Causal effects of hypertensive disorders of pregnancy on structural changes in specific brain regions: a Mendelian randomization study.

This study utilized Mendelian randomization to explore the impact of hypertensive disorders of pregnancy and their subtypes on brain structures, using genome-wide association study data from the FinnGen consortium for hypertensive disorders of pregnancy exposure and brain structure data from the ENIGMA consortium as outcomes. The inverse-variance weighted method, along with Cochran's Q test, Mendelian randomization-Egger regression, Mendelian randomization-PRESSO global test, and the leave-one-out approach, were applied to infer causality and assess heterogeneity and pleiotropy. Findings indicate hypertensive disorders of pregnancy are associated with structural brain alterations, including reduced cortical thickness in areas like the insula, isthmus cingulate gyrus, superior temporal gyrus, temporal pole, and transverse temporal gyrus, and an increased surface area in the superior frontal gyrus. Specific associations were found for hypertensive disorders of pregnancy subtypes: chronic hypertension with superimposed preeclampsia increased cortical thickness in the supramarginal gyrus; preeclampsia/eclampsia led to thinner cortex in the lingual gyrus and larger hippocampal volume and superior parietal lobule surface area. Chronic hypertension was associated with reduced cortical thickness in the caudal and rostral anterior cingulate and increased surface area of the cuneus and thickness of the pars orbitalis cortex. Gestational hypertension showed no significant brain region changes. These insights clarify hypertensive disorders of pregnancies' neurological and cognitive effects by identifying affected brain regions.

Echocardiographic assessment of left atrial mechanics in women with hypertensive disorders of pregnancy: A systematic review and meta-analysis.

OBJECTIVE: The influence of hypertensive disorders of pregnancy (HDP) on left atrial (LA) mechanics assessed by speckle tracking echocardiography (STE) has been poorly investigated. Accordingly, we performed a meta-analysis to summarize the main findings of STE studies who measured LA reservoir (LASr), conduit (LAScd) and contractile (LASct) strain in HDP women. STUDY DESIGN: All echocardiographic studies assessing LA strain parameters in HDP women vs. healthy controls, selected from PubMed and EMBASE databases, were included. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment of Case-Control Studies. Continuous data (LASr, LAScd and LASct) were pooled as standardized mean difference (SMD) comparing HDP group with healthy controls. The overall SMDs of LASr, LAScd and LASct were calculated using the random-effect model. RESULTS: The full-texts of 8 studies with 566 HDP women and 420 healthy pregnant women were analyzed. Average LASr (34.3 ± 6.4 vs 42.7 ± 5.3 %, P = 0.01) and LAScd (23.4 ± 6.3 vs 32.5 ± 6.0 %, P < 0.001) were significantly lower in HDP women than controls, whereas LASct (-13.0 ± 5.4 vs -13.7 ± 4.5 %, P = 0.18) was similar in the two groups of women. Substantial heterogeneity was detected among the studies evaluating LASr (I2 = 94.3 %), LAScd (I2 = 64.9 %) and LASct (I2 = 86.4 %). SMDs were large and statistically significant for LASr (-1.70, 95 %CI -2.34,-1.06, P < 0.001) and LAScd (-1.35, 95 %CI -1.69,-1.00, P < 0.001), small and not statistically significant for LASct (-0.11, 95 %CI -0.60,0.39, P = 0.678) assessment. Egger's test gave P-values of 0.10, 0.34 and 0.75 for LASr, LAScd and LASct measurement respectively, indicating no publication bias. On meta-regression analysis, none of the moderators was significantly associated with effect modification for LASr and its components (all P < 0.05). CONCLUSIONS: HDPs are independently associated with LASr impairment in pregnancy. STE allows to identify, among HDP women, those who might benefit from a more aggressive antihypertensive treatment and/or a closer clinical follow-up, aimed at reducing the risk of adverse maternal outcome and cardiovascular complications later in life.

Diffusion-Weighted MRI of the Fetal Brain in Fetal Growth Restriction With Maternal Preeclampsia or Gestational Hypertension.

BACKGROUND: The fetal neurodevelopmental microstructural alterations of intrauterine exposure to preeclampsia (PE) or gestational hypertension (GH) remain unknown. PURPOSE: To evaluate the differences in diffusion-weighted imaging (DWI) of the fetal brain between normotensive pregnancies and PE/GH pregnancies, with a focus on PE/GH pregnancies with fetal growth restriction (FGR). STUDY TYPE: Retrospective matched case-control study. POPULATION: 40 singleton pregnancies with PE/GH complicated by FGR, and 3 paired control groups (PE/GH without FGR, normotensive FGR, normotensive pregnancies) (28-38 gestational weeks). FIELD STRENGTH/SEQUENCE: DWI with single-shot echo-planar imaging at 1.5 Tesla. ASSESSMENT: The apparent diffusion coefficient (ADC) values were calculated in the centrum semi-ovale (CSO), parietal white matter (PWM), frontal white matter (FWM), occipital white matter (OWM), temporal white matter (TWM), basal ganglia, thalamus (THAL), pons, and cerebellar hemisphere. STATISTICAL TESTS: Student t test or Wilcoxon matched test was used to reveal the difference of ADC values among the investigated brain regions. A correlation between gestational age (GA) and ADC values was determined by linear regression analysis. RESULTS: Compared with fetuses in PE/GH without FGR and those with normotensive pregnancies, fetuses in the PE/GH with FGR group had significantly lower average ADC measurements of supratentorial regions (1.65 ± 0.09 vs. 1.71 ± 0.10 10-3 mm2 /sec; vs. 1.73 ± 0.11 10-3 mm2 /sec, respectively). Regions of significantly decreased ADC values in the fetal brain included CSO, FWM, PWM, OWM, TWM and THAL in cases of PE/GH with FGR. ADC values from supratentorial regions in PE/GH pregnancies were not significantly correlated with GA (P = 0.12, 0.26); however, this trend was statistically significant in the normotensive groups. DATA CONCLUSION: ADC values may indicate fetal brain developmental alterations in PE/GH with FGR fetuses but more microscopic and morphological studies are necessary to provide additional evidence to offer a different interpretation of this trend in fetal brain. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 3.

Ophthalmic artery Doppler and biomarkers of impaired placentation at 36 weeks' gestation in pregnancies with small fetuses.

OBJECTIVES: First, to compare ophthalmic artery peak systolic velocity (PSV) ratio and biomarkers of impaired placentation at 36 weeks' gestation in women who delivered a small-for-gestational-age (SGA) or growth-restricted (FGR) neonate, in the absence of hypertensive disorder, with those of women who developed pre-eclampsia (PE) or gestational hypertension (GH) and of women unaffected by SGA, FGR, PE or GH. Second, to examine the associations of PSV ratio, uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) with birth-weight Z-score or percentile. 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. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination of fetal anatomy and growth, and measurement of maternal ophthalmic artery PSV ratio, UtA-PI, PlGF and sFlt-1. Values of PSV ratio, UtA-PI, PlGF and sFlt-1 were converted to multiples of the median (MoM) or delta values. Median MoM or deltas of these biomarkers in the SGA, FGR, PE and GH groups were compared with those in the unaffected group. Regression analysis was used to examine the relationship of PSV ratio delta, UtA-PI MoM, PlGF MoM and sFlt-1 MoM with birth-weight Z-score, after exclusion of PE and GH cases. RESULTS: The study population of 9033 pregnancies included 7696 (85.2%) that were not affected by FGR, SGA, PE or GH, 182 (2.0%) complicated by FGR in the absence of PE or GH, 698 (7.7%) with SGA in the absence of FGR, PE or GH, 236 (2.6%) with PE and 221 (2.4%) with GH. Compared with unaffected pregnancies, in the FGR and SGA groups, the PSV ratio delta and sFlt-1 MoM were increased and PlGF MoM was decreased; UtA-PI MoM was increased in the FGR group but not the SGA group. The magnitude of the changes in biomarker values relative to the unaffected group was smaller in the FGR and SGA groups than that in the PE and GH groups. In non-hypertensive pregnancies, there were significant inverse associations of PSV ratio delta and UtA-PI MoM with birth-weight Z-score, such that the values were increased in small babies and decreased in large babies. There was a quadratic relationship between PlGF MoM and birth-weight Z-score, with low PlGF levels in small babies and high PlGF levels in large babies. There was no significant association between sFlt-1 MoM and birth-weight Z-score. CONCLUSIONS: Ophthalmic artery PSV ratio, reflective of peripheral vascular resistance, and UtA-PI, PlGF and sFlt-1, biomarkers of impaired placentation, are altered in pregnancies complicated by hypertensive disorder and, to a lesser extent, in non-hypertensive pregnancies delivering a SGA or FGR neonate. The associations between the biomarkers and birth-weight Z-score suggest the presence of a continuous physiological relationship between fetal size and peripheral vascular resistance and placentation, rather than a dichotomous relationship of high peripheral resistance and impaired placentation in small compared to non-small fetuses. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Ophthalmic artery Doppler in women with hypertensive disorders of pregnancy: relationship to blood pressure control and renal dysfunction at 6-9 weeks postnatally.

OBJECTIVES: To examine the postnatal course of ophthalmic artery (OA) Doppler in women with hypertensive disorders of pregnancy (HDP) and to evaluate the correlation between OA Doppler parameters and poor postnatal blood pressure control and renal dysfunction at 2-3 weeks and 6-9 weeks postnatally. METHODS: This was a prospective cohort study of women with a singleton pregnancy and HDP seen at a tertiary pregnancy hypertension clinic between 2019 and 2021. Three visits were included: Visit 1, the last visit to the antenatal hypertension clinic within 2 weeks prior to delivery; Visit 2, at 2-3 weeks postnatally; and Visit 3, at 6-9 weeks postnatally. At each visit, maternal demographic characteristics, medical history, blood pressure and OA Doppler were obtained. In addition, fetal growth and fetal Dopplers were examined antenatally and, at 6-9 weeks postnatally, estimated glomerular filtration rate and proteinuria were quantified. Study participants were divided into four hypertension groups, according to longitudinal changes in blood pressure at the three visits. For the postnatal visits, hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg in the absence of antihypertensive medication, and SBP ≥ 130 mmHg and/or DBP ≥ 80 mmHg whilst taking antihypertensives. Group 1 was hypertensive at all three visits; Group 2 was hypertensive at Visits 1 and 2 but normotensive at Visit 3; Group 3 was hypertensive at Visits 1 and 3 but normotensive at Visit 2; and Group 4 was hypertensive at Visit 1 but normotensive at Visits 2 and 3. The longitudinal changes in mean arterial pressure (MAP), peak systolic velocity (PSV) 1, PSV2 and the ratio of PSV2/PSV1 over the three timepoints were examined by a repeated-measures, multilevel, linear mixed-effects analysis, controlling for maternal age, weight at presentation and use of antihypertensive medication. In addition, we examined the longitudinal change in OA Doppler parameters in women with different degrees of postnatal blood pressure control and in those with and those without renal dysfunction at 6-9 weeks postnatally. RESULTS: A total of 108 women were recruited to the study, of whom 86 had new-onset hypertension and 22 had chronic hypertension. When controlling for maternal age, weight at presentation and use of antihypertensive medication, a significant decline in log10 MAP (P < 0.001), log10 PSV1 (P < 0.001) and log10 PSV2 (P = 0.01) was seen between Visits 1 and 3. Log10 PSVR did not change with time. When assessing OA Doppler against hypertension group, log10 PSV1 and log10 PSV2 did not differ between the hypertension groups, whilst Group 4 had a lower log10 PSVR compared with Group 1 (P < 0.01), Group 2 (P = 0.03) and Group 3 (P < 0.01). At 6-9 weeks postnatally, log10 PSVR was lower in those without compared to those with renal dysfunction (-0.021, P = 0.01), whilst log10 MAP, log10 PSV1 and log10 PSV2 values did not differ. Log10 PSVR did not change with time and remained at -0.12 (95% CI, -0.13 to -0.11) across the three visits. CONCLUSIONS: In women with HDP, the OA-PSVR was significantly higher in those with labile or persistently raised blood pressure postnatally compared to women whose blood pressure normalized. Similarly, the OA-PSVR at 6-9 weeks postnatally was significantly higher in women with renal dysfunction vs those without dysfunction. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

The value of TDI combined with myocardial strain parameters in quantitative evaluation of left heart function in parturient with pregnancy-induced hypertension.

This study aimed to investigate the value of tissue doppler imaging (TDI) and 4D myocardial strain parameters in evaluating left heart function of pregnant women with hypertension and the association between these parameters and relevant factors. Forty-five pregnant women with hypertensive disorder, including 20 with hypertension, 15 with mild preeclampsia, and 10 with severe preeclampsia, were recruited, and their cardiac functions were compared with those of 30 healthy pregnant women as controls. High Left ventricular end-systolic volume (LVESV), Left atrial volume index (LAVI), E/e were observed in hypertensive disorder, while Mitral peak diastolic velocity(E), Early diastolic peak velocity(e), E/A, Left ventricularglobal longitudinal strain (LVGLS), Left ventricularglobal area strain (LVGAS), and Left atrialglobal longitudinal strain (LAGLS) were decreased; for pre-eclampsia, Left ventricular end-systolic diameter (LVESD), Left atrial anteroposterior diameter (LAD-ap), LVESV, LAVI were significantly increased, LVGLS, LAGLS were significantly decreased, Left ventricular end-diastolic diameter (LVEDD), Left ventricular end-diastolic volume (LVEDV), A peak, E/e were increased, while E peak, E/A, e, Left ventricle global radial strain (LVGRS), Left ventricle global circumferential strain (LVGCS), LVGAS were decreased but not significantly; for severe preeclampsia, Left ventricular end diastolic diameter (LVEDD), LVESD, LAD-ap, Left ventricular end-diastolic volume (LVEDV), LVESV, LAVI, A, and E/e were significantly increased, while LVGLS, LVGRS, LVGCS, LVGAS, LAGLS, E peak, E/A, and e were significantly reduced. TDI combined with 4D myocardial strain parameters can detect early changes in cardiac function of hypertensive disorders in pregnancy, with LVGLS, LVGAS, and LAGLS being the most sensitive indicators for early changes. Such findings provide a basis for effective clinical treatment of these symptoms.

Serum Human Placental Lactogen Assays in Ultrasound Evaluated Pregnancy-Induced Hypertension: A Marker of Placental Function in Pregnancy.

Human placental lactogen (HPL) is a pregnancy-related hormone produced by the placenta. The overall functions of serum HPL impacts the developing fetus and placenta. The objective of this study was to determine the relationship between maternal serum concentration of HPL and sonographic fetal growth parameters in pregnancy induced hypertension as a marker of placental function. This prospective cross-sectional study was conducted over a 9-month period in the University of Calabar Teaching Hospital, Calabar, Nigeria that involved 100 women with pregnancy induced hypertension. An obstetric ultrasound scan was done on all the subjects and their blood was collected for HPL evaluation using Enzyme-linked Immunosorbent Assay (ELISA). SPSS version 20 was used to analyze the data. Maternal serum HPL had a significant positive correlation with PLA (P=0.000), estimated gestational age (P=0.000), estimated fetal weight (P=0.000) and amniotic fluid index AFI (P=0.000) and a significant negative correlation with proteinuria (P=0.047), fetal heart rate (P=0.032) and HC/AC (P=0.000). It is concluded that maternal serum HPL concentration increases as pregnancy advances and causes a significant increase in placental thickness, fetal weight and amniotic fluid volume, however, its reduction is significantly associated with the onset of pre-eclampsia, fetal distress and asymmetrical intra-uterine growth restriction. Thus, the evaluation of maternal serum HPL concentration is a reliable marker of placental function in the second half of pregnancy.

Clinical Analysis of Echocardiography and Serum IL-6 and TNF-α Changes in Pregnant Women with Hypertension.

In order to explore the changes and clinical significance of serum TNF-α and IL-6 and ET levels in the pathogenesis of hypertensive disorders of pregnancy (HDIP), echocardiography, and serum IL-6 and TNF-α changes in pregnant women with a hypertensive disorder, a clinical analysis method was proposed. A retrospective analysis of 59 pregnant women who visited the obstetrics department of a provincial hospital was divided into 2 groups. The normal control group consisted of 32 normal, uncomplicated pregnant women; the preeclampsia group included 27 patients with systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg who developed proteinuria after 20 weeks of gestation. The levels of TNF-α and IL-6 in serum of normal pregnant women and pregnant women with preeclampsia were detected by enzyme-linked immunosorbent assay (ELISA). The results showed that compared with normal pregnant women, the serum levels of TNF-α and IL-6 in the early pregnant women of Zizhi were significantly increased, and the trend of increased TNF-α and IL-6 levels was related to the severity of complications. With the mean pulmonary arterypressure > 50 mmHg, the serum TNF-α level of pregnant women was significantly higher than that of pregnant women with mean pulmonary arterypressure < 50 mmHg. The analysis found that the serum levels of TNF-α and IL-6 in patients with hypoxic gestational hypertension were significantly increased, and the results of lung tissue immunohistochemistry also showed that serum TNF-α and IL-6 levels in patients with hypoxic gestational hypertension were significantly increased. And serum TNF-α and IL-6 levels were positively correlated with right ventricular systolic blood pressure (RVSP). Conclusion. This study revealed that the elevated levels of serum TNF-α and IL-6 are closely related to the pathophysiological process of gestational hypertension. Serum levels of TNF-α and IL-6 and ET were significantly increased, and the changes of serum TNF-α and IL-6 and ET levels had important clinical value for closely monitoring the severity of the disease and the development of the disease.

Uterine Ultrasound Doppler Hemodynamics of Magnesium Sulfate Combined with Labetalol in the Treatment of Pregnancy-Induced Hypertension Using Empirical Wavelet Transform Algorithm.

The aim of this study was to explore the hemodynamic changes of magnesium sulfate combined with labetalol in the treatment of pregnancy-induced hypertension (PIH) under Doppler uterine ultrasound based on the empirical wavelet transform (EWT) algorithm. 500 patients with PIH in the hospital were selected and randomly divided into the control group (n = 250) and the observation group (n = 250). The control group was treated with conventional magnesium sulfate; the observation group was given labetalol based on magnesium sulfate drip in the control group. The uterine artery blood flow simulation model was established based on the EWT algorithm and compared with a short-time Fourier transform (STFT). The normalized root mean square error (NRMSE) of the STFT method was 0.19, and the NRMSE extracted by the EWT method was 0.13. After treatment, the blood pressure index, 24-hour urinary protein, and incidence of adverse birth outcomes in the observation group were lower than those in the control group; the effective rate of the control group (90.4%) was lower than that of the observation group (97.6%); the hemodynamic indexes of the uterine artery in the observation group were lower than those in the control group, and the differences were statistically significant (P < 0.05). The estimation accuracy of the EWT method was higher than that of the traditional STFT method; the combined treatment of magnesium sulfate and labetalol in patients with PIH had a remarkable effect, which could control the blood pressure index and reduce the 24-hour urinary protein; the uterine artery Doppler ultrasound examination could change hemodynamics and improve the adverse outcomes of mothers and infants.

Hypertensive disorders and maternal hemodynamic changes in pregnancy: monitoring by USCOM® device.

Hypertensive disorders are quite common, complicating about 10% of pregnancies, while preeclampsia occurs in 2-8% of cases. The most recognized etiopathogenetic factor for the development of preeclampsia is deficient remodeling of the spiral arteries during trophoblastic invasion. Recently, some authors speculated about the "cardiovascular origin of preeclampsia"; in particular, they postulate that placental dysfunction is not the primum movens of preeclampsia, but it could be caused by a failure of the maternal cardiovascular system to adapt to the pregnancy itself. Moreover, several studies have also shown that developing preeclampsia in pregnancy is associated with an increased risk of cardiovascular disease later in life. Due to the importance of this pathology, it would be crucial to have an effective screening in order to implement a prophylaxis; for this purpose, it could be useful to have an accurate and noninvasive device for the assessment of maternal hemodynamic variables. USCOM® (Ultrasonic Cardiac Output Monitor) is a noninvasive Doppler ultrasonic technology which combines accuracy, reproducibility, noninvasiveness, and a fast learning curve. Maternal hemodynamic evaluation is important in order to monitor the changes that the maternal organism encounters, in particular a reduction in blood pressure, a decrease in total peripheral resistances, and an increase in cardiac output, resulting in a hyperdynamic circle. These hemodynamic modifications are lacking in pregnancies complicated by preeclampsia. For these reasons, it is crucial to have a tool that allows these parameters to be easily evaluated in order to identify those women at higher risk of hypertensive complications and more severe outcomes.

Midgestation cardiovascular phenotype in women who develop gestational diabetes and hypertensive disorders of pregnancy: comparative study.

OBJECTIVE: Women with gestational diabetes mellitus (GDM) and/or hypertensive disorders of pregnancy (HDP) are at increased long-term cardiovascular risk. Mild cardiac functional alterations have been detected in women with GDM or HDP in midgestation, prior to clinical onset of the disease, but these functional alterations have not been found to be useful as screening tools. In contrast, increased impedance to peripheral blood flow, measured by echocardiography or ophthalmic artery Doppler, has been shown to provide incremental value to maternal characteristics for the prediction of pre-eclampsia. However, it is unknown whether similar changes can be detected in women at risk of GDM. In this study, we performed detailed cardiovascular phenotyping in a large, unselected population of women in midgestation to identify similarities and differences in cardiovascular adaptation in women who are at risk of GDM and/or HDP. METHODS: This was a prospective observational study in women attending for a routine hospital visit at 19 + 1 to 23 + 3 weeks' gestation. This visit included assessment of flow velocity waveforms from the maternal ophthalmic arteries, echocardiography for assessment of maternal cardiovascular function and measurement of uterine artery pulsatility index and serum placental growth factor (PlGF) for assessment of placental perfusion and function. The measured indices were converted to either multiples of the median (MoM) values or deviation from the median (delta) after adjusting for maternal characteristics and elements of medical history. Biomarker delta or MoM values in the GDM and HDP groups were compared with those in the unaffected group using 95% CI and t-tests. RESULTS: The study population of 5214 pregnancies contained 4429 (84.9%) that were unaffected by GDM or HDP, 509 (9.8%) complicated by GDM without HDP, 41 (0.8%) with GDM and HDP, and 235 (4.5%) with HDP without GDM. In HDP cases, with or without GDM, there was evidence of impaired placentation, with a decrease in PlGF, and increased impedance to flow in the peripheral circulation, suggested by an increase in ophthalmic artery peak systolic velocity (PSV) ratio, peripheral vascular resistance assessed on echocardiography and mean arterial pressure. In the GDM group without HDP, there was no evidence of altered placental perfusion or function and ophthalmic artery PSV ratio was not significantly different from that in the unaffected group; peripheral vascular resistance and mean arterial pressure were increased but to a lesser degree than in the HDP group. In the HDP group, there was an increase in global longitudinal systolic strain and slight increase in isovolumic relaxation time, while in the GDM group, there was an increase in mitral valve E/e', myocardial performance index and global longitudinal systolic strain. CONCLUSIONS: In midgestation, women who subsequently develop HDP or GDM have a mild subclinical reduction in left ventricular function. In HDP cases, with or without GDM, there is evidence of impaired placentation and all biomarkers of impedance to peripheral blood flow are consistently increased. In contrast, in the GDM group without HDP, biomarkers of placental function are normal and those of impedance to peripheral blood flow are either marginally increased or not significantly different from those in normal pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Ophthalmic artery Doppler at 19-23 weeks' gestation in pregnancies that deliver small-for-gestational-age neonates.

OBJECTIVES: First, to explore hemodynamic differences between pregnancies delivering a small-for-gestational-age (SGA) neonate in the absence of hypertensive disorders and those that develop pre-eclampsia (PE) or gestational hypertension (GH), by comparing the ophthalmic artery peak systolic velocity (PSV) ratio and first (PSV1) and second (PSV2) PSV at 19-23 weeks' gestation, and second, to compare these pregnancies for markers of placental perfusion and function. METHODS: This was a prospective observational study in women attending for a routine hospital visit at 19 + 1 to 23 + 3 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination for assessment of fetal anatomy and growth, and measurement of maternal ophthalmic artery PSV ratio, PSV1, PSV2, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF). The values of PSV ratio, PSV1, PSV2, MAP, UtA-PI and PlGF were converted to multiples of the median (MoM) or deltas. Mean MoMs or deltas of these biomarkers in the SGA, PE and GH groups were compared with those in the unaffected group. The definition of SGA was birth weight below the 10th percentile in the absence of PE or GH. RESULTS: The study population of 5214 pregnancies contained 4375 (83.9%) that were unaffected by SGA, PE or GH, 563 (10.8%) complicated by SGA, 157 (3.0%) with PE and 119 (2.3%) with GH. There were three main findings of the study. First, in the SGA, PE and GH groups, compared with unaffected pregnancies, the PSV ratio delta, PSV2 MoM, MAP MoM and UtA-PI MoM were increased and PlGF MoM was decreased; however, the magnitude of most changes was smaller in the SGA group than in PE and GH groups. Second, in the PE and GH groups, but not in the SGA group, PSV1 MoM was increased. Third, in general, in the pathological pregnancies, the magnitude of deviation of biomarkers from unaffected pregnancies was greater for those delivering at < 37 than at ≥ 37 weeks' gestation. CONCLUSION: In mid-gestation, pregnancies that subsequently develop hypertensive disorders and those delivering a SGA neonate, compared with unaffected pregnancies, have abnormal uteroplacental measurements and increased maternal ophthalmic artery PSV ratio. These data suggest similar pathophysiology in the two conditions, with evidence of placental dysfunction and increased peripheral vascular resistance, but the magnitude of abnormalities is greater in hypertensive disorders. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Predicting Hypertensive Disease in the First Trimester of Pregnancy: Risk Models and Analysis of Serum D-dimer Levels Combined with Plasma Pregnancy-Associated Protein A, Free ß-Subunit of Human Chorionic Gonadotropin, and Fetal Nuchal Translucency.

We aimed to investigate the predictive ability of serum levels of D-dimer (DD) in the first trimester for the occurrence of hypertensive disorders of pregnancy (HDP). In this retrospective, case-cohort study, we measured the levels of DD, plasma pregnancy-associated protein A (PAPP-A), and free ß-subunit of human chorionic gonadotropin (free ß-hCG) and analyzed fetal nuchal translucency (NT) in 150 healthy gravidas, 126 cases of gestational hypertension (GH), 53 cases of preeclampsia (PE), and 41 cases with severe preeclampsia (SPE). Likelihood ratio models and risk models were built using single markers (DD, PAPP-A, free ß-hCG, and NT) and combinations of those markers. Analyses showed that the levels of DD multiple of the median (MoM) in the GH, PE, and SPE groups were all significantly higher than those in the control group, with significant differences between groups (χ 2 = 70.325, P < 0.001). The area under curve (AUCs) for DD in the GH, PE, and SPE groups was 0.699, 0.784, and 0.893, respectively; the positive likelihood ratio (+LR) was 1.534, 1.804, and 2.941, respectively; and the negative likelihood ratio (-LR) was 0.022, 0.081, and 0, respectively. When the cut-off values of DD for the GH, PE, and SPE groups were 0.725, 0.815, and 0.945 MoM, respectively, the corresponding sensitivities were 0.992, 0.962, and 1.000, respectively. As gestational hypertension progressed, the levels of DD tended to increase gradually. The maternal serum level of DD in the first trimester had correlative and diagnostic value for HDP. The sensitivity and specificity of maternal serum levels of DD level in the first trimester for different types of HDP were significantly different; the best sensitivity and specificity were detected in the SPE group. First trimester DD level, combined with other biochemical markers, may improve our ability to diagnose HDP.

Longitudinal assessment of spiral artery and intravillous arteriole blood flow and adverse pregnancy outcome.

OBJECTIVE: Superb microvascular imaging (SMI) has been shown to improve visualization of small vessels by suppressing global motions while preserving low-flow components, such as the microvessels in the placenta. We sought to determine if SMI-aided visualization of flow velocity waveforms in the spiral arteries (SA) and intravillous fetal arterioles (IVA) could predict fetal growth restriction (FGR), gestational hypertension (GH) and/or pre-eclampsia (PE). METHODS: This was a prospective longitudinal study of singleton pregnancies without fetal anomaly, receiving prenatal care in one of two medical centers over a 5-year period. Using SMI-aided color Doppler, SA and IVA flow velocity was measured at three timepoints: 11 + 0 to 14 + 0, 18 + 0 to 22 + 6 and 28 + 0 to 34 + 6 weeks of gestation. SA and IVA flow velocity waveforms were reported as resistance indices (RI). RI values were analyzed using multilevel modeling; individual regression curves were estimated and combined to obtain the reference intervals for SA-RI and IVA-RI in uncomplicated pregnancies. The primary clinical outcome was FGR and secondary outcomes were PE and GH. FGR was defined as estimated fetal weight < 10th percentile. Student's t-test was used to compare deviation from expected RI between normal and complicated pregnancies. RESULTS: Among 540 pregnancies included in the analysis, 18 (3.3%) had FGR, 31 (5.7%) PE and 61 (11.3%) GH. In uncomplicated pregnancies, the SA-RI decreased progressively with advancing gestation, whereas the IVA-RI increased with gestational age. In the third trimester, the mean SA-RI and IVA-RI values were significantly higher in the FGR group compared with pregnancies that did not develop FGR, while the mean SA-RI was significantly higher in PE compared with non-PE pregnancies. There was no significant difference in mean SA-RI or IVA-RI between pregnancies with vs those without GH at any gestational age. When all three adverse outcomes were combined, SA-RI was significantly higher in pregnancies with these outcomes when compared to uncomplicated pregnancies in the third trimester (mean ± SD, 0.29 ± 0.12 vs 0.26 ± 0.12; P = 0.02). In screening for FGR using SA-RI, the areas under the receiver-operating-characteristics curves (AUC) were 0.68, 0.73 and 0.73 in the first, second and third trimesters, respectively. The respective AUCs for IVA-RI were 0.72, 0.72 and 0.73 for each trimester. CONCLUSIONS: SA-RI and IVA-RI, measured using SMI technology, were significantly higher in pregnancies at risk for FGR in late gestation. Larger studies are needed to determine if SA and IVA flow are reliable predictors of adverse pregnancy outcome. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Interleukin-6 and its correlations with maternal characteristics and echocardiographic parameters in pre-eclampsia, gestational hypertension and normotensive pregnancy.

BACKGROUND: Pre-eclampsia and gestational hypertension are pregnancy-related disorders with major maternal cardiovascular implications later in life. OBJECTIVES: The aim of this study was to determine interleukin-6 levels in women with pre-eclampsia and gestational hypertension and in healthy pregnant controls, and to examine their correlations with characteristics of the women and echocardiographic findings. METHODS: The ELISA method was used to determine serum interleukin-6 in 36 women with gestational hypertension, 37 women with pre-eclampsia and 50 pregnant controls. The echocardiographic examination was performed according to current recommendations by the European Association of Cardiovascular Imaging and the American Society of Echocardiography. RESULTS: Mean serum interleukin-6 levels were 2.77 pg/ml in the controls, 5.08 pg/ml in the gestational hypertension group and 8.06 pg/ml in the pre-eclampsia group. A significant difference in these levels was present between the controls and both hypertensive groups, but not between the two hypertensive groups. Higher levels correlated with heart chamber enlargement and worse ventricular function. CONCLUSION: Interleukin-6 levels in gestational hypertension and pre-eclampsia were significantly elevated compared to those in healthy pregnancy. Higher levels also corresponded to echocardiographical changes.

Peripartum echocardiographic changes in women with hypertensive disorders of pregnancy.

OBJECTIVE: Hypertensive disorders of pregnancy (HDP) are associated with significant myocardial dysfunction on echocardiography. The impact of hemodynamic changes related to volume redistribution following delivery on myocardial function in women with HDP has not been evaluated systematically. The aim of this study was to compare echocardiographic findings immediately before and after delivery in women with HDP. METHODS: This was a prospective longitudinal study including 30 women with a diagnosis of HDP who underwent two consecutive transthoracic echocardiographic (TTE) examinations, before delivery and in the early postpartum period. Paired comparisons of the findings from the two assessments were performed. RESULTS: Left-ventricular (LV) concentric remodeling or hypertrophy was detected in 21 (70%) patients. There was no significant difference in cardiac morphology indices such as LV mass index (78.9 ± 16.3 g/m2 vs 77.9 ± 15.4 g/m2 ; P = 0.611) or relative wall thickness (0.45 ± 0.1 vs 0.44 ± 0.1; P = 0.453) before vs after delivery. LV diastolic function did not demonstrate any peripartum variation, with similar left-atrial volume (52.4 ± 15.3 mL vs 51.0 ± 15.6 mL; P = 0.433), lateral E' (0.12 ± 0.03 m/s vs 0.12 ± 0.03 m/s; P = 0.307) and E/E' ratio (7.9 ± 2.2 vs 7.9 ± 1.7; P = 0.934) before vs after delivery. Systolic function indices, such as LV ejection fraction (57.5 ± 3.4% vs 56.4 ± 2.1%; P = 0.295) and global longitudinal strain (-15.3 ± 2.6% vs -15.1 ± 3.1%; P = 0.582), also remained unchanged between before vs after delivery. CONCLUSIONS: Maternal hemodynamic changes associated with delivery did not influence significantly peripartum TTE indices in women with HDP. Suboptimal maternal echocardiographic findings in HDP are likely to be the consequence of chronic pregnancy cardiovascular load changes or pre-existing maternal cardiovascular impairment. Severity and persistence of myocardial dysfunction in the postpartum period may be related to the long-term maternal cardiovascular disease legacy of HDP. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Changes in ophthalmic artery Doppler during acute blood-pressure control in hypertensive pregnant women.

OBJECTIVE: To examine the changes in ophthalmic artery Doppler indices and their association with changes in mean arterial blood pressure (MAP) and systolic (SBP) and diastolic (DBP) blood pressure, following acute antihypertensive treatment in women with hypertensive disorders of pregnancy presenting with high blood pressure. METHODS: This was a prospective cohort study of 31 pregnant women presenting at 30 + 0 to 39 + 6 weeks' gestation for management of their hypertension. Paired maternal blood-pressure and ophthalmic-artery-Doppler measurements were performed prior to and at 30 min and 60 min after starting antihypertensive medication. In patients who did not achieve blood-pressure control (i.e. when blood pressure was < 140/90 mmHg) by 60 min, paired readings were continued up to 120 min. If blood-pressure control was still not achieved at that point, patients were admitted to hospital. Univariate linear regression was performed to determine the association of ophthalmic artery peak systolic velocity (PSV) ratio with SBP, DBP and MAP before treatment and after blood-pressure control. The longitudinal changes in MAP, SBP, DBP and PSV ratio from pretreatment to 30 min and 60 min after commencement of antihypertensives were examined by repeated measure, multilevel, linear mixed-effects analysis. RESULTS: Antihypertensive treatment was associated with a decrease in SBP, DBP, MAP and PSV ratio. At 60 min following antihypertensive treatment, the decrease in SBP, DBP, MAP and PSV ratio was 12.1 mmHg (95% CI, 9.0-15.1 mmHg; P < 0.0001), 9.1 mmHg (95% CI, 6.5-11.5 mmHg; P < 0.0001), 10.0 mmHg (95% CI, 7.6-12.4 mmHg; P < 0.0001) and 0.07 (95% CI, 0.03-0.11 mmHg; P < 0.001), respectively. From the total cohort, 20 (64.5%) women had achieved blood-pressure control at 60 min and another seven (22.6%) by 120 min from commencement of antihypertensive treatment. Four (12.9%) women did not achieve blood-pressure control during this period and were admitted to hospital. The relationship between PSV ratio and SBP, DBP and MAP was assessed before treatment (n = 31) and at the point of blood-pressure control in women in whom this was achieved by 120 min (n = 27). Prior to treatment, there was a significant association between PSV ratio and MAP (P < 0.0001, R2 = 0.39). This was primarily due to the association of PSV ratio with DBP (P < 0.0001, R2 = 0.39) and less so due to its association with SBP (P = 0.02, R2 = 0.16). At the point of achieving blood-pressure control, there was no significant association between PSV ratio and MAP (P = 0.7), DBP (P = 0.5) or SBP (P = 0.7). CONCLUSIONS: Acute blood-pressure control in pregnancy is associated with a concomitant reduction in blood pressure and ophthalmic artery PSV ratio. In hypertensive pregnant women, there is a significant association of PSV ratio with MAP, SBP and DBP, which disappears after blood pressure is reduced to < 140/90 mmHg following antihypertensive treatment. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.