Trained Memory of Human Uterine NK Cells Enhances Their Function in Subsequent Pregnancies.

Natural killer cells (NKs) are abundant in the human decidua, regulating trophoblast invasion and angiogenesis. Several diseases of poor placental development are associated with first pregnancies, so we thus looked to characterize differences in decidual NKs (dNKs) in first versus repeated pregnancies. We discovered a population found in repeated pregnancies, which has a unique transcriptome and epigenetic signature, and is characterized by high expression of the receptors NKG2C and LILRB1. We named these cells Pregnancy Trained decidual NK cells (PTdNKs). PTdNKs have open chromatin around the enhancers of IFNG and VEGFA. Activation of PTdNKs led to increased production and secretion of IFN-γ and VEGFα, with the latter supporting vascular sprouting and tumor growth. The precursors of PTdNKs seem to be found in the endometrium. Because repeated pregnancies are associated with improved placentation, we propose that PTdNKs, which are present primarily in repeated pregnancies, might be involved in proper placentation.

Pregnancy trained decidual NK cells protect pregnancies from harmful Fusobacterium nucleatum infection.

Natural killer cells (NKs) found during pregnancy at the maternal-fetal interface named decidual (d)NKs, show signs of education following first pregnancy, resulting in better placentation and fetus-growth, hence termed pregnancy trained dNKs (PTdNKs). Here we show that PTdNKs provide increased protection of the fetus from Fusobacterium nucleatum (FN) infection. We demonstrate that PTdNKs secrete elevated amounts of the bacteriocidal protein granulysin (GNLY) upon incubation with FN compared to dNKs derived from first pregnancies, which leads to increased killing of FN. Furthermore, we showed mechanistically that the GNLY secretion is mediated through the interaction of the FN's Fap2 protein with Gal-GalNAc present on PTdNKs. Finally, we show in vivo, using GNLY-tg mice that enhanced protection of the fetuses from FN infection is observed, as compared to wild type and that this enhance protection is NK cell dependent. Altogether, we show a new function for PTdNKs as protectors of the fetus from bacterial infection.

Evaluating fetal tricuspid and mitral annular plane systolic excursion (TAPSE and MAPSE) using spatiotemporal image correlation (STIC) M-mode.

OBJECTIVES: This study aimed to evaluate the feasibility and reliability of tricuspid and mitral annular plane systolic excursion measurements (TAPSE and MAPSE) applying M-mode spatiotemporal image correlation (STIC) technology in low-risk pregnancies. METHODS: An initial retrospective pilot study was carried out to assess repeatability, followed by a larger mixed cross-sectional and prospective longitudinal study, both evaluating low-risk singleton pregnancies between 22+6 and 39+1 weeks. As only annuli capture was necessary, STIC acquisition parameters were set to the minimum volume angle of 15° and acquisition time of 7.5 s. RESULTS: A total of 330 volumes were analysed offline applying STIC M-mode. Acquisition rates were 96.9 % for TAPSE and 93.7 % MAPSE in the pilot study (n=32) and 98.0 % for both in the longitudinal study (n=102). Both study designs revealed good repeatability for both sides of the heart, with higher intraclass correlation coefficients (ICCs) for TAPSE (0.84-0.94) compared to MAPSE (0.80-0.88). Good repeatability was demonstrated for both sides of the heart, more so for TAPSE than MAPSE, with ICCs for TAPSE 0.84-0.91 and MAPSE 0.75-0.76, comparable to prior ICCs for STIC repeatability. CONCLUSIONS: Modified STIC acquisition settings specifically tailored for capturing the longitudinal annular displacement may improve STIC TAPSE and MAPSE acquisition rates, optimising image quality for precise measurement and potentially bringing these modalities closer to clinical application.

Fetal Inguinal Hernia: Case Report and Review of the Literature.

Fetal inguinal hernia (FIH) is a rare event and only few cases were published in the medical literature. In the present study, we aimed to characterize the sonographic features, clinical presentation, management, outcomes, and differential diagnoses of FIH. Accordingly, we reviewed all 17 cases of FIH published in the medical literature, including one new case evaluated by our group. All 17 cases (100%) were male, and FIH is presented as a scrotal mass with a mean diameter of 38 ± 9.5 mm. The right side was dominant (62%). Peristalsis was reported in 80% of the cases, and blood flow was reported in two-thirds. Most cases were diagnosed in the third trimester (88%) at a mean gestational age (GA) of 33.1 ± 5.2 weeks. 60% of the cases had isolated FIH, and 40% had another sonographic or genetic abnormality. Three cases (18%) were syndromic with multiple malformations: trisomy 18, skeletal anomalies due to Jarcho-Levin syndrome, and undefined multiple joint contractures. Two cases (12%) had copathologies in the gastrointestinal tract: one had an echogenic bowel due to homozygosity for cystic fibrosis, and the other had low anorectal malformation. Bowel loop dilatation was observed prenatally in both cases and in another one isolated case (18%). GA at delivery was 38 ± 1.8 weeks, and the median time between diagnosis and delivery was 3 weeks. All three cases of neonatal death occurred in syndromic fetuses. All patients with nonsyndromic inguinal hernias underwent definitive surgical repair at a median of 13 days postpartum. No signs of strangulation and only one case of edematous bowel without necrosis have been reported. In conclusion, FIH should be suspected in male fetuses when an intrascrotal mass with peristalsis is diagnosed during the third trimester. Close follow-up until term in the absence of signs of bowel obstruction is reasonable, and in isolated FIH, the prognosis is favorable.

[NUCHAL TRANSLUCENCY CONCURRENT WITH EARLY ANOMALY SCAN: TIME TO RECONSIDER].

INTRODUCTION: During the last decades, a major achievement was reported in detecting Down's syndrome in the first trimester of pregnancy. This is attributed to the use of high-resolution accurate ultrasound machine allowing the detection of a "nuchal translucency" in the back of the fetus during 11-14 weeks' gestation. This is considered to be a physiologic finding, but when increased, may alert for chromosomal abnormality (mainly Down's syndrome), cardiac and other organ anomalies and other genetic syndromes. Later additional sonographic findings were found, including nasal bone assessment, and Doppler flow studies of the ductus venosus and tricuspid regurgitation Technology advancement accompanied by sonographers' skills enhancement allows (at the time frame of the nuchal scan) a detailed anomaly scan. Additional screening for pregnancy complication was achieved using first trimester multi marker assessment, alerting for preeclamptic toxemia or placenta accreta. Currently, many national and international professional organizations recommend performing the nuchal scan concurrent with an early anomaly scan both at the same time of gestation. This approach is different than the one performed in Israel, whereas the nuchal scan is conducted separately and 2-3 weeks later an anomaly scan is offered. We call for reconsideration of the sequential approach and performing all the tests in a comprehensive first trimester clinic.

Improved differentiation between hypo/hypertelorism and normal fetuses based on MRI using automatic ocular biometric measurements, ocular ratios, and machine learning multi-parametric classification.

OBJECTIVES: To differentiate hypo-/hypertelorism (abnormal) from normal fetuses using automatic biometric measurements and machine learning (ML) classification based on MRI. METHODS: MRI data of normal (n = 244) and abnormal (n = 52) fetuses of 22-40 weeks' gestational age (GA), scanned between March 2008 and June 2020 on 1.5/3T systems with various T2-weighted sequences and image resolutions, were included. A fully automatic method including deep learning and geometric algorithms was developed to measure the binocular (BOD), inter-ocular (IOD), ocular (OD) diameters, and ocular volume (OV). Two new parameters, BOD-ratio and IOD-ratio, were defined as the ratio between BOD/IOD relative to the sum of both globes' OD, respectively. Eight ML classifiers were evaluated to detect abnormalities using measured and computed parameters. RESULTS: The automatic method yielded a mean difference of BOD = 0.70 mm, IOD = 0.81 mm, OD = 1.00 mm, and a 3D-Dice score of OV = 93.7%. In normal fetuses, all four measurements increased with GA. Constant values were detected for BOD-ratio = 1.56 ± 0.05 and IOD-ratio = 0.60 ± 0.05 across all GA and when calculated from previously published reference data of both MRI and ultrasound. A random forest classifier yielded the best results on an independent test set (n = 58): AUC-ROC = 0.941 and F1-Score = 0.711 in comparison to AUC-ROC = 0.650 and F1-Score = 0.385 achieved based on the accepted criteria that define hypo/hypertelorism based on IOD (< 5th or > 95th percentiles). Using the explainable ML method, the two computed ratios were found as the most contributing parameters. CONCLUSIONS: The developed fully automatic method demonstrates high performance on varied clinical imaging data. The new BOD and IOD ratios and ML multi-parametric classifier are suggested to improve the differentiation of hypo-/hypertelorism from normal fetuses. KEY POINTS: • A fully automatic method for computing fetal ocular biometry from MRI is proposed, achieving high performance, comparable to that of an expert fetal neuro-radiologist. • Two new parameters, IOD-ratio and BOD-ratio, are proposed for routine clinical use in ultrasound and MRI. These two ratios are constant across gestational age in normal fetuses, consistent across studies, and differentiate between fetuses with and without hypo/hypertelorism. • Multi-parametric machine learning classification based on automatic measurements and the two new ratios improves the identification of fetal ocular anomalies beyond the accepted criteria (<5th or >95th IOD percentiles).

A Scoring System Developed by a Machine Learning Algorithm to Better Predict Adnexal Torsion.

STUDY OBJECTIVE: To establish a clinically relevant prediction score for the diagnosis of adnexal torsion (AT) in women who were operated on for suspected AT. DESIGN: A retrospective cohort study conducted between 2014 and 2021. SETTING: A large tertiary teaching medical center. PATIENTS: Women who underwent urgent laparoscopy for suspected AT. INTERVENTIONS: Analyses included univariate and multivariate models combined with the machine learning (ML) Random Forest model, which included all information available about the women and reported the accuracy of the model and the importance of each variable. Based on this model, we created a predictive score and evaluated its accuracy by receiver operating characteristic (ROC) curve. MEASUREMENTS AND MAIN RESULTS: A total of 503 women were included in our study, 244 (49%) of whom were diagnosed with AT during the surgery, and 44 (8.8%) cases of necrotic ovary were found. Based on the Random Forrest and multivariate models, the most important preoperative clinical predictive variables for AT were vomiting, left-side complaints, and concurrent pregnancy; cervical tenderness and urinary symptoms decreased the likelihood of surgically confirmed AT. The most important sonographic findings that predicted increased risk of surgically confirmed AT were ovarian edema and decreased vascular flow; in contrast, hemorrhagic corpus luteum decreased the likelihood of surgically confirmed AT. The accuracy of the Random Forest model was 71% for the training set and 68% for the testing set, and the area under the curve for the multivariate model was 0.75 (95% confidence interval [CI] 0.69-0.80). Based on these models, we created a predictive score with a total score that ranges from 4 to 12. The area under the curve for this score was 0.72 (95% CI 0.67-0.76), and the best cutoff for the final score was >5, with a sensitivity, specificity, positive predictive value, and negative predictive value of 64%, 73%, 70%, and 67%, respectively. CONCLUSION: Clinical characteristics and ultrasound findings may be incorporated into the emergency room workup of women with suspected AT. ML in this setting has no diagnostic/predictive advantage over the performance of logistic regression methods. Additional prospective studies are needed to confirm the accuracy of this model.

[THE DIFFERENTIAL DIAGNOSIS OF EXTREMELY HIGH MATERNAL SERUM ALPHA FETOPROTEIN - A CASE REPORT].

INTRODUCTION: A 34 years-old woman was referred to genetic counseling due to extremely high maternal serum alpha fetoprotein (MSAFP) of 58 MoM (541 IU/mL, 654 ng/mL) in the second trimester biochemical test. The couple has five healthy children, three of them were delivered by cesarean section. Current pregnancy follow-up was uneventful except for the demonstration of placenta percreta during anomaly scan. The test also ruled out neural tube or abdominal wall defect. AFP levels in amniotic fluid were normal thus fetal disease was ruled out as the etiology. Total body MRI ruled out space occupying lesion as a source of ectopic secretion of AFP. After exclusion of other ominous etiologies for this extremely high MSAFP, it was related to the placental pathology and probably to abnormal feto-maternal shunts. Fetal fraction in cell free DNA was 18%, considered relatively high, a hint for those speculated shunts. We reviewed the literature regarding the differential diagnosis of high MSAFP including fetal, maternal and placental sources.

Bi-allelic PAGR1 variants are associated with microcephaly and a severe neurodevelopmental disorder: Genetic evidence from two families.

Exome and genome sequencing were used to identify the genetic etiology of a severe neurodevelopmental disorder in two unrelated Ashkenazi Jewish families with three affected individuals. The clinical findings included a prenatal presentation of microcephaly, polyhydramnios and clenched hands while postnatal findings included microcephaly, severe developmental delay, dysmorphism, neurologic deficits, and death in infancy. A shared rare homozygous, missense variant (c.274A > G; p.Ser92Gly, NM_024516.4) was identified in PAGR1, a gene currently not associated with a Mendelian disease. PAGR1 encodes a component of the histone methyltransferase MLL2/MLL3 complex and may function in the DNA damage response pathway. Complete knockout of the murine Pagr1a is embryonic-lethal. Given the available evidence, PAGR1 is a strong candidate gene for a novel autosomal recessive severe syndromic neurodevelopmental disorder.

An integrated model of preeclampsia: a multifaceted syndrome of the maternal cardiovascular-placental-fetal array.

Maternal tolerance of the semiallogenic fetus necessitates conciliation of competing interests. Viviparity evolved with a placenta to mediate the needs of the fetus and maternal adaptation to the demands of pregnancy and to ensure optimal survival for both entities. The maternal-fetal interface is imagined as a 2-dimensional porous barrier between the mother and fetus, when in fact it is an intricate multidimensional array of tissues and resident and circulating factors at play, encompassing the developing fetus, the growing placenta, the changing decidua, and the dynamic maternal cardiovascular system. Pregnancy triggers dramatic changes to maternal hemodynamics to meet the growing demands of the developing fetus. Nearly a century of extensive research into the development and function of the placenta has revealed the role of placental dysfunction in the great obstetrical syndromes, among them preeclampsia. Recently, a debate has arisen questioning the primacy of the placenta in the etiology of preeclampsia, asserting that the maternal cardiovascular system is the instigator of the disorder. It was the clinical observation of the high rate of preeclampsia in hydatidiform mole that initiated the focus on the placenta in the etiology of the disease. Over many years of research, shallow trophoblast invasion with deficient remodeling of the maternal spiral arteries into vessels of higher capacitance and lower resistance has been recognized as hallmarks of the preeclamptic milieu. The lack of the normal decrease in uterine artery resistance is likewise predictive of preeclampsia. In abdominal pregnancies, however, an extrauterine pregnancy develops without remodeling of the spiral arteries, yet there is reduced resistance in the uterine arteries and distant vessels, such as the maternal ophthalmic arteries. Proponents of the maternal cardiovascular model of preeclampsia point to the observed maternal hemodynamic adaptations to pregnancy and maladaptation in gestational hypertension and preeclampsia and how the latter resembles the changes associated with cardiac disease states. Recognition of the importance of the angiogenic-antiangiogenic balance between placental-derived growth factor and its receptor soluble fms-like tyrosine kinase-1 and disturbance in this balance by an excess of a circulating isoform, soluble fms-like tyrosine kinase-1, which competes for and disrupts the proangiogenic receptor binding of the vascular endothelial growth factor and placental-derived growth factor, opened new avenues of research into the pathways to normal adaptation of the maternal cardiovascular and other systems to pregnancy and maladaptation in preeclampsia. The significance of the "placenta vs heart" debate goes beyond the academic: understanding the mutuality of placental and maternal cardiac etiologies of preeclampsia has far-reaching clinical implications for designing prevention strategies, such as aspirin therapy, prediction and surveillance through maternal hemodynamic studies or serum placental-derived growth factor and soluble fms-like tyrosine kinase-1 testing, and possible treatments to attenuate the effects of insipient preeclampsia on women and their fetuses, such as RNAi therapy to counteract excess soluble fms-like tyrosine kinase-1 produced by the placenta. In this review, we will present an integrated model of the maternal-placental-fetal array that delineates the commensality among the constituent parts, showing how a disruption in any component or nexus may lead to the multifaceted syndrome of preeclampsia.

Boosting maternal and neonatal humoral immunity following SARS-CoV-2 infection using a single messenger RNA vaccine dose.

BACKGROUND: Post-COVID-19 vaccine boosting is a potent tool in the ongoing pandemic. Relevant data regarding this approach during pregnancy are lacking, which affects vaccination policy guidance, public acceptance, and vaccine uptake during pregnancy. We aimed to investigate the dynamics of anti-SARS-CoV-2 antibody levels following SARS-CoV-2 infection during pregnancy and to characterize the effect of a single postinfection vaccine booster dose on the anti-SARS-CoV-2 antibody levels in parturients in comparison with the levels in naïve vaccinated and convalescent, nonboosted parturients. STUDY DESIGN: Serum samples prospectively collected from parturients and umbilical cords at delivery at our university-affiliated urban medical center in Jerusalem, Israel, from May to October 2021, were selected and analyzed in a case-control manner. Study groups comprised the following participants: a consecutive sample of parturients with a polymerase chain reaction-confirmed history of COVID-19 during any stage of pregnancy; and comparison groups selected according to time of exposure comprising (1) convalescent, nonboosted parturients with polymerase chain reaction-confirmed COVID-19; (2) convalescent parturients with polymerase chain reaction-confirmed COVID-19 who received a single booster dose of the BNT162b2 messenger RNA vaccine; and (3) infection-naïve, fully vaccinated parturients who received 2 doses of the BNT162b2 messenger RNA vaccine. Outcomes that were determined included maternal and umbilical cord blood anti-SARS-CoV-2 antibody levels detected at delivery, the reported side effects, and pregnancy outcomes. RESULTS: A total of 228 parturients aged 18 to 45 years were included. Of those, samples from 64 were studied to characterize the titer dynamics following COVID-19 at all stages of pregnancy. The boosting effect was determined by comparing (1) convalescent (n=54), (2) boosted convalescent (n=60), and (3) naïve, fully vaccinated (n=114) parturients. Anti-SARS-CoV-2 antibody levels detected on delivery showed a gradual and significant decline over time from infection to delivery (r=0.4371; P=.0003). Of the gravidae infected during the first trimester, 34.6% (9/26) tested negative at delivery, compared with 9.1% (3/33) of those infected during the second trimester (P=.023). Significantly higher anti-SARS-CoV-2 antibody levels were observed among boosted convalescent than among nonboosted convalescent (17.6-fold; P<.001) and naïve vaccinated parturients (3.2-fold; P<.001). Similar patterns were observed in umbilical cord blood. Side effects in convalescent gravidae resembled those in previous reports of mild symptoms following COVID-19 vaccination during pregnancy. CONCLUSION: Postinfection maternal humoral immunity wanes during pregnancy, leading to low or undetectable protective titers for a marked proportion of patients. A single boosting dose of the BNT162b2 messenger RNA vaccine induced a robust increase in protective titers for both the mother and newborn with moderate reported side effects.

The many etiologies of nonimmune hydrops fetalis diagnosed by exome sequencing.

OBJECTIVE: To explain the importance of identifying an etiology for the pathological finding of nonimmune hydrops fetalis (NIHF) and to explore the impact of exome sequencing in recurrent NIHF. In addition, we present two cases of pregnancies affected with recurrent NIHF, in which genetic investigation was advantageous. METHODS: Our study aimed to investigate the genetic background, if available, of all fetuses with NIHF referred to our tertiary medical center from January 2013 to August 2020. We summarized the etiology of NIHF if known, sonographic findings, genetic investigation and the pregnancies' outcomes. RESULTS: We encountered 144 families with NIHF. Genetic investigation was performed by chromosomal microarray analysis (CMA) in 63 (63/144. 44%) fetuses. Seventeen of 63 (27%) had a positive CMA result. In the negative CMA group, 15 (15/46, 33%) opted for exome sequencing, of which seven exomes were positive (47%). Among these, there were four couples with recurrent pregnancies affected by hydrops. Among the remaining 11 exome investigations for non-recurrent hydrops, another three were diagnostic. CONCLUSION: As identifying the etiology of the NIHF is an invaluable tool for the prognosis of the pregnancy, exome sequencing can provide further elucidation of the underlying pathogenesis of NIHF. Thus, genetic investigation should be recommended for cases of NIHF.

Vaginal birth after cesarean in women with no prior vaginal delivery carrying a large for gestational age baby.

BACKGROUND: To study the factors associated with successful labor after cesarean (LAC) among women with no prior vaginal delivery, delivering a large for gestational age (LGA) baby. METHODS: A retrospective case-control study at two tertiary medical centers in Israel, including all women undergoing LAC with no prior vaginal delivery during 2010-2020, delivering a singleton LGA newborn. Factors associated with successful vaginal delivery were examined by a multivariable analysis. RESULTS: Overall, 323/505 (64.0%) had a successful LAC. Arrest of labor as the indication for previous CD was less common in the LAC success group [39 (12.1%) vs. 58 (31.9%), P < .001]. The rate of epidural analgesia was higher in the LAC success group [249 (77.1%) vs. 122 (67.0%), P = .014]. The rate of weight centile ≥97th was lower in the LAC success group [64 (19.8%) vs. 51 (28.0%), P = .035], as well as the rate of higher LAC birthweight than previous cesarean birthweight [264 (81.7%) vs. 162 (89.0%), P = .030]. In a multivariable logistic regression analysis, maternal height (aOR [95% CI]:1.09 (1.01, 1.17), P = .014) and epidural anesthesia (aOR [95% CI]:3.68 (1.31, 10.32), P = .013) were the only independent factors associated with LAC success. CONCLUSIONS: Among primiparous women undergoing LAC carrying LGA newborns, the vaginal delivery rate is acceptable; however, uterine rupture risk is increased. Epidural administration is a modifiable factor and should be taken into consideration during LAC management.

Prediction of successful preterm vaginal birth after cesarean among women who never delivered vaginally.

PURPOSE: We aimed to determine the factors associated with a successful trial of labor after cesarean (TOLAC) in the setting of preterm delivery of women with no prior vaginal delivery. METHODS: A retrospective cohort study conducted at two tertiary medical centers during 2010-2020, including all TOLACs with a single cesarean delivery and no prior vaginal delivery, delivering a singleton preterm newborn. Factors associated with successful vaginal delivery were examined by multivariable analysis. RESULTS: Of the 232 women with TOLAC who constituted the study cohort, 178 (76.7%) successfully delivered vaginally. Previous cesarean delivery characteristics did not differ between study groups. Maternal characteristics did not differ between TOLAC success and failure groups. The median gestational age at delivery was 35 3/7 weeks (IQR 34 0/7-36 0/7). The rate of epidural analgesia administration was higher in the TOLAC success group (54.5% vs. 35%, p = 0.013). Preterm premature rupture of membranes (PPROM) rate was lower in the TOLAC success group (53.9% vs. 83%, p < 0.001). The rate of induction of labor did not differ between TOLAC success and TOLAC failure groups. There were no cases of uterine rupture. In a multivariable logistic regression analysis, PPROM was the only independent factor associated with TOLAC success [adjusted OR (95% CI) 0.29 (0.10-0.83), p = 0.030]. CONCLUSION: TOLAC in preterm deliveries among women with no prior vaginal delivery is safe, has a high success rate and PPROM is the only negatively associated predictor.

Trial of labor after cesarean in primiparous women with fetal macrosomia.

KEY MESSAGE: Spontaneous labor onset, epidural anesthesia and prior cesarean for non-arrest disorders are strong predictors of successful vaginal birth after cesarean in women delivering a macrosomic fetus. PURPOSE: Lower rates of successful vaginal birth after cesarean in association with increasing birthweight were previously reported. We aimed to determine the factors associated with successful trial of labor after cesarean (TOLAC) among primiparous women with fetal macrosomia. METHODS: A retrospective cohort study conducted during 2005-2019 at two university hospitals, including all primiparous women delivering a singleton fetus weighing ≥ 4000 g, after cesarean delivery at their first delivery. A multivariate analysis was performed to evaluate the characteristics associated with TOLAC success (primary outcome). RESULTS: Of 551 primiparous women who met the inclusion criteria, 50.1% (n = 276) attempted a TOLAC and 174 (63.0%) successfully delivered vaginally. In a multivariate analysis, spontaneous onset of labor (aOR [95% CI] 3.68 (2.05, 6.61), P < 0.001), epidural anesthesia (aOR [95% CI] 2.38 (1.35, 4.20), P = 0.003) and history of cesarean delivery due to non-arrest disorder (aOR [95% CI] 2.25 (1.32, 3.85), P = 0.003) were the only independent factors associated with TOLAC success. Successful TOLAC was achieved in 82.0% (82/100) in the presence of all three favorable factors, 61.3% (65/106) in the presence of two factors and 38.6% (27/70) in the presence of one or less of these three factors (P < 0.001). CONCLUSION: Spontaneous onset of labor, epidural anesthesia and prior cesarean delivery due to non-arrest disorders were independently associated with higher vaginal birth after cesarean rate among women with fetal macrosomia, with an overall favorable success rate in the presence of these factors. These findings should be implemented in patient counseling in those contemplating a vaginal birth in this setting.

Normal labor curve in twin gestation.

BACKGROUND: Failure to progress is one of the leading indications for cesarean delivery in trials of labor in twin gestations. However, assessment of labor progression in twin labors is managed according to singleton labor curves. OBJECTIVE: This study aimed to establish a partogram for twin deliveries that reflects normal and abnormal labor progression and customized labor curves for different subgroups of twin labors. STUDY DESIGN: This was a multicenter, retrospective cohort analysis of twin deliveries that were recorded in 3 tertiary medical centers between 2003 and 2017. Eligible parturients were those with twin gestations at ≥34 weeks' gestation with cephalic presentation of the presenting twin and ≥2 cervical examinations during labor. Exclusion criteria were elective cesarean delivery without a trial of labor, major fetal anomalies, and fetal demise. The study group comprised twin gestations, whereas singleton gestations comprised the control group. Statistical analysis was performed using Python 3.7.3 and SPSS, version 27. Categorical variables were analyzed using chi-square tests. Student t test and Mann-Whitney U test were applied to analyze the differences in continuous variables, as appropriate. RESULTS: A total of 1375 twin deliveries and 142,659 singleton deliveries met the inclusion criteria. Duration of the active phase of labor was significantly longer in twin labors than in singleton labors in both nulliparous and multiparous parturients; the 95th percentile duration was 2 hours longer in nulliparous twin labors and >3.5 hours longer in multiparous twin labors than in singleton labors. The cervical dilation progression rate was significantly slower in twin deliveries than in singleton deliveries with a mean rate in twin deliveries of 1.89 cm/h (95th percentile, 0.51 cm/h) and a mean rate of 2.48 cm/h (95th percentile, 0.73 cm/h) in singleton deliveries (P<.001). In addition, epidural use further slowed labor progression in twin deliveries. The second stage of labor was also markedly longer in twin deliveries, both in nulliparous and multiparous women (95th percentile, 3.04 vs 2.83 hours, P=.002). CONCLUSION: Twin labors are characterized by a slower progression of the active phase and second stage of labor compared with singleton labors in nulliparous and multiparous parturients. Epidural analgesia further slows labor progression in twin labors. Implementation of these findings in clinical management might lower cesarean delivery rates among cases with protracted labor in twin gestations.

Transporting an Artificial Intelligence Model to Predict Emergency Cesarean Delivery: Overcoming Challenges Posed by Interfacility Variation.

Research using artificial intelligence (AI) in medicine is expected to significantly influence the practice of medicine and the delivery of health care in the near future. However, for successful deployment, the results must be transported across health care facilities. We present a cross-facilities application of an AI model that predicts the need for an emergency caesarean during birth. The transported model showed benefit; however, there can be challenges associated with interfacility variation in reporting practices.

The Relation between Head Circumference and Mid-Pelvic Circumference: A Simple Index for Cephalopelvic Disproportion Evaluation.

INTRODUCTION: Cephalopelvic disproportion (CPD) is one of the most common obstetric complications. Since CPD is the disproportion between the fetal head and maternal bony pelvis, evaluation of the head circumference (HC) relative to the maternal bony pelvis may be a useful adjunct to pre-labor CPD evaluation. The aim of the present study was a proof-of-concept evaluation of the ratio between HC and pelvic circumference (PC) as a predictor of CPD. METHODS: Of 11,822 deliveries, 104 cases that underwent an abdominopelvic CT for any medical indication and who underwent normal vaginal deliveries (NVDs) (n = 84) or cesarean deliveries (CD) due to CPD (n = 20) were included retrospectively. Maternal pelvis dimensions were reconstructed and neonatal HC, as a proxy for fetal HC, was measured. The correlation between cases of CPD and cephalopelvic circumference index (CPCI), which represents the ratio between the HC and PC in percentage (HC/PC × 100), was evaluated. RESULTS: The mid-pelvis CPCI (MP-CPCI) was larger in CD groups as compared to the NVD group: 103 ± 11 versus 97 ± 8%, respectively (p = 0.0003). In logistic regression analysis, the MP-CPCI was found to be independently associated with CD due to CPD: each 1% increase in MP-CPCI increased the likelihood of CD for CPD by 11% (adjusted odds ratio [aOR] 1.11, 95% CI, 1.03-1.19, p = 0.004). The aOR for CD due to CPD increased incrementally as the MP-CPCI increased, from 3.56 (95% CI, 1.01-12.6) at MP-CPCI of 100 to 5.6 (95% CI, 1.63-19.45) at 105, 21.44 (95% CI, 3.05-150.84) at 110, and 28.88 (95% CI, 2.3-362.27) at MP-CPCI of 115. CONCLUSIONS: The MP-CPCI, representing the relative dimensions of the fetal HC and maternal PC, is a simple tool that can potentially distinguish between parturients at lower and higher risk of CPD. Prospective randomized studies are required to evaluate the feasibility of prenatal pelvimetry and MP-CPCI to predict the risk of CPD during labor.

Real-time data analysis using a machine learning model significantly improves prediction of successful vaginal deliveries.

BACKGROUND: The process of childbirth is one of the most crucial events in the future health and development of the offspring. The vulnerability of parturients and fetuses during the delivery process led to the development of intrapartum monitoring methods and to the emergence of alternative methods of delivery. However, current monitoring methods fail to accurately discriminate between cases in which intervention is unnecessary, partly contributing to the high rates of cesarean deliveries worldwide. Machine learning methods are applied in various medical fields to create personalized prediction models. These methods are used to analyze abundant, complex data with intricate associations to aid in decision making. Initial attempts to predict vaginal delivery vs cesarean deliveries using machine learning tools did not utilize the vast amount of data recorded during labor. The data recorded during labor represent the dynamic process of labor and therefore may be invaluable for dynamic prediction of vaginal delivery. OBJECTIVE: We aimed to create a personalized machine learning-based prediction model to predict successful vaginal deliveries using real-time data acquired during the first stage of labor. STUDY DESIGN: Electronic medical records of labor occurring during a 12-year period in a tertiary referral center were explored and labeled. Four different models were created using input from multiple maternal and fetal parameters. Initial risk assessments for vaginal delivery were calculated using data available at the time of admission to the delivery unit, followed by models incorporating cervical examination data and fetal heart rate data, and finally, a model that integrates additional data available during the first stage of labor was created. RESULTS: A total of 94,480 cases in which a trial of labor was attempted were identified. Based on approximately 180 million data points from the first stage of labor, machine learning models were developed to predict successful vaginal deliveries. A model using data available at the time of admission to the delivery unit yielded an area under the curve of 0.817 (95% confidence interval, 0.811-0.823). Models that used real-time data increased prediction accuracy. A model that includes real-time cervical examination data had an initial area under the curve of 0.819 (95% confidence interval, 0.813-0.825) at first examination, which increased to an area under the curve of 0.917 (95% confidence interval, 0.913-0.921) by the end of the first stage. Adding the real-time fetal heart monitor data provided an area under the curve of 0.824 (95% confidence interval, 0.818-0.830) at first examination, which increased to an area under the curve of 0.928 (95% confidence interval, 0.924-0.932) by the end of the first stage. Finally, adding additional real-time data increased the area under the curve initially to 0.833 (95% confidence interval, 0.827-0.838) at the first cervical examination and up to 0.932 (95% confidence interval, 0.928-0.935) by the end of the first stage. CONCLUSION: Real-time data acquired throughout the process of labor significantly increased the prediction accuracy for vaginal delivery using machine learning models. These models enable translation and quantification of the data gathered in the delivery unit into a clinical tool that yields a reliable personalized risk score and helps avoid unnecessary interventions.