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.

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.

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..

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.

Antenatal betamethasone and the risk of neonatal hypoglycemia: it's all about timing.

INTRODUCTION: Our objective was to evaluate whether there is a relationship between the "time during the day" of maternal betamethasone administration between 24 and 34 weeks' gestation and the risk for neonatal hypoglycemia. MATERIAL AND METHODS: A retrospective study included cases between 2008 and 2018. Eligible cases were pregnant women with singleton pregnancies who received a single course of betamethasone between 24 and 34 weeks' gestation. Each woman was allocated into one of four pre-defined groups based on the time when intramuscular betamethasone was administered. Group 1 (23:00-04:59) represents the lowest daily natural corticosteroids' activity, group 2 (05:00-10:59) represents the peak daily natural corticosteroids' activity, whereas group 3 (11:00-16:59) and group 4 (17:00-22:59) present an intermediate natural state of steady corticosteroids' secretion and activity. The primary outcome of the study was the incidence of neonatal hypoglycemia (glucose level of less than 40 mg/dL). RESULTS: We have identified 868 women who received a single complete course of betamethasone, of which 353 women (40.7%) had a steroid treatment latency to delivery up to 14 days. The incidence of neonatal hypoglycemia was significantly higher in group 2 (39.5%, 30/76, p = 0.0063), compared to group 1, who had the lowest incidence of neonatal hypoglycemia (16.9%, 12/71), and to group 3 and group 4. CONCLUSIONS: The "time during the day" when betamethasone administered is important when considering the risk for neonatal hypoglycemia. The risk was significantly higher when betamethasone was administered during the peak time and significantly lower when administered at the nadir time of maternal endogenous corticosteroid activity.

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.

Lockdown with a Price: The impact of the COVID-19 Pandemic on Prenatal Care and Perinatal Outcomes in a Tertiary Care Center.

BACKGROUND: The World Health Organization classified coronavirus disease-19 (COVID-19) as a pandemic and recommends strict restrictions regarding most aspects of daily activities. OBJECTIVES: To evaluate whether the pandemic has changed the prenatal care and pregnancy outcome in pregnant women without COVID-19. METHODS: The authors conducted a cross-sectional study to describe changes in outpatient clinic visits and to compare the rates of cesarean and instrumental deliveries between two periods of time: March-April 2020 (during the COVID-19 outbreak) with March-April of the preceding year, 2019. RESULTS: During the COVID-19 outbreak, visits to obstetric triage, gynecologic triage, high-risk clinic, and ultrasound units decreased by 36.4%, 34.7%, 32.8%, and 18.1%, respectively. The medical center experienced a 17.8% drop in the total number of births (610 births) compared with March and April 2019 (742 births). During the outbreak women were more likely to be nulliparous (33.3% vs. 27.6%, P = 0.02) and present with hypertensive disorders during pregnancy (7.5% vs. 4%, P = 0.005) or gestational diabetes (13% vs. 10%, P = 0.03). More epidural analgesia was used (83.1% vs. 77.1%, P = 0.006). There were more operative vaginal deliveries during the outbreak (16.7% vs. 6.8%, P = 0.01). All other maternal and neonatal outcomes were comparable between the two periods. CONCLUSIONS: The medical facility experienced a major decline in all aspects of the routine obstetrics activities during the time of the pandemic. The higher rate of operative vaginal deliveries among nulliparous may be associated with the pandemic effect on the rate of high-risk patients.

The impact of extending the second stage of labor to prevent primary cesarean delivery on maternal and neonatal outcomes.

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 χ2 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.

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.

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.

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.

Interpregnancy interval after vacuum delivery and subsequent perinatal outcomes.

OBJECTIVE: To evaluate whether a short interpregnancy interval (IPI) after vacuum extraction (VE), poses similar perinatal risks in a subsequent pregnancy. METHODS: This was a retrospective, single-center cohort study between 2011 and 2021. Nulliparous women with term, singleton VE deliveries and with known pregnancy outcomes in their subsequent pregnancy were eligible for inclusion in the study. Each woman was allocated into one of two groups based on the IPI, <18 months and between 18 and 60 months. The primary outcome was the risk of spontaneous preterm birth (PTB) <37 weeks in the consecutive birth. RESULTS: We included 1094 pregnancies: 212 (19.4%) with IPI <18 months and 882 (80.6%) with IPI between 18 and 60 months following the previous VE delivery. The VE characteristics were comparable between the groups. Young maternal age was a risk factor for a short IPI (28.0 ± 4.8 vs 30.3 ± 4 years, P < 0.01). Spontaneous PTB <37 weeks was significantly higher in the IPI <18 months group with 18-60 months (7.1% vs 2.6%, P = 0.002). Polynomial regression analysis also confirmed a significantly increased risk of preterm birth <37 weeks (P < 0.01). Short IPI <18 months was also associated with an increase in the risk of low birthweight <2500 g (6.1% vs 2.8%, P = 0.02) and admission to the neonatal intensive care unit (6.1% vs 2.6%, P = 0.013). The incidence of recurrent VE, albeit significant (2.3% vs 4.9%, P = 0.049), was low in both groups. No differences were noted in any of the other secondary outcomes. CONCLUSION: Short IPI (<18 months) following term VE delivery is associated with higher neonatal risks, particularly PTB, in the subsequent pregnancy. These findings are particularly important when counseling women planning an optimal IPI.

Prophylactic maternal N-acetylcysteine in rats prevents maternal inflammation-induced offspring cerebral injury shown on magnetic resonance imaging.

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.

Measurements of the lower uterine segment during gestation.

PURPOSE: To establish normal values for the lower uterine segment (LUS) thickness and to recognize factors that may affect these values. METHODS: In this cross-sectional study, we measured the LUS thickness in women between 11 and 41 weeks gestation. Women with placental abnormalities and fetal anomalies were excluded. Fetal weight, location of placental implantation, and cervical length were estimated. The LUS was examined to identify the thinnest zone and evaluated using the transvaginal approach with an empty urinary bladder. Full LUS thickness was measured with a caliper at the inner surface of the posterior bladder wall and another caliper at the interface between the amniotic fluid and the decidua. The myometrium was measured with the first caliper at the interface between the amniotic fluid and the deciduas and the second between the bladder wall and the myometrium. Normal values for the LUS were established throughout gestation, and correlations between the LUS gestational age, fetal weight, previous cesarean section, and other parameters were examined. RESULTS: Overall, 350 women were included in our study. Median parity was 1 (0-6) and the majority (62%, 218/350) of women have not had a previous cesarean section. The LUS thickness inversely correlated with gestational week (Pearson's r = -0.11, p < 0.03). When stratifying the linear regression model to women with and without a history of a previous cesarean section, it was demonstrated that gestational age was moderately correlated with LUS only in the second group of patients (Pearson's r = -0.16, p = 0.1 and Pearson's r = -0.47, p < 0.0001, respectively). During the post term period, patients who had had a previous cesarean section had significantly thinner LUS compared with patients who had not had a previous cesarean section (46 mm ± 20 versus 59 mm ± 20, p = 0.002, respectively). Neither parity nor the number of previous cesarean sections were found to correlate with the thickness of the LUS (p > 0.05). Multivariate linear regression (R(2) = 0.215, F(2, 63) = 9.021, p < 0.001) demonstrated that both gestational week (ß = -0.13, p < 0.04) and cesarean section (ß = -0.01, p < 0.0001) were independent factors associated with the thickness of the LUS; for every 1 week increase in gestational week, there was a 1.3 mm decrease in the total thickness of the LUS CONCLUSIONS: We have established reference ranges for LUS thickness throughout gestation. The LUS thickness decreases throughout gestation in singleton pregnancies and is significantly thinner in postterm period pregnant women with a previous cesarean section.