th centile at any scan during target window) or group 2 (those where the umbilical artery pulsatility index was ≤95th centile at all scans). p-Values and odds ratios were calculated. Logistic regression was used to compute odds ratios adjusted for baseline estimated weight z-score, gestational age at delivery, and labor induction. RESULTS: After exclusions, there were 202 pregnancies in group 1 and 7950 in group 2. Differences in baseline characteristics between the groups include age (median age was 30 for group 1 and 32 for group 2, p < .001), smoking (group 1 were more likely to smoke, p < .001) and labor induction (more common in group 1, p = .03). Among those delivering ≥34 + 0, group 1 were more likely to be small-for-gestational-age and have an abnormal cerebro-placental ratio at the final scan (OR 6.76, CI 4.23-10.80 and OR 5.07, CI 3.37-7.63 respectively), and to develop features of growth restriction (OR 9.85, CI 6.27-15.49). Group 1 were also more likely to deliver <37 + 0 weeks' gestation (OR 1.71, CI 1.13-2.58) and to have birthweight <10th or <3rd centile (OR 5.26, CI 3.65-7.58 and OR 6.13, CI 3.00-12.54 respectively). These associations remained significant when adjusted for estimated weight at the initial scan. CONCLUSIONS: These data suggest that raised umbilical artery pulsatility index in an appropriately grown fetus at 28 + 0 to 33 + 6 weeks' gestation is associated with subsequent development of growth restriction markers and an increased risk of moderate and severe small-for-gestational-age at birth. This is independent of the estimated weight of these babies at the index scan.

Clinical risk factors for vasculo-placental disorders: results from a prospective case-control study nested in HEMOTHEPP French cohort study.

OBJECTIVE: Determine clinical risk factors for vasculo-placental disorders in singleton pregnancies. DESIGN: Prospective case-control study nested in HEMOTHEPP French cohort. SETTING: Women delivered between June, 2015 and January, 2019 in any maternity ward of Finistère. POPULATION: Cases were women with vasculo-placental disorders (pre-eclampsia, intrauterine growth restriction (IUGR), placental abruption or stillbirth). Controls were women matched for age at delivery and parity. METHODS: Clinical data were collected by obstetricians or midwives during antenatal care visits and delivery, and recorded by trained research assistants. MAIN OUTCOME MEASURES: Occurrence of a vasculo-placental disorder. RESULTS: 505 women with vasculo-placental disorder (299 pre-eclampsia, 253 IUGR, 44 placental abruptions, 11 stillbirths) and 1515 matched controls were selected out of 20,075 participants. In multivariable analysis, four clinical parameters were associated with pre-eclampsia: obesity (Odd ratio (OR) = 3.11, 95%CI 2.11-4.58), French overseas origin (OR = 4.41, 95%CI 1.87-10.42), previous vasculo-placental disorder (OR = 5.14, 95%CI 2.72-9.70), aspirin during pregnancy (OR = 10.10, 95%CI 1.99-51.08). Three clinical parameters were associated with IUGR: auto-immune/inflammatory disorder (OR = 3.75, 95%CI 1.83-7.68), previous vasculo-placental disorder (OR = 3.63, 95%CI 2.06-6.41), smoking during pregnancy (OR = 2.66, 95%CI 1.91- 3.71). A previous venous thromboembolism (VTE) was associated with IUGR in univariable but not in multivariable analysis (OR = 3.72, 95%CI 0.82-17.00, p = 0.09). CONCLUSIONS: Clinical risk factors differ between IUGR and pre-eclampsia, the later, but not the former, being associated with cardiovascular risk factors.

Solomon versus selective fetoscopic laser photocoagulation for twin-twin transfusion syndrome: A systematic review and meta-analysis.

This meta-analysis aims to compare the perinatal outcome of twin-twin transfusion syndrome (TTTS) pregnancies undergoing selective versus vascular equator (Solomon) fetoscopic laser photocoagulation (FLP). We performed a systematic search in PubMed and Web of Science from inception up to 25 July 2021. Studies comparing the Solomon and selective techniques of FLP for treatment of TTTS pregnancies were eligible. Random-effects or fixed-effect models were used to pool standardized mean differences (SMD) and log odds ratio. Seven studies with a total of 1664 TTTS pregnancies (n = 671 undergoing Solomon and n = 993 selective techniques) were included. As compared to the selective FLP, Solomon was associated with a lower risk of recurrent TTTS compared to the selective technique (Log odds ratio [OR]: -1.167; 95% credible interval [CrI]: -2.01, -0.33; p = 0.021; I2 : 67%). In addition, Solomon was significantly associated with a higher risk of placental abruption than the selective technique (Log [OR]: 1.44; 95% CrI: 0.45, 2.47; p = 0.012; I2 : 0.0%). Furthermore, a trend for the higher risk of preterm premature rupture of membranes was observed among those undergoing Solomon (Log [OR]: 0.581; 95% CrI: -0.43, 1.49; p = 0.131; I2 : 17%). As compared to selective FLP, the Solomon technique for TTTS pregnancies is associated with a significantly lower recurrence of TTTS; however, it significantly increases the risk of placental abruption.

MORPHOMETRIC CHARACTERISTICS OF PLACENTA IN WOMEN WITH PREECLAMPSIA AND OBESITY COMPARED TO WOMEN WITH NORMAL BODY WEIGHT.

OBJECTIVE: The aim: to investigate the morphometric characteristics of placentas in women with comorbidity of preeclampsia and obesity compared to women with physiological body weight, and to assess the efficacy of the prophylactic therapy course developed to prevent the occurrence of preeclampsia in pregnant women with obesity. PATIENTS AND METHODS: Materials and methods: 25 biopsy samples of placental tissue were taken from women between 37 and 40 weeks of gestation with a physiological body weight and with class II obesity. The women were divided into five groups of five women in each: the 1st group included women with physiological body weight without obstetric and somatic pathology; the 2nd group involved women with physiological body weight, whose pregnancy was complicated with preeclampsia; the 3rd group was made up of women with class II obesity whose pregnancy was complicated with preeclampsia; the 4th group consisted of women with class II obesity, who received the special prophylactic therapy course, and the 5th group included women with class II obesity, who did not receive the prophylactic therapy course. RESULTS: Results: The analysis of morphometric parameters of placenta samples taken from women with preeclampsia and obesity demonstrates a number of com-pensatory and adaptive changes in placenta under hypoxic conditions, and the most important of them include a significant decrease in the number and the mean diameter of the terminal villi, the reduction of volume of villious tree, an increase in the diameter of the capillaries of terminal villi. The morphometric parameters and histological structure in placenta samples from women with obesity, who received the special the prophylactic therapy course, as well as in placenta samples of the control group were similar to the gestational normative values. CONCLUSION: Conclusions: The morphometric investigation of placenta samples taken from women with comorbidity of preeclampsia and obesity has shown a significant decrease in the mean diameter of the terminal villi and an increase in the diameter of the capillaries of these terminal villi when compared with a group of women with preeclampsia and physiological body weight. The study has also demonstrated the distortion of the percentage ratio of the volume of the intervil¬lous space and the ratio of medium-calibre villi. The combination of these changes indicates a lack of adaptive capabilities in the placenta during preeclampsia under increasing hypoxic condition.