Epigenetic regulation by hypoxia, N-acetylcysteine and hydrogen sulphide of the fetal vasculature in growth restricted offspring: A study in humans and chicken embryos.

Fetal growth restriction (FGR) is a common outcome in human suboptimal gestation and is related to prenatal origins of cardiovascular dysfunction in offspring. Despite this, therapy of human translational potential has not been identified. Using human umbilical and placental vessels and the chicken embryo model, we combined cellular, molecular, and functional studies to determine whether N-acetylcysteine (NAC) and hydrogen sulphide (H2S) protect cardiovascular function in growth-restricted unborn offspring. In human umbilical and placental arteries from control or FGR pregnancy and in vessels from near-term chicken embryos incubated under normoxic or hypoxic conditions, we determined the expression of the H2S gene CTH (i.e. cystathionine γ-lyase) (via quantitative PCR), the production of H2S (enzymatic activity), the DNA methylation profile (pyrosequencing) and vasodilator reactivity (wire myography) in the presence and absence of NAC treatment. The data show that FGR and hypoxia increased CTH expression in the embryonic/fetal vasculature in both species. NAC treatment increased aortic CTH expression and H2S production and enhanced third-order femoral artery dilator responses to the H2S donor sodium hydrosulphide in chicken embryos. NAC treatment also restored impaired endothelial relaxation in human third-to-fourth order chorionic arteries from FGR pregnancies and in third-order femoral arteries from hypoxic chicken embryos. This NAC-induced protection against endothelial dysfunction in hypoxic chicken embryos was mediated via nitric oxide independent mechanisms. Both developmental hypoxia and NAC promoted vascular changes in CTH DNA and NOS3 methylation patterns in chicken embryos. Combined, therefore, the data support that the effects of NAC and H2S offer a powerful mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy. KEY POINTS: Gestation complicated by chronic fetal hypoxia and fetal growth restriction (FGR) increases a prenatal origin of cardiovascular disease in offspring, increasing interest in antenatal therapy to prevent against a fetal origin of cardiovascular dysfunction. We investigated the effects between N-acetylcysteine (NAC) and hydrogen sulphide (H2S) in the vasculature in FGR human pregnancy and in chronically hypoxic chicken embryos. Combining cellular, molecular, epigenetic and functional studies, we show that the vascular expression and synthesis of H2S is enhanced in hypoxic and FGR unborn offspring in both species and this acts to protect their vasculature. Therefore, the NAC/H2S pathway offers a powerful therapeutic mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy.

Optimization of Annealing and Metal Films Radiofrequency Heating Procedures for Vitrified Umbilical Arteries.

Vitrification is well known for its application in the cryopreservation of blood vessels, which will address the supply-demand imbalance in vascular grafts for the treatment of cardiovascular disease. Thermal stress damage and devitrification injury in umbilical arteries (UAs) require attention and resolution during the vitrification and rewarming process. In this study, we validated several cooling annealing protocols with temperatures (-130 to -100 °C) and annealing duration durations (10-20 s). Among these, the umbilical artery subjected to annealing at -110 °C for 10 s exhibited the most favorable glass transition and retained 93% of its elastic modulus (0.625 ± 0.030 MPa) compared to the fresh group. Extended annealing temperatures and durations can effectively reduce thermal stress damage, leading to improved mechanical properties by minimizing temperature gradients during cooling. Furthermore, three metal radiofrequency methods were utilized for rewarming, including the use of additional metal films and different magnetic field strengths (20, 25 kA/m). Metal radiofrequency (adding an extra metal film for cryoprotectants rewarming, 20 kA/m) achieved faster and more uniform rewarming, preserving the extracellular matrix (ECM), collagen fibers, and elastic fibers without significant differences compared to the fresh group (P < 0.05). Moreover, its preservation of the biomechanical properties of blood vessels was better than that of water bath heating. Theoretical analysis supports these findings, indicating that radiofrequency heating (RFH) with metal films reduces temperature gradients and thermal stresses during arterial rewarming. RFH contributes to the cryopreservation and clinical application of large-lumen biomaterials, overcoming challenges associated with vascular vitrification and rewarming.

Effect of maternal hyperoxygenation on neonatal outcomes among women in labour with pathological cardiotocography: an open-label randomized controlled trial.

BACKGROUND: Hyperoxygenation has shown promise in improving suspicious fetal heart patterns in women in labor. However, the effect of hyperoxygenation on neonatal outcomes in women in labor with pathologic fetal heart rate tracing has not been studied. OBJECTIVE: This study aimed to evaluate the effect of fractional inspiration of oxygen of 80% compared with fractional inspiration of oxygen of 40% on neonatal outcomes in women with pathologic fetal heart rate tracing. STUDY DESIGN: This randomized, open-label, parallel arm, outcome assessor-blinded clinical trial was conducted in a large tertiary care university hospital. Singleton parturients aged ≥18 years at term gestation in active labor (cervical dilatation of ≥6 cm) with pathologic fetal heart rate tracing were recruited in the study. Pathologic fetal heart rate tracing was defined according to the International Federation of Gynecology and Obstetrics 2015 guidelines. The International Federation of Gynecology and Obstetrics classifies fetal heart rate tracings into 3 categories (normal, suspicious, and pathologic) based on rate, variability, and deceleration. Women in the intervention arm received oxygen at 10 L/min via a nonrebreathing mask, and those in the usual care arm received oxygen at 6 L/min with a simple face mask. Oxygen supplementation was continued until cord clamping. The primary outcome measure was a 5-minute Apgar score. The secondary outcome measures were the proportion of neonatal intensive care unit admission, umbilical cord blood gas variables, level of methyl malondialdehyde in the cord blood, and mode of delivery. RESULTS: Overall, 148 women (74 women in the high fractional inspiration of oxygen arm and 74 in the low fractional inspiration of oxygen arm) with pathologic fetal heart rate tracing were analyzed. The demographic data, obstetrical profiles, and comorbidities were comparable. The median 5-minute Apgar scores were 9 (interquartile range, 8-10) in the hyperoxygenation arm and 9 (interquartile range, 8-10) in the usual care arm (P=.12). Furthermore, the rate of neonatal intensive care unit admission (9.5% vs 12.2%; P=.6) and the requirement of positive pressure ventilation (6.8% vs 8.1%; P=.75) were comparable. Concerning cord blood gas parameters, the hyperoxygenation arm had a significantly higher base deficit in the umbilical vein and lactate level in the umbilical artery. The cesarean delivery rate was significantly lower in women who received hyperoxygenation (4.1% [3/74]) than in women who received normal oxygen supplementation (25.7% [19/74]) (P=.00). In addition, umbilical vein malondialdehyde level in the umbilical vein was lower in the hyperoxygenation group (8.28±4.65 µmol/L) than in the normal oxygen supplementation group (13.44±8.34 µmol/L) (P=.00). CONCLUSION: Hyperoxygenation did not improve the neonatal Apgar score in women with pathologic fetal heart rate tracing. In addition, neonatal intensive care unit admission rate and blood gas parameters remained comparable. Therefore, the results of this trial suggest that a high fractional inspiration of oxygen supplementation confers no benefit on neonatal outcomes in women with pathologic fetal heart rate tracings and normal oxygen saturation.

The association between discordant umbilical arterial resistance in growth-restricted fetuses and adverse outcomes.

BACKGROUND: Assessing the umbilical artery pulsatility index via Doppler measurements plays a crucial role in evaluating fetal growth impairment. OBJECTIVE: This study aimed to investigate perinatal outcomes associated with discordant pulsatility indices of umbilical arteries in fetuses with growth restriction. STUDY DESIGN: In this retrospective cohort study, all singleton pregnancies were included if their estimated fetal weight and/or abdominal circumference fell below the 10th percentile for gestational age (2017-2022). Eligible cases included singleton pregnancies with concurrent sampling of both umbilical arteries within 14 days of birth at the ultrasound evaluation closest to delivery. The exclusion criteria included births before 22 weeks of gestation, evidence of absent or reverse end-diastolic flow in either umbilical artery, and known fetal genetic or structural anomalies. The study compared cases with discordant umbilical artery pulsatility index values (defined as 1 umbilical artery pulsatility index at ≤95th percentile and the other umbilical artery pulsatility index at >95th percentile for gestational age) to pregnancies where both umbilical artery pulsatility indices had normal pulsatility index values and those with both umbilical arteries displaying abnormal pulsatility index values. The primary outcome assessed was the occurrence of composite adverse neonatal outcomes. Multivariable logistic regressions were performed, adjusting for relevant covariates. RESULTS: The study encompassed 1014 patients, including 194 patients (19.1%) with discordant umbilical artery pulsatility index values among those who had both umbilical arteries sampled close to delivery, 671 patients (66.2%) with both umbilical arteries having normal pulsatility index values, and 149 patients (14.7%) with both umbilical arteries exhibiting abnormal values. Pregnancies with discordant umbilical artery pulsatility index values displayed compromised sonographic parameters compared with those with both umbilical arteries showing normal pulsatility index values. Similarly, the number of abnormal umbilical artery pulsatility index values was associated with adverse perinatal outcomes in a dose-response manner. Cases with 1 abnormal (discordant) umbilical artery pulsatility index value showed favorable sonographic parameters and perinatal outcomes compared with cases with both abnormal umbilical artery pulsatility index values, and cases with both abnormal umbilical artery pulsatility index values showed worse sonographic parameters and perinatal outcomes compared with cases with discordant UA PI values. Multivariate analysis revealed that discordant umbilical artery pulsatility indices were significantly and independently associated with composite adverse perinatal outcomes, with an adjusted odds ratio of 1.75 (95% confidence interval, 1.24-2.47; P = .002). CONCLUSION: Evaluating the resistance indices of both umbilical arteries may provide useful data and assist in assessing adverse perinatal outcomes among fetuses with growth restriction.

Umbilical artery eucapnic pH to assess fetal well-being.

BACKGROUND: Umbilical artery gas results help obstetricians assess fetal well-being during labor and guide screening decisions on eligibility for therapeutic hypothermia (ie, whole-body or head cooling). The accuracy of results, especially for the base deficit on arterial cord gas analysis, in predicting brain injury is questioned. A novel biomarker specifically calculated for fetal acid-base physiology and response to asphyxia-neonatal eucapnic pH as a marker of neonatal metabolic acidosis-has the potential to be an accurate predictor of hypoxic-ischemic encephalopathy. OBJECTIVE: We aimed to compare false-negative rates of hypoxic-ischemic encephalopathy for umbilical artery pH, base deficit, and neonatal eucapnic pH in assessing fetal acid-base balance as a marker of fetal well-being and predicting acute brain injury. STUDY DESIGN: This is a retrospective single-center cohort study of newborns ≥ 35 weeks of gestation diagnosed with hypoxic-ischemic encephalopathy. We compared false-negative rates for any grade of hypoxic-ischemic encephalopathy using unilateral paired chi-square statistical analysis based on cutoff values for umbilical artery pH ≤7.00, base deficit ≥16 mmol/L, base deficit ≥12 mmol/L and neonatal eucapnic pH ≤7.14. We performed an analysis of variance between umbilical artery pH, base deficit, and neonatal eucapnic pH for each hypoxic-ischemic encephalopathy grade. RESULTS: We included 113 newborns. False-negative rate for hypoxic-ischemic encephalopathy was significantly higher for base deficit <16 mmol/L (n=78/113; 69.0%) than <12 mmol/L (n=46/113; 40.7%), pH >7.00 (n=41/113; 36.3%), or neonatal eucpanic pH >7.14 (n=35/113; 31.0%) (P<.0001). All true-positive cases were identified using only umbilical artery pH and neonatal eucapnic pH. Base deficit ≥16 or ≥12 mmol/L did not add any value in identifying newborns with hypoxic-ischemic encephalopathy when using umbilical artery pH and neonatal eucapnic pH. No association emerged between any marker and hypoxic-ischemic encephalopathy severity grading. CONCLUSION: Our findings support the accuracy of neonatal eucapnic pH to assess fetal well-being during labor and to improve predictive performance for acute brain injury. Neonatal eucpanic pH, in addition to umbilical artery pH, may be a viable alternative in identifying newborns at risk for hypoxic-ischemic encephalopathy.

Society for Maternal-Fetal Medicine Consult Series #72: Twin-twin transfusion syndrome and twin anemia-polycythemia sequence.

Thirty percent of spontaneously occurring twins are monozygotic, of which two-thirds are monochorionic, possessing a single placenta. A common placental mass with shared intertwin placental circulation is key to the development and management of complications unique to monochorionic gestations. In this Consult, we review general considerations and a contemporary approach to twin-twin transfusion syndrome and twin anemia-polycythemia sequence, providing management recommendations based on the available evidence. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend routine first-trimester sonographic determination of chorionicity and amnionicity (GRADE 1B); (2) we recommend that ultrasound surveillance for twin-twin transfusion syndrome begin at 16 weeks of gestation for all monochorionic-diamniotic twin pregnancies and continue at least every 2 weeks until delivery, with more frequent monitoring indicated with clinical concern (GRADE 1C); (3) we recommend that routine sonographic surveillance for twin-twin transfusion syndrome minimally include assessment of amniotic fluid volumes on both sides of the intertwin membrane and evaluation for the presence or absence of urine-filled fetal bladders, and ideally incorporate Doppler study of the umbilical arteries (GRADE 1C); (4) we recommend fetoscopic laser surgery as the standard treatment for stage II through stage IV twin-twin transfusion syndrome presenting between 16 and 26 weeks of gestation (GRADE 1A); (5) we recommend expectant management with at least weekly fetal surveillance for asymptomatic patients continuing pregnancies complicated by stage I twin-twin transfusion syndrome, and consideration for fetoscopic laser surgery for stage I twin-twin transfusion syndrome presentations between 16 and 26 weeks of gestation complicated by additional factors such as maternal polyhydramnios-associated symptomatology (GRADE 1B); (6) we recommend an individualized approach to laser surgery for early- and late-presenting twin-twin transfusion syndrome (GRADE 1C); (7) we recommend that all patients with twin-twin transfusion syndrome qualifying for laser therapy be referred to a fetal intervention center for further evaluation, consultation, and care (Best Practice); (8) after laser therapy, we suggest weekly surveillance for 6 weeks followed by resumption of every-other-week surveillance thereafter, unless concern exists for post-laser twin-twin transfusion syndrome, post-laser twin anemia-polycythemia sequence, or fetal growth restriction (GRADE 2C); (9) following the resolution of twin-twin transfusion syndrome after fetoscopic laser surgery, and without other indications for earlier delivery, we recommend delivery of dual-surviving monochorionic-diamniotic twins at 34 to 36 weeks of gestation (GRADE 1C); (10) in twin-twin transfusion syndrome pregnancies complicated by posttreatment single fetal demise, we recommend full-term delivery (39 weeks) of the surviving co-twin to avoid complications of prematurity unless indications for earlier delivery exist (GRADE 1C); (11) we recommend that fetoscopic laser surgery not influence the mode of delivery (Best Practice); (12) we recommend that prenatal diagnosis of twin anemia-polycythemia sequence minimally require either middle cerebral artery Doppler peak systolic velocity values >1.5 and <1.0 multiples of the median in donor and recipient twins, respectively, or an intertwin Δ middle cerebral artery peak systolic velocity >0.5 multiples of the median (GRADE 1C); (13) we recommend that providers consider incorporating middle cerebral artery Doppler peak systolic velocity determinations into all monochorionic twin ultrasound surveillance beginning at 16 weeks of gestation (GRADE 1C); and (14) consultation with a specialized fetal care center is recommended when twin anemia-polycythemia sequence progresses to a more advanced disease stage (stage ≥II) before 32 weeks of gestation or when concern arises for coexisting complications such as twin-twin transfusion syndrome (Best Practice).

Doppler ultrasound of umbilical and middle cerebral artery in third trimester small-for-gestational age fetuses to decide on timing of delivery for suspected fetal growth restriction: A cohort with nested RCT (DRIGITAT).

OBJECTIVE: To assess the association of the umbilicocerebral ratio (UCR) with adverse perinatal outcome in late preterm small-for-gestational age (SGA) fetuses and to investigate the effect on perinatal outcomes of immediate delivery. DESIGN: Multicentre cohort study with nested randomised controlled trial (RCT). SETTING: Nineteen secondary and tertiary care centres. POPULATION: Singleton SGA pregnancies (estimated fetal weight [EFW] or fetal abdominal circumference [FAC] <10th centile) from 32 to 36+6 weeks. METHODS: Women were classified: (1) RCT-eligible: abnormal UCR twice consecutive and EFW below the 3rd centile at/or below 35 weeks or below the 10th centile at 36 weeks; (2) abnormal UCR once or intermittent; (3) never abnormal UCR. Consenting RCT-eligible patients were randomised for immediate delivery from 34 weeks or expectant management until 37 weeks. MAIN OUTCOME MEASURES: A composite adverse perinatal outcome (CAPO), defined as perinatal death, birth asphyxia or major neonatal morbidity. RESULTS: The cohort consisted of 690 women. The study was halted prematurely for low RCT-inclusion rates (n = 40). In the RCT-eligible group, gestational age at delivery, birthweight and birthweight multiple of the median (MoM) (0.66, 95% confidence interval [CI] 0.59-0.72) were significantly lower and the CAPO (n = 50, 44%, p < 0.05) was more frequent. Among patients randomised for immediate delivery there was a near-significant lower birthweight (p = 0.05) and higher CAPO (p = 0.07). EFW MoM, pre-eclampsia, gestational hypertension and Doppler classification were independently associated with the CAPO (area under the curve 0.71, 95% CI 0.67-0.76). CONCLUSIONS: Perinatal risk was effectively identified by low EFW MoM and UCR. Early delivery of SGA fetuses with an abnormal UCR at 34-36 weeks should only be performed in the context of clinical trials.

Fetal cardiovascular changes during open and fetoscopic in-utero spina bifida closure.

OBJECTIVE: Fetoscopic closure of spina bifida using heated and humidified carbon dioxide gas (hhCO2) has been associated with lower maternal morbidity compared with open closure. Fetal cardiovascular changes during these surgical interventions are poorly defined. Our objective was to compare fetal bradycardia (defined as fetal heart rate (FHR) < 110 bpm for 10 min) and changes in umbilical artery (UA) Doppler parameters during open vs fetoscopic closure. METHODS: This was a prospective cohort study of 22 open and 46 fetoscopic consecutive in-utero closures conducted between 2019 and 2023. Both cohorts had similar preoperative counseling and clinical management. FHR and UA Doppler velocimetry were obtained systematically during preoperative assessment, every 5 min during the intraoperative period, and during the postoperative assessment. FHR, UA pulsatility index (PI) and UA end-diastolic flow (EDF) were segmented into hourly periods during surgery, and the lowest values were averaged for analysis. Umbilical vein maximum velocity was measured in the fetoscopic cohort. At each timepoint at which FHR was recorded, maternal heart rate and systolic and diastolic blood pressure were measured. RESULTS: Fetal bradycardia occurred in 4/22 (18.2%) cases of open closure and 21/46 (45.7%) cases of fetoscopic closure (P = 0.03). FHR decreased gradually in both cohorts after administration of general anesthesia and decreased further during surgery. FHR was significantly lower during hour 2 of surgery in the fetoscopic-repair cohort compared with the open-repair cohort. The change in FHR from baseline in the final stage of fetal surgery was significantly more pronounced in the fetoscopic-repair cohort compared with the open-repair cohort (mean, -32.4 (95% CI, -35.7 to -29.1) bpm vs -23.5 (95% CI, -28.1 to -18.8) bpm; P = 0.002). Abnormal UA-EDF (defined as absent or reversed EDF) occurred in 3/22 (13.6%) cases in the open-repair cohort and 23/46 (50.0%) cases in the fetoscopic-repair cohort (P = 0.004). There were no differences in UA-EDF or UA-PI between closure techniques at the individual stages of assessment. CONCLUSIONS: We observed a decrease in FHR and abnormalities in UA Doppler parameters during both open and fetoscopic spina bifida closure. Fetal bradycardia was more prominent during fetoscopic closure following hhCO2 insufflation, but FHR recovered after cessation of hhCO2. Changes in FHR and UA Doppler parameters during in-utero spina bifida closure were transient, no cases required emergency delivery and no fetoscopic closure was converted to open closure. These observations should inform algorithms for the perioperative management of fetal bradycardia associated with in-utero spina bifida closure. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Maternal vascular indices at 36 weeks' gestation in pregnancy with small or growth-restricted fetus.

OBJECTIVE: To compare maternal vascular indices and hemodynamic parameters at 35-37 weeks' gestation in pregnancies complicated by delivery of a small-for-gestational-age (SGA) or growth-restricted (FGR) neonate. METHODS: This was a prospective observational study of women with a singleton pregnancy attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. The visit included recording of maternal demographic characteristics, medical history, vascular indices and hemodynamic parameters, which were obtained using a non-invasive operator-independent device and included pulse-wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressure, total peripheral resistance and heart rate. Women with hypertensive disorders of pregnancy were excluded. SGA was diagnosed if birth weight was < 10th percentile. FGR was diagnosed if, in addition to birth weight < 10th percentile, at the 35-37-week scan, uterine artery or umbilical artery pulsatility index (PI) was > 95th percentile or fetal middle cerebral artery PI was < 5th percentile. RESULTS: Among the 6413 women included in the study, there were 605 (9.4%) cases of SGA, 133 (2.1%) cases of FGR and 5675 (88.5%) cases that were unaffected by SGA or FGR. Women with SGA or FGR, compared to unaffected pregnancies, had increased peripheral vascular resistance and reduced cardiac output. Central systolic and diastolic blood pressure were increased in the FGR group compared with the unaffected group. Aortic stiffness, as assessed by pulse-wave velocity, and augmentation index did not differ between affected and unaffected pregnancies. In the FGR group, compared with the SGA group, central systolic and diastolic blood pressure were higher, whereas heart rate was lower. CONCLUSIONS: SGA and FGR pregnancies exhibit deranged maternal hemodynamic responses compared with unaffected pregnancies. Pregnancies with FGR have higher central blood pressure compared to those with SGA, but it remains unclear whether these differences are driven by the size of the fetus or pathological fetal growth. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Trends in Apgar scores and umbilical artery pH: a population-based cohort study on 10,696,831 live births in Germany, 2008-2022.

Low Apgar scores and low umbilical arterial (UA) blood pH are considered indicators of adverse perinatal events. This study investigated trends of these perinatal health indicators in Germany. Perinatal data on 10,696,831 in-hospital live births from 2008 to 2022 were obtained from quality assurance institutes. Joinpoint regression analysis was used to quantify trends of low Apgar score and UA pH. Additional analyses stratified by mode of delivery were performed on term singletons with cephalic presentation. Robustness against unmeasured confounding was analyzed using the E-value sensitivity analysis. The overall rates of 5-min Apgar scores < 7 and UA pH < 7.10 in liveborn infants were 1.17% and 1.98%, respectively. For low Apgar scores, joinpoint analysis revealed an increase from 2008 to 2011 (annual percent change (APC) 5.19; 95% CI 3.66-9.00) followed by a slower increase from 2011 to 2019 (APC 2.56; 95% CI 2.00-3.03) and a stabilization from 2019 onwards (APC - 0.64; 95% CI - 3.60 to 0.62). The rate of UA blood pH < 7.10 increased significantly between 2011 and 2017 (APC 5.90; 95% CI 5.15-7.42). For term singletons in cephalic presentation, the risk amplification of low Apgar scores was highest after instrumental delivery (risk ratio 1.623, 95% CI 1.509-1.745), whereas those born spontaneous had the highest increase in pH < 7.10 (risk ratio 1.648, 95% CI 1.615-1.682).          Conclusion: Rates of low 5-min Apgar scores and UA pH in liveborn infants increased from 2008 to 2022 in Germany. What is Known: • Low Apgar scores at 5 min after birth and umbilical arterial blood pH are associated with adverse perinatal outcomes. • Prospective collection of Apgar scores and arterial blood pH data allows for nationwide quality assurance. What is New: • The rates of liveborn infants with 5-min Apgar scores < 7 rose from 0.97 to 1.30% and that of umbilical arterial blood pH < 7.10 from 1.55 to 2.30% between 2008-2010 and 2020-2022. • In spontaneously born term singletons in cephalic presentation, the rate of metabolic acidosis with pH < 7.10 and BE < -5 mmol/L in umbilical arterial blood roughly doubled between the periods 2008-2010 and 2020-2022.

Exploring the Topography of the Obturator Artery and Corona Mortis: a Detailed Analysis with Surgical Implications.

INTRODUCTION AND HYPOTHESIS: The obturator artery (ObA) is described as a branch of the anterior division of the internal iliac artery. It arises close to the origin of the umbilical artery, where it is crossed by the ureter. The main goal of the present study was to create an anatomical map of the ObA demonstrating the most frequent locations of the vessel's origin and course. METHODS: In May 2022, an evaluation of the findings from 75 consecutive patients who underwent computed tomography angiography studies of the abdomen and pelvis was performed. RESULTS: The presented results are based on a total of 138 arteries. Mostly, ObA originated from the anterior trunk of the internal iliac artery (79 out of 138; 57.2%). The median ObA diameter at its origin was found to be 3.34 mm (lower quartile [LQ] = 3.00; upper quartile [UQ] = 3.87). The median cross-sectional area of the ObA at its origin was found to be 6.31 mm2 (LQ = 5.43; UQ = 7.32). CONCLUSIONS: Our study developed a unique arterial anatomical map of the ObA, showcasing its origin and course. Moreover, we have provided more data for straightforward intraoperative identification of the corona mortis through simple anatomical landmarks, including the pubic symphysis. Interestingly, a statistically significant difference (p < 0.05) between the morphometric properties of the aberrant ObAs and the "normal" ObAs originating from the internal iliac artery was found. It is hoped that our study may aid in reducing the risk of serious hemorrhagic complications during various surgical procedures in the pelvic region.

Uterine contractile activity and neonatal outcome - A blind analysis of a randomized controlled trial cohort.

INTRODUCTION: Sufficient contractions are necessary for a successful delivery but each contraction temporarily constricts the oxygenated blood flow to the fetus. Individual fetal or placental characteristics determine how the fetus can withstand this temporary low oxygen saturation. However, only a few studies have examined the impact of uterine activity on neonatal outcome and even less attention has been paid to parturients' individual characteristics. Our objective was therefore to find out whether fetuses compromised by maternal or intrapartum risk factors are more vulnerable to excessive uterine activity. MATERIAL AND METHODS: Uterine contractile activity was assessed by intrauterine pressure catheters. Women (n = 625) with term singleton pregnancies and fetus in cephalic presentation were included in this secondary, blind analysis of a randomized controlled trial cohort. Intrauterine pressure as Montevideo units (MVU), contraction frequency/10 min and uterine baseline tone were calculated for 4 h prior to birth or the decision to perform cesarean section. Uterine activity in relation to umbilical artery pH linearly or ≤7.10 was used as the primary outcome. Need for operative delivery (either cesarean section or vacuum-assisted delivery) due to fetal distress was analyzed as a secondary outcome. In addition, belonging to vulnerable subgroups with, for example, chorioamnionitis, hypertensive or diabetic disorders, maternal smoking or neonatal birthweight <10th percentile were investigated as additional risk factors. RESULTS: A linear decline in umbilical artery pH was seen with increasing intrauterine pressure in all deliveries (p < 0.001). Among parturients with suspected chorioamnionitis, every increasing 10 MVUs increased the likelihood of umbilical artery pH ≤7.10 (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.02-1.34, p = 0.023). The need for operative delivery due to fetal distress was increased among all laboring women by every increasing 10 MVUs (OR 1.05, 95% CI 1.01-1.09, p = 0.015). This association with operative deliveries was further increased among parturients with hypertensive disorders (OR 1.23, 95% CI 1.05-1.43, p = 0.009) and among those with diabetic disorders (OR 1.13, 95% CI 1.04-1.28, p = 0.003). CONCLUSIONS: Increasing intrauterine pressure impairs umbilical artery pH especially among parturients with suspected chorioamnionitis. Fetuses in pregnancies affected by chorioamnionitis, hypertensive or diabetic disorders are more vulnerable to high intrauterine pressure.

Diagnosis of single umbilical artery and risk of foetal congenital malformations by prenatal ultrasound: a retrospective study.

BACKGROUND: Single umbilical artery (SUA) is strongly associated with foetal structural abnormalities; however, the exact pattern of this association has not been described. We aimed to investigate the occurrence of malformations in singleton pregnancies with SUA in China and to study the association between the absent side of the umbilical artery and foetal malformations. METHODS: This was a retrospective study of singleton pregnancies for which routine first-trimester anatomical screening was performed at 11+ 0-13+ 6 gestational weeks and, if the pregnancy continued, a second-trimester scan was performed at 20+ 0-24+ 0 weeks. Data were extracted from records at the referral centre, the Obstetrics and Gynecology Hospital of Fudan University, between January 2011 and April 2019 (n = 47,894). Using logistic regression, the odds ratios (OR) with 95% confidence intervals (CIs) were calculated for malformations associated with SUA. RESULTS: The incidence of SUA in our study was 2.0% (970/47,894). Of all foetuses with SUA, 387 (39.9%) had structural malformations. The malformation type varied, with cardiovascular complications being the most common. A robust association was observed between SUA and oesophageal stenosis or atresia (OR: 25.33), followed by cardiovascular (OR: 9.98-24.02), scoliosis (OR: 18.62), genitourinary (OR: 2.45-15.66), and brain malformations (OR: 4.73-9.12). The absence of the left umbilical artery (n = 445, 45.9%) was consistent with that of the right umbilical artery (n = 431, 44.4%). Furthermore, a significantly higher rate of an absent right than the left umbilical artery (p<0.01) was observed in SUA with foetal abnormalities than in SUA with no malformations. CONCLUSIONS: Overall, we observed a higher risk of various specific malformations in foetuses with SUA, and a strong association between SUA and oesophageal stenosis or atresia. The absence of the right umbilical artery was most common in foetuses with SUA and structural malformations. This study provides a reference for ultrasonographers in conducting foetal structural screening for pregnant women with SUA.

Management of fetuses with apparent normal growth and abnormal cerebroplacental ratio: A risk-based approach near term.

INTRODUCTION: Cerebroplacental ratio (CPR) has been shown to be an independent predictor of adverse perinatal outcome at term and a marker of failure to reach the growth potential (FRGP) regardless of fetal size, being abnormal in compromised fetuses with birthweight above the 10th centile. The main aim of this study was to propose a risk-based approach for the management of pregnancies with normal estimated fetal weight (EFW) and abnormal CPR near term. MATERIAL AND METHODS: This was a retrospective study of 943 pregnancies, that underwent an ultrasound evaluation of EFW and CPR at or beyond 34 weeks. CPR values were converted into multiples of the median (MoM) and EFW into centiles according to local references. Pregnancies were then divided into four groups: normal fetuses (defined as EFW ≥10th centile and CPR ≥0.6765 MoM), small for gestational age (EFW <10th centile and CPR ≥0.6765 MoM), fetal growth restriction (EFW <10th centile and CPR <0.6765 MoM), and fetuses with apparent normal growth (EFW ≥10th centile) and abnormal CPR (<0.6765 MoM), that present FRGP. Intrapartum fetal compromise (IFC) was defined as an abnormal intrapartum cardiotocogram or pH requiring cesarean delivery. Risk comparisons were performed among the four groups, based on the different frequencies of IFC. The risks of IFC were subsequently extrapolated into a gestational age scale, defining the optimal gestation to plan the birth for each of the four groups. RESULTS: Fetal growth restriction was the group with the highest frequency of IFC followed by FRGP, small for gestational age, and normal groups. The "a priori" risks of the fetal growth restriction and normal groups were used to determine the limits of two scales. One defining the IFC risk and the other defining the appropriate gestational age for delivery. Extrapolation of the risk between both scales placed the optimal gestational age for delivery at 39 weeks of gestation in the case of FRGP and at 40 weeks in the case of small for gestational age. CONCLUSIONS: Fetuses near term may be evaluated according to the CPR and EFW defining four groups that present a progressive risk of IFC. Fetuses in pregnancies complicated by FRGP are likely to benefit from being delivered at 39 weeks of gestation.

Umbilical artery thrombosis risk factors and perinatal outcomes.

PURPOSE: The purpose of this study was to investigate the risk factors for umbilical artery thrombosis (UAT) and the relationship between umbilical artery thrombosis and perinatal outcomes. METHODS: This was a retrospective study that enrolled singleton pregnant women who were diagnosed with umbilical artery thrombosis. The control group recruited pregnant woman with three umbilical vessels or those with isolated single umbilical artery (iSUA) who were matched with umbilical artery thrombosis group. The risk factors and perinatal outcomes were compared between the groups. RESULTS: Preconception BMI (OR [95%CI]: 1.212 [1.038-1.416]), abnormal umbilical cord insertion (OR [95%CI]: 16.695 [1.333-209.177]) and thrombophilia (OR [95%CI]: 15.840 [1.112-223.699]) were statistically significant risk factors for umbilical artery thrombosis. An elongated prothrombin time (OR [95%CI]: 2.069[1.091-3.924]) was strongly associated with the occurrence of UAT. The risks of cesarean delivery, preterm birth, fetal growth restriction, neonatal asphyxia, and intraamniotic infection were higher in pregnancies with UAT than in pregnancies with three umbilical vessels or isolated single umbilical artery (P<0.05). Additionally, the incidence of thrombophilia was higher in pregnant women with umbilical artery thrombosis than those with isolated single umbilical artery (P = 0.032). Abnormal umbilical cord insertion was also found to be associated with an elevated risk of iSUA (OR [95%CI]: 15.043[1.750-129.334]). CONCLUSIONS: Abnormal umbilical cord insertion was the risk factor for both umbilical artery thrombosis and isolated single umbilical artery. The pregnancies with umbilical artery thrombosis had a higher risk of the adverse perinatal outcomes.

Ultrasound parameters of arteries and heart in normal fetuses.

BACKGROUND: Currently, no normal ultrasound data of the fetuses during the 20-40 gestation have been obtained for references of fetal growth and development. If such ultrasound data existed for prenatal diagnosis of possible diseases and abnormalities, neonates would be able to get timely treatment immediately after birth. This study was thus performed to obtain ultrasound parameters of normal fetuses during the 20-40 week gestation and the distribution of ultrasound parameters with the gestational age for references of detecting potential fetal diseases and abnormalities. METHODS: Normal fetuses without any abnormalities were enrolled, and the ultrasound parameters of the general biology, arteries, and aorta were measured and analyzed. RESULTS: 417 normal fetuses were enrolled. A significant (P < 0.05) negative correlation with the gestational age was detected in the peak systolic velocity/peak diastolic velocity (S/D), pulsatility index (PI) and resistance index (RI) of the umbilical artery (UA). A relatively stable relationship with the gestational age was detected in the fetal weight%, S/D, PI and RI of the middle cerebral artery (MCA), peak systolic velocity (PSV) and velocity time integral (VTI) of the intra-abdominal UA, fetal heart to chest ratio, mitral valve (MV)- and tricuspid valve (TV)-E/A peak flow velocity, aortic isthmic Z-score and displacement, distance between the brachiocephalic artery-left common carotid artery (BA-LCCA) and LCCA-left subclavian artery (LSA), Z-score of aorta, ascending aorta (AAO), pulmonary artery (PA), main pulmonary artery (MPA), and descending aorta (DAO). A significant (P < 0.05) positive correlation with the gestational age was detected in the fetal biological data, MCA PSV and VTI, free-UA PSV and VTI and cardio-thoracic ratio, cardiac parameters, ductus arteriosus (DA) and isthmus diameter, aortic parameters, PA and MPA diameter, MPA PSV and VTI, isthmus flow volume and velocity and PA flow volume, DA and BA parameters, and LCCA and LSA parameters (flow volume, PSV, and VTI). CONCLUSION: A certain correlation and distribution trend is detected in the ultrasound parameters of normal fetuses, and the ratios among different parameters remain relative stable. These findings can be used for determination of abnormal growth of the fetuses in prenatal ultrasound scan.

Association of low pregnancy associated plasma protein-A with increased umbilical artery pulsatility index in cases of fetal weight between the 3rd and 10th percentiles: a retrospective cohort study.

OBJECTIVES: This study aims to evaluate if low levels of serum maternal pregnancy associated plasma protein-A (PAPP-A) during the first trimester are related to increased umbilical artery pulsatility index (UA PI) later in pregnancy, in cases of estimated fetal weight between the 3rd and 10th percentiles, in order to establish PAPP-A as a predictor of this particular cases of fetal growth restriction (FGR). METHODS: An observational, retrospective cohort study, conducted at a tertiary University Hospital located in Oporto, Portugal. Pregnant women who did the first trimester combined screening, between May 2013 and June 2020 and gave birth in the same hospital, with an estimated fetal weight (EFW) between the 3rd and 10th percentiles were included. The primary outcome is the difference in increased UA PI prevalence between two groups: PAPP-A<0.45 MoM and PAPP-A≥0.45 MoM. As secondary outcomes were evaluated differences in neonatal weight, gestational age at delivery, cesarean delivery, neonatal intensive care unit hospitalization, 5-min Apgar score below 7 and live birth rate between the same two groups. RESULTS: We included 664 pregnancies: 110 cases of PAPP-A<0.45 MoM and 554 cases with PAPP-A≥0.45 MoM. Increased UA PI prevalence, which was the primary outcome of this study, was significantly different between the two groups (p=0.005), as the PAPP-A<0.45 MoM group presents a higher prevalence (12.7 %) when compared to the PAPP-A≥0.45 MoM group (5.4 %). The secondary outcome cesarean delivery rate was significantly different between the groups (p=0.014), as the PAPP-A<0.45 MoM group presents a higher prevalence (42.7 %) than the PAPP-A≥0.45 MoM group (30.1 %). No other secondary outcomes showed differences between the two groups. CONCLUSIONS: There is an association of low serum maternal PAPP-A (<0.45 MoM) during the first trimester and increased UA PI (>95th percentile) later in pregnancy, in cases of EFW between the 3rd and 10th percentiles. However, this association is not strong enough alone for low PAPP-A to be a reliable predictor of increased UA PI in this population.

Effects of sildenafil on Doppler parameters, maternal and neonatal outcomes in the active labor phase of low-risk pregnancies: a randomized clinical trial.

OBJECTIVES: The benefits of sildenafil by increasing blood flow in the improvement of Doppler parameters of umbilical (UA), uterine (UtA), and fetal middle cerebral arteries (MCA) remain uncertain. On the other hand, insufficient blood flow during uterine contractions in labor can lead to decrease blood supply and fetal distress. Therefore, we aimed to assess the changes in fetal Doppler indices and maternal and neonatal outcomes following the use of sildenafil in the active phase of labor in low-risk pregnancies with healthy fetuses. METHODS: This randomized double-blinded controlled trial was conducted on 70 pregnant single low-risk, pregnant women. The patients were randomly assigned into two groups receiving sildenafil (n=35) or placebo (n=35) when the active phase of labor was initiated. Doppler parameters were assessed at baseline as well as 3 h after that. Indeed, the maternal and neonatal outcomes were compared between groups. RESULTS: The Doppler parameters including the pulsatility index of MCA, UA, and left and right UtA remained unchanged after the administration of sildenafil. Neonatal outcomes including birth weight, PH of the umbilical artery, Apgar score, respiratory distress syndrome, and neonatal intensive care unit admission as well as maternal outcomes such as cesarean section rate and the occurrence of intrapartum/postpartum hemorrhage had no difference between groups. CONCLUSIONS: The use of sildenafil in the active phase of labor in low-risk pregnancies may not be beneficial in improving Doppler parameters in MCA, umbilical, and uterine arteries and thus may not improve pregnancy outcomes.

The changing Doppler patterns and perinatal outcomes of monochorionic diamniotic twins with selective fetal growth restriction.

OBJECTIVES: To investigate the clinical outcomes and Doppler patterns changes in monochorionic diamniotic (MCDA) twins with selective fetal growth restriction (sFGR). METHODS: We retrospectively analyzed 362 sFGR cases from January 2010 to May 2016 at a single tertiary referral center. The Doppler waveforms of umbilical artery end-diastolic flow were collected, and all neonates were subjected to an early neonatal brain scan. RESULTS: A total of 66/100 (66 %) type I cases were stable, whereas 25/100 (25 %) cases changed to type II and 9/100 (9 %) changed to sFGR complicated twin-twin transfusion syndrome (TTTS). A total of 48.9 % (22/45) sFGR cases were complicated with polyhydramnios and 30.4 % (7/23) sFGR cases were complicated with oligohydramnios, both of which were progressed to sFGR with TTTS. Mild cerebral injury was significantly associated with Doppler flow abnormalities, earlier gestational age at delivery and type of sFGR diagnosis. Severe cerebral injury was significantly associated with gestational age at delivery (31.6 vs. 34.1, p=0.002) and larger birthweight discordance (43.9 vs. 29.3 %, p=0.011). CONCLUSIONS: Doppler patterns in sFGR can gradually change, with important consequences with regard to management and outcomes. Along with abnormal Doppler findings, earlier occurrence of sFGR and delivery are associated with subsequent neonatal cerebral injury.

Does maternal oxygen administration during non-reassuring fetal status affect the umbilical artery gas measures and neonatal outcomes?

PURPOSE: To clarify whether maternal oxygen administration during vaginal delivery improves umbilical artery (UA) gas measurements and neonatal outcomes. METHODS: Singleton pregnancies requiring operative vaginal delivery or emergency cesarean section (CS) due to non-reassuring fetal status (NRFS) during vaginal delivery at our hospital from 2018 to 2021 were retrospectively investigated. Intrapartum fetal wellbeing was evaluated based on the 5-tier fetal heart rate (FHR) pattern which is a delivery management method widely used in Japan. Operative vaginal deliveries or emergency CS was performed under integrated judgment in NRFS. Patients were divided into the oxygen group to whom oxygen (10 L/min) was supplied by a facemask and the room air group. The UA gas measurements and neonatal outcomes were compared. The oxygen administration was classified by conditions before and after the coronavirus disease 2019 pandemic. As a secondary evaluation, stratification of FHR pattern levels and factors associated with UA pH < 7.15 were examined. RESULTS: A total of 250 patients required obstetric surgical delivery due to NRFS, including 140 (56%) and 110 (44%) in the oxygen and room air groups, respectively. No differences in maternal background factors were found between both groups, except for maternal age. UA gas measurements and neonatal outcomes also showed no significant differences. No significant factors were extracted in the multivariate analysis for UA pH < 7.15. CONCLUSIONS: Trans-maternal oxygen administration for intrapartum NRFS did not affect neonatal cord blood gasses or neonatal outcomes. Thus, routine oxygen administration for intrapartum NRFS may not always be necessary.