Maternal Mean Arterial Pressure Research Articles

AT1-AA Is Produced in Offspring in Response to Placental Ischemia and Is Lowered by B-Cell Depletion Without Compromising Overall Offspring Health.

Preeclampsia, new-onset hypertension during pregnancy alongside other organ dysfunction, is the leading cause of mortality for the mother and low birth weight for the baby. Low birth weight contributes to high risk of cardiovascular disorders later in life. Women with preeclampsia have activated B cells producing agonistic autoantibodies to AT1-AA (angiotensin II type I receptor). We hypothesize that rituximab, a B cell-depleting chemotherapeutic, will deplete maternal B cells in reduced uterine perfusion pressure (RUPP) rats without worsening the effect of placental ischemia on pup growth and survival. To test this hypothesis, the RUPP procedure was performed, and rituximab was continuously infused via miniosmotic pump. Maternal blood and tissues were collected. A separate group of dams were allowed to deliver, pup weights were recorded, and at 4 months of age, tissues were collected from offspring. Immune cells were measured via flow cytometry, and AT1-AA was quantified using a contraction bioassay. Blood pressure increased in RUPP rats and was normalized with rituximab treatment. RUPP offspring also had increased circulating B cells, cytolytic natural killer cells, and increased circulating AT1-AA, which were normalized with maternal rituximab treatment. This is the first study to analyze the AT1-AA in RUPP offspring, which was normalized with rituximab. Our findings indicate that perinatal rituximab lowers maternal mean arterial pressure in RUPP rats and improves birth weight, circulating AT1-AA, and circulating natural killer cells, indicating that rituximab improves adverse fetal outcomes in response to placental ischemia.

Validation of machine-learning model for first-trimester prediction of pre-eclampsia using cohort from PREVAL study.

Effective first-trimester screening for pre-eclampsia (PE) can be achieved using a competing-risks model that combines risk factors from the maternal history with multiples of the median (MoM) values of biomarkers. A new model using artificial intelligence through machine-learning methods has been shown to achieve similar screening performance without the need for conversion of raw data of biomarkers into MoM. This study aimed to investigate whether this model can be used across populations without specific adaptations. Previously, a machine-learning model derived with the use of a fully connected neural network for first-trimester prediction of early (< 34 weeks), preterm (< 37 weeks) and all PE was developed and tested in a cohort of pregnant women in the UK. The model was based on maternal risk factors and mean arterial blood pressure (MAP), uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A). In this study, the model was applied to a dataset of 10 110 singleton pregnancies examined in Spain who participated in the first-trimester PE validation (PREVAL) study, in which first-trimester screening for PE was carried out using the Fetal Medicine Foundation (FMF) competing-risks model. The performance of screening was assessed by examining the area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% screen-positive rate (SPR). These indices were compared with those derived from the application of the FMF competing-risks model. The performance of screening was poor if no adjustment was made for the analyzer used to measure PlGF, which was different in the UK and Spain. Therefore, adjustment for the analyzer used was performed using simple linear regression. The DRs at 10% SPR for early, preterm and all PE with the machine-learning model were 84.4% (95% CI, 67.2-94.7%), 77.8% (95% CI, 66.4-86.7%) and 55.7% (95% CI, 49.0-62.2%), respectively, with the corresponding AUCs of 0.920 (95% CI, 0.864-0.975), 0.913 (95% CI, 0.882-0.944) and 0.846 (95% CI, 0.820-0.872). This performance was achieved with the use of three of the biomarkers (MAP, UtA-PI and PlGF); inclusion of PAPP-A did not provide significant improvement in DR. The machine-learning model had similar performance to that achieved by the FMF competing-risks model (DR at 10% SPR, 82.7% (95% CI, 69.6-95.8%) for early PE, 72.7% (95% CI, 62.9-82.6%) for preterm PE and 55.1% (95% CI, 48.8-61.4%) for all PE) without requiring specific adaptations to the population. A machine-learning model for first-trimester prediction of PE based on a neural network provides effective screening for PE that can be applied in different populations. However, before doing so, it is essential to make adjustments for the analyzer used for biochemical testing. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

First trimester risk of preeclampsia and rate of spontaneous birth in patients without preeclampsia

First-trimester screening for preeclampsia (PE), by a combination of maternal risk factors and mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and placental growth factor (PlGF), as proposed by the Fetal Medicine Foundation (FMF) provides effective prediction of preterm PE. Placental dysfunction is a potential precursor of spontaneous birth. The objective of this study is to examine whether the estimated risk of PE is associated with the gestational age at onset of spontaneous delivery in the absence of PE. This was a secondary analysis of the data from the SPREE trial, in which there was comparison in the performance of first-trimester screening for preterm PE by the FMF model vs. a traditional history-based risk scoring system. The population for the present study included only the subgroup of women with spontaneous onset of delivery (labor with intact membranes or preterm prelabor rupture of membranes) and was arbitrarily divided into three groups according to the risk for preterm PE assessed by the FMF model at 11-13 weeks' gestation: group 1 (low risk, ˂1/100), group 2 (intermediate-risk, 1/50 to 1/100) and group 3 (high-risk, ˃1/50). A survival analysis was carried out with Kaplan-Meier estimator and a Cox regression analysis stratified according to three PE risk groups. Gestational age at spontaneous birth in the study groups was compared by means of Log-rank test and Hazard Ratio (HR). The study population comprised of 10,820 cases with delivery after spontaneous onset of labor, among the total of 16,451 cases participating in SPREE. There were 9795 cases in group 1,583 in group 2, and 442 in group 3. The gestational age at delivery was <28, <32, <35, <37 and <40 weeks in 0.29%, 0.64%, 1.68%, 4.52% and 44.97%, respectively, in group 1, 0.69%, 1.71%, 3.26%, 7.72% and 55.23% in group 2 and 0.45%, 1.81%, 5.66%, 13.80% and 63.12% in group 3. The curve profile of gestational age at spontaneous birth in the three study groups was significantly different overall and in pairwise comparisons (p-values <0.001). Cox regression analysis showed risks increase for spontaneous birth of 18% when comparing intermediate-risk vs. low-risk (p˂0.001) and 41% when comparing high-risk vs. low-risk categories (p˂0.001). In this study investigating birth after spontaneous onset of labor in women without PE, there are two major findings. First, the duration of pregnancy decreases with increasing first-trimester risk for PE. Second, in a high-risk group, compared to a low-risk group, the risk of spontaneous birth is 4-times higher at 24-26 weeks, 3-times higher at 28-32 weeks, and 2-times higher at 34-39 weeks. These differences present major clinical implications for antepartum counselling, monitoring and interventions in these pregnancies.

Biomarkers at 6 weeks' gestation in the prediction of early miscarriage in pregnancy following assisted reproductive technology.

Miscarriage is a major concern in early pregnancy among women having conceived with assisted reproductive treatments. This study aimed to examine potential miscarriage-related biophysical and biochemical markers at 6 weeks' gestation among women with confirmed clinical pregnancy following in vitro fertilization (IVF)/embryo transfer (ET) and evaluate the performance of a model combining maternal factors, biophysical and biochemical markers at 6 weeks' gestation in the prediction of first trimester miscarriage among singleton pregnancies following IVF/ET. A prospective cohort study was conducted in a teaching hospital between December 2017 and January 2020 including women who conceived through IVF/ET. Maternal mean arterial pressure, ultrasound markers including mean gestational sac diameter, fetal heart activity, crown rump length and mean uterine artery pulsatility index (mUTPI) and biochemical biomarkers including maternal serum soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), kisspeptin and glycodelin-A were measured at 6 weeks' gestation. Logistic regression analysis was carried out to determine significant predictors of miscarriage prior to 13 weeks' gestation and performance of screening was estimated by receiver-operating characteristics curve analysis. Among 169 included pregnancies, 145 (85.8%) pregnancies progressed to beyond 13 weeks' gestation and had live births whereas 24 (14.2%) pregnancies resulted in a miscarriage during the first trimester. In the miscarriage group, compared to the live birth group, maternal age, body mass index, and mean arterial pressure were significantly increased; mean gestational sac diameter, crown rump length, mUTPI, serum sFlt-1, glycodelin-A, and the rate of positive fetal heart activity were significantly decreased, while no significant differences were detected in PlGF and kisspeptin. Significant prediction for miscarriage before 13 weeks' gestation was provided by maternal age, fetal heart activity, mUTPI, and serum glycodelin-A. The combination of maternal age, ultrasound (fetal heart activity and mUTPI), and biochemical (glycodelin-A) markers achieved the highest area under the curve (AUC: 0.918, 95% CI 0.866-0.955), with estimated detection rates of 54.2% and 70.8% for miscarriage before 13 weeks' gestation, at fixed false positive rates of 5% and 10%, respectively. A combination of maternal age, fetal heart activity, mUTPI, and serum glycodelin-A at 6 weeks' gestation could effectively identify IVF/ET pregnancies at risk of first trimester miscarriage.

A Correlational Study of Ophthalmic Artery Doppler Parameters and Maternal Blood Pressure in Normotensive and Pre-eclamptic Pregnancies at a Tertiary Care Hospital.

Background Hypertensive disorders are one of the most common complications of pregnancy. This study aimed to investigate the relationship between ophthalmic artery Doppler indices and preeclampsia development and evaluate differences in these indices between normotensive and hypertensive pregnancies. Methods A hospital-based cross-sectional observationalstudy was conducted involving a sample size of 80 pregnant women: 40 normotensive and 40 preeclamptic. The participants' ophthalmic artery Doppler parameters were evaluated using ultrasonography. Various clinical and demographic factors were also collected for analysis. Results Significant differences in the pulsatility index (PI) and end-diastolic volume (EDV) of the ophthalmic arteries were found between the normotensive and preeclamptic participants (p < 0.05). An inverse correlation was observed between the ophthalmic artery PI (OAPI) and mean maternal arterial pressure, suggesting reduced orbital vascular resistance and increased orbital flow. Moreover, the decrease in PI was more significant in severely preeclamptic women than in mildly preeclamptic and normotensive women. The findings indicated a significant correlation between ophthalmic artery Doppler parameters and the development of preeclampsia. The decrease in OAPI was particularly profound in women with severe preeclampsia. However, the study was limited by its small sample size and the lack of matching of participants based on maternal age, gestational age, and other factors. Conclusions The study results suggest that ophthalmic artery Doppler parameters, mainly PI and EDV, could serve as reliable indicators for the development of preeclampsia. Given their safety, cost-effectiveness, and accessibility, these parameters can help differentiate between preeclamptic and normotensive pregnancies in late gestation. Further research with larger sample sizes and matched participant groups is recommended for more conclusive results.

First Trimester Evaluation of Maternal Visceral Fat and Its Relationship with Adverse Pregnancy Outcomes.

Obese women are more likely to experience pregnancy complications. The distribution of fat, and more particularly the rise in visceral fat, is well established to be more closely linked to the onset of cardiovascular disease and metabolic syndrome than obesity itself. We aim to examine the relationship between maternal visceral fat assessment in the first trimester and the appearance of adverse pregnancy outcomes. A prospective cohort study including 416 pregnant women was conducted. During the first trimester scan (11-13 + 6 weeks), all individuals had their visceral fat and subcutaneous thicknesses measured by ultrasonography. Blood samples were obtained, and maternal demographics and clinical information were documented. After delivery, the obstetric outcomes were evaluated. We contrasted two groups: one with healthy pregnancies and the other with adverse pregnancy outcomes (APO), defined as the development of at least one of the following complications: gestational diabetes mellitus, hypertensive disorders of pregnancy, abnormal fetal growth, preterm delivery or preterm premature rupture of membranes. Median maternal age was 33 and 34 years old for the uncomplicated and adverse pregnancy outcomes groups, respectively. We found that women with adverse pregnancy outcomes had higher VFT (median 30 vs. 26.5 mm, p = 0.001) and SFT (median 18.9 vs. 17.1 mm, p = 0.03). However, the visceral/subcutaneous fat ratio was not statistically different between groups. Finally, we performed a subanalysis for metabolic and placental vascular dysfunction complications. After performing a multivariate logistic regression analysis adjusted for maternal age, smoking, and mean arterial pressure, both the VFT (aOR 1.03, p < 0.001) and the ratio of visceral/subcutaneous fat (aOR 1.37, p = 0.04) were significantly associated with the development of adverse pregnancy outcomes; however, the associations of VFT and the VFT-to-SFT ratio were higher for the occurrence of gestational diabetes (aOR 1.07, p < 0.001; aOR 2.09, p = 0.001; respectively) and showed no relationships with placental complications. When conducting a first-trimester ultrasound assessment, sonographers may measure VFT without additional time or cost involved. Identification of pregnant women with increased VFT (>37 mm) may benefit from a close follow-up, especially for the development of gestational diabetes, independent of BMI.

Peripartum Screening for Postpartum Hypertension in Women With Hypertensive Disorders of Pregnancy

BackgroundChronic hypertension (CHT) is the main risk factor for cardiovascular diseases in women with a history of hypertensive disorders of pregnancy (HDP). ObjectivesThis study sought to assess the effectiveness of peripartum screening in predicting CHT after HDP. MethodsIn this longitudinal prospective study, women with HDP underwent peripartum transthoracic echocardiography and were evaluated for CHT (blood pressure ≥140/90 mm Hg or on antihypertensive medication) at least 3 months postpartum. Univariable and multivariable analyses assessed the association between clinical and transthoracic echocardiography data and a postpartum diagnosis of CHT. ResultsAt a median postpartum follow-up of 124 days (IQR: 103-145 days), 70 (33.2%) of 211 women remained hypertensive. Compared with normotensive women, women with CHT were older (35.5 ± 5.0 years vs 32.9 ± 5.6 years; P = 0.001), were more likely to be Afro-Caribbean (27.1% vs 7.8%; P < 0.0001), had higher body mass index (33.4 ± 5.9 kg/m2 vs 31.2 ± 5.4 kg/m2; P = 0.006), and had higher mean arterial pressure (106.5 ± 8.4 mm Hg vs 103.3 ± 7.0 mm Hg; P = 0.004). Moreover, they showed significantly higher left ventricular mass index (84.0 ± 17.9 g/m2 vs 76.3 ± 14.8 g/m2; P = 0.001), higher relative wall thickness (0.46 ± 0.10 vs 0.40 ± 0.10; P < 0.0001), and lower global longitudinal strain (–15.6% ± 2.7% vs –16.6% ± 2.2%; P = 0.006) than normotensive women. A prediction model combining clinical (maternal age and first trimester mean arterial pressure) and echocardiographic features (left ventricular mass index >75 g/m2, relative wall thickness >0.42, and E/e′ ratio >7) showed excellent accuracy in identifying women with persistent hypertension after HDP (area under the curve: 0.85; 95% CI: 0.79-0.90). ConclusionsThis peripartum screening approach might be used to identify women at risk of CHT who would benefit from intensive blood pressure monitoring and pharmacological strategies from the early postpartum period to prevent cardiovascular disease.

Virtual reality is beneficial in decreasing pain in labouring women: A preliminary study.

Women use a range of non-pharmacological pain relief methods to reduce labour pain intensity and to help manage labour pain. The purpose of this intervention study was to determine whether virtual reality would have an effect on labour pain intensity. Virtual reality has been shown to be effective in reducing pain in other acute pain settings. This study was an intervention study in labour in a cross-over within-subjects design (Clinical Trials Registry Number: ACTRN12618001776291P). Fourteen participants reported their pain and had their heart rate and blood pressure measured during active labour while using and not using virtual reality. There were significantly lower reported pain scores (6.14 compared to 7.61, P< 0.001) and maternal heart rate (79.86 beats per minute compared to 85.57, P =0.033) and mean arterial pressure (88.78 mmHg compared to 92.61 mmHg, P= 0.022) were lower when using virtual reality compared to when not using virtual reality during active labour. This study makes an important contribution to the field of virtual reality in labour and birth. It is consistent with other recent findings of reduced pain in labour and links decreased pain scales to heart rate and blood pressure, the physiological markers of pain.

Neurodevelopmetal effects of maternal blood pressure management with noradrenaline during general anaesthesia for nonobstetric surgery in the pregnant rabbit model.

In pregnant women, anaesthesia-induced hypotension is commonly treated using phenylephrine or noradrenaline, the rationale being to maintain uterine perfusion pressure and thereby uterine blood flow. Evidence for this strategy during general anaesthesia for nonobstetric surgery is absent. To analyse the effects of treating anaesthesia-induced hypotension with noradrenaline on brain development of rabbit foetuses of mothers subjected to general anaesthesia for nonobstetric surgery. We hypothesised that treatment of maternal hypotension would improve foetal outcomes. Randomised controlled laboratory study using 21 pregnant rabbits (does) at 28 days of gestation. Two hours of sevoflurane anaesthesia for a laparotomy without treatment of anaesthesia-induced hypotension (hypotension group) or with maintaining maternal mean arterial pressure above 80% of the awake value using noradrenaline (noradrenaline group). In the control group, does remained untouched. At term, all pups were delivered by caesarean section. One day later, the neurobehaviour of the pups was assessed and brains were harvested. Neuron density in the frontal cortex for the comparison of noradrenaline groups versus hypotension groups was the primary outcome; the neurobehavioural scores and other histological outcomes were secondary outcomes. In the noradrenaline groups and hypotension groups, neuron density in the frontal cortex was similar (1181 ± 162 versus 1189 ± 200 neurons mm-2, P = 0.870). However, significantly less foetal survival, lower sensory scores in neurobehavioural assessment and less proliferation were observed in the noradrenaline group when compared with the hypotension group. Neuron densities in other regions, total cell densities, biometrics and synaptogenesis were not affected. There were no differences between the control group and hypotension group. During general anaesthesia for nonobstetric surgery in rabbits, treatment of anaesthesia-induced hypotension using noradrenaline did not affect neuron densities but was associated with impaired foetal outcomes according to several secondary outcome parameters. Further studies are needed to investigate any clinical relevance and to determine the target blood pressure in pregnant women during general anaesthesia.KEY POINTSIn pregnant women, anaesthesia-induced hypotension is commonly treated using phenylephrine or noradrenaline, with the rationale to maintain uterine perfusion pressure and thereby uterine blood flow.Evidence for this strategy during general anaesthesia for nonobstetric surgery is absent.We investigated the effects of treating anaesthesia-induced hypotension with noradrenaline on the brain development of rabbit foetuses, of mothers subjected to general anaesthesia for nonobstetric surgery.We hypothesised that treatment of maternal hypotension would improve foetal outcomes.Neuron densities were similar but significantly less foetal survival, impaired neurobehaviour and less proliferation were observed after treatment of anaesthesia-induced hypotension with noradrenaline, compared with untreated hypotension.

Association between placental global DNA methylation and blood pressure during human pregnancy.

Gene-specific placental DNA methylation patterns differ between normal pregnancies and pregnancies complicated by hypertension. However, whether global placental DNA methylation is associated with maternal blood pressure remains controversial. Using multiple linear regression models, we analysed the association between maternal mean arterial pressure (MAP) at the third trimester of pregnancy and global DNA methylation in the placenta in 922 mothers using LC-ESI-MS/MS. To better characterize the contribution of genetic or epigenetic mechanisms, we performed isolated analyses in mothers with and without a family history of hypertension. Mean placental global DNA methylation was 3.00 ± 0.46%. A significant negative correlation between placental global DNA methylation and mean arterial blood pressure (MAP) in the third trimester could be observed (P = 0.023, r = -0.075). This association remained significant after adjusting for confounders. In placenta samples from mothers with a family history of hypertension, mean maternal MAP was higher (86.1 ± 8.1 vs. 84.6 ± 7.5, P < 0.01) and placental global DNA methylation was lower (2.94 ± 0.43 vs. 3.04 ± 0.47, P < 0.01) compared with samples without a family history of hypertension. Furthermore, the significant independent negative correlation between global placental DNA methylation and MAP was only found in mothers without a family history of hypertension. This study showed an independent negative correlation between placental global DNA methylation and maternal MAP in mothers without a family history of hypertension.

Ophthalmic artery peak systolic velocity ratio distinguishes pre-eclampsia from chronic and gestational hypertension: Aprospective cohort study.

To examine whether the ophthalmic artery peak systolic velocity ratio (OA PSV-ratio) is higher in women with pre-eclampsia compared with gestational hypertension (GH) and chronic hypertension (CH), after controlling for confounding variables. Prospective cohort. Specialist hypertension clinic in a tertiary referral centre. Singleton pregnancies presenting between 32+0 and 36+6 weeks of gestation with pre-eclampsia (n=50), GH (n=54) and CH (n=56). Paired measurements of maternal mean arterial pressure (MAP) and OA PSV-ratio were performed by trained sonographers. Multiple linear regression was fitted to the OA PSV-ratio, including maternal characteristics and medical history, GH, pre-eclampsia and MAP and use of antihypertensive medication. Whether pre-eclampsia is independently associated with higher OA PSV-ratio. MAP was significantly higher in both GH (p=0.0015) and pre-eclampsia (p=0.008) than in CH pregnancies. There was no significant difference between pre-eclampsia and GH (0.670). The OA PSV-ratio was significantly higher in pre-eclampsia than CH (p=0.0008) and GH (p=0.015). There was no significant difference between the OA PSV-ratio in CH and GH (p=0.352). Multiple linear regression modelling showed that the OA PSV-ratio was influenced by maternal weight (p=0.005), maternal age (p=0.014), antihypertensive medications (p=0.007) and MAP (p<0.0001). After controlling for these variables, the OA PSV-ratio was still significantly higher in those with pre-eclampsia (p=0.0002). The OA PSV-ratio is influenced by maternal weight, age, antihypertensive medications and MAP. Pre-eclampsia is an independent predictor of OA PSV-ratio, which therefore may be a useful point-of-care test when assessing women presenting with hypertension.

Prediction of small for gestational age neonates by combining maternal risk factors with biophysical markers

Studies have suggested a role for biophysical markers (BPM) including uterine artery Doppler (UAD) and maternal mean arterial pressure (MAP) in prediction of neonatal SGA. We sought to determine if the addition of flow velocities in spiral artery (SA), UAD, MAP and maternal risk factors could improve prediction of neonatal SGA, compared with using maternal risk factors alone.

Effectiveness of Combined Strategies for the Prevention of Hypothermia Measured by Noninvasive Zero-Heat Flux Thermometer During Cesarean Section.

Background: Perioperative hypothermia (body temperature <36°C) is a common complication of anesthesia increasing the risk for maternal cardiovascular events and coagulative disorders, and can also influence neonatal health. The aim of our work was to evaluate the impact of combined warming strategies on maternal core temperature, measured with the SpotOn. We hypothesized that combined modalities of active warming prevent hypothermia in pregnant women undergoing cesarean delivery with spinal anesthesia.Methods: Seventy-eight pregnant women were randomly allocated into three study groups receiving warmed IV fluids and forced-air warming (AW), warmed IV fluids (WF), or no warming (NW). Noninvasive core temperature device (SpotOn) measured maternal core temperature intraoperatively and for 30 min after surgery. Maternal mean arterial pressure, incidence of shivering, thermal comfort and newborn's APGAR, axillary temperature, weight, and blood gas analysis were also recorded.Results: Incidence of hypothermia was of 0% in AW, 4% in WF, and 47% in NW. Core temperature in AW was constantly higher than WF and NW groups. Incidence of shivering in perioperative time was significantly lower in AW and WF groups compared with the NW group (p < 0.04). Thermal comfort was higher in both AW and WF groups compared with NW group (p = 0.02 and p = 0.008, respectively). There were no significant differences among groups for the other evaluated parameters.Conclusion: Combined modalities of active warming are effective in preventing perioperative hypothermia. The routine uses of combined AW are suggested in the setting of cesarean delivery.

A new risk score model to predict preeclampsia using maternal factors and mean arterial pressure in early pregnancy

The purpose of this study was to establish a multivariable risk-scoring model for preeclampsia (PE) prediction based on maternal characteristics and mean arterial pressure (MAP). Multivariate logistic regression analysis from 4600 pregnancies during a 10-year period was used to create the best fitting model. Significant risk factors and weighted scores consisted of age ≥30 years (3), BMI ≥25 kg/m2 (2), multifetal pregnancy (9), history of PE (9), adverse perinatal outcomes (6), pregnancy interval >10 years (5), nulliparous (5), underlying renal disease (10), chronic hypertension (6), autoimmune disease (5), diabetes (2) and MAP ≥95 mmHg (5). The model achieved an ROC area 0.771 with detection rates of 34%, 44%, 53% and 58% at 5%, 10%, 15% and 20% fixed false-positive rates, respectively. The new risk score model could be a clinically useful screening tool for PE. Pregnant women who have total scores of 9–13 (high risk) and more than 14 (very high risk) should receive aspirin prophylaxis. Impact Statement What is already known on this subject? Preeclampsia (PE) is the major cause of maternal and perinatal mortality and morbidity; it can be prevented by antiplatelet agents. What the results of this study add? A new model for identifying maternal at risk for PE using clinical risk factors and MAP was created. Weighted scores were defined for each variable for easy use in clinical practice. According to their probability for PE, pregnant women were classified into three subgroups: low risk (score 0–8), high risk (score 9–13) and very high risk groups (score ≥ 14). Aspirin should be prescribed to high risk and very high risk groups. For safety concerns, very high risk pregnancies should have close antenatal surveillance in a tertiary care hospital to reduce adverse outcomes during pregnancy and childbirth. What the implications are of these findings for clinical practice and/or further research? This new model for identifying pregnant women at high risk for PE has the potential to reduce the morbidity and mortality associated with this disease.

Fetal heart rate monitoring during fetoscopic repair of open spinal neural tube defects: a single-centre observational cohort study

BackgroundDuring fetal surgery, the haemodynamic stability of the fetus depends on the haemodynamic stability of the mother. The primary objective of this study was to assess changes in fetal heart rate (FHR) throughout the different stages of surgery. The secondary objective was to assess potential changes in maternal physiological parameters and their association with FHR. MethodsThis was a single-center observational cohort study conducted between 2015 and 2019 in 26 women undergoing intra-uterine fetoscopic repair of open spina bifida. The primary outcome was FHR. Maternal physiologic parameters were measured at the beginning, during and after surgery. The linear mixed-effects model fitted by maximum likelihood was used to assess changes in each variable at specific times throughout the surgery, and the repeated measures correlation coefficient was used to study the association between FHR and maternal physiological parameters. ResultsOne (3.8%) case of fetal bradycardia (FHR <110 beats per minute) required the administration of intramuscular atropine. No other significant FHR changes were observed during surgery. Maternal oesophageal temperature (P <0.001), lactate levels (P=0.002), and mean arterial pressure (P=0.016) changed significantly during surgery, although none of these changes was clinically relevant. The FHR showed a significant association with maternal carbon dioxide tension (r=0.285, 95% CI 0.001 to 0.526) and maternal heart rate (r=0.302, 95% CI 0.025 to 0.535). ConclusionThe FHR remained stable during intra-uterine fetoscopic repair of open spina bifida. Maternal carbon dioxide tension and heart rate may have a mild influence on FHR.

A systematic review with network meta-analysis on mono strategy of anaesthesia for preeclampsia in caesarean section

The aim of this study was to reveal the effects of anaesthesia strategies on maternal mean arterial pressure (MAP), heart rate, vasopressor consumption, adverse events, and neonatal resuscitation when women with preeclampsia (PE) undergo caesarean section (CS). Three major databases were searched for randomized controlled trials (RCTs) and prospective controlled studies (PCSs). Two authors independently screened, extracted, and checked eligibility and outcome data. Outcomes involved MAP, vasopressor use, maternal adverse events, APGAR scores, and neonatal resuscitation. Pooled estimates were carried out by contrast-based network meta-analysis, and pooled effect sizes were presented with 95% confidence interval (CI). Eleven RCTs and one PCS (n = 782) formed three-node network meta-analysis, and non-significant differences were observed in MAP, 5-min APGAR score, and neonatal intubation rate among the three anaesthesia strategies. General anaesthesia had significantly lower vasopressor consumption than spinal anaesthesia did (standardised mean difference = − 1.19, 95% confidence interval [CI]: − 1.76 to − 0.63), but it had higher maternal adverse event rate (risk ratio = 2.00, 95% CI 1.16–3.47). Because no optimal anaesthesia strategy has been shown to achieve a balanced maternal and neonatal outcome, therefore a shared decision-making process may be required regarding the most suitable choice of anaesthetic strategy for individual preeclamptic mother undergoing CS. Future larger studies may need to focus on evaluating the role of vasopressors on maternal hemodynamic as well as factors affecting maternal outcomes for different anaesthetic techniques in preeclamptic women undergoing CS.

A risk model that combines MAP, PlGF, and PAPP-A in the first trimester of pregnancy to predict hypertensive disorders of pregnancy.

Whether the first trimester maternal mean arterial pressure (MAP), placental growth factor (PlGF), and pregnancy-associated plasma protein A (PAPP-A) can predict hypertensive disorders of pregnancy (HDP) is unclear. We conducted a retrospective case-control study with the total population of 539 gravidas, of these 447 had normal pregnancy, 27 had gestational hypertension (GH), 36 had preeclampsia (PE), and 29 had preeclampsia with severe features (SPE). Prediction for HDP was determined by the area under curve (AUC). Compared to the healthy group, the multiple of the median (MoM) for MAP was increased in the study groups, while PlGF and PAPP-A were decreased. When the cutoff values for MAP, PlGF, and PAPP-A were 1.069, 0.769, and 0.673 MoM, respectively, the sensitivities for predicting HDP were 0.517, 0.446, and 0.500 and the specificities were 0.744, 0.826, and 0.769, respectively. To predict GH, the highest AUC was 0.755 (95% CI: 0.655-0.856, p < 0.001) based on MAP, PlGF, and PAPP-A. The combined PlGF and PAPP-A had the highest AUC (0.683 [95% CI: 0.584-0.782, p < 0.001] and 0.755 [95% CI: 0.682-0.829, p < 0.001]) for prediction of PE and SPE. We found that MAP, serum levels of PlGF, and PAPP-A in the first trimester pregnancy are markers that predict HDP in the third trimester. The combination of markers is far superior to single markers alone. To improve the diagnostic value, specific cutoff values should be applied to GH, PE, SPE in each condition.

Effect of sildenafil on maternal hemodynamics in pregnancies complicated by severe early-onset fetal growth restriction: planned subgroup analysis from a multicenter randomized placebo-controlled double-blind trial.

Fetal growth restriction (FGR) is associated with maternal cardiovascular changes. Sildenafil, a phosphodiesterase type-5 inhibitor, potentiates the actions of nitric oxide, and it has been suggested that it alters maternal hemodynamics, potentially improving placental perfusion. Recently, the Dutch STRIDER trial was stopped prematurely owing to excess neonatal mortality secondary to pulmonary hypertension. The main aim of this study was to investigate the effect of sildenafil on maternal hemodynamics in pregnancies with severe early-onset FGR. This was a cardiovascular substudy within a UK multicenter, placebo-controlled trial, in which 135 women with a singleton pregnancy and severe early-onset FGR (defined as a combination of estimated fetal weight or abdominal circumference below the 10th centile and absent/reversed end-diastolic flow in the umbilical artery on Doppler velocimetry, diagnosed between 22 + 0 and 29 + 6 weeks' gestation) were assigned randomly to receive either 25 mg sildenafil three times daily or placebo until 32 + 0 weeks' gestation or delivery. Maternal blood pressure (BP), heart rate (HR), augmentation index, pulse wave velocity (PWV), cardiac output, stroke volume (SV) and total peripheral resistance were recorded before randomization, 1-2 h and 48-72 h post-randomization, and 24-48 h postnatally. For continuous data, analysis was performed using repeated measures ANOVA methods including terms for timepoint, treatment allocation and their interaction. Included were 134 women assigned randomly to sildenafil (n = 69) or placebo (n = 65) who had maternal BP and HR recorded at baseline. At 1-2 h post-randomization, compared with baseline values, sildenafil increased maternal HR by 4bpm more than did placebo (mean difference, 5.00 bpm (95% CI, 1.00-12.00 bpm) vs 1.25 bpm (95% CI, -5.38 to 7.88 bpm); P = 0.004) and reduced systolic BP by 1 mmHg more (mean difference, -4.13 mmHg (95% CI, -9.94 to 1.44 mmHg) vs -2.75 mmHg (95% CI, -7.50 to 5.25 mmHg); P = 0.048). Even after adjusting for maternal mean arterial pressure, sildenafil reduced aortic PWV by 0.60 m/s more than did placebo (mean difference, -0.90 m/s (95% CI, -1.31 to -0.51 m/s) vs -0.26 m/s (95% CI, -0.75 to 0.59 m/s); P = 0.001). Sildenafil was associated with a non-significantly greater decrease in SV index after 1-2 h post-randomization than was placebo (mean difference, -5.50 mL/m2 (95% CI, -11.00 to -0.50 mL/m2 ) vs 0.00 mL/m2 (95% CI, -5.00 to 4.00 mL/m2 ); P = 0.056). Sildenafil in a dose of 25 mg three times daily increases HR, reduces BP and reduces arterial stiffness in pregnancies complicated by severe early-onset FGR. These changes are short term, modest and consistent with the anticipated vasodilatory effect. They have no short- or long-term clinical impact on the mother. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

The need for implementation of first trimester screening for preeclampsia and fetal growth restriction in low resource settings

Background Preeclampsia [PE] and fetal growth restriction [FGR] is a major cause of perinatal morbidity in both developed and developing countries but the disease leaves a severe impact in developing countries, due to the late presentation of cases where prevention and treatment becomes impossible. Routine antenatal ultrasound and health checkups in periphery are usually done in first trimester for dating and viability scan, in midtrimester for anomaly scan and in third trimester for safe confinement. Underlying disorder of deep placentation which is unidentified can lead to increased maternal morbidity and fetal compromise between 26 to 34 weeks of gestation The complications present at an irreversible stage where there is no sufficient time even for referral to tertiary care center. Frequent antenatal visits as suggested by WHO would definitely bring down maternal mortality but this increased surveillance when offered to all might be a huge burden to health care providers in low resource settings. An acceptable screening test should help in triaging the high risk group in first trimester itself targeting about only one third of the population for prophylactic therapy and increased antenatal surveillance.The objective of this study is to evaluate the performance and feasibility of different screening protocols in low resource settings. Methodology Screening for PE and FGR was done at the 11–14 weeks aneuploidy scan as per FMF guidelines. Group I included 6289 women whose risk prediction was done with maternal characteristics [MC], mean arterial pressure [MAP] and Uterine artery Doppler [UAD]. Group II included 2067 women whose risk was predicted with MC, MAP, UAD and PAPP-A. Group III included 576 women whose risk prediction included all parameters with PLGF. Results Two thousand five hundred fifty-seven cases were screen positive in group I and 602 were screen positive in group II. In group III which included PLGF, 24 were positive for early onset PE and 36 for late onset PE. The number needed to treat [NNT] was 35.9, 29.1 and 10% in Group I, II and III respectively. The detection rate [DR] for PE and FGR was 60% in Group I and DR for FGR in Group II was 85%. In Group III, for early onset PE the DR was 98% and 68% for late onset PE. Conclusion Screening for PE with available resources in the periphery needs to be implemented to avoid its grave complications. Traditional screening for PE by NICE guidelines can be adopted but may have a detection rate of only 30–40%. Though screening by ACOG criteria may have good detection rates but more than two thirds of the population would become screen positive which nullifies this approach as a good screening methodology in low resource settings. Multiparametric approach for screening in first trimester serves as a better screening tool to enable higher detection rate of disease with least false positive rates. Uterine artery Doppler when combined with maternal characteristics and mean arterial pressure could achieve a detection rate of about 60% and would still target only one third of the population for increased antenatal surveillance. This requires training healthcare professionals in the periphery for this approach and this should be our prime focus in the current scenario. Inclusion of serum biochemistry would still bring down the target population to 10% and increase the DR and can be considered as an additional test in economically feasible population. In low resource settings a better screening approach to PE would be a combination of maternal history, biophysical or biochemical parameters whichever is feasible considering the economy and availability of resources.

From first-trimester screening to risk stratification of evolving pre-eclampsia in second and third trimesters of pregnancy: comprehensive approach.

Preeclampsia and associated hypertensive disorders of pregnancy represent a leading cause of global maternal and neonatal morbidity and mortality. Identification of women at high risk for developing preterm-preeclampsia and prophylaxis with low-dose aspirin has the potential to significantly reduce the rate of preterm-preeclampsia. In addition, risk assessment and monitoring of women in the second and third trimester of pregnancy, to aid in early detection of evolving disease, timely referral to specialist care, and active monitoring of women with confirmed or suspected preeclampsia is essential for improving maternal and neonatal outcomes. The angiogenesis-related biomarkers sFlt-1 and PlGF have been shown to have clinical value to aid in the prediction, diagnosis, and risk stratification of preeclampsia when used either alone or in combination with other risk factors. However, currently there is no consensus on the optimum strategy to link first trimester screening for preterm-preeclampsia with appropriate second and third trimester risk assessment strategies. This opinion paper will outline the current evidence for first trimester preeclampsia screening and prevention, as well as the evidence for various risk stratification approaches for detection of evolving preeclampsia through the second and third trimesters of pregnancy, and proposes a potential model integrating these tools. This article is protected by copyright. All rights reserved.