Fixed-time interval vs on-demand oral analgesia after vaginal delivery: a randomized controlled trial.

BACKGROUND: Scheduled administration of analgesics was proven superior to on-demand dosing following cesarean deliveries. However, this protocol was not compared after vaginal delivery. OBJECTIVE: To compare the efficacy of a fixed- vs on-demand analgesic protocol for the management of pain in the first 24 hours after a vaginal delivery. STUDY DESIGN: This randomized, prospective, controlled trial was conducted at a single tertiary medical center between June 1, 2020 and June 30, 2022. Vaginally delivered patients were randomly assigned to receive oral analgesics (paracetamol 1 g + ibuprofen 400 mg) either every 6 hours for the first 24 hours postpartum (scheduled analgesia group) or as needed (on-demand group). Pain level during the first 24 hours postdelivery was measured using a 10-point visual analog scale. RESULTS: A total of 200 patients were randomized 1:1 to the 2 cohorts. Baseline and delivery characteristics, including oxytocin augmentation, epidural anesthesia, episiotomy rate, and neonatal birthweight, were comparable between groups. Patients in the scheduled group received more paracetamol and ibuprofen doses in the first 24 hours (2.9±1.3 and 2.9±1.2 doses vs 0.8±1.1 and 0.7±1.1 doses, respectively; P<.001). Pain score was comparable between study groups (5.31±1.92 vs 5.29±1.67; P=.626) even after subanalysis for primiparity, episiotomy, and vacuum-assisted delivery (P>.05). However, patients on a fixed treatment schedule were more likely to breastfeed their baby (98% vs 88%; P=.006) as than those receiving treatment on demand. In addition, they were more satisfied with their labor and delivery experience, as evaluated by Birth Satisfaction Scale questionnaires quality control (37.9±4.7 vs 31.1±5.2; P=.0324), patient attributes (35.0±5.1 vs 30.3±6.3; P=.0453), and stress experienced (58.1±8.5 vs 50.1±8.3; P=.0398). No side effects or adverse outcomes were reported in either group. CONCLUSION: A scheduled analgesic protocol for postpartum pain management following vaginal delivery revealed similar pain scores compared with an on-demand protocol, although it was associated with higher breastfeeding rates and higher maternal satisfaction.

Hypoxia leads to diminished ovarian reserve in an age dependent manner.

OBJECTIVES: Perinatal hypoxia causes premature activation and initiation of growth in dormant follicles, leading to diminished ovarian reserve. An indirect mechanism such as the release of stress-related hormones, may influence ovarian follicle recruitment under hypoxic conditions. We wanted to determine whether hypoxic ovarian damage results from increased follicle growth and "burnout" or from increased apoptosis, and whether this damage is age-dependent. DESIGN: Animal study Participants/Materials, Setting, Methods: Using adult 6-week-old (n=8) and one-day-old newborn (n=20) ICR (CD-1) female mice, ovarian follicular counts were conducted on H&E-stained sections. METHODS: Immunohistochemistry was performed on sections stained with Ki-67, anti-Caspase 3 and anti-FOXO3A. RESULTS: Exposure to hypoxia resulted in significantly reduced proportion of primordial follicles vs normoxia in both adult dams and newborn pups (3.17±2.75% vs. 17.89±4.4%; p=0.004; 40.59±14.88% vs. 81.92±31.56%, p=0.001, respectively), concomitant with increased growing- primary and secondary follicles, and more pronounced in adult dams vs newborn pups (6-fold vs. 2-fold, respectively). Ki67 staining revealed higher scores of cell proliferation in follicular granulosa cells after exposure to hypoxia than normoxia. However, Caspase 3 and Foxo3A staining did not show any differences in these markers of apoptosis in oocytes, granulosa cells, theca cells, or stromal cells when exposed to hypoxia versus normoxia. LIMITATIONS: The current study has several limitations; first, the sample size for each group is relatively small, which could limit the generalizability of the findings. Second, the study uses an ex vivo culture system, which may not fully capture the complex interactions that occur in the whole animal. Third, the exposure to hypoxia only lasted for 3 hours, which may not be long enough to observe all the potential effects. In addition, the study only analyzed specific markers of apoptosis in a few cell types, and other cell types or apoptotic pathways might be involved. Lastly, the study provides evidence for accelerated follicular activation and decreased ovarian reserve, but the underlying mechanisms are not fully explored. Conclusions Direct tissue hypoxia led to premature activation and initiation of growth in dormant follicles leading to diminished ovarian reserve. Hypoxic damage is age-dependent, with adult ovaries more susceptible than newborn ovaries. These findings support the possibility of follicular "burn out" as a potential mechanism responsible for hypoxia-induced loss of ovarian reserve.

Exploring the Optimal Intertwin Delivery Interval for Vaginal Delivery.

The effect of prolonged intertwin delivery interval (IDI) is not well studied. This work aimed to assess the inflection point for Cesarean delivery (CD) and associated adverse maternal and neonatal outcomes. This was a retrospective cohort study at a single tertiary care center. The study included women with twin pregnancies in 2010-2019 who reached the second stage of labor, and assessed the most predictive cutoff for CD using Youden J statistic and compared adverse maternal and neonatal outcomes between short and prolonged intertwin delivery intervals. A total of 461 gravidas reached the second stage of labor and were included in the study. Using the ROC curve and Youden J statistic, the IDI cutoff was set at 15 min (80% sensitivity, 75% specificity, p < 0.001), with 312 women in the short and 149 in the prolonged IDI groups. Women in the prolonged IDI group were less likely to deliver the second twin vaginally (75.8% vs. 93.3%, p < 0.001). Postpartum hemorrhage (PPH) (39.1% vs. 24.7%, p = 0.01), and placental abruption (4% vs. 1%, p = 0.03) were more likely to occur in the prolonged IDI group. An increased rate of neonatal acidemia and low 5-min Apgar score were also found in the prolonged IDI group (15.7% vs. 4.3%, P = 0.01, 9.7% vs. 3.5%, p = 0.008; respectively). IDIs of more than 15 min are associated with increased risk of adverse maternal and neonatal outcomes. These findings should be used for counseling and managing twin pregnancies attempting vaginal delivery.

The optimal cutoff for intertwin delivery interval: A retrospective cohort study.

OBJECTIVE: To determine the cutoff of intertwin delivery intervals (IDIs) as a predictor for neonatal acidemia. METHOD: This retrospective cohort study was conducted at a single tertiary care center. Women attempting vaginal delivery of twins between 2010 and 2019 and who reached the second stage of labor were included. The cutoff point for prolonged IDI was established using a receiver operating characteristic (ROC) curve and Youden's J statistic. Maternal and neonatal outcomes were compared between short and prolonged IDI cohorts. RESULTS: A total of 461 women were included in the study. A cutoff time of 10 min was found to be the best predictor for neonatal acidemia (arterial cord pH ≤ 7.1), with a sensitivity of 90% and a specificity of 59%. Second twins delivered more than 10 min after the first twin were more likely to be acidemic and to have a 5-min Apgar score of 7 or less (13.5% vs 3.3%, P = 0.01, and 8.4% vs 3.2%, P = 0.02, respectively). An IDI of more than 10 min was also associated with increased rate of cesarean delivery and placental abruption (13.5% vs 0.8%, P < 0.001, and 3.4% vs 0.8%, P = 0.047, respectively). No other adverse maternal or neonatal outcomes were statistically significant between cohorts. CONCLUSION: An IDI of more than 10 min is associated with a higher risk for neonatal academia, with a low 5-min Apgar score, and higher cesarean delivery and placental abruption rates. These findings provide insights that are valuable when counseling and managing twin pregnancies attempting vaginal delivery. Interventions aimed at shortening the IDI should be considered to prevent adverse neonatal outcomes.

Does delayed vacuum-assisted delivery harbor greater maternal or neonatal complications?

OBJECTIVE: To compare maternal and fetal outcomes between early (<2 h) and delayed (>2 h) vacuum extraction (VE) deliveries. METHODS: We performed a retrospective cohort study in a single, university-affiliated medical center (2014-2021). We included term singleton pregnancies delivered by VE, allocated into one of two groups according to second stage duration: <2 h or >2 h. Primary outcome was maternal composite adverse outcome (included chorioamnionitis, 3-4 degree lacerations, and postpartum hemorrhage [PPH]). RESULTS: We included 2521 deliveries: 2261 (89.6%) with early VE and 260 (10.4%) with delayed VE. Study groups' characteristics were not different, except of parity. Maternal composite outcome almost reached a significance (P = 0.054) comparing between the groups. Comparing second stage length up to 2 h versus more, there was similar rate of advance maternal lacerations. However, extending the second stage to more than 3 h was associated with third degree lacerations compared to 2-3 h (9.8% vs 3%, P = 0.011). There were significantly more PPH events in the later VE group (P = 0.004), but the need for blood transfusions was similar. The rates of 5 min Apgar score ≤7 (P = 0.001) and umbilical artery pH <7.0 were significantly higher in group 2 compared with group 1. The effect was much more pronounced when second stage was >3 h. After conducting multiregression analysis, the results became insignificant. CONCLUSION: Our study suggests that VE performed in the late second stage of labor, up to 3 h, is safe as VE performed in the early stages regarding maternal and neonatal outcomes. Extra caution is needed with extended second stage to more than 3 h.

Pre-labour Rupture of Membranes at Term in Women With Gestational Diabetes and the Risk of Neonatal Hypoglycemia.

OBJECTIVES: The management for improving maternal and neonatal outcomes of women with gestational diabetes mellitus (GDM) arriving at the delivery ward with pre-labour rupture of membranes (PROM) has not been elucidated. We tested the hypothesis that prolonged PROM in women with GDM would result in higher rates of neonatal hypoglycemia. METHODS: We retrospectively enrolled women with diet or insulin-controlled GDM who presented with spontaneous clear PROM. Each woman was allocated into one of two groups based on the PROM-delivery time: <18 hours (group 1) and ≥18 hours (group 2). The primary outcome was the incidence of neonatal hypoglycemia, defined as glucose <40 mg/dL (2.2 mmol/L) within 24 hours of birth. RESULTS: We ultimately analyzed 631 cases of GDM (6.7%), 371 with PROM-delivery <18 hours, and 260 with PROM-delivery ≥18 hours. The incidence of neonatal hypoglycemia did not differ between the two groups, reaching 7.3%. Women in group 2 were at increased risk of both cesarean delivery (20% vs. 12.4%, P < 0.01) and maternal chorioamnionitis morbidity (6.5% vs. 1.3%, P < 0.001). CONCLUSIONS: In a sub-group of women with GDM, a PROM-delivery time ≥18 hours is not associated with higher rates of neonatal hypoglycemia, but higher rates of chorioamnionitis and cesarean delivery were noted. Therefore, we suggest consideration for early delivery when managing women with GDM and PROM.

Fetal Renal Duplicated Collecting System at 14-16 Weeks of Gestation.

(1) Background: To examine the incidence of the prenatal diagnosis of the renal double-collecting system (rDCS) and describe its clinical outcome and associated genetic abnormalities. (2) Methods: This retrospective study included women who attended the obstetric clinic for early fetal anatomic sonography with findings of a renal DCS. Diagnosis was conducted by an expert sonographer using defined criteria. (3) Results: In total, 29,268 women underwent early ultrasound anatomical screening at 14-16 weeks, and 383 cases of rDCS were diagnosed (prevalence: 1:76). Associated abnormalities were diagnosed in eleven pregnancies; four had chromosomal aberrations. No chromosomal abnormalities were reported in isolated cases. Ectopic uretrocele and dysplastic kidney were diagnosed in 6 (1.5%) and 5 (1.3%) fetuses, respectively. One girl was diagnosed with vesicoureteral reflux and recurrent UTIs, and two boys were diagnosed with undescended testis. The recurrence rate of rDCS was 8% in subsequent pregnancies. (4) Conclusions: In light of its benign nature, we speculate that isolated rDCS may be considered a benign anatomic variant, but a repeat examination in the third trimester is recommended to assess hydronephrosis.

Continuous vs intermittent induction of labor with oxytocin in nulliparous patients: a randomized controlled trial.

BACKGROUND: Oxytocin is considered the drug of choice for the induction of labor, although the optimal protocol and infusion duration remain to be determined. OBJECTIVE: This study aimed to assess whether the duration of oxytocin infusion increases 24-hour delivery rates and affects the length of time-to-delivery and patient's experience. STUDY DESIGN: A randomized controlled trial was performed at a single tertiary medical center, between January 1, 2020 and June 30, 2022. Nulliparous patients with a singleton pregnancy at a vertex presentation and a Bishop score ≥6 were randomly assigned to receive either continuous (16 hours, with a 4 hours pause in between infusions) or intermittent (8 hours, with a 4 hours pause in between infusions) oxytocin infusion, until delivery. In both groups, infusion was halted when signs of maternal or fetal compromise were observed. Randomization was conducted with a computer randomization sequence generation program. The primary outcome was delivery within 24 hours from the first oxytocin infusion and the secondary outcome included time-to-delivery, mode of delivery, and additional maternal and neonatal outcomes. Seventy-two patients per group were randomized to reach 80% statistical power with a 20% difference in the primary outcome according to previous studies. RESULTS: A total of 153 patients were randomized, 72 to the continuous oxytocin infusion group and 81 to the intermittent infusion group. The total oxytocin infusion time was similar between the groups. Patients in the continuous arm were more likely to deliver within 24 hours from oxytocin initiation (79.73% vs 62.96%, P<.05), and had a shorter oxytocin-to-delivery time interval, compared with patients receiving intermittent treatment (9.3±3.7 hours vs 21±11.7 hours, P<.001). Furthermore, time from ruptured membranes to delivery was shorter (9.3±3.7 hours vs 21±11.7 hours; P<.0001) and chorioamnionitis was less frequent (9.46% vs 21%; P<.05) in the continuous compared with the intermittent arm. Cesarean delivery rate was 20% in both groups (P=.226). There was no difference in postpartum hemorrhage, or adverse neonatal outcomes between the groups. Patients receiving continuous oxytocin infusion were more satisfied with the birthing experience. CONCLUSION: Continuous infusion of oxytocin for labor induction in nulliparous patients with a favorable cervix may be superior to intermittent oxytocin infusion, because it shortens time-to-delivery, decreases chorioamnionitis rate, and improves maternal satisfaction, without affecting adverse maternal or neonatal outcomes.

Two distinct molecular faces of preeclampsia revealed by single-cell transcriptomics.

INTRODUCTION: Preeclampsia is a multisystemic, pregnancy-specific disorder united by new-onset hypertension but with considerable variation in clinical manifestation, onset, and severity. For symptoms to regress, delivery of the placenta is required. For symptoms to regress, delivery of the placenta is required, making the placenta central to preeclampsia pathophysiology. To dissect which placental functions were impacted in two forms of preeclampsia, we studied molecular changes across the cell types of the placenta. METHODS: We performed a transcriptomic survey of single-cells and single-nuclei on cases of early- and late-onset preeclampsia with gestation-matched controls. FINDINGS: Our data revealed massive dysregulation of gene expression in all cell classes that was almost exclusive to early preeclampsia. For example, an important known receptor/ligand imbalance hallmarking angiogenic disfunction, sFLT1/placental growth factor (PGF), was reflected in striking, cell-autonomous dysregulation of FLT1 and PGF transcription in the syncytium in early preeclampsia only. Stromal cells and vasculature echoed an inflamed, stressed, anti-angiogenic environment. Finally, the placental immune niche set the tone for inflammation in early but not late preeclampsia. Here, fetal-origin Hofbauer and maternal-origin TREM2 macrophages were revealed as surprising main actors, while local cells of the adaptive immune system were largely unaffected. Late preeclampsia showed minimal cellular impact on the placenta. CONCLUSIONS: Our survey provides systematic molecular evidence for two distinct diseases. We resolved systematic molecular dysregulation to individual cell types with strong implications for definition, early detection, diagnosis, and treatment. FUNDING: Funded by the Preeclampsia Foundation through the Peter Joseph Pappas Research Grant.

Risk Factors for Prolonged Intertwin Delivery Interval and Associated Maternal and Second Twin Morbidity.

OBJECTIVE: This work aimed to identify possible risk factors and the morbidity associated with prolonged intertwin delivery interval (IDI). STUDY DESIGN: A retrospective cohort study at a single tertiary care center. Women with twin gestations who reached the second stage of labor between January 2010 and December 2019 were included in the study. Demographic and clinical characteristics were compared between short IDI (≤15 minutes) and prolonged IDI (>15 minutes). The primary outcome was the rate of 5-minute Apgar score ≤ 7. RESULTS: A total of 461 women were included; 312 of whom were in the short IDI group and 149 were in the prolonged IDI group. Rates of 5-minute Apgar score ≤ 7 and neonatal acidemia were significantly higher in the prolonged IDI group (3.5 vs. 9.7%, p = 0.008; 4.3 vs. 15.7%, p = 0.01, respectively). Vaginal delivery was less likely to occur in the prolonged IDI group (75.8 vs. 93.3%). Placental abruption and hemoglobin drop ≥ 3 g/dL were more prevalent in the prolonged IDI group (4 vs. 1%, p = 0.03; 39.1 vs. 24.7%, p = 0.01, respectively). In the multivariate analysis, age ≥ 30 years (adjusted odds ratio [aOR]: 1.76, p = 0.01), nulliparity (aOR: 1.66, p = 0.03), and birth weight ratio ≥ 1.2 (aOR: 1.92, p < 0.05) were associated with prolonged IDI. CONCLUSION: Prolonged IDI is associated with an increased risk for neonatal acidemia and low 5-minute Apgar score, and with an increased rate of cesarean delivery, placental abruption, and hemoglobin drop ≥ 3 g/dL. Advanced maternal age, nulliparity, and twin birth weight ratio ≥ 1.2 are associated with prolonged IDI. KEY POINTS: · Prolonged was found to be associated with higher neonatal acidemia and lower 5-minute Apgar score.. · Prolonged IDI is also associated with increased rate of cesarean delivery, placental abruption, and blood loss.. · Advanced maternal age, birth weight discordancy, and nulliparity were associated with prolonged IDI..

Intermittent vs continuous catheterization for postpartum urinary retention: A multicenter randomized controlled trial.

BACKGROUND: Postpartum urinary retention is a common complication in the immediate postpartum period. However, there is no consensus regarding optimal management. OBJECTIVE: This study aimed to compare 2 catheterization strategies for the treatment of postpartum urinary retention. STUDY DESIGN: A multicenter prospective randomized controlled trial was conducted at 4 university-affiliated medical centers between January 2020 and June 2022. Individuals with postpartum urinary retention (bladder volume of >150 mL) up to 6 hours after vaginal or cesarean delivery were randomly allocated to 1 of 2 protocols: intermittent catheterization every 6 hours, up to 4 times, or continuous catheterization with an indwelling urinary catheter for 24 hours. If postpartum urinary retention was not resolved after 24 hours, an indwelling catheter was inserted for an additional 24 hours in both groups. The primary endpoint was the mean time to postpartum urinary retention resolution. The secondary endpoints included postcatheter urinary tract infection rate and length of hospital stay. The satisfaction rate was estimated using the 30-Item Birth Satisfaction Scale questionnaire. RESULTS: After randomization, 73 individuals were allocated to the intermittent catheterization group, and 74 individuals were allocated to the continuous catheterization group. The mean time to postpartum urinary retention resolution was significantly shorter in the intermittent catheterization group than in the continuous catheterization group (10.2±11.8 vs 26.5±9.0 hours; P<.001), with 75% and 93% resolution rates after 1 and 2 catheterizations, respectively. The number of individuals who achieved resolution at 24 hours was 72 (99%) in the intermittent catheterization group and 67 (91%) in the continuous catheterization group (P=.043). The satisfaction rate was higher in all categories in the intermittent catheterization group than in the continuous catheterization group (P<.001). No intercohort difference was found in the urinary tract infection rates (P=.89) or hospital stay length (P=.58). CONCLUSION: Compared with indwelling catheterization, intermittent catheterization for urinary retention after delivery was associated with quicker postpartum urinary retention resolution and a higher satisfaction rate without increasing the complication rates.

The impact of extending the second stage of labor on repeat cesarean section and maternal and neonatal outcome.

OBJECTIVE: To evaluate the effects of extending the second stage of labor in women attempting a trial of labor after a cesarean section (TOLAC). METHOD: A retrospective cohort study comparing maternal and neonatal outcomes following TOLAC over two periods: period I whose prolonged second stage was considered 2 h, and period II whose prolonged second stage was considered 3 h. The primary outcome was repeat cesarean delivery (CD) rate. RESULTS: Incidence of repeat CD was significantly lower in period II (18.1% vs 29.7%, P < 0.001). Incidence of uterine rupture was significantly higher in period II (P < 0.001). Instrumental delivery rates were significantly higher in period II (26.2% vs 15.6%, odds ratio [OR] 1.67, 95% CI 1.21-3.56, P < 0.001). Rates of third- and fourth-degree perineal lacerations, chorioamnionitis, and length of hospital stay were similar between groups. Incidence of fetal acidemia was significantly higher in period II (1.5% vs 0.7%, OR 2.14, 95% CI 1.32-5.63, P < 0.001), and incidence of neonatal intensive care unit (NICU) admission was significantly higher (2.5% vs 1.6%, P = 0.004). CONCLUSION: Extension of the second stage of labor is associated with a decrease in repeat CD rate with a concomitant increase in instrumental delivery rates, uterine rupture, fetal acidemia, and NICU admissions. These findings may warrant further consideration of allowing a prolonged second stage in patients attempting TOLAC.

The optimal induction timing in prelabor rupture of membranes: a retrospective study.

OBJECTIVE: Term prelabour rupture of membrane (PROM) occurs in 8% of term deliveries, but it is unclear when to initiate induction. Our objective was to assess the optimal timing of oxytocin induction in the management of term PROM in terms of maternal and neonatal outcomes. METHODS: A retrospective cohort study was performed at a single tertiary care center from 2010 to 2020. All singleton pregnancies with PROM beyond 37 weeks gestation, without regular uterine contractions, were included. Eligible women were divided into three groups according to the timing of oxytocin induction (≤12; 12-24; ≥24 h) following PROM. RESULTS: Of 9,443 women presented with the term PROM, 1676 were included. They were classified according to the timing of oxytocin induction initiation following PROM: 1,127 within 12 h; 285 within 12-24 h; 264 after 24 h. There were no significant differences in baseline demographic characteristics between groups. Women who presented at our emergency department were induced earlier delivered significantly sooner than those who received oxytocin later (45 vs. 28.2 vs. 23.2 h, respectively, p < .001. Maternal infection rate was similar and unrelated to oxytocin starting time. Induction at <12 h from PROM was associated with reduced rate of antibiotic administration compared with other timings (26.8% vs. 38.6% vs. 33.33%, respectively; p < .001), and the same was found for neonatal composite adverse outcomes (RR = 1.27, p = .0307). CONCLUSION: In term PROM, early induction (within 12 h of PROM) may be recommended to reduce the time-do-delivery interval and increase the delivery rate within 24 h. It may be of economic significance and improve women satisfaction. Furthermore, early induction may also improve neonatal outcomes, without worsening maternal outcomes.

Intestine and brain TLR-4 modulation following N-acetyl-cysteine treatment in NEC rodent model.

Necrotizing enterocolitis (NEC) brain injury is mediated through Toll-like receptor 4 (TLR4) on the intestinal epithelium and brain microglia. Our aim was to determine whether postnatal and/or prenatal NAC can modify NEC associated intestinal and brain TLR4 expression and brain glutathione levels in a rat model of NEC. Newborn Sprague-Dawley rats were randomized into three groups: Control (n = 33); NEC (n = 32)-hypoxia and formula feeding; and NEC-NAC (n = 34)-received NAC (300 mg/kg IP) in addition to NEC conditions. Two additional groups included pups of dams treated once daily with NAC (300 mg/kg IV) for the last 3 days of pregnancy: NAC-NEC (n = 33) or NAC-NEC-NAC (n = 36) with additional postnatal NAC. Pups were sacrificed on the fifth day, and ileum and brains harvested for TLR-4 and glutathione protein levels. Brain and ileum TLR-4 protein levels were significantly increased in NEC offspring as compared to control (brain 2.5 ± 0.6 vs. 0.88 ± 0.12 U and ileum 0.24 ± 0.04 vs. 0.09 ± 0.01, p < 0.05). When NAC was administered only to dams (NAC-NEC) a significant decrease in TLR-4 levels was demonstrated in both offspring brain (1.53 ± 0.41 vs. 2.5 ± 0.6 U, p < 0.05) and ileum (0.12 ± 0.03 vs. 0.24 ± 0.04 U, p < 0.05) as compared to NEC. The same pattern was demonstrated when NAC was administered only or postnatally. The decrease in brain and ileum glutathione levels observed in NEC offspring was reversed with all NAC treatment groups. NAC reverses the increase in ileum and brain TLR-4 levels and the decrease in brain and ileum glutathione levels associated with NEC in a rat model, and thus may protect from NEC associated brain injury.

Associations of maternal and placental extracellular vesicle miRNA with preeclampsia.

Introduction: Gestational vascular complications (GVCs), including gestational hypertension and preeclampsia, are leading causes of maternal morbidity and mortality. Elevated levels of extracellular vesicles (EVs), in GVC have been linked to vascular injury. This study aims to characterize placental and circulating EV miRNA in GVCs, and explores the involvement of EV-miRNA in GVC, and whether they may be used to distinguish between placental and maternal pathologies. Methods: Blood samples were obtained from 15 non-pregnant (NP), 18 healthy-pregnant (HP), and 23 women with GVC during the third trimester. Placental sections were obtained after caesarian section. Platelet-poor-plasma (PPP) and EV pellets were characterized: EV size/concentration, protein content and miRNA expression were measured by nanoparticle tracking analysis, western blot, nano-string technology and RT-PCR. The effects of EVs on trophoblasts and EC miRNA expression were evaluated. Results: Higher EVs concentrations were observed in HP-PPP and GVC-PPP (p < 0.0001) compared to the NP-PPP. The concentration of large EVs (>100 nm) was higher in PPP and EV pellets of HP and GVC compared to the NP group. EV pellets of pregnant women demonstrated lower expression of exosomal markers CD63/CD81 compared to NP-EVs. GVC-EVs expressed more human placental lactogen (hPL) hormone than HP-EVs, reflecting their placental origin. Screening of miRNAs in EV pellets and in PPP identified certain miRNAs that were highly expressed only in EVs pellets of the HP (13%) and GVC groups (15%), but not in the NP group. Differences were detected in the expression of hsa-miR-16-5p, hsa-miR-210, and hsa-miR-29b-3p. The expression of hsa-miR-16-5p and hsa-miR-210 was low in EV pellets obtained from NP, higher in HP-EVs, and significantly lower in GVC-EVs. Except for hsa-miR-29b-3p, which was upregulated in GVC, no significant differences were found in the levels of other miRNAs in placental sections. Exposure to GVC-EVs resulted in higher expression of hsa-miR-29b-3p compared to cells exposed to HP-EVs in villous trophoblasts, but not in EC. Conclusion: Expression of hsa-miR-16-5p and hsa-miR-210 reflects maternal pathophysiological status, while hsa-miR-29b-3p reflects placental status. These findings suggest that EV-miRNA are involved in GVC, and that they may be used to distinguish between pathologies of placental and maternal origins in preeclampsia.

COVID-19 Quarantine and Sexual Function after First Vaginal Delivery.

OBJECTIVES: Sexual function is an important part of quality of life at all ages. Childbirth brings many changes that may affect sexual function. During COVID-19 global pandemic, nuclear families were forced to stay home. The goal of this study was to evaluate sexual function during the COVID-19 quarantine, in postpartum couples in the first months following their first vaginal childbirth. DESIGN: This is a single-center, prospective study of females following their first vaginal delivery and their male partners. Participants were recruited in the maternity ward after their first delivery at Rambam Medical Center. Both spouses signed a consent form for answering the sexual function questionnaires. PARTICIPANTS: Participants were interviewed by telephone during the last week of the first COVID-19 quarantine, according to Arizona Sexual Experience Scale (ASEX). MAIN OUTCOME MEASURES: pre- and post-quarantine sexual function according to ASEX scores. ASEX is a survey that assesses sexual drive, arousal, vaginal lubrication, the ability to reach orgasm, and satisfaction from orgasm. Responses are scored on a 1-6 Likert scale with a potential range of 5-30, where the highest scores indicate worse sexual function. RESULTS: The participants were 38 women and 29 men. The average time from delivery to the interviews was 182.8 ± 84.7 days; 56% of the spouses were under quarantine. The median baseline total ASEX score was 13 (sexual drive 3, arousal 2.5, vaginal lubrication 2.5, ability to reach orgasm 2, orgasm satisfaction 2) for women and 11 (sexual drive 3, arousal 2, penile erection 1, ability to reach orgasm 2, orgasm satisfaction 2) for men. Sixteen percent of the women and none of the men had a baseline sexual dysfunction (ASEX score >19). Significant differences were not observed in total ASEX scores before and during the quarantine. LIMITATIONS: Sexual function at the end of the quarantine was evaluated prospectively and pre-quarantine sexual function was evaluated retrospectively, with the limitation of recall bias. CONCLUSIONS: COVID-19 quarantine did not seem to have a significant effect on female or male sexual function, three to 9 months after the first vaginal delivery. The current study is the first to describe primiparous postpartum sexual function as median ASEX score.

Late preterm delivery has a distinctive second-stage duration and characteristics.

BACKGROUND: Late preterm neonates born between 34.0 and 36.6 weeks' gestation are at increased risk for short- and long-term morbidity and mortality when compared with their term counterparts. Currently, no separate labor curve is available for late preterm births, and this group's optimal duration of the second stage of labor has never been defined separately. OBJECTIVE: This study aimed to compare the second stage duration between late preterm and term births. STUDY DESIGN: This was a retrospective study from May 2014 until May 2021. Eligible were women with a singleton pregnancy, vertex presentation, spontaneous or induced onset of labor, and those who delivered vaginally beyond 34.0 weeks of gestation. The primary outcome of our study was to compare and characterize the second stage of labor duration between late preterm and term births. RESULTS: We analyzed 962 late preterm and 9476 term vaginal deliveries. Women who delivered during the late preterm period were more likely to be multiparous (52.4% vs 45.2%; P<.001) and fewer required oxytocin during labor (41.2% vs 54.4%; P<.001) or used epidural analgesia (75.2% vs 83.6%; P<.001). The overall mean duration of the second stage of labor was significantly shorter in the late preterm period than at term (1.08±1.09 hours vs 1.49±1.22 hours; P<.001). This was even more pronounced for nulliparous women (1.05±1.00 hours vs 2.10±1.17 hours; P<.001). Among multiparous women, epidural use significantly affected the duration of the second stage of labor, and the second stage was relatively longer during the late preterm period than at term in this subgroup (1.16 vs 0.5 hours; P<.001). Using a multivariate Cox regression, variables such as maternal age (hazard ratio, 1.02; 95% confidence interval, 1.01-1.04), parity (hazard ratio, 4.11; 95% confidence interval, 3.65-4.63), preterm birth (hazard ratio, 2.08; 95% confidence interval, 1.4-3.10), and birthweight at delivery (hazard ratio, 1.15; 95% confidence interval, 1.01-1.30) shortened the second stage, whereas induction of labor (hazard ratio, 0.75; 95% confidence interval, 0.66-0.86) and epidural use (hazard ratio, 0.68; 95% confidence interval, 0.64-0.86) extended its total duration. Regardless of parity, lower rates of operative vaginal deliveries were observed in the late preterm period than at term (3.7% vs 15.5%; P<.001). This period was also associated with lower rates of third- and fourth-degree perineal lacerations (0.2% vs 2.2%; P<.001) but higher rates of chorioamnionitis (1.7% vs 0.1%; P<.001), Apgar score at 5 minutes <7 (1.0% vs 0.2%; P<.001), and admission to the neonatal intensive care unit (19.3% vs 1.0%; P<.001). CONCLUSION: Women who delivered vaginally during the late preterm period had a distinctive second-stage duration. Primarily, it was shown to be significantly shorter for nulliparous and multiparous women. Future studies should further clarify the optimal duration of this stage in relation to neonatal outcomes at such a vulnerable period.

Q fever screening among pregnant women with pre-term delivery in northern Israel: An observational study.

The relationship between Q fever, caused by Coxiella burnetii, and obstetrical complications is debatable. Since Q fever is endemic in Israel, we aimed to assess its seroprevalence and clinical characteristics in pre-term deliveries. Between 1 August 2017 and 31 December 2019, we conducted serological screening for C. burnetii in pregnant women who presented to Rambam Health Care Campus with pre-term delivery (before 37 weeks of gestation). Anti-C. burnetii antibodies were tested first by enzyme-linked immunosorbent assay for the detection of phase I-IgG, phase II-IgG and phase II-IgM. Positive results were confirmed by indirect immunofluorescence with titre determination. Seropositivity was classified into past, acute and chronic infection. Demographic and clinical data of mothers and neonates were collected and compared between seropositive and seronegative women. Out of 386 pregnant women screened for anti-C. burnetii antibodies, 16 (4.1%) were seropositive, of whom three were diagnosed with past, 12 with acute and one with chronic infection. A higher percentage of seropositive women were immunosuppressed, 2/16 (12.5%) compared with 7/370 (1.9%) in seronegative women, (p = .05). Neonates with small for gestational age were born to 2/16 (12.5%) seropositive women compared with 29/370 (7.8%) to seronegative women, (p = .35). The seroprevalence of Q fever among pregnant women with pre-term birth reached 4% in northern Israel. This high rate in an endemic setting encourages investigating the role of routine screening for Q fever during pregnancy. Special attention should be given to pregnant immunosuppressed women at risk for exposure to Q fever.

Postpartum cervical length as a predictor of subsequent preterm birth-novel insights on an old enigma.

BACKGROUND: Preterm birth poses one of the biggest challenge in modern obstetrics. Prediction of preterm birth has previously been based on patient history of preterm birth, short cervical length around midtrimester, and additional maternal risk factors. Little is known about cervical length and physiology during the postpartum period and any associations between postpartum cervical features and subsequent preterm birth. OBJECTIVE: This study aimed to determine the feasibility and utility of postpartum cervical length measurements in prediction of subsequent spontaneous preterm birth. STUDY DESIGN: This was a prospective cohort study in a single tertiary center, conducted during a 5-year period (2017-2021). We evaluated the mean postpartum cervical length in patients after both preterm birth and term deliveries at 4 time periods: 8, 24, and 48 hours, and 6 weeks postpartum, with follow-up in their subsequent pregnancies to evaluate gestational age at delivery. The mean postpartum cervical length in different populations stratified by gestational age at delivery was assessed in phase 1 of the study, and the gestational age at subsequent delivery was assessed in phase 2. RESULTS: A total of 1384 patients participated in phase 1. Mean postpartum cervical length was significantly shorter in the preterm birth (<34 weeks' gestation) group than in the term group at 8 hours (8.4±4.2 vs 22.3±3.5 mm; P<.0001), 24 hours (13.2±3.8 vs 33.2±3.1 mm; P<.0001), and 48 hours (17.9±4.4 vs 40.2±4.2 mm; P<.0001) postpartum. There was no significant difference in mean postpartum cervical length between the preterm birth group and the term group at 8, 24, and 48 hours postpartum. Cervical length was similar between the groups at 6 weeks postpartum. A total of 891 patients participated in phase 2. The area under the curve was higher for preterm birth screening based on a history of a short postpartum cervix alone than for a history of spontaneous preterm birth alone (0.66 [95% confidence interval, 0.63-0.69] vs 0.57 [95% confidence interval, 0.54-0.61]; P<.0001). Combining both a history of spontaneous preterm birth and a short postpartum cervix resulted in additional benefit, with an area under the curve of 0.74 (95% confidence interval, 0.73-0.84; P<.0001). CONCLUSION: Postpartum cervical length measurements may assist in detecting the group of patients at higher risk of subsequent spontaneous preterm birth. It may be beneficial to consider an increased follow-up regimen and earlier interventions in this group to reduce adverse perinatal outcomes.