Maternal Artery Research Articles

Resistance artery vasodilator pathways involved in the antihypertensive effects of cocoa shell extract in rats exposed to fetal undernutrition.

Fetal undernutrition establishes the foundations for hypertension development, with oxidative stress being a key hallmark. A growing interest in nutraceuticals for treating hypertension and environmental waste concerns prompted the present study aiming to evaluate whether supplementation with a polyphenol enriched extract from cocoa shell (CSE), a by-product from the chocolate industry with antioxidant properties, reduces hypertension of developmental origin, thus improving mesenteric resistance artery (MRA) vasodilatation. Adult male and female offspring from rats exposed to 50% food restriction from mid-gestation (maternal undernutrition, MUN) and controls were used. Supplementation was given through a gelatine (vehicle, VEH) or containing CSE (250mgkg-1day-1) 5daysweek-1 for 3weeks. Systolic blood pressure (SBP) was assessed by tail-cuff plethysmography. MRA function was studied by wire myography, and superoxide anion and nitric oxide were investigated by fluorescent indicators and confocal microscopy. Compared to control-VEH, MUN-VEH males showed significantly higher SBP, reduced MRA as well as relaxation to ACh, sodium nitroprusside and the AMPK agonist 5-aminoimidazole-4-carboxamide riboside, but not to isoproterenol. In MUN males, endothelial endothelium-derived hyperpolarizing factor and nitric oxide were unaltered, but MRA released a vasoconstrictor prostanoid and produced higher levels of superoxide anion. CSE normalized blood pressure and improved all above-mentioned MRA alterations in MUN males without an effect on control counterparts, except the reduction of superoxide anion. MUN-VEH females were normotensive and only showed a tendency towards larger superoxide anion production, which was abolished by CSE. CSE supplementation reduces SBP improving endothelium-dependent and independent MRA vasodilatation, related to local superoxide anion reduction, being a potential nutraceutical ingredient to counteract hypertension, in addition to contributing to the circular economy. KEY POINTS: Fetal undernutrition induces hypertension in males associated with deficient resistance artery vasodilatation, being normalized by cocoa shell extract (CSE). Release of a cyclooxygenase-derived contractile factor is the main endothelial alteration, which is abolished by CSE. AMPK and soluble guanylyl cyclase-mediated relaxation are also reduced in smooth muscle cells from maternal undernutrition resistance arteries, being improved by CSE. Vascular oxidative damage caused by excess superoxide anion generation can account for impaired vasodilatation, which is improved by CSE. The capacity of CSE to improve relaxation is probably related to its antioxidant bioactive factors, and thus cocoa shell is a potential food by-product to treat hypertension.

Association of Prenatal Maternal Fever and Neonatal Umbilical Artery Blood-Gas Analysis: Evidence from a Tertiary Center at China

Background: Neonatal umbilical artery blood-gas analysis is a diagnostic procedure performed shortly after birth to assess the acid-base balance, oxygenation, and metabolic status of a newborn infant. This retrospective study aimed to investigate the association of prenatal maternal fever with neonatal umbilical artery blood-gas analysis. Methods: A retrospective analysis was conducted on data from 333 parturients and their newborns. Demographic characteristics, clinical information, and neonatal umbilical artery blood gas analysis data were analyzed to evaluate the association between prenatal maternal fever and neonatal blood-gas analysis. Pregnant women with fever (≥38.0 °C) during labor were compared with those without fever. Neonatal umbilical artery blood gas parameters were assessed in relation to the degree and duration of maternal fever. Results: The incidence of the adverse delivery outcome of parturients with high prenatal fever and long duration of fever was significantly higher than that of the low fever, short-term fever, and normal parturients (p < 0.05). The pH of neonatal umbilical veins in the high fever groups was reduced compared with the control group (p < 0.05). Lactic acid (Lac) of neonatal umbilical vein in the low fever and high fever groups was enhanced compared with the control group (p < 0.05). The pH of neonatal umbilical veins in the short-term fever and long-term fever groups was elevated compared with the control group (p < 0.05). The umbilical artery pH and base excess (BE) were positively correlated with maternal peak fever temperature (r = 0.20, r = 0.22, p < 0.05). The umbilical Lac was negatively correlated with maternal peak fever temperature (r = –0.22, p < 0.05). Moreover, the umbilical artery pH and BE were positively correlated with maternal duration of fever (r = 0.29, r = 0.21, p < 0.05). The umbilical artery Lac was negatively correlated with maternal duration of fever (r = –0.25, p < 0.05). Conclusions: The findings suggested that maternal fever during labor was associated with alterations in neonatal umbilical artery blood gas analysis. Understanding the influence of prenatal fever on delivery outcomes is crucial for optimizing maternal and neonatal health.

Correlation between anesthetic concentration and low Apgar scores in neonates born via Cesarean sections under general anesthesia

ObjectivesThis study aimed to compare plasma concentrations of anesthetic drugs administered during Cesarean section with low Apgar score in neonates deliveried under general anesthesia and analyze associated risk factors.MethodsData from 76 neonates undergoing Cesarean section under general anesthesia with blood concentrations of anesthetic drugs were analyzed. A low Apgar score was defined as ≤ 7. Perioperative maternal and neonatal data were collected and analyzed. Neonates were divided into a control group (Group CON, n = 65) and a low Apgar score group (Group LAS, n = 11) based on Apgar score.ResultsThere were no significant differences in the plasma concentrations of anesthetic drugs in maternal artery, umbilical vein or umbilical artery blood between the two groups. Risk factors for neonatal low Apgar scores during Cesarean section under general anesthesia were premature delivery (aOR 10.2, 95% CI = 1.8–56.9) and preoperative fetal distress (aOR 9.6, 95% CI = 1.3–69.0). The prediction model was: probability = 1/(e‑Y), Y= -4.607 + 2.318× (premature delivery) + 2.261× (fetal distress) (yes = 1, no = 0). The Hosmer–Lemeshow test showed χ²= 9.587, P = 0.213, and the area under the curve (AUC) was 0.850 (0.670 ~ 1.000). With a cutoff value of 0.695, sensitivity and specificity were 81.8% and 87.7%, respectively.ConclusionsThere was no correlation between blood concentration of general anesthetic drugs and Apgar score or occurrence of neonatal low Apgar scores. Premature delivery and preoperative fetal distress were identified as independent risk factors for neonatal low Apgar scores after Cesarean section under general anesthesia.

Evidence that systemic vascular resistance is increased before the development of gestational diabetes mellitus

The ophthalmic artery, which is the first branch of the internal carotid artery, has a Doppler velocity waveform with two systolic peaks. The ratio of the peak systolic velocity (PSV) of the second wave divided by that of the first wave, reflects increased peripheral resistance. Previous studies in the first, second and third trimesters of pregnancy have reported that in pregnancies that subsequently develop preeclampsia (PE) the PSV ratio is increased. Both PE and gestational diabetes mellitus (GDM) are associated with endothelial dysfunction and an increased risk of cardiovascular diseases during the first decade following pregnancy. To compare the ophthalmic artery PSV ratio at 11-13 weeks' gestation in women who subsequently develop GDM to unaffected pregnancies and those who develop PE. This was a prospective observational study in women attending for a routine hospital visit at 11+0 - 13+6 weeks' gestation at King's College Hospital, London, UK. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination for fetal anatomy and growth, assessment of flow velocity waveforms from the maternal ophthalmic arteries and calculation of the PSV ratio, and measurement of mean arterial pressure (MAP). Linear regression was performed for the prediction of ophthalmic artery PSV ratio, from maternal characteristics and MAP. The PSV ratio in the group with GDM was compared to that of PE and unaffected pregnancies. 3999 women were included in the study, including 375 (9.8%) who developed GDM and 101 (2.5%) who developed PE. In the GDM group, 161 (43.3%) were treated by diet alone, 130 (34,1%) were treated with metformin and 84 (22.6%) received insulin ± metformin. Significant prediction of PSV ratio was provided by development of PE, maternal age, body mass index, MAP, first degree family history of diabetes mellitus, family history of PE, Asian ethnicity, and smoking. There was no significant contribution from GDM. In women who developed GDM requiring insulin treatment, ophthalmic artery PSV ratio (0.67 ± 0.09) was higher (p <0.001) than in unaffected pregnancies (0.63 ± 0.10), but it was not significantly different from that in the PE group (0.69 ± 0.10; p=0.90). In women who develop severe GDM, requiring insulin treatment, there is evidence of increased peripheral resistance which is apparent from the first-trimester of pregnancy.

The potential of repeated mean arterial pressure measurements for predicting early- and late-onset pre-eclampsia in twin pregnancies: Prediction model study.

To investigate the contribution of longitudinal mean arterial pressure (MAP) measurement during the first, second, and third trimesters of twin pregnancies to the prediction of pre-eclampsia. A retrospective cohort study was conducted on women with twin pregnancies. Historical data between 2019 and 2021 were analyzed, including maternal characteristics and mean artery pressure measurements were obtained at 11-13, 22-24, and 28-33 weeks of gestation. The outcome measures included pre-eclampsia with delivery <34 and ≥34 weeks of gestation. Models were developed using logistic regression, and predictive performance was evaluated using the area under the curve, detection rate at a given false-positive rate of 10%, and calibration plots. Internal validation was conducted via bootstrapping. A total of 943 twin pregnancies, including 36 (3.82%) women who experienced early-onset pre-eclampsia and 93 (9.86%) who developed late-onset pre-eclampsia, were included in this study. To forecast pre-eclampsia during the third trimester, the most accurate prediction for early-onset pre-eclampsia resulted from a combination of maternal factors and MAP measured during this trimester. The optimal predictive model for late-onset pre-eclampsia includes maternal factors and MAP data collected during the second and third trimesters. The areas under the curve were 0.937 (95% confidence interval [CI] 0.894-0.981) and 0.887 (95% CI 0.852-0.921), respectively. The corresponding detection rates were 83.33% (95% CI 66.53%-93.04%) for early-onset pre-eclampsia and 68.82% (95% CI 58.26%-77.80%) for late-onset pre-eclampsia. Repeated measurements of MAP during pregnancy significantly improved the accuracy of late-onset pre-eclampsia prediction in twin pregnancies. The integration of longitudinal data into pre-eclampsia screening may be an effective and valuable strategy.

Exploring the Therapeutic Potential of C-Type Natriuretic Peptide for Preeclampsia.

Preeclampsia is a serious condition of pregnancy, complicated by aberrant maternal vascular dysfunction. CNP (C-type natriuretic peptide) contributes to vascular homeostasis, acting through NPR-B (natriuretic peptide receptor-B) and NPR-C (natriuretic peptide receptor-C). CNP mitigates vascular dysfunction of arteries in nonpregnant cohorts; this study investigates whether CNP can dilate maternal arteries in ex vivo preeclampsia models. Human omental arteries were dissected from fat biopsies collected during cesarean section. CNP, NPR-B, and NPR-C mRNA expression was assessed in arteries collected from pregnancies complicated by preeclampsia (n=6) and normotensive controls (n=11). Using wire myography, we investigated the effects of CNP on dilation of arteries from normotensive pregnancies. Arteries were preconstricted with either serum from patients with preeclampsia (n=6) or recombinant ET-1 (endothelin-1; vasoconstrictor elevated in preeclampsia; n=6) to model vasoconstriction associated with preeclampsia. Preconstricted arteries were treated with recombinant CNP (0.001-100 µmol/L) or vehicle and vascular relaxation assessed. In further studies, arteries were preincubated with NPR-B (5 µmol/L) and NPR-C (10 µmol/L) antagonists before serum-induced constriction (n=4-5) to explore mechanistic signaling. CNP, NPR-B, and NPR-C mRNAs were not differentially expressed in omental arteries from preeclamptic pregnancies. CNP potently stimulated maternal artery vasorelaxation in our model of preeclampsia (using preeclamptic serum). Its vasodilatory actions were driven through the activation of NPR-B predominantly; antagonism of this receptor alone dampened CNP vasorelaxation. Interestingly, CNP did not reduce ET-1-driven omental artery constriction. Collectively, these data suggest that enhancing CNP signaling through NPR-B offers a potential therapeutic strategy to reduce systemic vascular constriction in preeclampsia.

High C-Reactive Protein Serum Levels as a Risk Factor for Preeclampsia

Introduction: Preeclampsia is a hypertensive syndrome in pregnancy characterized by increased blood pressure, proteinuria, and complications such as liver dysfunction and visual impairment. This condition is associated with an inflammatory reaction and failure of trophoblast invasion of maternal arteries, which involves an increase in proinflammatory cytokines that indirectly induce CRP production. However, data showing the value of CRP levels as an indicator of the incidence of preeclampsia in Indonesia is minimal. This study aims to evaluate CRP levels as a predictor of preeclampsia.Methods: This case-control study involved pregnant women with preeclampsia and normal pregnant women who went to the Obstetric Emergency Installation at Prof. Hospital. Dr. I.G.N.G Ngoerah Denpasar. All data were obtained from patient medical records and then analyzed using the SPSS v.22.Results: This study involved 56 pregnant women consisting of 28 normotensive pregnant women (control) and 28 pregnant women with preeclampsia (cases) at Prof. Dr. I.G.N.G. Ngoerah General Hospital Denpasar from January to December 2023. The median age was 27.5 years (control) and 26.0 years (cases), with an age range of 18–40 years. The median BMI WAS 21.65 kg/m2 (controls) and 21.80 kg/m2 (cases). Most patients in both groups were nulliparous (50.0%, controls; 42.9%, cases). Based on ROC analysis, the CRP cut-off value of 7.76 mg/dL has a sensitivity of 76.7%, specificity of 78.6%, and an area under the curve (AUC) of 0.737, where pregnant women with high CRP (≥7.76 mg/dL) had a 12.048-fold higher risk (95%CI 3.496–41.515; p &lt; 0.001) of experiencing preeclampsia compared to pregnant women with low CRP levels.Conclusion: High serum CRP levels are a risk factor for preeclampsia. These findings indicate that measuring CRP levels can be a potential tool for identifying the risk of preeclampsia in the pregnant population.

Cardiovascular morbidity and mortality following hypertensive disorders of pregnancy

ObjectivesTo determine whether hypertensive disorders of pregnancy (HDP) are associated with maternal coronary artery disease (CAD) and other cardiovascular (CV) diseases within 10–20 years following delivery. Study designRetrospective cohort including all women who delivered ≥ 1 pregnancy ≥ 20 weeks’ gestation within a single health system from 1998 to 2008. We excluded those with CV risk factors preceding first delivery or with no follow-up after delivery. The exposure of interest was any HDP, determined by ICD coding. Main outcome measuresThe primary outcome was a composite of ICD codes for CAD, peripheral vascular disease, and CV events (myocardial infarction, stroke, and death). Multivariable Cox proportional hazards estimated the association between exposure and outcomes. A nested cohort of women who underwent cardiac catheterization had a primary outcome of angiographic CAD, and multivariable logistic regression estimated the association between HDP and CAD. ResultsOf 33,959 women included, 2,385 women had HDP. HDP was associated with the composite outcome (adjusted HR 1.50, 95 % CI 1.11, 2.03). There was a significant difference in event-free survival between groups (p = 0.003) with a median follow-up of 17.3 years. 592 women (1.7 %) underwent cardiac catheterization: 20 of 90 women with HDP had CAD (22.2 %) on angiography vs 49 of 502 without HDP (9.8 %, p < 0.001). HDP was associated with angiographic CAD (adjusted OR 2.08, 95 % CI 1.05, 4.11). ConclusionsWomen with HDP had twice the incidence of CAD on angiography compared to parous women without HDP. Obstetric history may inform the decision to perform cardiac catheterization in relatively young women.

Angiogenic and vasoactive proteins in the maternal-fetal interface in healthy pregnancies and preeclampsia

Preeclampsia is characterized by maternal endothelial activation and placental dysfunction. Imbalance in maternal angiogenic and vasoactive factors has been linked to the pathophysiology. The contribution of the placenta as a source to these factors remains unclear. Furthermore, little is known about fetal angiogenic and vasoactive proteins and the relation between maternal and fetal levels. We describe Placental growth factor (PGF), soluble Fms-like tyrosine kinase 1 (sFLT1), soluble Endoglin (sENG), as well as Endothelin 1, 2 and 3 (EDN1, EDN2 and EDN3) in five vessels in healthy pregnancies, early onset (EOPE) and late onset (LOPE) preeclampsia. Specifically, we aimed to 1) compare protein abundance in vessels at the maternal-fetal interface between EOPE, LOPE and healthy pregnancies, 2) describe placental uptake and release of proteins, and 3) describe protein abundance in the maternal vs fetal circulations. Samples were collected from the maternal radial artery, uterine vein and antecubital vein as well as the fetal umbilical vein and artery in 75 healthy and 37 preeclamptic mother-fetus pairs (including 19 EOPE and 18 LOPE), during scheduled cesarean delivery. This method allows estimation of placental release and uptake of proteins by calculation of venoarterial differences on each side of the placenta. The microarray based SomaScan assay quantified the proteins. Abundance of sFLT1 and EDN1 was higher in the maternal vessels in preeclampsia as compared to healthy pregnancies, with highest abundance in EOPE. PGF was lower in the maternal vessels in EOPE as compared to both healthy and LOPE. Maternal EDN2 was higher in preeclampsia, with LOPE having the highest abundance. Our model confirmed placental release of PGF and sFLT1 to the maternal circulation in all groups. The placenta released sFLT1 into the fetal circulation in healthy and LOPE pregnancies. Fetal EDN1 and sFLT1 were higher in early onset preeclampsia, whereas sENG and EDN3 were lower in both preeclampsia groups, compared to healthy. Across groups, abundances of PGF, sFLT1 and EDN3 were higher in the maternal artery as compared to the fetal umbilical vein, whereas EDN2 was lower. Increasing abundance of maternal sFLT1 and EDN1 across the groups healthy, LOPE and EOPE combined with a positive correlation may suggest that these proteins are associated with the pathophysiology and severity of the disease. Elevated EDN1 in the fetal circulation in EOPE represents a novel finding. Long term effects of altered protein abundance in preeclampsia on fetal development and health remain unknown. Further investigation of these proteins' involvement in the pathophysiology and as treatment targets is warranted.

Preeclampsia Management and Maternal Ophthalmic Artery Doppler Measurements between 19 and 23 Weeks of Gestation.

Background: The ophthalmic Doppler is a reliable and impartial way to assess the severity of preeclampsia (PE). The study aimed to assess the potential utility of Doppler measurements of the maternal ophthalmic arteries during the weeks 19-23 of gestation, both independently and in combination with established biomarkers for PE. Methods: A prospective cohort study was conducted involving women who were recruited from a variety of standard appointments, including booking, scanning, and regular prenatal visits. A total of 200 women that were divided into high-risk and low-risk groups for developing PE were involved during the period between April 2023 and November 2023. Results: The ophthalmic ratio had significantly higher values in high-risk patients than in low-risk women (p = 0.000). There was a significant relationship between PSV2/PSV1 and gestational age at birth in women with PE compared to the ones who did not develop PE. Conclusions: An ophthalmic artery Doppler can play a crucial role in the early detection of PE, allowing for timely intervention and management. Incorporating the ophthalmic artery Doppler as a screening tool for PE in Bulgaria has the potential to improve early detection, risk stratification, and overall maternal and fetal health outcomes.

Ophthalmic artery Doppler at 36 weeks' gestation in prediction of pre-eclampsia: validation and update of previous model.

To validate and extend a model incorporating maternal ophthalmic artery Doppler at 35-37 weeks' gestation in the prediction of subsequent development of pre-eclampsia (PE). This was a prospective validation study of screening for PE (defined according to the 2019 American College of Obstetricians and Gynecologists criteria) by maternal ophthalmic artery peak systolic velocity (PSV) ratio in 6746 singleton pregnancies undergoing routine care at 35 + 0 to 36 + 6 weeks' gestation (validation dataset). Additionally, the data from the validation dataset were combined with those of 2287 pregnancies that were previously used for development of the model (training dataset), and the combined data were used to update the original model parameters. The competing-risks model was used to estimate the individual patient-specific risk of delivery with PE at any time and within 3 weeks from assessment by a combination of maternal demographic characteristics and medical history with PSV ratio alone and in combination with the established PE biomarkers of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1). We evaluated the predictive performance of the model by examining, first, the ability to discriminate between the PE and non-PE groups using the area under the receiver-operating-characteristics curve and the detection rate (DR) at fixed screen-positive (SPR) and false-positive rates of 10% and, second, calibration by measuring the calibration slope and calibration-in-the-large. McNemar's test was used to compare the performance of screening by a biophysical test (maternal factors, MAP, UtA-PI and PSV ratio) vs a biochemical test (maternal factors, PlGF and sFlt-1), low PlGF concentration (< 10th percentile) or high sFlt-1/PlGF concentration ratio (> 90th percentile). In the validation dataset, the performance of screening by maternal factors and PSV ratio for delivery with PE within 3 weeks and at any time after assessment was consistent with that in the training dataset, and there was good agreement between the predicted and observed incidence of PE. In the combined data from the training and validation datasets, good prediction for PE was achieved in screening by a combination of maternal factors, MAP, UtA-PI, PlGF, sFlt-1 and PSV ratio, with a DR, at a 10% SPR, of 85.0% (95% CI, 76.5-91.4%) for delivery with PE within 3 weeks and 65.7% (95% CI, 59.2-71.7%) for delivery with PE at any time after assessment. The performance of a biophysical test was superior to that of screening by low PlGF concentration or high sFlt-1/PlGF concentration ratio but not significantly different from the performance of a biochemical test combining maternal factors with PlGF and sFlt-1 for both PE within 3 weeks and PE at any time after assessment. Maternal ophthalmic artery PSV ratio at 35-37 weeks' gestation in combination with other biomarkers provides effective prediction of subsequent development of PE. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Commentary on: Increased stiffness of omental arteries from late pregnant women at advanced maternal age.

Worldwide, pregnancy at age 35 or older, termed 'advanced maternal age (AMA)', is increasing exponentially. As the incidence of pregnancy at AMA has increased, a growing body of evidence has suggested that AMA is also associated with increased risk for adverse maternal and fetal outcomes outside of genetic anomalies. Importantly, despite the mounting evidence and the increased global risk of adverse perinatal outcomes observed, few studies have examined the potential mechanisms underlying this elevated risk in pregnant people ≥35 years of age. Wooldridge and colleagues begin to address this gap in the literature. In their recent report, they examine vessel stiffness in omental resistance vessels obtained from pregnant individuals ≥35 years of age compared with pregnant individuals <35 years of age. Omental arteries were isolated and assessed via pressure myography (mechanical properties) and histological analysis for collagen and elastin content. Overall, the findings from this investigation report that maternal resistance arteries collected from women of AMA were less compliant and had less elastin than arteries obtained from women <35 years of age, suggesting that maternal resistance vessel stiffening in AMA may contribute to increased risk of adverse pregnancy outcomes. The authors should be commended for completing these studies in human resistance vessels, which now open new avenues for investigation and provoke a cascade of questions related to maternal cardiovascular adaptations to pregnancy in women ≥35 years of age.

Maternal body mass index, birthweight, and placental glucose metabolism: evidence for a role of placental hexokinase

BackgroundThe principal fetal energy source is glucose provided by placental transfer of maternal glucose. However, the placenta’s glucose consumption exhibits considerable variation. Hexokinase is the first and one of the rate-limiting enzymes of glycolysis that phosphorylates glucose to glucose 6-phosphate. The role of placental hexokinase activity in human placental glucose metabolism is unknown. ObjectivesTo test the hypothesis that placental hexokinase activity is related to maternal body mass index, placental glucose uptake and consumption, and birth weight. Study designSixty-seven healthy pregnant participants at term were included in this study at Oslo University Hospital, Norway. Placental hexokinase activity was measured by using a colorimetric assay. The mass of glucose taken up by the uteroplacental unit and the fetus was obtained by measuring arterio-venous glucose differences combined with Doppler assessment of uterine and umbilical blood flow. Blood samples were obtained from the maternal radial artery, uterine vein, and umbilical artery and vein. The uteroplacental glucose consumption constituted the difference between uteroplacental and fetal glucose uptake. Spearman’s rank correlation was performed for statistical analyses to study the correlation of placental hexokinase activity (mU/mg protein) with prepregnancy body mass index, maternal glucose and insulin, birth weight, uteroplacental glucose uptake and consumption, and fetal glucose uptake (μmol/min). Partial rank correlation analysis was performed when controlling for hours of fasting or placental weight. ResultsHexokinase activity was detectable in all placental tissue samples. Mean (SD) activity was 19.6 (4.64) mU/mg of protein. Placental hexokinase activity correlated positively with prepregnancy body mass index (Spearman’s rho (ρ)=0.33; P=0.006). Upon controlling for hours of fasting, hexokinase activity showed positive correlations with both maternal glucose (r=0.30; P=0.01) and insulin (r=0.28; P=0.02). Hexokinase activity was positively correlated with uteroplacental glucose uptake (ρ=0.31; P=0.01) and consumption (ρ=0.28; P=0.02). Hexokinase activity did not correlate with fetal glucose uptake. Upon controlling for placental weight, hexokinase activity showed a positive correlation with birth weight (r=0.31; P=0.01). ConclusionOur findings suggest that placental hexokinase, being crucial for uteroplacental retention of glucose for own disposition, is related to both maternal body mass index and birth weight independent of placental weight. Placental hexokinase may play a central role in the relationship between maternal glucose dysregulation and fetal growth. Thus, the current study supports the need to develop clinically useful tools to assess the metabolic properties of the placenta.

Anesthetic drug concentrations and placental transfer rate in fetus between term and preterm infants, twins, and singletons.

Objective: This study aims to determine the drug concentration of etomidate, remifentanil, and rocuronium bromide for general anesthesia in fetus as well as the placental transport rate between term and preterm delivery, twins, and singleton. Study design: Sixty parturients with 72 fetuses undergoing cesarean section under general anesthesia were included. According to whether the fetus was a twin or premature, parturients were divided into Group I (term singleton), Group II (premature singleton), Group III (term twins), and Group IV (premature twins). The preoperative demographic characteristics and laboratory examination of parturients, hemodynamic indicators, the Apgar score of neonates at 1, 5, and 10min after delivery and at specific assigned values, umbilical artery blood gas analysis results, neonatal weight, and resuscitative measures were recorded. Anesthetic drug concentrations in maternal arterial (MA), umbilical arterial (UA), and umbilical venous (UV) blood were detected by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). Result: No significant differences were observed in the concentrations of etomidate, remifentanil, and rocuronium bromide in MA, UV, and UA blood, or in the UV/MA and UA/UV ratios between term and preterm infants, twins, and singletons. Moreover, there was no variation in the anesthetic drug concentration among each pair of twins. Additionally, no correlation was found between the neonatal weight and the plasma concentrations of anesthetic drugs in UV and UA blood, except for remifentanil in UA blood. Conclusion: Preterm or twin deliveries do not affect the neonatal concentration of etomidate, remifentanil, and rocuronium bromide used in general anesthesia for cesarean sections. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2100046547.

Evaluating circulating soluble markers of endothelial dysfunction and risk factors associated with PE: A multicentre longitudinal case control study in northern Ghana

Serpin E1/PAI-1, N-terminal pro-brain natriuretic peptide (NTpro-BNP) and neuropilin-1 are markers which have been associated with endothelial dysfunction. However, data on the levels of these markers in PE is limited. The limited data on the pathophysiology of PE in relation to these markers necessitated the study.This was a multicentre case-control study conducted at the Obstetrics and Gynaecology Department of the Tamale Teaching Hospital, the Bawku Presbyterian Hospital and the Bolgatanga Regional Hospital. Out of 520 consenting pregnant women, 127 pregnant women met the inclusion criteria (53 with PE and 74 controls) and were included in this study. Venous, placental, cord and peripheral blood were collected for biomarker assay, haematological parameters and placental parasite determination. Placental tissue sections were obtained for placental malaria and histopathological lesions associated with hypoperfusion. Maternal heart rate and foetal umbilical artery Doppler impedance indices; resistance index (RI) and systolic diastolic (SD) ratio were determined to confirm utero-placental hypoperfusion.Significantly higher proportions of foeto-maternal complications; eclampsia, low birth weight (LBW), neonatal intensive care unit admissions (NICU), intrauterine growth restriction (IUGR), caesarian deliveries and early gestational age at delivery were associated with PE. Women with PE had lower concentrations of platelet (p = 0.02) whereas red cell distribution width (RDW) was markedly elevated (p = 0.01). NTPro-BNP concentration was markedly elevated (p = 0.01) in women with PE whereas neuropilin-1 concentration was lower (p = 0.03) compared to the non-PE group. Maternal heart rate was elevated in women with PE and Doppler resistance indices (RI and SD) were significantly elevated in foetuses of PE women than foetuses of the controls. Placental mal-perfusion lesions were higher in women with PE compared to the non-PE group.Women with PE had increased risk of adverse foeto-maternal complications, significantly associated with placental mal-perfusion lesions, had reduced platelet concentration and elevated RDW-CV levels. NTPro-BNP, RI and SD are elevated in women with PE whereas neuropilin-1 concentration is reduced. Significant changes in these pathological variables in PE women is indicative of significant derangement in endothelial function culminating in adverse maternal and perinatal outcomes of pregnancy.

The effect of maternal position on placental blood flow and fetoplacental oxygenation in late gestation fetal growth restriction: a magnetic resonance imaging study.

Fetal growth restriction (FGR) and maternal supine going-to-sleep position are both risk factors for late stillbirth. This study aimed to use magnetic resonance imaging (MRI) to quantify the effect of maternal supine position on maternal-placental and fetoplacental blood flow, placental oxygen transfer and fetal oxygenation in FGR and healthy pregnancies. Twelve women with FGR and 27 women with healthy pregnancies at 34-38weeks' gestation underwent MRI in both left lateral and supine positions. Phase-contrast MRI and a functional MRI technique (DECIDE) were used to measure blood flow in the maternal internal iliac arteries (IIAs) and umbilical vein (UV), placental oxygen transfer (placental flux), fetal oxygen saturation (FO2 ), and fetal oxygen delivery (delivery flux). The presence of FGR, compared to healthy pregnancies, was associated with a 7.8% lower FO2 (P=0.02), reduced placental flux, and reduced delivery flux. Maternal supine positioning caused a 3.8% reduction in FO2 (P=0.001), and significant reductions in total IIA flow, placental flux, UV flow and delivery flux compared to maternal left lateral position. The effect of maternal supine position on fetal oxygen delivery was independent of FGR pregnancy, meaning that supine positioning has an additive effect of reducing fetal oxygenation further in women with FGR, compared to women with appropriately grown for age pregnancies. Meanwhile, the effect of maternal supine positioning on placental oxygen transfer was not independent of the effect of FGR. Therefore, growth-restricted fetuses, which are chronically hypoxaemic, experience a relatively greater decline in oxygen transfer when mothers lie supine in late gestation compared to appropriately growing fetuses. KEY POINTS: Fetal growth restriction (FGR) is the most common risk factor associated with stillbirth, and early recognition and timely delivery is vital to reduce this risk. Maternal supine going-to-sleep position is found to increase the risk of late stillbirth but when combined with having a FGR pregnancy, maternal supine position leads to 15 times greater odds of stillbirth compared to supine sleeping with appropriately grown for age (AGA) pregnancies. Using MRI, this study quantifies the chronic hypoxaemia experienced by growth-restricted fetuses due to 13.5% lower placental oxygen transfer and 26% lower fetal oxygen delivery compared to AGA fetuses. With maternal supine positioning, there is a 23% reduction in maternal-placental blood flow and a further 14% reduction in fetal oxygen delivery for both FGR and AGA pregnancies, but this effect is proportionally greater for growth-restricted fetuses. This knowledge emphasises the importance of avoiding supine positioning in late pregnancy, particularly for vulnerable FGR pregnancies.

Prolonged Anesthesia Induction to Delivery Time Did Not Influence Plasma Remifentanil Concentration in Neonates.

Remifentanil, in combination with etomidate and sevoflurane, is commonly used in clinics for general anesthesia induction in cesarean section (CS). This study aimed to evaluate the correlation between the induction to delivery (I-D) time and neonatal plasma drug concentration and anesthesia, as well as its effects on neonates. Fifty-two parturients in whom general anesthesia was induced for CS were divided into group A (I-D<8 min) and group B (I-D≥8 min). Maternal arterial (MA), umbilical venous (UV), and umbilical arterial (UA) blood samples were collected at delivery to analyze the remifentanil and etomidate concentrations using liquid chromatography-tandem mass spectrometry. There were no statistically significant differences between the two groups in terms of plasma concentrations of remifentanil in the MA, UA, and UV blood (P > 0.05). The plasma concentration of etomidate in MA and UV was higher in group A than that in group B (P<0.05), whereas the UA/UV ratio of etomidate was higher in group B than that in group A (P<0.05). The Spearman rank correlation test showed no correlation between the I-D time and plasma remifentanil concentration in the MA, UA, and UV plasma (P>0.05). The concentrations of etomidate in the MA and UV were negatively correlated with the I-D time (P < 0.05). Prolonged I-D time did not significantly influence the maternal or neonatal plasma concentration of remifentanil. It is safe to administer remifentanil target-controlled infusion in combination with etomidate and sevoflurane for general anesthesia induction during CS.

Spatial multiomics map of trophoblast development in early pregnancy

The relationship between the human placenta—the extraembryonic organ made by the fetus, and the decidua—the mucosal layer of the uterus, is essential to nurture and protect the fetus during pregnancy. Extravillous trophoblast cells (EVTs) derived from placental villi infiltrate the decidua, transforming the maternal arteries into high-conductance vessels1. Defects in trophoblast invasion and arterial transformation established during early pregnancy underlie common pregnancy disorders such as pre-eclampsia2. Here we have generated a spatially resolved multiomics single-cell atlas of the entire human maternal–fetal interface including the myometrium, which enables us to resolve the full trajectory of trophoblast differentiation. We have used this cellular map to infer the possible transcription factors mediating EVT invasion and show that they are preserved in in vitro models of EVT differentiation from primary trophoblast organoids3,4 and trophoblast stem cells5. We define the transcriptomes of the final cell states of trophoblast invasion: placental bed giant cells (fused multinucleated EVTs) and endovascular EVTs (which form plugs inside the maternal arteries). We predict the cell–cell communication events contributing to trophoblast invasion and placental bed giant cell formation, and model the dual role of interstitial EVTs and endovascular EVTs in mediating arterial transformation during early pregnancy. Together, our data provide a comprehensive analysis of postimplantation trophoblast differentiation that can be used to inform the design of experimental models of the human placenta in early pregnancy.

Effect of maternal autoimmune diseases on fetal pulmonary artery Doppler indices: A case-control study.

To compare the fetal pulmonary artery Doppler indices of pregnant women with autoimmune diseases such as systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and antiphospholipid syndrome (APS) with healthy pregnant women. Thirty-nine pregnancies were included in the case group, 19 of them SLE, 12 with SS, and eight with APS. The gestational age-matched 54 healthy pregnant women were included in the control group. Peak systolic velocity, time-averaged velocity, systolic/diastolic ratio, pulsatility index, resistance index, acceleration time (AT), ejection time (ET), and AT/ET ratio were obtained from pulmonary artery waveform by using spectral Doppler ultrasound. Significantly shorter AT and lower AT/ET ratio were detected in the case group (p=<.001, p=<.001, respectively). The shortening of AT and decreasing of the AT/ET ratio were more predominant in the APS group. However, there was no significant difference between the SLE, SS, and APS groups in fetal pulmonary artery Doppler indices. Also, a moderate correlation was found between maternal disease duration (years) and fetal pulmonary artery AT (r=-.516, p=.001) and AT/ET ratio (r=-.558, p=<.001). Fetal pulmonary artery Doppler indices may be affected in maternal autoimmune diseases. Further studies are needed to evaluate fetal pulmonary Doppler indices such as AT and AT/ET ratio to predict neonatal respiratory morbidity and lung maturation in pregnant women with SLE, SS, and APS.

Association between maternal pre-pregnancy BMI category and fetal umbilical artery pH

To evaluate the association between maternal pre-pregnancy body mass index (BMI kg/m2) and fetal umbilical arterial pH at the time of delivery in nulliparous women. We performed a secondary analysis of the nuMoM2b study. Subjects in this study were nulliparous with a singleton pregnancy. Subjects with fetal anomalies or missing fetal umbilical artery pH were excluded. Subjects were categorized based on pre-pregnancy BMI (less than 18.5, 18.5-24.9, 25-29.9, 30-34.9, 35-39.9, and 40 or greater). Our primary outcome was an umbilical artery pH at the time of delivery. We also examined base deficit, the rate of fetal acidosis defined as pH < 7.0, and the need for advanced neonatal resuscitation. Analyses were stratified by the route of delivery. Multivariable linear or logistic regression models were used to calculate adjusted P-values or adjusted odds ratios (95% confidence intervals), controlling for confounders. Of 3,015 subjects, 1,870 (62%) had a vaginal delivery, and 1,145 (38%) had a cesarean delivery. There were significant differences in demographics across the BMI categories in both subjects who had a vaginal delivery and cesarean delivery (age, race, chronic hypertension, gestational diabetes, pregestational diabetes, preeclampsia, and gestational hypertension). Among subjects who had a vaginal delivery, there was no difference in fetal umbilical artery pH (p=0.31) across the BMI categories (Table 1). Base deficit of subjects with BMI < 18.5 and BMI 40 or greater was significantly lower than that of subjects with BMI 18.5-24.9 (adjusted p< 0.05). Among subjects who had a cesarean delivery, the fetal umbilical arterial pH of subjects with BMI 30-34.9 and BMI 40 or greater was significantly lower than that of subjects with BMI 18.5-24.9 (adjusted p< 0.05) (Table 2). In nulliparous subjects with a singleton pregnancy, obesity was associated with decreased fetal umbilical arterial pH at the time of cesarean delivery. However, this finding was not observed in subjects who had a vaginal delivery.View Large Image Figure ViewerDownload Hi-res image Download (PPT)