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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., (Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Maternal inflammation may induce placental cytokine production resulting in fetal exposure, and development of neonatal neurologic injury. Maternal magnesium sulphate (MG) is used as neuroprotective in preventing white matter brain injury. We sought to determine whether maternal MG can prevent placental activation of inflammatory pathways associated with fetal injury., Methods: Pregnant Sprague Dawley rats at gestational day 20 (E20) (n = 24) received injections of intraperitoneal lipopolysaccharide (LPS; 500 μg/kg) or saline (SAL) at time 0. Dams were randomized to treatment with subcutaneous saline or MG for 2 h prior to and 2 h following LPS/saline injections. Four hours following first injection rats were sacrificed. Placentas were collected from all treatment groups (LPS/SAL, LPS/MG, SAL/MG, SAL/SAL). Placental Caspase 3, NF-kB p65, neuronal nitric oxide synthase (phospho-nNos) interleukin (IL)-6 and tumor necrotic factor-α (TNF-α) protein levels were determined by western blot and compared., Results: Maternal LPS at E20 significantly increased protein levels of placental caspase 3 (0.22 ± 0.01 vs. 0.12 ± 0.01 u), NFkB p65 (0.27 ± 0.01 vs. 0.10 ± 0.01 u), phospho-nNOS (0.20 ± 0.01 vs. 0.10 ± 0.01 u) as well as IL-6 and TNF-α compared to control. MG treatment to LPS dams significantly reduced all placental mediators to levels similar to SAL/SAL controls (p < 0.05)., Discussion: Maternal inflammation-induced fetal brain injury may be mediated via placental activation of inflammation, oxidative stress, and apoptotic pathways. The prevention of preterm brain injury could possibly intervene also via inhibition of one or more of these putative pathways., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Study Objective: The Hominis surgical system is a novel robot-assisted system, designed specifically for robotic vaginal natural orifice transluminal endoscopic surgery (RvNOTES). We presented our experience of the first 30 RvNOTES hysterectomies assessing the feasibility and safety of this technology., Design: A two-center prospective study., Setting: Academic tertiary referral centers. The ethics committees approved the study in both centers., Patients: Thirty women with benign indication for hysterectomy., Intervention: RvNOTES hysterectomy performed by the Hominis surgical system., Measurements and Main Results: The primary outcome of the study was the rate of conversion to open or conventional laparoscopic approaches. Secondary outcomes included intra- and postoperative adverse events, operative time, estimated blood loss, length of hospital stay, and 6-week follow-up assessment. A total of 15 women were enrolled at each site. The median age was 59 years (range: 37-79) and the median body mass index was 25.4 kg/m 2 (range: 17.6-40.0). Twenty-four women (80%) had comorbidities. All the procedures were completed successfully without conversion to open abdominal, traditional vaginal, or conventional laparoscopic surgery. No intraoperative complications were observed. Median blood loss and procedure duration were 50 mL (range: 20-400) and 57 minutes (range: 24-88), respectively. Postoperative pain was minimal, with a median visual analog scale of 3 (range: 1-5) for the first 24 hours following surgery. The median hospital stay was 3 days (range: 2-8). According to the treating physicians' evaluations, the vaginal cuff was fully healed in all patients at the 6-week postoperative follow-up visit., Conclusions: This is the first publication of robot-assisted vaginal hysterectomy using the Hominis surgical system. The positive results of this study show this new technology to be a safe and effective tool for vaginal natural orifice transluminal endoscopic surgery, enabling surgeons to operate vaginally with the known advantages of robotic modality., (Copyright © 2020. Published by Elsevier Inc.)

Background: Sacrocolpopexy is a commonly performed procedure for repair of apical compartment prolapse. A Y-shaped mesh is attached to the prolapsed cervix or vagina and suspended to the anterior longitudinal ligament of the sacrum. In addition to conventional laparoscopic and multi-port robotic routes, the robotic laparoendoscopic single-site approach has emerged as a viable, feasible, and widely applicable minimally invasive approach to sacrocolpopexy., Objective: To compare robotic laparoendoscopic single-site with multi-port robotic sacrocolpopexy for women with either utero-vaginal or vaginal apical prolapse., Materials and Methods: In this single-center randomized controlled trial, 70 women at Pelvic Organ Prolapse Quantitative stages 2-4 were assigned randomly to undergo sacrocolpopexy by robotic laparoendoscopic single-site or multi-port robotic approaches from August 2017 to November 2018. Of 35 women randomized to each group, 32 underwent sacrocolpopexy. Operating time was the primary outcome of the trial. Secondary outcomes included intraoperative bleeding, length of hospitalization, pain during the first postoperative 24 hours (according to a 0-10 visual analogue scale), need for analgesics, and intraoperative and postoperative adverse events. At 6 weeks and 6 months after surgery, patients underwent a physical examination according to Pelvic Organ Prolapse Quantitative measurements, to assess the anatomical success of the surgery. The Pelvic Floor Distress Inventory-20 and Pelvic Organ Prolapse/Urinary Incontinence Sexual-12 questionnaires were administered prior to surgery and at 6-month follow-up. The Patient Scar Assessment Questionnaire and the Activity Assessment Scale were administered at 6 weeks and 6 months after the surgery. Exclusion criteria included contraindication to general anesthesia, a history of prior sacrocolpopexy, suspicious adnexal masses, suspicious thickened endometrium, and morbid obesity (body mass index of 40 kg/m 2 or more)., Results: The mean age of the patients was 58.4 years. More than half of the patients (54%) had stage III prolapse. Mean total operative times were 181.3 ± 32.6 and 157.5 ± 42 minutes for robotic laparoendoscopic single-site and multi-port robotic sacrocolpopexy, respectively; the difference was 23.8 minutes (95% confidence interval, 4.2-43.4, P = .018). The mean differences in duration between the procedures were as follows: 29.8 minutes, 95% confidence interval, 9.2-50.4, P = .005 for anesthesia time; 33.1 minutes, 95% confidence interval, 16.5-49.7, P < .0001 for console time; 8.6 minutes, 95% confidence interval, 1.1-16.3, P = .025 for supracervical hysterectomy time; 8.3 minutes, 95% confidence interval, 1.8-14.8, P = 0.03 for mesh suturing and fixation to the promontory; and 4.7 minutes, 95% confidence interval, 1.5-7.7, P = .004 for peritoneum suturing. Statistically significant differences were not observed between the groups in regard to estimated blood loss, intraoperative complications, and demand for analgesics during hospital stay. Quality-of-life parameters were similar. Patients' assessments of their scars were more favorable in the robotic laparoendoscopic single-site group., Conclusion: For sacrocolpopexy, the operative time was longer for the robotic laparoendoscopic single-site than for the multi-port robotic approach. Both approaches are feasible, and short-term outcomes, quality-of-life parameters, and anatomic repair are comparable. Our results are generalizable only to the specific robotic platforms used in the study., (Copyright © 2019. Published by Elsevier Inc.)

Background: A low rate of primary cesarean delivery is expected to reduce some of the major complications that are associated with a repeat cesarean delivery, such as uterine rupture, adhesive placental disorders, hysterectomy, and even maternal death. Since 2014, and in alignment with the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine, we changed our approach to labor dystocia, defined as abnormal progression of labor, by allowing a longer duration of the second stage of labor., Objective: To examine the effect of prolonging the second stage of labor on the rate of cesarean delivery, and maternal and neonatal outcomes., Materials and Methods: In a historical control group, we compared maternal and neonatal outcomes over 2 periods. Period I (9300 patients): from May 2011 until April 2014, when a prolonged second stage in nulliparous women was considered after 3 hours with regional anesthesia or 2 hours if no such anesthesia was provided. Second-stage arrest was defined in multiparous women after 2 hours with regional anesthesia or 1 hour without it. Period II (10,531 patients): from May 2014 until April 2017, allowed nulliparous and multiparous women continuing the second stage of labor an additional 1 hour before diagnosing second-stage arrest. Singleton deliveries at or beyond 37 weeks' gestation were initially considered for eligibility. We excluded women with high-risk pregnancies and known fetal anomalies. For comparing means, we used the t test. If variables were not normally distributed, we used the Mann-Whitney test instead. For comparing proportions, we used the χ 2 test with continuity correction., Results: The primary cesarean delivery was decreased in nulliparous women from 23.3% (819 of 3515) in period I to 15.7% (596 of 3796) in period II (relative risk [RR], 0.67; 95% CI, 0.61-0.74), a trend that was also significant in multiparous women (10.9%, 623 of 5785, in period I vs 8.1%, 544 of 6735, in period II; RR, 0.75; 95% CI, 0.67-0.84). The rate of operative vaginal deliveries in nulliparous women was higher in period II than in period I (19.2%, 732 of 3515, vs 17.7%, 622 of 3796, P < .0001). Rates of third- and fourth-degree laceration and of shoulder dystocia were also higher in period II. The rate of arterial cord pH < 7.0 and the rate of admission to the neonatal intensive care unit were higher in period II, but the early neurological outcome was not different when comparing the 2 periods., Conclusion: The new policy of labor management successfully decreased primary cesarean deliveries, with a small rise in instrumental deliveries. However, it also increased the other immediate maternal and neonatal complications. A higher rate of lower umbilical artery cord pH was the most significant finding; however, the early neurological outcome did not change. It is possible that the ongoing adjustment to the new labor protocol will avoid, in the future, maternal and neonatal complications. The long-term maternal and neonatal consequences of our new approach will be evaluated in future studies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Maternal inflammation is a risk factor for neonatal brain injury and future neurological deficits. Pomegranates have been shown to exhibit anti-inflammatory, anti-apoptotic and anti-oxidant activities., Objective: We hypothesized that pomegranate juice (POM) may attenuate fetal brain injury in a rat model of maternal inflammation., Study Design: Pregnant rats (24 total) were randomized for intraperitoneal lipopolysaccharide (100 μg/kg) or saline at time 0 at 18 days of gestation. From day 11 of gestation, 12 dams were provided ad libitum access to drinking water, and 12 dams were provided ad libitum access to drinking water with pomegranate juice (5 mL per day), resulting in 4 groups of 6 dams (saline/saline, pomegranate juice/saline, saline/lipopolysaccharide, pomegranate juice/lipopolysaccharide). All dams were sacrificed 4 hours following the injection and maternal blood and fetal brains were collected from the 4 treatment groups. Maternal interleukin-6 serum levels and fetal brain caspase 3 active form, nuclear factor-κB p65, neuronal nitric oxide synthase (phosphoneuronal nitric oxide synthase), and proinflammatory cytokine levels were determined by enzyme-linked immunosorbent assay and Western blot., Results: Maternal lipopolysaccharide significantly increased maternal serum interleukin-6 levels (6039 ± 1039 vs 66 ± 46 pg/mL; P < .05) and fetal brain caspase 3 active form, nuclear factor-κB p65, phosphoneuronal nitric oxide synthase, and the proinflammatory cytokines compared to the control group (caspase 3 active form 0.26 ± 0.01 vs 0.20 ± 0.01 U; nuclear factor-κB p65 0.24 ± 0.01 vs 0.1 ± 0.01 U; phosphoneuronal nitric oxide synthase 0.23 ± 0.01 vs 0.11 ± 0.01 U; interleukin-6 0.25 ± 0.01 vs 0.09 ± 0.01 U; tumor necrosis factor-α 0.26 ± 0.01 vs 0.12 ± 0.01 U; chemokine (C-C motif) ligand 2 0.23 ± 0.01 vs 0.1 ± 0.01 U). Maternal supplementation of pomegranate juice to lipopolysaccharide-exposed dams (pomegranate juice/lipopolysaccharide) significantly reduced maternal serum interleukin-6 levels (3059 ± 1121 pg/mL, fetal brain: caspase 3 active form (0.2 ± 0.01 U), nuclear factor-κB p65 (0.22 ± 0.01 U), phosphoneuronal nitric oxide synthase (0.19 ± 0.01 U) as well as the brain proinflammatory cytokines (interleukin-6, tumor necrosis factor-α and chemokine [C-C motif] ligand 2) compared to lipopolysaccharide group., Conclusion: Maternal pomegranate juice supplementation may attenuate maternal inflammation-induced fetal brain injury. Pomegranate juice neuroprotective effects might be secondary to the suppression of both the maternal inflammatory response and inhibition of fetal brain apoptosis, neuronal nitric oxide synthase, and nuclear factor-κB activation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Maternal magnesium administration has been shown to protect the preterm fetus from white- and gray-matter injury, although the mechanism is unknown., Objective: The purpose of the study is to test the following hypotheses: (1) maternal infections/inflammation activate fetal neuronal N-methyl-D-aspartate receptors that up-regulate neuronal nitric oxide synthase and nuclear factor kappa-light-chain-enhancer of activated B cells pathways; and (2) maternal magnesium sulfate attenuates fetal brain neuronal nitric oxide synthase and nuclear factor kappa-light-chain-enhancer of activated B cells activation through N-methyl-D-aspartate receptors., Study Design: Pregnant rats at embryonic day 16 and embryonic day 18 (n = 6, 48 total) received injections of intraperitoneal lipopolysaccharide 500 μg/kg or saline at time 0. Dams were randomized for treatment with subcutaneous magnesium sulfate (270 mg/kg) or saline for 2 hours prior to and following lipopolysaccharide/saline injections. At 4 hours after lipopolysaccharide administration, fetal brains were collected from the 4 treatment groups (lipopolysaccharide/saline, lipopolysaccharide/magnesium sulfate, saline/magnesium sulfate, saline/saline), and phosphoneuronal nitric oxide synthase, nuclear factor kappa-light-chain-enhancer of activated B cells p65, and chemokine (C-C motif) ligand 2 protein levels were determined by Western blot. An additional group of pregnant rats (n = 5) received N-methyl-D-aspartate-receptor antagonist following the lipopolysaccharide injection to study magnesium sulfate protective mechanism., Results: Lipopolysaccharide (lipopolysaccharide/saline) significantly increased fetal brain phosphoneuronal nitric oxide synthase, nuclear factor kappa-light-chain-enhancer of activated B cells p65, and chemokine (C-C motif) ligand 2 protein levels compared to the saline/saline group at both embryonic day 16 (phosphoneuronal nitric oxide synthase 0.23 ± 0.01 vs 0.11 ± 0.01 U; nuclear factor kappa-light-chain-enhancer of activated B cells 0.24 ± 0.01 vs 0.14 ± 0.01 U; chemokine (C-C motif) ligand 2 0.28 ± 0.01 vs .01 ± 0.01 U) and embryonic day 18 (phosphoneuronal nitric oxide synthase 0.28 ± 0.01 vs 0.12 ± 0.01 U; nuclear factor kappa-light-chain-enhancer of activated B cells 0.12 ± 0.01 vs 0.1 ± 0.01 U; chemokine (C-C motif) ligand 2 0.27 ± 0.01 vs 0.11 ± 0.01 U). Magnesium sulfate treatment to lipopolysaccharide dams (lipopolysaccharide/magnesium sulfate) significantly decreased fetal brain phosphoneuronal nitric oxide synthase, nuclear factor kappa-light-chain-enhancer of activated B cells, and chemokine (C-C motif) ligand 2 protein levels compared to lipopolysaccharide/saline dams at both embryonic day 16 (neuronal nitric oxide synthase 0.17 ± 0.02 U; nuclear factor kappa-light-chain-enhancer of activated B cells 0.17 ± 0.03 U; chemokine (C-C motif) ligand 2 0.18 ± 0.01 U) and embryonic day 18 (phosphoneuronal nitric oxide synthase 0.1 ± 0.01 U; nuclear factor kappa-light-chain-enhancer of activated B cells 0.09 ± 0.01 U; chemokine (C-C motif) ligand 2 0.21 ± 0.01 U). Notably, maternal lipopolysaccharide at embryonic day 16 activated nuclear factor kappa-light-chain-enhancer of activated B cells twice as often compared to dams induced at embryonic day 18. N-methyl-D-aspartate-receptor antagonist decreased fetal brain phosphoneuronal nitric oxide synthase and nuclear factor kappa-light-chain-enhancer of activated B cells levels comparable to magnesium sulfate., Conclusion: Lipopolysaccharide-simulated inflammation during pregnancy may cause brain injury through activation of neuronal nitric oxide synthase and nuclear factor kappa-light-chain-enhancer of activated B cells pathways and, potentially, production of excitotoxic nitric oxide and inflammatory mediators. The increased susceptibility to brain injury in preterm fetuses may be due to enhanced nuclear factor kappa-light-chain-enhancer of activated B cells activation. Magnesium sulfate protective effects may be secondary, in part, to inhibition of neuronal nitric oxide synthase and nuclear factor kappa-light-chain-enhancer of activated B cells activation and decrease proinflammatory cytokine production through blocking nuclear factor kappa-light-chain-enhancer of activated B cells receptors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Maternal chorioamnionitis is associated with newborn neurologic injury. Recent evidence suggests that maternal administration of magnesium sulphate (MG) may protect fetuses from white matter injury. Previously we demonstrated evidence by magnetic resonance imaging that MG may prevent maternal inflammation-induced gray matter injury of offspring. Thus, we sought to determine the potential of maternal inflammation to induce fetal neurological/behavioral deficits and assess whether maternal MG attenuates these effects., Study Design: Pregnant rats at day 18 received injections of intraperitoneal lipopolysaccharide (LPS) or saline. Dams were treated with subcutaneous saline/MG (270 mg/kg followed by 27 mg/kg every 20 minutes) for 2 hours before and following LPS/saline injections. Pups were delivered spontaneously. At 1 and 3 months of age, 11-12 offspring of each group (saline, LPS, MG, LPS-MG) underwent a 2-way shuttle box avoidance testing. The shuttle box is divided in half and the animal moves between compartments to avoid an electric shock in response to an auditory stimulus., Results: Control offspring demonstrated significantly improved learning and memory abilities from age 1 to 3 months. At 1 month, LPS-treated dams' offspring were similar to controls with no improvement in learning abilities at 3 months. MG treatment of LPS dams significantly improved offspring learning at 3 months, to equal or better than that of controls., Conclusion: LPS-stimulated inflammation during pregnancy impairs offspring learning ability and memory, which is ameliorated by maternal MG treatment. These results suggest that maternal MG therapy may prevent white and gray matter injuries associated with maternal infection/inflammation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To evaluate the ability to diagnose structural fetal anomalies during or soon after an extended nuchal translucency (NT) examination., Methods: The study population included all women who had a routine NT examination in the ultrasound division of one of three centers. Also included in the study were women referred to these centers following an abnormal NT examination. The sonographers were instructed to pay attention to fetal anomalies while performing the NT examination. Each examination was initially attempted transabdominally. Failure to obtain adequate views transabdominally was an indication for a transvaginal examination. When a structural fetal anomaly was detected or suspected, a full fetal anomaly scan was performed. When a diagnosis could not be established, fetal anatomy scan was repeated after 14 weeks of gestation. Fetal cardiac scanning was performed transvaginally, immediately or within 3 days after an increased NT was observed. When fetal anomalies were diagnosed the patients were informed about the possibilities of terminating the pregnancy or continuing the work-up and follow-up. Overall, ascertainment of fetal outcome was available in 85% of the study population., Results: We performed 4467 NT examinations during the study period and additional 123 fetal cardiac scanning following an abnormal NT examination. Overall, we performed 365 fetal cardiac scanning between 11 and 14 weeks of gestation. The fetal anomalies detected included the following: three skeletal anomalies, seven brain anomalies, four urinary system anomalies, four abdominal anomalies, two facial anomalies, and 13 cardiac anomalies. Six of the 13 cardiac anomalies were found in the atrioventricular canal. One third of the patients (11/33) elected to discontinue the pregnancy a short time after the detection of the congenital anomaly (until 14 weeks of gestation) and half of the patients (16\33) asked for termination of pregnancy later. More than 60% of the patients (20/33) with congenital anomalies detected following the NT examination refused to have chorionic villous sampling (CVS) or amniocentesis., Conclusion: The opportunity to scan the fetal anatomy in the early stages of pregnancy, when the NT examination is performed, justifies the approach of extended NT examination., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: Maternal infection or inflammation may induce fetal inflammatory responses associated with fetal injury and cerebral palsy. We sought to assess the inflammation-associated neuroprotective potential of prophylactic N-acetyl-cysteine (NAC). We examined the effect of NAC on prevention of maternal lipopolysaccharide (LPS)-induced neonatal brain injury using magnetic resonance imaging., Study Design: Pregnant Sprague Dawley dams (n = 5-8) at embryonic day 18 received intraperitoneal injection of LPS or saline at time 0. Animals were randomized to receive 2 intravenous injections of NAC or saline (time -30 and 120 minutes). Pups were delivered spontaneously and allowed to mature until postnatal day 25. Female offspring were examined by magnetic resonance brain imaging and analyzed using voxel-based analysis after spatial normalization. T2 relaxation time was used to assess white matter injury and diffusion tensor imaging for apparent diffusion coefficient (ADC) to assess white and gray matter injury., Results: Offspring of LPS-treated dams exhibited significantly increased T2 levels and increased ADC levels in white and gray matter (eg, hypothalamus, motor cortex, corpus callosum, thalamus, hippocampus), consistent with diffuse cerebral injury. In contrast, offspring of NAC-treated LPS dams demonstrated similar T2 and ADC levels as control in both white and gray matter., Conclusion: Maternal NAC treatment significantly reduced evidence of neonatal brain injury associated with maternal LPS. These studies suggest that maternal NAC therapy may be effective in human deliveries associated with maternal/fetal inflammation., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: Maternal infection is associated with oxidative stress and inflammation. We sought to determine whether N-acetyl-cysteine can decrease maternal oxidative stress and the inflammatory response in preterm gestation., Study Design: Pregnant rats 16 days, were treated with (1) lipopolysaccharide, (2) N-acetyl-cysteine 120 minutes after lipopolysaccharide, or (3) saline solution (intraperitoneal). Six hours after lipopolysaccharide administration, serum lipid peroxide formation (LPO), tumor necrosis factor-α, interleukin-6, and interleukin-1β levels in maternal serum and amniotic fluid were determined., Results: Lipopolysaccharide significantly increased maternal serum lipid peroxide formation (24-118.5 nmol/mL; P < .05), and maternal serum and amniotic fluid tumor necrosis factor-α, interleukin-6, and interleukin-1β. N-acetyl-cysteine treatment after lipopolysaccharide significantly attenuated lipid peroxide formation (47.5 nmol/mL) and proinflammatory cytokines response in maternal serum and amniotic fluid., Conclusion: Maternal and amniotic fluid oxidative stress and inflammatory stimulation are attenuated by N-acetyl-cysteine even when administered after lipopolysaccharide. These results suggest that N-acetyl-cysteine may protect the fetus from adverse sequelae associated with inflammatory stimulation., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objective: Because the fetal innate immune system is responsive, while still maturing during the preterm period, we hypothesized that the early activation of fetal inflammatory pathways may have an impact on the ultimate expression of immune competency., Study Design: Pregnant Sprague Dawley rats (n = 7; Harlan Sprague Dawley Inc, Jerusalem, Israel) at 18 days gestation received intraperitoneal injections of saline solution or lipopolysaccharides (500 microg/kg). Pups were delivered spontaneously. At postnatal day 24, pups received intraperitoneal lipopolysaccharide (100 microg/kg), and plasma cytokine levels were measured before and 4 hours after lipopolysaccharide administration., Results: In response to lipopolysaccharides, pups of the lipopolysaccharide-injected dams had significantly (P < .05) reduced interleukin-6 (median [25th,75th percentile], 229 [84,6086] vs 4745 [2765,6643] pg/mL), interleukin-1beta (median [25th,75th percentile], 820 [125,1196] vs 1682 [1515,2127] pg/mL), tumor necrosis factor-alpha (median [25th,75th percentile], 4.8 [1.2,91] vs 163 [46,205] pg/mL), and interleukin-10 responses, when compared with saline solution-injected dams., Conclusion: Maternal lipopolysaccharide exposure suppresses offspring innate immune response to inflammatory stimuli. These results suggest that maternal inflammatory exposures during pregnancy may impair newborn infant innate responses and increase susceptibility to infection., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Objective: Maternal infection or inflammation may induce fetal inflammatory responses and potentially fetal brain injury. We sought to determine whether prophylactic n-acetylcysteine (NAC), a known antiinflammatory, may modulate the fetal cytokine response to maternal lipopolysaccharide (LPS)., Study Design: Pregnant Sprague Dawley rats (20/21 days = 0.95 gestation; n = 35) received intraperitoneal NAC (300 mg/kg) or saline at time 0 and LPS (500 microg/kg) or saline at 30 minutes. An additional group received NAC following saline. At 6 hours, rats were killed and interleukin (IL)-6, IL-1 beta, and IL-10 levels were determined in fetal and maternal blood., Results: Following maternal LPS, fetal blood IL-6 (median [25th, 75th] 50 [27, 50] to 2072 [448, 4853] pg/mL) and IL-1 beta (74 [10, 139] to 391 [284, 797] pg/mL) significantly increased. NAC before LPS significantly reduced the fetal IL-6 and IL-1 beta response. Fetal IL-10 was not attenuated by any treatment. NAC attenuated both maternal pro- and antiinflammatory responses to LPS., Conclusion: Maternal NAC suppressed fetal and maternal inflammatory responses to maternal LPS. These results suggest that prophylactic NAC may protect the fetus from maternal inflammation.

Objective: The purpose of this study was to evaluate the ability to screen for structural fetal anomalies during the nuchal translucency (NT) ultrasound examination, without performing a complete anatomic fetal scan, by using the sagittal views of the fetus., Study Design: In a prospective study, we evaluated all the suspected structural findings observed during the NT examinations performed in our Division of Maternal-Fetal Medicine in 2004-2005. The purpose of the examination was to screen for fetal chromosome abnormalities by using the fetal NT measurements. However, the sonographers were instructed to pay attention to any abnormality observed while obtaining the sagittal views of the fetus. Other views were not to be obtained and fetal anatomy scan was performed only if a structural fetal anomaly was suspected when viewing the fetus in sagittal planes. When a structural fetal anomaly was suspected, a fetal anatomy scan was performed, and then a diagnosis was established at 14-16 weeks' gestation or later., Results: We performed 1723 NT examinations during the study period. The sonographers suspected structural fetal anomalies in 22 cases (1.3%), most of them performed between 11.2 and 13 weeks' gestation. Further evaluation of these cases diagnosed 9 fetuses (0.52%) with structural anomalies including: acrania, holoprosencephaly, Dandy-Walker syndrome, cerebellar agenesis, prune belly syndrome, 2 cases of omphalocele, and 2 cases of cleft lip. The NT was abnormal (greater than 3 mm) in only 1 case (omphalocele). None of the additional 8 cases diagnosed with structural anomalies had a positive maternal serum screening result for trisomy 21. Eight of these 9 fetal structural anomalies were sonographically confirmed at 14-16 weeks' gestation and the remaining 1 was confirmed at 20 weeks' gestation. An additional 13 noncardiac structural anomalies were detected in the study group during routine fetal anatomy scan performed at 14-16 or at 18-24 weeks' gestation. Four of these 9 fetal cardiac defects (44%) were diagnosed by an early fetal echocardiography performed for an increased fetal NT., Conclusion: In addition to chromosomal anomalies and congenital cardiac defects, the NT examination can provide an opportunity to screen for structural fetal anomalies when viewing within the sagittal planes of the fetus. The NT examination can be used as a screening test for those who require an early fetal anatomy scan without performing an additional early anatomy scan to all patients.

Objective: The purpose of this study was to evaluate the characteristics and outcomes of patients who had abnormal glucose challenge test results and subsequent normal oral glucose tolerance test results and to assess whether such patients are at a greater risk than normal pregnant patients for adverse perinatal outcome., Study Design: In this retrospective cohort study that was conducted between June and December 2003, 101 pregnant women (group A) had an abnormal glucose challenge test result and a normal oral glucose tolerance test result. Data were also collected on 2 control groups: 100 pregnant women with normal glucose challenge test results (group B) and all 76 pregnant women who were diagnosed with gestational diabetes mellitus during this period of time (group C). Patients with multiple pregnancies, chronic hypertension, pregestational diabetes mellitus, or any other maternal or fetal problems that were diagnosed before 24 weeks (when the glucose challenge test was performed) were excluded from the study groups. The following data were collected and analyzed: maternal age, maternal weight and height, parity and gravidity, diabetes mellitus in first-degree relatives, medical and obstetric history, ethnicity, complications during the third trimester of pregnancy, birth weight, gestational age at delivery, mode of delivery, Apgar scores, cord blood gas results, maternal complications of labor and during the postpartum period, and infant admission to the neonatal intensive care unit. For comparison between groups, we used the Student t test, 1-way analysis of variance, the chi-square test, and stepwise logistic regression., Results: Patients in groups A and C were significantly older compared with group B (29.2 +/- 5.6 years and 30.4 +/- 5.5 years, respectively, vs 24.8 +/- 5.5 years; P < .01), had a lesser rate of primiparity (48% and 31%, respectively, vs 24%; P < .05), had greater body mass index (30.8 +/- 5 kg/m2 and 31.3 +/- 6 kg/m2, respectively, vs 29.2 +/- 4.4 kg/m2; P < .01), had a greater rate of previous gestational diabetes mellitus (6% and 20%, respectively, vs 0%; P < .05), and had a greater rate of first-degree family members with diabetes mellitus (21% and 21%, respectively, vs 3%; P < .01). None of the outcome parameters was statistically significant when group A was compared with group B., Conclusion: Patients with an abnormal glucose challenge test result and a subsequent normal oral glucose tolerance test result have different maternal characteristics and backgrounds compared with patients in whom both test results are normal, yet both groups have normal outcomes. We should continue to consider patients who have an abnormal glucose challenge test result and subsequent normal oral glucose tolerance test result as low-risk; however, these findings may represent an indication of an increased likelihood for the development of overt diabetes mellitus later in life.

Objective: This study was undertaken to assess the accuracy of both clinical and sonographic estimations of the fetal weight (EFW) performed during the active phase of labor by residents., Methods: The study protocol consisted of achieving clinical, followed by sonographic EFW by the admitting resident during the active phase of labor. Patients who had an EFW (clinical or sonographic) within the last 2 weeks were excluded from the study. In addition, the effect of the following variables on the accuracy of the EFW were examined: maternal age, maternal weight and body mass index, parity, the Bishop score before obtaining the EFW, gestational age, birth weight, and the postgraduate year of the examiner. The Pearson correlation, chi2 test, and Student t test were the statistical analyses used. We also calculated the sensitivity, specificity, and positive and negative predictive values for clinical and sonographic EFW for detecting macrosomia (birth weight > or = 4000 g)., Results: A total of 192 patients participated in this study. The coefficient of correlation between the clinical and sonographic EFW and the actual birth weight was 0.59 (P < .0001) and 0.65 (P < .0001), respectively. Clinical EFW was correct (within +/-10%) in 72% of the cases and the sonographic EFW was correct (within +/-10%) in 74% of the cases. However, the sensitivity of predicting birth weight of 4 kg or more was only 50% for both clinical and sonographic EFW, with 95% and 97% specificity, respectively. None of the clinical variables that were tested were significantly associated with the accuracy of the EFW., Conclusion: Both clinical and sonographic EFW performed during the active phase of labor by residents correlate with the actual birth weight but have poor sensitivity in detecting macrosomic fetuses. Sonographic EFWs offer no advantage over clinical EFWs.

We report 2 cases of 47,XXX that were diagnosed prenatally and were screened positive for trisomy 21 by biochemical and ultrasound markers. These cases underline the importance of discussing the sex chromosome abnormalities during the genetic counseling after an abnormal triple screen test or ultrasound examination.

Objective: Our goal was to assess the effect of uterine activity on fetal heart rate indexes during the active phase of labor with a computerized fetal heart rate monitoring system., Study Design: Twenty-six healthy women were studied in active labor without analgesia. Fetal heart rate was analyzed by a computerized system (Sonicaid, System 8000), providing a numeric analysis of the fetal heart rate indexes. Montevideo and Alexandria units were used for quantitative assessment of contractions., Results: A significant correlation was found between Montevideo units and short-term variation (r = -0.62, p < 0.001), episodes of high (r = -0.48, p < 0.01) and low (r = 0.58, p < 0.01) fetal heart rate variation, and frequency of large accelerations (r = -0.49, p < 0.01). A significant correlation was also found between Alexandria units and short-term variation (r = -0.645, p < 0.001), episodes of high fetal heart rate variation (r = -0.58, p < 0.01), and frequency of large accelerations (r = -0.49, p < 0.01)., Conclusions: In active labor fetal heart rate variability is significantly affected by the intensity and duration of contractions.

Objective: Our purpose was to compare the efficacy of triple-marker screening (alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin) with alpha-fetoprotein plus free beta-human chorionic gonadotropin., Study Design: Free beta-human chorionic gonadotropin was concurrently assayed in 2349 maternal serum samples. Trivariate and bivariate algorithms were used to calculate the risk for fetal Down syndrome by the two protocols. Free beta-human chorionic gonadotropin from 12 cases of fetal Down syndrome previously screened with the triple marker was retrospectively assayed., Results: Mean maternal age of our study was 29.8 years (range 14 to 51 years). The initial screen-positive rate with the triple marker was 8.0% compared with 12.8% for alpha-fetoprotein plus free beta-human chorionic gonadotropin. All three cases of fetal Down syndrome ascertained in our prospective study were detected by the triple marker; in contrast, one of three was detected by alpha-fetoprotein plus free beta-human chorionic gonadotropin. By adding 12 additional cases of fetal Down syndrome, 12 of 15 (80%) were screen positive with triple marker and nine of 15 (60%) were screen positive with alpha-fetoprotein plus free beta-human chorionic gonadotropin., Conclusion: The detection rate of fetal Down syndrome was greater by use of a triple marker screen than when using alpha-fetoprotein plus free beta-human chorionic gonadotropin. Our data do not support the claims of other studies that suggest that alpha-fetoprotein plus free beta-human chorionic gonadotropin is superior to triple markers.

Objective: Our purpose was to assess the utility of triple-marker serum screening for chromosomal abnormalities., Study Design: Our laboratory received 10,605 samples that were between 15 and 22 weeks' gestation for maternal serum screening of chromosomal abnormalities. Triple-marker maternal serum screening consisted of alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol in conjunction with maternal age. Women > or = 35 years old were first offered amniocentesis. If they refused amniocentesis, they were offered the screening test. A second-trimester risk for trisomy 21 > or = 1:270 was considered screen positive. Patients were screen positive for trisomy 18 if all three markers were low: alpha-fetoprotein < or = 0.75 multiples of the median, unconjugated estriol < or = 0.60 multiples of the median, and human chorionic gonadotropin < or = 0.55 multiples of the median., Results: The initial screen-positive rate was 8.3% (880 women); amniocentesis was offered to 766 (7.2%). Twelve of 16 ascertained cases of trisomy 21 (75%), two of three cases of trisomy 18 (67%), five cases of 45,X karyotype, and one case each of 45,X/46,XX, 47,XXY, 47,XYY, 46,XX,ins(2)(q21p13p15)mat, and 69,XXX karyotypes were identified in the screen-positive patients. All four known cases of trisomy 21 in the 886 women > or = 35 years old who were screened were detected, with a 21% false-positive rate. Omitting unconjugated estriol from our screening program would have resulted in detecting nine of 16 trisomy 21 and six of 12 other chromosomal abnormalities. The false-positive rate would have remained the same., Conclusion: In our sample cohort addition of unconjugated estriol to the screening program resulted in an increased detection rate of chromosomal abnormalities with no change in the false-positive rate. Considering the advancement in screening for chromosomal abnormalities, maternal age alone as an indication for amniocentesis should be reevaluated.

Objective: Our purpose was to evaluate whether computerized analysis of fetal heart rate variation may improve fetal surveillance in postterm pregnancy., Study Design: Three hundred thirty-seven pregnant women who were delivered after 41 weeks' gestation and who had 610 antenatal tests were included in this study. Fetal tests included a nonstress test with a computerized analysis of the fetal heart rate, Doppler examination of the umbilical artery, and a biophysical profile, performed every 2 to 4 days. Induction of labor was performed when the fetal heart rate variation was reduced (< 30 msec), when fetal heart rate decelerations appeared, or when the amniotic fluid index was < or = 5. The results of the fetal surveillance tests were compared with the results of the intrapartum fetal heart rate monitoring and with the metabolic status of the babies at delivery. Sensitivity and specificity of the various tests in predicting intrapartum fetal distress and acidosis at delivery were described by means of the receiver-operator characteristic curve., Results: Ten of 12 fetuses with reduced fetal heart rate variation had a trial of labor. Nine of these 10 fetuses had fetal distress during labor. Seven of the 12 fetuses with reduced fetal heart rate variation were acidotic at delivery (umbilical artery pH < 7.2). Overall, there were 10 acidotic fetuses at delivery in the study group. Only two of them had an umbilical systolic/diastolic ratio > 95th percentile, three had an amniotic fluid index < or = 5, and five had fetal heart rate decelerations before labor. Fetuses who demonstrated an abnormal intrapartum fetal heart rate tracing or who were acidotic at delivery had a significantly higher rate of reduced fetal heart rate variation or decelerations before labor. The largest area under the receiver-operator curve curve for predicting fetal acidosis at delivery or fetal distress during labor was achieved by means of computerized analysis of fetal heart rate variation., Conclusion: A computerized numeric analysis of fetal heart rate variation may improve fetal surveillance in postterm pregnancy.

Objectives: Our purpose was to study hemodynamic changes in peripheral and central blood vessels and to correlate these changes with the computerized fetal heart rate pattern in fetuses with absent end-diastolic velocity in the umbilical artery., Study Design: Doppler studies of the umbilical artery, the middle cerebral artery, and aortic and pulmonic outflow, together with computerized fetal heart rate monitoring, were performed every 2 to 4 days until delivery in 13 fetuses with absent end-diastolic velocity in the umbilical artery. The pulsatility index was calculated from the flow velocity waveforms obtained from the umbilical and middle cerebral arteries. The velocity time integral (an index of cardiac output) and the heart rate were calculated from the flow velocity waveforms obtained from the aortic and pulmonic outflow., Results: Two fetuses were delivered immediately after the first examination because of repetitive fetal heart rate decelerations. One fetus was excluded from the study because of major malformations. Ten had three to eight tests each. Six had a biphasic change of the middle cerebral artery, which consisted of a decrease (p < 0.001) followed by an increase in the pulsatility index (p < 0.05). When the middle cerebral artery lost its vasodilation, there was an increase in the middle cerebral artery/umbilical artery pulsatility index ratio (p < 0.05). Left cardiac output decreased (p < 0.05), resulting in an increase in the pulmonary/aortic velocity time integral x heart rate ratio (p < 0.05). Reduced fetal heart rate variation (< 30 msec) developed in all six fetuses, and they were delivered because of repetitive fetal heart rate decelerations. Four fetuses with only a decrease in the middle cerebral artery pulsatility index did not have reduced fetal heart rate variation or decelerations, the aortic velocity time integral x heart rate didn't decrease, and the pulmonic/aortic velocity time integral x heart rate ratio didn't increase. These fetuses were delivered for reasons other than fetal distress. The middle cerebral artery pulsatility index correlated with the aortic velocity time integral x heart rate (r = -0.53, p < 0.0001), and the middle cerebral artery/umbilical artery pulsatility index correlated with the pulmonic/aortic velocity time integral x heart rate (r = 0.56, p < 0.0001)., Conclusion: Abnormal fetal heart rate patterns occur in fetuses with absent end-diastolic velocity in the umbilical artery when the middle cerebral artery begins to lose its compensatory maximal dilation. The increase in the middle cerebral artery pulsatility index is associated with a significant reduction in left ventricular output without significant changes in right ventricular function. Thus it appears that a loss of autonomic reactivity occurs in the brain first and is followed within a few days by a similar response in the heart, as shown by the decreased fetal heart rate variation.