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.

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..

Fetal Trigonocephaly (Strawberry Skull) in Early Pregnancy.

Trigonocephaly was previously described prenatally in association with severe abnormalities, mostly observed after 18 weeks of gestation. We describe our experience with this finding in early pregnancy, between 14 and 17 weeks of gestation. Our series includes 18 cases of trigonocephaly with several etiologies; trisomy 18, de novo translocation, thanatophoric dysplasia, and open spina bifida without hydrocephalus. Two fetuses had no other significant abnormalities and a spontaneous normalization of the skull shape was observed on follow-up. Both had normal genetic testing and postnatal outcome. These two cases represent a new phenomenon of an isolated transient form with normal outcome.

Higher risk of hemorrhage and maternal morbidity in vaginal birth after second stage of labor C-section.

PURPOSE: This study evaluated the association between timing and indication for previous cesarean section (C-section) and its association with postpartum risks for adverse maternal outcomes, primarily postpartum hemorrhage (PPH) in vaginal birth after cesarean (VBAC). METHODS: This retrospective case-control study examined women following term vaginal delivery in a university-affiliated medical center between 2008 and 2018. Postpartum complications were compared between women who had their first VBAC and a control group comprised of women who had vaginal delivery without prior C-section. Additional analysis was performed to evaluate the association between the timing of previous C-section and the severity of postpartum adverse outcomes. RESULTS: Of the women meeting the inclusion criteria (n = 2879), 1,455 had VBAC and 1,424 were in the control group. Overall, significant postpartum complications, primarily PPH, were observed in the VBAC group compared to controls. Women who underwent C-section during second-stage of labor experienced higher PPH rates and increased drop in hemoglobin levels compared to women who underwent C-section during the first stage of labor or an elective C-Sect. (4.3 ± 0.9 g/dL vs. 2.8 ± 1.1 g/dL vs. 2.4 ± 0.8, p = 0.033). Concomitant increased need for blood transfusion (8.1% vs. 3.5% vs. 2.9%, respectively, p < 0.0001) and uterine atony (12.6% vs. 6.2% vs. 4.4%, respectively, p = 0.009) were also observed. No significant differences were demonstrated in other postpartum adverse effects evaluated. CONCLUSION: VBAC is associated with higher rates of postpartum complications, primarily PPH. The risk is significantly increased in VBAC following a second stage cesarean section. This data should be taken into consideration in the management of laboring women after C-section.

Maternal N-acetyl-cysteine prevents neonatal brain injury associated with necrotizing enterocolitis in a rat model.

INTRODUCTION: Preterm infants with necrotizing enterocolitis (NEC) are at increased risk of cerebral injury and neurodevelopmental dysfunction. N-acetyl-cysteine (NAC) is a known anti-inflammatory and antioxidant agent. Currently, there is no prophylactic treatment in clinical use to prevent NEC and its neurodevelopmental sequelae. We sought to determine whether brain inflammation/apoptosis accompanies NEC systemic inflammation, and whether it can be attenuated by maternal NAC treatment during pregnancy and/or in the neonatal period in a rat model. MATERIAL AND METHODS: An established NEC newborn model (hypoxia 5% O2 for 10 min and formula feeding thrice daily, beginning on day 1 for 4 days) was used in Sprague-Dawley rat pups (n = 32). An additional group of pups (n = 33) received NAC (300 mg/kg intraperitoneal thrice daily) in addition to NEC conditions (NEC-NAC). Control pups (n = 33) were nursed and remained with the dam in room air. Two additional groups included pups of dams treated once daily with NAC (300 mg/kg intravenous) in the last 3 days of pregnancy. After birth, pups were randomized into NAC-NEC (n = 33) with NEC conditions and NAC-NEC-NAC (n = 36) with additional postnatal NAC treatment. Pups were sacrificed on the fifth day of life. Pup serum interleukin (IL)-6 protein levels, and brain nuclear factor kappa B (NF-κB) p65, neuronal nitric oxide synthase (nNOS), Caspase 3, tumor necrosis factor alpha (TNF-α), IL-6 and IL-1ß protein levels were determined by ELISA, western blot and TUNEL staining, and the groups were compared using analysis of variance (ANOVA). RESULTS: NEC pups had significantly increased serum IL-6 levels compared with the control group as well as increased neuronal apoptosis and brain protein levels of NF-κB, nNOS, Caspase 3, TNF-α, IL-6 and IL-1ß compared with control. In all NAC treatment groups, levels of serum IL-6, neuronal apoptosis and brain NF-κB, nNOS, Caspase 3, TNF-α, IL-6 and IL-1ß protein levels were significantly reduced compared with the NEC group. The most pronounced decrease was demonstrated within the NAC-NEC-NAC group. CONCLUSIONS: NAC treatment can attenuate newborn inflammatory response syndrome and decrease offspring brain neuroapoptosis and inflammation in a rat model of NEC by inhibition of NF-κB, nNOS and Caspase 3 pathways.

Early Prenatal Diagnosis of Double Aortic Arch: Prevalence, Associated Anomalies and Outcome.

PURPOSE: Our aims were to describe the feasibility of diagnosis of DAA in early pregnancy and to assess its prenatal prevalence, associated anomalies and outcome. MATERIALS AND METHODS: A retrospective cohort review of all DAA cases diagnosed by early prenatal transvaginal scans at 12-17 weeks of gestation between the years 2007-2018 was performed. Associated anomalies, genetic abnormalities and long-term postnatal outcome were evaluated. RESULTS: 12 cases of DAA were diagnosed by early prenatal transvaginal scans at a median of 15 (range: 12-17) weeks of gestation out of a total of 28 654 early scans preformed with a prevalence of at least 1:2378. Associated anomalies/genetic abnormalities were found in 5/12 (42 %) cases. The diagnosis was confirmed postnatally in all newborns. In two cases termination of pregnancy was performed. Four patients (40 %) were symptomatic. Six patients (60 %) underwent surgery due to symptoms or due to severe obstruction on imaging with resolution of symptoms in all except one patient. CONCLUSION: DAA can be readily diagnosed transvaginally even in the first trimester. Its prevalence is 1:2387. A search for associated anomalies and genetic abnormalities should be performed. If DAA is isolated, the prognosis with or without surgery is usually good.

Maternal N-Acetyl-Cysteine Prevents Neonatal Hypoxia-Induced Brain Injury in a Rat Model.

Perinatal hypoxia is a major cause of infant brain damage, lifelong neurological disability, and infant mortality. N-Acetyl-Cysteine (NAC) is a powerful antioxidant that acts directly as a scavenger of free radicals. We hypothesized that maternal-antenatal and offspring-postnatal NAC can protect offspring brains from hypoxic brain damage.Sixty six newborn rats were randomized into four study groups. Group 1: Control (CON) received no hypoxic intervention. Group 2: Hypoxia (HYP)-received hypoxia protocol. Group 3: Hypoxia-NAC (HYP-NAC). received hypoxia protocol and treated with NAC following each hypoxia episode. Group 4: NAC Hypoxia (NAC-HYP) treated with NAC during pregnancy, pups subject to hypoxia protocol. Each group was evaluated for: neurological function (Righting reflex), serum proinflammatory IL-6 protein levels (ELISA), brain protein levels: NF-κB p65, neuronal nitric oxide synthase (nNOS), TNF-α, and IL-6 (Western blot) and neuronal apoptosis (histology evaluation with TUNEL stain). Hypoxia significantly increased pups brain protein levels compared to controls. NAC administration to dams or offspring demonstrated lower brain NF-κB p65, nNOS, TNF-α and IL-6 protein levels compared to hypoxia alone. Hypoxia significantly increased brain apoptosis as evidenced by higher grade of brain TUNEL reaction. NAC administration to dams or offspring significantly reduce this effect. Hypoxia induced acute sensorimotor dysfunction. NAC treatment to dams significantly attenuated hypoxia-induced acute sensorimotor dysfunction. Prophylactic NAC treatment of dams during pregnancy confers long-term protection to offspring with hypoxia associated brain injury, measured by several pathways of injury and correlated markers with pathology and behavior. This implies we may consider prophylactic NAC treatment for patients at risk for hypoxia during labor.

Early sonographic manifestation of fetal congenital lobar emphysema.

Advanced fetal sonographic equipment has contributed to the increase in prenatal diagnosis of congenital thoracic malformations. Among these anomalies is congenital lobar emphysema (CLE), a rare congenital anomaly characterized by over distention and overexpansion of the involved fetal pulmonary lobe. Several studies addressed the prenatal diagnosis of CLE in mid second or early third trimester. The early prenatal diagnosis and the outcome of a case of CLE are reported in this study.

Maternal pomegranate juice attenuates maternal inflammation-induced fetal brain injury by inhibition of apoptosis, neuronal nitric oxide synthase, and NF-κB in a rat model.

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.

Characteristics and Outcomes of Ptyalism Gravidarum.

BACKGROUND: Ptyalism gravidarum (PG) is a condition of hypersalivation that affects pregnant women early in gestation. Symptoms include massive saliva volumes (up to 2 liters per day), swollen salivary glands, sleep deprivation, significant emotional distress, and social difficulties. OBJECTIVES: To examine maternal and fetal characteristics and pregnancy outcomes of patients with PG. METHODS: Patients diagnosed with PG in our clinic during the years 2001-2016 were identified and contacted. Demographic data were extracted from patient charts and clinical and outcome data was collected via telephone interviews. RESULTS: The incidence of PG was 1/963 (0.09%) in our sample. Eleven out of 22 women (40%) with PG were also diagnosed with hyperemesis gravidarum. Fetal gender did not increase the risk. Of the mothers presenting with PG, 37% had a positive family history for this condition. There was no associated increase in the rate of fetal or maternal complications. Two women reported a resolution of the symptoms immediately following hypnosis with acupuncture treatment. CONCLUSIONS: Although PG represents an unpleasant mental and physical condition, it does not pose any specific risk to the health of the mother or increase adverse perinatal outcomes for the fetus. Alternative medicine could play a role in the treatment of PG.

The recurrence of sonographic 'soft markers': ominous sign or 'just' genetics?

OBJECTIVES: 'Soft markers' (SMs) are nonspecific findings that might convey a higher risk for Down syndrome. We sought to determine the recurrence rate of the most common SM in subsequent pregnancies. METHODS: This is a retrospective study of all women who underwent early or late fetal sonographic anatomical screening in our ultrasound unit. The examined SMs were pyelectasis, thickened nuchal fold (TNF) and echogenic intracardiac foci (EIF). Data on recurrence and pregnancy outcome were retrieved retrospectively. RESULTS: The database included 20 672 singleton pregnancies; SMs were detected in 2347 (11.1%) of the fetuses and were isolated in 1739 (74%). Rates of solitary findings in the pregnancies were 6.5% (1360/20 672) EIF, 3% (624/18 850) TNF and 1.7% (363/20 672) pyelectasis. The recurrence rate of EIF, TNF and pyelectasis in subsequent consecutive pregnancies was 21%, 27% and 16%, respectively. Overall, 62 cases of Down syndrome were diagnosed in (1 : 333 pregnancies). No cases were diagnosed in patients with recurrent SMs. CONCLUSION: The high recurrence rate of solitary SM implies for genetic predisposition. These results might improve our counseling for pregnant women affected by the reappearance of solitary SM. Further studies are needed to assess the likelihood ratio for SM if recurrence occurs. © 2017 John Wiley & Sons, Ltd.

IUGR induced by maternal chronic inflammation: long-term effect on offspring's ovaries in rat model-a preliminary report.

PURPOSE: Excess maternal inflammation and oxidative stress while in utero have been known to affect gross fetal development. However, an association between the inflammatory process in utero and the effects on ovarian development and future fertility has not yet been demonstrated. This study focused on LPS-induced chronic inflammation in early pregnancy and its effect on ovarian development and reserves of the offspring, using a rat model. Our aim was to determine whether maternal inflammation in utero disturbs reproductive system development in the offspring, given that maternal inflammation and oxidative stress has been shown to affect gross fetal development. METHODS: Prospective case control rat model. Sprague-Dawley pregnant rats (n = 11) received intraperitoneal lipopolysaccharide (LPS group) (50 µg/kg bodyweight) or saline solution (control group) on day 14, 16, and 18 of gestation. Pups were delivered spontaneously. At 3 months, female offspring were weighed and killed. Ovaries were harvested for (1) follicle count using hematoxylin and eosin staining, (2) apoptosis: ovaries were stained for caspase, and (3) serum CRP and AMH levels were determined. RESULTS: Birth weights of pups were significantly lower in the LPS group compared to the control group (6.0 ± 0.6 vs. 6.6 ± 0.4 gr; P = 0.0003). The LPS group had fewer preantral follicles, and increased intensity of Caspase 3 staining (510 vs. 155.5 u; P = 0.007). AMH levels were significantly lower in the LPS group (4.15 ± 0.46 vs 6.08 ± 1.88 ng/ml; P = 0.016). There was no significant difference in the CRP and MCP-1 levels between the two groups. CONCLUSIONS: Chronic maternal inflammation induced intrauterine growth restriction in offspring and a decrease in the proportion of follicles. This change might be due to premature apoptosis. These preliminary results suggest that maternal inflammation has a detrimental effect on the development of the female reproductive system of the offspring and thus, future fertility.

Ultrasound diagnosis and management of acquired uterine enhanced myometrial vascularity/arteriovenous malformations.

BACKGROUND: Arteriovenous malformation is a short circuit between an organ's arterial and venous circulation. Arteriovenous malformations are classified as congenital and acquired. In the uterus, they may appear after curettage, cesarean delivery, and myomectomy among others. Their clinical feature is usually vaginal bleeding, which may be severe, if curettage is performed in unrecognized cases. Sonographically on 2-dimensional grayscale ultrasound scanning, the pathologic evidence appears as irregular, anechoic, tortuous, tubular structures that show evidence of increased vascularity when color Doppler is applied. Most of the time they resolve spontaneously; however, if left untreated, they may require involved treatments such as uterine artery embolization or hysterectomy. In the past, uterine artery angiography was the gold standard for the diagnosis; however, ultrasound scanning has diagnosed successfully and helped in the clinical management. Recently, arteriovenous malformations have been referred to as enhanced myometrial vascularities. OBJECTIVES: The purpose of this study was to evaluate the role of transvaginal ultrasound scanning in the diagnosis and treatment of acquired enhanced myometrial vascularity/arteriovenous malformations to outline the natural history of conservatively followed vs treated lesions. METHODS: This was a retrospective study to assess the presentation, treatment, and clinical pictures of patients with uterine Enhanced myometrial vascularity/arteriovenous malformations that were diagnosed with transvaginal ultrasound scanning. We reviewed both (1) ultrasound data (images, measured dimensions, and Doppler blood flow that were defined by its peak systolic velocity and (2) clinical data (age, reproductive status, clinical presentation, inciting event or procedure, surgical history, clinical course, time intervals that included detection to resolution or detection to treatment, and treatment rendered). The diagnostic criteria were "subjective" with a rich vascular network in the myometrium with the use of color Doppler images and "objective" with a high peak systolic velocity of ≥20 cm/sec in the vascular web. Statistical analysis was performed and coded with statistical software where necessary. RESULTS: Twenty-seven patients met the diagnostic criteria of uterine enhanced myometrial vascularity/arteriovenous malformation. Mean age was 31.8 years (range, 18-42 years). Clinical diagnoses of the patients included 10 incomplete abortions, 6 missed abortions, 5 spontaneous complete abortions, 5 cesarean scar pregnancies, and 1 molar pregnancy. Eighty-nine percent of patients had bleeding (n = 24/27), although 1 patient was febrile, and 2 patients were asymptomatic. Recent surgical procedures were performed in 55.5% patients (15/27) that included curettage (n = 10), cesarean deliveries (n = 5), or both (n = 1); 4 patients had a remote history of uterine surgery that included myomectomy. Treatment was varied and included expectant treatment alone in 48% of the patients with serial ultrasound scans and serum human chorionic gonadotropin until resolution (n = 13/27 patients), uterine artery embolization (29.6%; 8/27 patients), methotrexate administration (22.2%; 6/27 patients), hysterectomy (7.4%; 2/27 patients), and curettage (3.7%; 1/27 patients). Three patients required a blood transfusion. Of the 9 patients whose condition required embolization, the conditions of 7 patients resolved after the procedure although 1 patient's condition required operative hysteroscopy and 1 patient's condition required hysterectomy for intractable bleeding. Average peak systolic velocity after embolization in the 9 patients was 85.2 cm/sec (range, 35-170 cm/sec); the average peak systolic velocity of the 16 patients with spontaneous resolution was 58.5 cm/sec (range, 23-90 cm/sec). CONCLUSIONS: Acquired enhanced myometrial vascularity/arteriovenous malformations occurred after unsuccessful pregnancies or treatment procedures that included uterine curettage, cesarean delivery, or cesarean scar pregnancy. Triage of patients for expectant treatment vs intervention with uterine artery embolization based on their clinical status, which was supplemented by objective measurements of blood velocity measurement in the arteriovenous malformation, appears to be a good predictor of outcome. Ultrasound evaluation of patients with early pregnancy failure and persistent bleeding should be considered for evaluation of a possible enhanced myometrial vascularity/arteriovenous malformation.

Maternal magnesium sulfate fetal neuroprotective effects to the fetus: inhibition of neuronal nitric oxide synthase and nuclear factor kappa-light-chain-enhancer of activated B cells activation in a rodent model.

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.

Magnesium sulfate prevents maternal inflammation-induced impairment of learning ability and memory in rat offspring.

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.

Cesarean scar pregnancies: experience of 60 cases.

OBJECTIVES: To evaluate the management, clinical courses, and outcomes of cesarean scar pregnancies diagnosed in the first trimester. METHODS: We identified 60 cases of cesarean scar pregnancies diagnosed between 5 and 14 weeks. Group A contained 48 patients with fetal/embryonic cardiac activity; group B comprised 12 patients without cardiac activity; and group C included 11 patients with cardiac activity who chose expectant management. RESULTS: Five of the 48 patients (10.4%) in group A were successfully treated for vaginal bleeding. Thirty-three (68.7%) received methotrexate injections, and all had full resolution. Three (6.3%) required uterine artery embolization for late-developing arteriovenous malformations. Ten of the 12 patients (83.3%) in group B were managed expectantly and had full recovery. Two of the 10 (20.0%) had arteriovenous malformations; 1 had unsuccessful uterine artery embolization followed by a hysterectomy, and the second requested a hysterectomy. Ten of the 11 patients (90.9%) in group C continued the pregnancies. One declined local injection. Four of the 10 (40.0%) delivered live offspring by successive elective cesarean deliveries. Three (30.0%) had hysterectomies for placenta percreta, and 1 did not have a hysterectomy after delivery. Five (50%) had second-trimester complications, all leading to hysterectomies. Of the 60 patients, 20 (33.3%) had serious complications: 5 had arteriovenous malformations; 4 had uterine artery embolization; and 11 had hysterectomies. CONCLUSIONS: A cesarean scar pregnancy is a serious complication for patients who have had cesarean deliveries. Counseling, treatment, and follow-up are challenging for patients and caregivers. However, emerging data from different management approaches confirm that a cesarean scar pregnancy may progress and result in a live neonate at the expense of further fertility. This study confirmed that expectant management of a cesarean scar pregnancy is associated with a high risk of hysterectomy due to morbidly adherent placenta.

Fetal demise in the early second trimester: sonographic findings.

PURPOSE: To report the etiology and the sonographic findings of fetal demise at 14-17 weeks' gestation. METHODS: A prospective transvaginal sonographic search of fetal anomalies was performed in 61 early second-trimester cases of fetal demise. The findings were compared with the results of sonographic examinations of 22,500 viable fetuses between weeks 14 and 17. RESULTS: Of 61 cases of early fetal demise in 60 women (1:370), more than half of the fetuses (35/61, 57%) were associated with fetal edema, ranging from nuchal edema and cystic hygroma to fetal hydrops. In 9/61 (14.7%) fetuses, major anatomic anomalies were detected. There was no significant difference between the study group (nonviable fetuses) and the control group (viable fetuses) regarding maternal age and the prevalence of maternal fever, maternal thrombophilic mutations, vaginal bleeding, fertility treatments, maternal diseases, or use of medications. CONCLUSIONS: The incidence of early midtrimester fetal demise is 1:370 pregnancies. The sonographic findings in fetal demise in the early second trimester suggest that 57% of them are associated with fetal edema and 14.7% are associated with major fetal malformations. We did not identify any significant maternal risk factor for fetal demise in the study group.

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.

Delivery mode after cervical ripening among patients with no prior vaginal births.

PURPOSE: To compare mode of delivery and maternal and neonatal outcomes using cervical ripening balloon (CRB) for induction of labor (IOL) in nulliparous patients vs. those undergoing first trial of labor after cesarean (TOLAC). METHODS: Retrospective cohort study including data from two tertiary medical centers. Included were all patients with a singleton pregnancy and a gestational age > 37+0 weeks and no prior vaginal birth undergoing IOL with CRB. Nulliparous patients (nulliparous group) were compared to patients with one prior cesarean delivery (CD) and no prior vaginal delivery (TOLAC group). Patients who withdrew consent for trial of labor at any time in both groups were excluded. The primary outcome was mode of delivery. RESULTS: Overall, 161 patients were included in the TOLAC group and 1577 in the nulliparous group. The rate of CD was similar in both groups and remained similar after adjusting for confounders (29.8 % vs. 28.9 %, p = 0.86, OR 1.1, 95 %, CI 0.76-1.58). CD due to fetal distress was more common in the TOLAC group (75 % vs. 56 %, p = 0.014). Other maternal outcomes and neonatal outcomes were similar in the two groups. CONCLUSION: Comparable vaginal delivery rates may be achieved in patients with or without a previous CD attempting their first trial of labor, with a cervical ripening balloon for labor induction, without increasing adverse maternal or neonatal outcomes.