BACKGROUND:Placental histopathology provides important insights into maternal and fetal health, yet the organ's spatial heterogeneity poses significant challenges for objective and reproducible histological analysis. Systematic assessment of cellular and structural composition across placental slides remains limited by the scale and subjectivity of manual evaluation. Quantitative approaches are therefore needed to characterise placental responses to injury beyond visually apparent lesions. METHODS:We applied the Histology Analysis Pipeline.PY (HAPPY), a biologically inspired hierarchical deep learning framework for quantitative single-cell-resolution analysis of Haematoxylin and Eosin (H&E) slides, to 130 placental parenchyma slides from 62 singleton full-term live births. The dataset included healthy normal controls and four common placental lesion types: infarction, perivillous fibrin, avascular villi, and intervillous thrombosis. Cell-type and tissue-structure compositions were quantified, and slide-level deviation from a healthy reference was assessed using compositional data analysis. RESULTS:Placental slides with lesions exhibited significant cellular composition differences compared with healthy controls, including increased extravillous trophoblast and leukocyte densities and decreased Hofbauer cell densities. These cellular changes were accompanied by tissue-level alterations, particularly increased fibrin deposition and changes in villous structure. Compositional deviation increased with infarction size but not with other lesion types. Notably, compositional differences were also detected in slides without an apparent lesion from placentas with lesion(s) elsewhere, indicating organ-wide responses extending beyond focal pathology. CONCLUSIONS:Quantitative deep phenotyping reveals widespread cellular and structural changes associated with placental lesions, including effects not evident on routine histological assessment. These findings demonstrate the potential of AI-based digital histology to complement conventional placental pathology in research and clinical settings.

Placenta pathology provides diagnostic insights for understanding pregnancy complications and guides maternal and perinatal care. While placental abnormalities reflect both acute and chronic maternal-fetal health states, the organ's spatial and temporal heterogeneity poses significant challenges for systematic histological analysis. To date, there has been no analysis of cell populations and their relationship to placental lesions due to the scale of annotations required by expert pathologists. The Histology Analysis Pipeline.PY (HAPPY), previously published by our group, is a hierarchical deep learning approach for quantitative single-cell resolution analysis of H&E slides. Here we apply HAPPY to analyse 130 slides from 62 live full-term pregnancies across healthy controls and four common placental lesion types (infarction, perivillous fibrin, avascular villi, and intervillous thrombosis). We computed cell-type and tissue-structure compositions, established the expected range of healthy variation, and quantified slide-level deviation from this reference using compositional data analysis. Our results reveal significant cellular composition differences between histologically normal and lesioned placentas, including increased extra-villous trophoblasts and leukocytes, coupled with decreases in Hofbauer cells. These changes accompanied distinctive tissue microstructural alterations, particularly increased fibrin deposition and changes to the villous structures. The magnitude of compositional deviation increased with infarction size but not with intervillous thrombosis. Importantly, many differences extend beyond visibly affected areas, indicating organ-wide adaptive responses rather than purely discrete focal pathologies. This quantitative characterisation provides insights into relationships between specific pathologies and placental structure, demonstrating the potential of AI-based methods to enhance conventional histopathological assessment for research and clinical practice.

Accurate placenta pathology assessment is essential for managing maternal and newborn health, but the placenta’s heterogeneity and temporal variability pose challenges for histology analysis. To address this issue, we developed the ‘Histology Analysis Pipeline.PY’ (HAPPY), a deep learning hierarchical method for quantifying the variability of cells and micro-anatomical tissue structures across placenta histology whole slide images. HAPPY differs from patch-based features or segmentation approaches by following an interpretable biological hierarchy, representing cells and cellular communities within tissues at a single-cell resolution across whole slide images. We present a set of quantitative metrics from healthy term placentas as a baseline for future assessments of placenta health and we show how these metrics deviate in placentas with clinically significant placental infarction. HAPPY’s cell and tissue predictions closely replicate those from independent clinical experts and placental biology literature.

Introduction and objectivesIntrahepatic cholestasis of pregnancy (ICP) is often accompanied by fetal and maternal complications.Materials and methodsRetrospective review of the clinical course of women with ICP and their neonates treated at our medical center over a 10-year period. Special attention was paid to the maternal and neonatal response to 2 different modes of ursodeoxycholic acid (UDCA) administration.ResultsNeonates of mothers with high total bile acid levels had a poorer composite neonatal outcome. Twenty-seven women who presented at an advanced stage of their pregnancies did not receive UDCA. UDCA was administered in 2 modes: either a full dose at admission (76 women) or a gradually increasing dose until the desired dosage was reached (25 women). The mean gestational age at delivery for the 94 neonates that were exposed to full UDCA dose was the lowest (36±2.3 weeks for the full dose, 37±1.4 weeks for the 30 neonates from the gradually increasing dose, 38±1.6 weeks for the 29 neonates from the no treatment group, p<0.001). The group of neonates that were exposed to full UDCA dose had the highest rate of unfavorable composite neonatal outcome (53% for full dose, 30% for gradually increasing dose, 24% for the no treatment group, p=0.006).ConclusionsCompared to the administration of a full UDCA dose, the administration of a gradually increasing dose of UDCA may be associated with a greater gestational age at delivery and fewer events of unfavorable composite neonatal outcomes. These novel findings should be retested prospectively in a large cohort of patients.

Many recent methods for the analysis of histology whole slide images (WSIs) have used graph neural networks (GNNs) to aggregate visual information over a large image resolution. However, domain shift is a significant challenge in computational histopathology, due to differences in WSI appearance between institutes, and the effect of these differences on training GNNs has not been explored. In this work, we present the Multiple Embedding Graph Augmentation (MEGA) strategy to improve the cross-institute generalisation of GNNs in histology. We show that by introducing image augmentation and normalisation to the node features used to train a GNN, we can train a model that is robust to domain shift without additional labels or further training of the feature extractor. We compare MEGA to noise-based regularisation and demonstrate its effectiveness in a node classification tissue prediction task in placenta histology.

Background: Chromosomal-microarray-analysis (CMA) may reveal susceptibility-loci (SL) of varied penetrance for autism-spectrum-disorder (ASD) and other neurodevelopmental conditions. Attitudes of women/parents to disclosure of SL during pregnancy are understudied.Methods: A multiple-choice questionnaire was distributed to postpartum women. Data were collected on women's interest to receive prenatal genetic information with various levels of penetrance.Results: Women's (n = 941) disclosure choices were dependent on the magnitude of risk: approximately 70% supported disclosure of either full or 40% penetrance, 53% supported disclosure at a 20% risk threshold, and 40% supported disclosure at 10% or less. Although most women supported, rejected or were indecisive about disclosure consistently across all risk levels, nearly one-quarter (24%) varied their responses based on penetrance, and this was associated with religiosity, education, parity and concern about fetal health (p-values <0.04). Among those who varied their choices, the risk threshold was lower among secular women (20%) than among ultraorthodox women (40%). In a multivariable analysis, ultraorthodox women were much less likely to vary their choices on ASD disclosure compared with secular women (aOR = 0.37, p < 0.001).Conclusion: Women's attitudes toward disclosure are influenced by the level of risk and their individual characteristics. We therefore encourage engaging women/couples in disclosure decisions regarding uncertain and probabilistic results from prenatal genomic tests.

Background Advanced prenatal genomic technologies can identify risks for adult-onset (AO) conditions in the fetus, challenging the traditional purpose of prenatal testing. Professional guidelines commonly support disclosure of high-penetrance AO actionable conditions, yet attitudes of women/parents to these findings and factors affecting their attitudes are understudied. Methods We explored 941 (77% response rate) postpartum women's attitudes towards receiving prenatal genetic information, and associations of sociodemographic, medical and psychological characteristics with their choices, focusing on AO conditions. Results Women largely support the disclosure of actionable AO findings (58.4%), in line with professional guidelines. A third of the women also supported the disclosure of non-actionable AO conditions. Stronger religious observance (p < 0.001) and higher psychological distress (p = 0.024) were associated with decreased interest in receiving actionable AO conditions, whereas higher concern for fetal health yielded increased interest (p = 0.032). Attitudes towards disclosure were strongly associated with women's perceived benefit of such information for their own, partner's, and future child's health. Termination of pregnancy based on such information received very little support. Conclusion In-light of the demonstrated understanding of nuanced genetic information and the observed diversity in attitudes, a culturally competent opt-in/out policy could be considered. If full-disclosure is practiced, support should be provided to those expressing higher levels of distress.

We introduce a new benchmark dataset, Placenta, for node classification in an underexplored domain: predicting microanatomical tissue structures from cell graphs in placenta histology whole slide images. This problem is uniquely challenging for graph learning for a few reasons. Cell graphs are large (>1 million nodes per image), node features are varied (64-dimensions of 11 types of cells), class labels are imbalanced (9 classes ranging from 0.21% of the data to 40.0%), and cellular communities cluster into heterogeneously distributed tissues of widely varying sizes (from 11 nodes to 44,671 nodes for a single structure). Here, we release a dataset consisting of two cell graphs from two placenta histology images totalling 2,395,747 nodes, 799,745 of which have ground truth labels. We present inductive benchmark results for 7 scalable models and show how the unique qualities of cell graphs can help drive the development of novel graph neural network architectures.

BACKGROUND:With increasing longevity and quality of life in adults with Cystic fibrosis (CF), growing maternity rates are reported. Women with severe CF are becoming pregnant, with unpredictable maternal and fetal outcomes.AIM:To determine how baseline disease severity, pancreatic insufficiency (PI) and Pseudomonas aeruginosa (PA) infection affect fertility, the pregnancy course, delivery, neonatal outcome, and subsequent disease progression.METHODS:A multicenter-retrospective cohort study. Data on patients that had been pregnant between 1986-2018 was collected from ten CF centers worldwide. Disease severity [mild or moderate-severe (mod-sev)] was defined according to forced expiratory volume % predicted in 1 second (FEV1) and body mass index (BMI). Three time periods were compared, 12 months prior to conception, the pregnancy itself and the 12 months thereafter.RESULTS:Data was available on 171 pregnancies in 128 patients aged 18-45 years; 55.1% with mod-sev disease, 43.1% with PI and 40.3% with PA. Women with mod-sev disease had more CF-related complications during and after pregnancy and delivered more preterm newborns. However, FEV1 and BMI decline were no different between the mild and mod-sev groups. A more rapid decline in FEV1 was observed during pregnancy in PI and PA infected patients, though stabilizing thereafter. PI was associated with increased risk for small for gestational age infants.CONCLUSION:Baseline disease severity, PA infection and PI have an adverse impact on infant outcomes, but do not impact significantly on disease progression during and after pregnancy. Consequently, pregnancies in severe CF patients can have a good prognosis.

Epidural analgesia (EA) is an established option for efficient intrapartum analgesia. Meta-analyses have shown that EA differentially affects the first stage of labor but prolongs the second. The question of EA timing remains open. We aimed to investigate whether EA prolongs delivery in total and whether the EA administration timing vis-à-vis cervical dilation at catheter insertion is associated with a modulation of its effects on the duration of the first and second stages, as well as the rate of instrumental vaginal delivery in primiparas and multiparas. A retrospective electronic medical records-based study of 18 870 singleton term deliveries occurring in our institution from 2003 to 2015. Cervical dilation was determined within a half-hour of EA administration. We examined whether cervical dilation at EA administration correlated with the duration of the first and/or second stage, with the rate of prolonged second stage, and with the rate of interventional delivery. The study group was stratified to 10 subgroups defined by 1-cm intervals of cervical dilation at EA administration. Logistic regression modeling was applied to analyze the association between EA timing and rate of instrumental delivery while controlling for possible confounders. In primiparas, receiving EA correlated with longer medians of active first stage (+51 minutes; P  < .001) and second stage (+55 minutes; P  < .001). In multiparas, median increases in active first stage (+43 minutes; P  < .001) and second stage (+8 minutes; P  < .001) were noted. The timing of EA, vis-à-vis cervical dilation (1-10 cm) was not associated with a substantial modulation of these effects. Logistic regression showed that cervical dilation at EA was not associated with a higher instrumental vaginal delivery rate. Epidural analgesia prolonged the first and second stages of labor vs no epidural. Having EA was associated with a higher instrumental delivery rate but not with higher rates of maternal or neonatal complications, in primi- and multiparas. Importantly, the timing of EA, vis-à-vis cervical dilation, was not associated with substantial changes in the duration of labor stages or the instrumental delivery rate. Thus, EA may be offered early in the first stage of labor.

AIM:To examine the effectiveness of the Paula Method exercises in comparison to standard care on resumption of gastrointestinal (GI) activity in women postelective caesarean delivery (CD).DESIGN:Randomized controlled trial on a postpartum unit of a university medical centre.METHODS:Sixty-four women following elective CD performed under regional anaesthesia were recruited between 2 February-3 July 2018. Participants were randomized into two groups: The Paula Method exercise group (intervention group) and the control group. Women in the intervention group performed circular muscle exercises according to the Paula Method and received standard care, while those in the control group were treated only with standard care. Time to first bowel sounds, passage of first flatus and first defecation after CD were measured.RESULTS:A significant difference was found in the time to passage of first flatus, in favour of the intervention group (24.07 [6.85] hours versus 39.07 [10.37] hours; p < .001). No significant differences between the groups were found for other main outcome measures.CONCLUSION:Paula Method exercises post CD can serve as natural and convenient alternative to the standard, conservative treatment to promote resumption of GI activity.IMPACT:CD can be associated with postoperative ineffective peristalsis that can lead to a paralytic ileus. Since standard methods are not sufficient for all women, there is a need for alternative modalities to accelerate the resumption of bowel functioning. In the Paula Method exercise group, time to first flatus passage occurred significantly sooner compared with the control group. Time to first defecation was earlier in the Paula Method exercise group but this difference did not reach statistical significance. Along with gum chewing, Paula Method exercises can be part of a simple and inexpensive GI activation strategy post CD. Further research should be performed using these exercises post other operative procedures.

(Acta Obstet Gynecol Scand. 2020;99:1039–1049) Although epidural analgesia (EA) is used in over 60% of deliveries in Western countries with high patient satisfaction, it has been associated with risk of prolonged second stage of labor and instrumental vaginal delivery. The optimal time to administer EA based on cervical dilation is unknown, and whether the timing of its administration affects the duration of the first and second stages of labor or maternal or fetal outcomes. The aim of this study was to determine if the cervical dilation at the time of epidural placement impacts the duration of the first and/or second stage of labor and correlates with the rate of instrumental vaginal delivery.

To investigate optimal timing of dressing and staples removal after cesarean delivery (CD).

Background: Castor oil is a substance used for labor induction in an inpatient setting. However, its efficacy as an agent for the induction of labor, for post-date pregnancies in an outpatient setup is unknown. Objective: Efficacy of castor oil as an agent for the induction of labor, for post-date pregnancies in outpatient settings. Methods: Eighty-one women with a low-risk post-date singleton pregnancy with a Bishop score <= 7, without effective uterine contractions were randomized to the intervention, 60 ml of castor oil, or the control, 60 ml of sun-flower oil. The primary outcome was proportion of women entering the active phase of labor 24, 36, 48 h after ingestion. Secondary outcomes included meconium stained amniotic fluid, abnormal fetal heart rate tracing, cesarean section rate, instrumental deliveries, birth weight, 5 min Apgar score, chorioamnionitis, hypertensive complications, retained placenta, and post-partum hemorrhage. Findings: Intervention and control groups included 38 and 43 women, respectively. No differences in baseline characteristics, except for age were noted. The observed interaction between castor oil and parity was significant (p(interaction) = 0.02). Multiparous women in the intervention group exhibited a significant beneficial effect on entering active labor within 24, 36 and 48 h after castor oil consumption compared with the placebo (Hazard Ratio = 2.93, p = 0.048; Hazard Ratio = 3.29, p = 0.026; Hazard Ratio = 2.78, p = 0.042 respectively). This effect was not noted among primiparous women. No differences in rate of obstetric complications or adverse neonatal outcomes were noted. Conclusion: Castor oil is effective for labor induction, in post-date multiparous women in outpatient settings. (c) 2017 Published by Elsevier Ltd on behalf of Australian College of Midwives.

OBJECTIVE: To evaluate whether full-term deliveries resulting in neonates diagnosed with hypoxic-ischemic encephalopathy are associated with a significant increase in the rate of subsequent unscheduled cesarean deliveries.METHODS: We conducted a retrospective chart review study and examined all deliveries in the Department of Obstetrics and Gynecology at Hadassah University Hospital, Mt. Scopus campus, Jerusalem, Israel, during 2009-2014. We reviewed all cases of hypoxic-ischemic encephalopathy in singleton, term, liveborn neonates and identified seven such cases, three of which were attributed to obstetric mismanagement and four that were not. We measured the rate of unscheduled cesarean deliveries before and after the events and their respective hazard ratio.RESULTS: Before a mismanaged delivery resulting in hypoxic-ischemic encephalopathy, the baseline rate of unscheduled cesarean deliveries was approximately 80 unscheduled cesarean deliveries for every 1,000 deliveries. In the first 4 weeks immediately after each of the three identified cases, there was a significant increase in the rate of unscheduled cesarean deliveries by an additional 48 unscheduled cesarean deliveries per 1,000 deliveries (95% confidence interval [CI] 27-70/1,000). This increase was transient and lasted approximately 4 weeks. We estimated that each case was associated with approximately 17 additional unscheduled cesarean deliveries (95% CI 8-27). There was no increase in the rate of unscheduled cesarean deliveries in cases of hypoxic-ischemic encephalopathy that were not associated with mismanagement.CONCLUSION: The increase in the rate of unscheduled cesarean deliveries after a catastrophic neonatal outcome may result in short-term changes in obstetricians' risk evaluation.

We aimed to assess the incidence and risk factors for Pelvic Floor Disruption (PFD) in primiparous women after their first Vaginal Delivery (VD) using three-dimensional transperineal ultrasound (3D-TPUS). This is a prospective-cohort study. Primiparous women, 10-14 months after their first VD were reached by phone and invited to our ultrasound unit for an assessment including 3D-TPUS and completing St. Marks Incontinence Score (SMIS) questionnaire (figure 1). 3D-TPUS was performed by ultrasound specialists who were blinded to information regarding delivery, risk factors for PFD and SMIS results. Inclusion criteria included: primiparity, VD, singleton, birth weight > 3000 grams, women who did not give birth since the studied delivery and were not pregnant again. Exclusion criteria included: women who suffered from anal incontinence prior to the studied pregnancy. Primary outcome was assessing the incidence and risk factors for PFD using 3D-TPUS. Secondary outcome was evaluating clinical degree of incontinence using SMIS. Data regarding labor and delivery were extracted from electronic medical records. Overall 26 women participated. They underwent 3D-TPUS and were evaluated using SMIS. Incidence of PFD following VD in primiparous women was 23% (6 patients). Of which, 5 patients had levator ani disruption and one patient had anal sphincter disruption (figure 2). The patient with anal sphincter injury demonstrated using 3D-TPUS was diagnosed during labor as having third degree perineal tear (3C) with immediate surgical repair. In assessing different risk factors, epidural anesthesia during delivery was found to be significantly protective from PFD (P < 0.05). Prolonged second stage of labor and prolonged pregnancy was higher in women diagnosed with PFD, however, this was not statistically significant. As for clinical evaluation of incontinence, positive SMIS score was higher in women with sonographically diagnosed PFD. PFD following first VD is not a rare finding. 3D-TPUS helps to diagnose PFD in women with so called "uneventful" delivery.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

OBJECTIVES:We evaluated primiparous women with clinically diagnosed third- and fourth-degree and anal sphincter tears, to evaluate the rate of levator ani muscle injury compared to primiparous women without sphincter tears.METHODS:Primiparous women delivering in our maternity ward with intrapartum diagnoses of third- or fourth-degree anal sphincter tears, repaired by the overlapping technique, were recruited to undergo 3-dimensional transperineal sonography of the pelvic floor anatomy, including the anterior and posterior compartments. Primiparas with uncomplicated vaginal deliveries were recruited as a comparison group. Patient files were examined, and maternal backgrounds and delivery and neonatal details were extracted for all patients.RESULTS:Ninety-four women with tears were recruited to the study group, and 464 women with normal vaginal deliveries constituted the comparison group. The groups differed significantly in the rates of levator ani defects: 38 of 94 women (40.4%) in the study group versus 75 of 464 (16.2%) in the comparison group (P < .001; odds ratio, 3.53; 95% confidence interval, 2.18–5.7). Neonatal head circumference differed significantly between the study and comparison groups: (mean ・} SD, 34.5 ・} 1.3 cm in the study group versus 33.9 ・} 1.3 cm in the comparison group; P= .005), as did birth weight (3322 ・} 430 g in the study group versus 3169 ・} 458 g in the comparison group; P= .007). The groups did not differ in maternal age, gestational age at delivery, length of second stage of labor, and rates of epidural anesthesia, episiotomy, and vacuum extraction.CONCLUSIONS:Third- and fourth-degree intrapartum sphincter tears are associated with levator ani avulsion. Knowledge of complex pelvic floor damage may allow for prompt referral to secondary preventive measures for pelvic floor disorders.

Introduction: Re-laparotomy following caesarean delivery (CD) is a rare yet serious complication. The aim of this study was to identify risk factors, diagnostic features and outcomes following re-laparotomy.Materials and methods: This retrospective cohort study reviewed cases of re-laparotomy following CD performed at Hadassah-Hebrew University Medical Center. Occurrences were identified via the electronic medical record database.Results: During the study period, 17213 women underwent CD, of which 55 (0.3%) underwent re-laparotomy during the same hospitalization. Main indications for re-laparotomy were intra-peritoneal bleeding (62%) and wound infection/dehiscence (22%). During re-laparotomy, the bleeding source was found and ligated in 85% of the cases. Age, parity, previous CD, induction of labor, anesthesia type and operative duration were significant risk factors for re-laparotomy. In a selected group of patients, trial of conservative treatment was made. However, in 76% of these women a re-laparotomy was required.Discussion: Risk factors for re-laparotomy following CD should be identified, thus enabling more intensified monitoring of patients considered at risk for this complication. When intra-peritoneal bleeding following CD is suspected, conservative management has a high failure rate and should be reserved for a selected group of stable patients.

Purpose: Group B Streptococcus (GBS) infection is a major cause of neonatal sepsis. The objective of this study was to estimate the prevalence and risk factors for GBS carriership among parturient women in Jerusalem. Methods: A cross-sectional study of 436 parturient Jewish women at Hadassah-Hebrew University Medical Center, Mount Scopus. The study included patient interview and vagino-rectal swab for culture. Main outcome measures were the prevalence of GBS carriership among study population. Results: Of the 436 participants, 77 had a positive culture for GBS, giving a carrier rate of 17.7%. No differences were found between carriers and non-carriers in age, BMI or parity. Orthodox Jewish women had a significantly higher carrier rate compared with secular Jewish women (20.6% vs. 12.8% respectively), yielding an age, education and BMI adjusted odds ratio (OR) of 1.9 (95% confidence interval (CI): 1.06 - 3.40). Similarly, ritual immersion was associated with increased risk of carrier state with an adjusted OR of 2.01 (95% CI: 1.03 - 3.92, P = 0.039). Conclusions: Our study suggests an association between ritual immersion in the Mikveh and GBS carriership.

Objective: To investigate rates and range of pelvic floor dysfunction complaints, including anterior and posterior compartments and sexual function, in an unselected population of primiparous women one year from delivery, and examine the degree of bother they cause.Study design: Cross sectional study. Primiparous women who delivered their first child in our delivery wards 10-14 months previously, were approached by phone and asked to complete the Pelvic Floor Symptom Bother Questionnaire (PFBQ) and provide general demographic information. Details regarding participants' labor and delivery were extracted from electronic medical records. PFBQ score was correlated to demographic and labor and delivery parameters.Results: 198 women completed the questionnaire. Response rate was 94%. Scores ranged from 0 to 44.4 (out of a possible 100). At least one symptom of PFD was reported by 64% of respondents. Various degrees of urinary incontinence were reported by 9.1-12.1% of women. Some degree of fecal or flatus incontinence was reported by 10.1% of women; 11.1% reported some degree of obstructed defecation. Severe degree of bother from one or more PFD symptoms was reported by 40.1-90.9%. Some level of dyspareunia was reported by 37.3%. A "dose response" trend between mode of delivery and rate of dyspareunia was observed.Conclusions: Two-thirds of primiparous women one year after delivery suffer PFD symptoms that cause some degree of bother. When asked, women are willing to discuss pelvic floor function; caregivers should initiate discussion and refer women promptly to interventions where necessary. (C) 2015 Elsevier Ireland Ltd. All rights reserved.