Transcription Factor PU.1 Represses and Activates Gene Expression in Early T Cells by Redirecting Partner Transcription Factor Binding.

Transcription factors normally regulate gene expression through their action at sites where they bind to DNA. However, the balance of activating and repressive functions that a transcription factor can mediate is not completely understood. Here, we showed that the transcription factor PU.1 regulated gene expression in early T cell development both by recruiting partner transcription factors to its own binding sites and by depleting them from the binding sites that they preferred when PU.1 was absent. The removal of partner factors Satb1 and Runx1 occurred primarily from sites where PU.1 itself did not bind. Genes linked to sites of partner factor "theft" were enriched for genes that PU.1 represses despite lack of binding, both in a model cell line system and in normal T cell development. Thus, system-level competitive recruitment dynamics permit PU.1 to affect gene expression both through its own target sites and through action at a distance.

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.

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.

Combinatorial Assembly of Modular Glucosides via Carboxylesterases Regulates C. elegans Starvation Survival.

The recently discovered modular glucosides (MOGLs) form a large metabolite library derived from combinatorial assembly of moieties from amino acid, neurotransmitter, and lipid metabolism in the model organism C. elegans. Combining CRISPR-Cas9 genome editing, comparative metabolomics, and synthesis, we show that the carboxylesterase homologue Cel-CEST-1.2 is responsible for specific 2-O-acylation of diverse glucose scaffolds with a wide variety of building blocks, resulting in more than 150 different MOGLs. We further show that this biosynthetic role is conserved for the closest homologue of Cel-CEST-1.2 in the related nematode species C. briggsae, Cbr-CEST-2. Expression of Cel-cest-1.2 and MOGL biosynthesis are strongly induced by starvation conditions in C. elegans, one of the premier model systems for mechanisms connecting nutrition and physiology. Cel-cest-1.2-deletion results in early death of adult animals under starvation conditions, providing first insights into the biological functions of MOGLs.

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.

Prediction of vaginal birth after cesarean deliveries using machine learning.

BACKGROUND: Efforts to reduce cesarean delivery rates to 12-15% have been undertaken worldwide. Special focus has been directed towards parturients who undergo a trial of labor after cesarean delivery to reduce the burden of repeated cesarean deliveries. Complication rates are lowest when a vaginal birth is achieved and highest when an unplanned cesarean delivery is performed, which emphasizes the need to assess, in advance, the likelihood of a successful vaginal birth after cesarean delivery. Vaginal birth after cesarean delivery calculators have been developed in different populations; however, some limitations to their implementation into clinical practice have been described. Machine-learning methods enable investigation of large-scale datasets with input combinations that traditional statistical analysis tools have difficulty processing. OBJECTIVE: The aim of this study was to evaluate the feasibility of using machine-learning methods to predict a successful vaginal birth after cesarean delivery. STUDY DESIGN: The electronic medical records of singleton, term labors during a 12-year period in a tertiary referral center were analyzed. With the use of gradient boosting, models that incorporated multiple maternal and fetal features were created to predict successful vaginal birth in parturients who undergo a trial of labor after cesarean delivery. One model was created to provide a personalized risk score for vaginal birth after cesarean delivery with the use of features that are available as early as the first antenatal visit; a second model was created that reassesses this score after features are added that are available only in proximity to delivery. RESULTS: A cohort of 9888 parturients with 1 previous cesarean delivery was identified, of which 75.6% of parturients (n=7473) attempted a trial of labor, with a success rate of 88%. A machine-learning-based model to predict when vaginal delivery would be successful was developed. When features that are available at the first antenatal visit are used, the model showed a receiver operating characteristic curve with area under the curve of 0.745 (95% confidence interval, 0.728-0.762) that increased to 0.793 (95% confidence interval, 0.778-0.808) when features that are available in proximity to the delivery process were added. Additionally, for the later model, a risk stratification tool was built to allocate parturients into low-, medium-, and high-risk groups for failed trial of labor after cesarean delivery. The low- and medium-risk groups (42.4% and 25.6% of parturients, respectively) showed a success rate of 97.3% and 90.9%, respectively. The high-risk group (32.1%) had a vaginal delivery success rate of 73.3%. Application of the model to a cohort of parturients who elected a repeat cesarean delivery (n=2145) demonstrated that 31% of these parturients would have been allocated to the low- and medium-risk groups had a trial of labor been attempted. CONCLUSION: Trial of labor after cesarean delivery is safe for most parturients. Success rates are high, even in a population with high rates of trial of labor after cesarean delivery. Application of a machine-learning algorithm to assign a personalized risk score for a successful vaginal birth after cesarean delivery may help in decision-making and contribute to a reduction in cesarean delivery rates. Parturient allocation to risk groups may help delivery process management.

Cervical dilation at the time of epidural catheter insertion is not associated with the degree of prolongation of the first or second stages of labor, or the rate of instrumental vaginal delivery.

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Unplanned Cesarean Delivery in the Second Stage of Labor Holds Higher Odds of Complications than in the First Stage, while Similar in Primiparas and Multiparas.

BACKGROUND: While endeavors to reduce cesarean delivery (CD) rates are given priority worldwide, it is important to evaluate if these efforts place parturients and neonates at risk. CD performed in the second stage of labor carries higher risks of maternal and fetal complications and is a more challenging surgical procedure than that performed in the first stage or before labor. In a population with a low CD rate, we sought to evaluate the rate of maternal and fetal complications associated with unplanned CD (UCD) performed in the second vs. the first stage of labor, in primiparas and multiparas, as well as the risk factors leading to and the complications associated with UCD in the second stage of labor in this low-CD rate setting. METHODS: This was a retrospective, electronic medical record-based study of 7,635 term and preterm singletons born via UCD in the period 2003-2015. Maternal and neonatal background and outcome parameters were compared between groups. Logistic regression modeling was applied to adjust for clinically and statistically significant risk factors. RESULTS: UCD was more likely to be performed in the second stage of labor in mothers delivering larger fetuses (head circumference and body weight ≥90 centile) and those with persistent occiput posterior (POP) presentation. UCD in the second stage was strongly associated with serious maternal complications (excessive hemorrhage and fever) compared to UCD performed in the first stage, in both primiparas and multiparas. CONCLUSIONS: UCD performed in the second stage of labor, while less frequent than first-stage UCD, is more likely with larger neonates and POP presentation, and is associated with a higher rate of maternal complications in primiparas and multiparas. Complication rates in our low-CD-rate population did not exceed those reported in the literature from high-CD-rate areas.

Sonographic large fetal head circumference and risk of cesarean delivery.

BACKGROUND: Persistently high rates of cesarean deliveries are cause for concern for physicians, patients, and health systems. Prelabor assessment might be refined by identifying factors that help predict an individual patient's risk of cesarean delivery. Such factors may contribute to patient safety and satisfaction as well as health system planning and resource allocation. In an earlier study, neonatal head circumference was shown to be more strongly associated with delivery mode and other outcome measures than neonatal birthweight. OBJECTIVE: In the present study we aimed to evaluate the association of sonographically measured fetal head circumference measured within 1 week of delivery with delivery mode. STUDY DESIGN: This was a multicenter electronic medical record-based study of birth outcomes of primiparous women with term (37-42 weeks) singleton fetuses presenting for ultrasound with fetal biometry within 1 week of delivery. Fetal head circumference and estimated fetal weight were correlated with maternal background, obstetric, and neonatal outcome parameters. Elective cesarean deliveries were excluded. Multinomial regression analysis provided adjusted odds ratios for instrumental delivery and unplanned cesarean delivery when the fetal head circumference was ≥35 cm or estimated fetal weight ≥3900 g, while controlling for possible confounders. RESULTS: In all, 11,500 cases were collected; 906 elective cesarean deliveries were excluded. A fetal head circumference ≥35 cm increased the risk for unplanned cesarean delivery: 174 fetuses with fetal head circumference ≥35 cm (32%) were delivered by cesarean, vs 1712 (17%) when fetal head circumference <35 cm (odds ratio, 2.49; 95% confidence interval, 2.04-3.03). A fetal head circumference ≥35 cm increased the risk of instrumental delivery (odds ratio, 1.48; 95% confidence interval, 1.16-1.88), while estimated fetal weight ≥3900 g tended to reduce it (nonsignificant). Multinomial regression analysis showed that fetal head circumference ≥35 cm increased the risk of unplanned cesarean delivery by an adjusted odds ratio of 1.75 (95% confidence interval, 1.4-2.18) controlling for gestational age, fetal gender, and epidural anesthesia. The rate of prolonged second stage of labor was significantly increased when either the fetal head circumference was ≥35 cm or the estimated fetal weight ≥3900 g, from 22.7% in the total cohort to 31.0%. A fetal head circumference ≥35 cm was associated with a higher rate of 5-minute Apgar score ≤7: 9 (1.7%) vs 63 (0.6%) of infants with fetal head circumference <35 cm (P = .01). The rate among fetuses with an estimated fetal weight ≥3900 g was not significantly increased. The rate of admission to the neonatal intensive care unit did not differ among the groups. CONCLUSION: Sonographic fetal head circumference ≥35 cm, measured within 1 week of delivery, is an independent risk factor for unplanned cesarean delivery but not instrumental delivery. Both fetal head circumference ≥35 cm and estimated fetal weight ≥3900 g significantly increased the risk of a prolonged second stage of labor. Fetal head circumference measurement in the last days before delivery may be an important adjunct to estimated fetal weight in labor management.

Higher Rates of Operative Delivery and Maternal and Neonatal Complications in Persistent Occiput Posterior Position with a Large Head Circumference: A Retrospective Cohort Study.

INTRODUCTION: We investigated whether large head circumference (HC) combined with persistent occiput posterior (OP) position is associated with higher rates of operative delivery and obstetric and neonatal complications than OP deliveries without large HC or in occiput anterior (OA) position. MATERIALS AND METHODS: Term singleton deliveries in our centers from January 2010 to December 2014, delivered in cephalic OA (n = 41,038) or OP position (n = 1,740), were assessed. We compared delivery modes, maternal and neonatal complications in OA versus OP deliveries, and HC ≥90th centile versus HC <90th centile in persistent OP position. RESULTS: Persistent OP position combined with HC ≥90th centile was associated with higher rates of vacuum extraction and unplanned cesarean delivery than HC <90th centile in OP position (20.1 vs. 17.2%, OR 1.53 [95% CI 0.99-2.36], and 23.4 vs. 9.2%, OR 3.326 [95% CI 2.17-5.11], respectively). Rates of prolonged second stage of labor and neonatal intensive care unit admission were also increased compared to those in either OA position with HC ≥90th centile or OP position with HC <90th centile. DISCUSSION: Large HC combined with OP position is associated with higher rates of operative delivery and prolonged second stage of labor compared to OP delivery with HC <90th centile. HC might be included with other measures to assess women in labor, as it is associated with fetal outcomes in OP deliveries.

[PROLONGED SECOND STAGE OF LABOR: CAUSES AND OUTCOMES].

INTRODUCTION: Professional bodies have published guidelines defining the length of the second stage of labor and when it is "prolonged", according to parity and epidural anesthesia administration. Recently these guidelines have been extended, aiming to reduce rates of unplanned cesarean deliveries. AIMS: To examine the risk factors and outcomes of a prolonged second stage of labor, in order to understand its causes and implications for mothers and neonates, including the delivery mode. METHODS: A retrospective study based on 26,476 electronic medical records of deliveries to primiparous mothers of a term singleton fetus, at Hadassah Medical Center, between 2003 and 2015. RESULTS: A prolonged second stage of labor was recorded in 3,225 (12.2%) of mothers (i.e. exceeding 2 hours without epidural anesthesia and 3 hours with it). Epidural anesthesia, persistent occiput posterior, and head circumference or birth weight above the 90th percentile, increased the risk of the prolonged second stage. The risk of unplanned cesarean delivery rose significantly before the 2- or 3-hour cut-off defining a prolonged second stage. Risks of maternal and neonatal complications included: grade III-IV perineal tear, maternal hemorrhage, 5-minute Apgar≤7, umbilical artery pH<7.1, neonatal intensive care admission were also increased. CONCLUSIONS: Epidural anesthesia and fetal parameters increased the risk of prolonged second stage; risks of maternal and fetal complications were also increased. The risk of interventional delivery increased significantly well before the defined cut-off. DISCUSSION: Prolongation of the second stage of labor is a common pathway of many obstetric outcomes. Obstetric management should be based on considerations of individual maternal and neonatal well-being, rather than administrative goals. While reducing cesarean rates is an important goal, attempts to achieve this by prolonging the second stage of labor exposes mothers and neonates to excess risk of cesarean and vacuum delivery as well as obstetric and neonatal complications.

Biosynthesis of Modular Ascarosides in C. elegans.

The nematode Caenorhabditis elegans uses simple building blocks from primary metabolism and a strategy of modular assembly to build a great diversity of signaling molecules, the ascarosides, which function as a chemical language in this model organism. In the ascarosides, the dideoxysugar ascarylose serves as a scaffold to which diverse moieties from lipid, amino acid, neurotransmitter, and nucleoside metabolism are attached. However, the mechanisms that underlie the highly specific assembly of ascarosides are not understood. We show that the acyl-CoA synthetase ACS-7, which localizes to lysosome-related organelles, is specifically required for the attachment of different building blocks to the 4'-position of ascr#9. We further show that mutants lacking lysosome-related organelles are defective in the production of all 4'-modified ascarosides, thus identifying the waste disposal system of the cell as a hotspot for ascaroside biosynthesis.

Third- or Fourth-Degree Intrapartum Anal Sphincter Tears Are Associated With Levator Ani Avulsion in Primiparas.

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, 2.18­5.7). 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.

Third- or Fourth-Degree Intrapartum Anal Sphincter Tears Are Associated With Levator Ani Avulsion in Primiparas.

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.

A large head circumference is more strongly associated with unplanned cesarean or instrumental delivery and neonatal complications than high birthweight.

OBJECTIVE: Fetal size impacts on perinatal outcomes. We queried whether the fetal head, as the fetal part interfacing with the birth canal, might impact on obstetric outcomes more than birthweight (BW). We examined associations between neonatal head circumference (HC) and delivery mode and risk of perinatal complications as compared to high BW. STUDY DESIGN: This was an electronic medical records-based study of term singleton births (37-42 weeks' gestation) from January 2010 through December 2012 (N = 24,780, 6343 primiparae). We assessed risks of unplanned cesarean or instrumental delivery and maternal and fetal complications in cases with HC or BW ≥95th centile (large HC, high BW) vs those with parameters <95th centile (normal). Newborns were stratified into 4 subgroups: normal HC/normal BW (reference, n = 22,548, primiparae 5862); normal HC/high BW (n = 817, P = 213); large HC/normal BW (n = 878, P = 265); and large HC/high BW (n = 537, P = 103). Multinomial multivariable regression provided adjusted odds ratio (aOR) while controlling for potential confounders. RESULTS: Infants with HC ≥95th centile (n = 1415) were delivered vaginally in 62% of cases, unplanned cesarean delivery 16%, and instrumental delivery 11.2%; 78.4% of infants with HC <95th centile were delivered vaginally, 7.8% unplanned cesarean, and 6.7% instrumental delivery. Odds ratio (OR) for unplanned cesarean was 2.58 (95% confidence interval [CI], 2.22-3.01) and for instrumental delivery OR was 2.13 (95% CI, 1.78-2.54). In contrast, in those with BW ≥95th centile (n = 1354) 80.3% delivered vaginally, 10.2% by unplanned cesarean (OR, 1.2; 95% CI, 1.01-1.44), and 3.4% instrumental delivery (OR, 0.46; 95% CI, 0.34-0.62) compared to infants with BW <95th centile: spontaneous vaginal delivery, 77.3%, unplanned cesarean 8.2%, instrumental 7.1%. Multinomial regression with normal HC/normal BW as reference group showed large HC/normal BW infants were more likely to be delivered by unplanned cesarean (aOR, 3.08; 95% CI, 2.52-3.75) and instrumental delivery (aOR, 3.03; 95% CI, 2.46-3.75). Associations were strengthened in primiparae. Normal HC/high BW was not associated with unplanned cesarean (aOR, 1.18; 95% CI, 0.91-1.54), while large HC/high BW was (aOR, 1.93; 95% CI, 1.47-2.52). Analysis of unplanned cesarean indications showed large HC infants had more failure to progress (27.7% vs 14.1%, P < .001), while smaller HC infants had more fetal distress (23.4% vs 16.9%, P < .05). CONCLUSION: A large HC is more strongly associated with unplanned cesarean and instrumental delivery than high BW. Prospective studies are needed to test fetal HC as a predictive parameter for prelabor counseling of women with "big babies."