Maternal Systolic Blood Pressure Research Articles

Perinatal Survival and Predictors of Mortality among Mothers with Hypertensive Disorders of Pregnancy at Antenatal care Clinics in Gamo Zone Public Hospitals.

Pregnancy induced hypertension represents a significant public health problem throughout the world, which may complicate 0.5%-10% of all pregnancies. It is the leading cause of maternal as well perinatal mortality and morbidity worldwide. Pregnancy induced hypertension is a multisystem disorder unique to pregnancy and results in high perinatal mortality. The objective of this study was to determine the survival status, incidence and predictors of perinatal mortality among mothers with pregnancy induced hypertension at antenatal clinics of Gamo Zone public hospitals. Facility-based retrospective cohort study was conducted among selected 576(192 exposed and 384 unexposed) antenatal care attendants' record at Gamo Zone public hospitals from 1st January 2018 to 31st December 2018. Data were entered into Epi data version 3.02 and exported to SPSS V 25 for analysis. Kaplan Meier survival curve together with log rank test was fitted to test the survival time. Statistical significance was declared at P-value ≤0.05 using cox proportional hazard model. The incidence of perinatal mortality was 124/1000 births. The cumulative proportion of surviving at the end of 4th, 8th, 12th and 16th weeks of follow-up among the exposed groups was 96.9%, 93.5%, 82.1% and 61.6% respectively whereas it was 99.5%, 98.9% and 98.5% at the end of 4th, 8th and 12th weeks of follow-up for the non-exposed groups respectively. Parity of ≥5(AHR: 6.3; 95%CI: 1.36,10.55), mothers who delivered at <34 weeks of gestation(AHR:7.8; 95%CI: 2.6,23.1), being preterm(AHR:6; 95%CI: 5.3,19.2), perinatal birth weight ≤2500gm(AHR:6.1; 95&CI: 1.01,37.9), vaginal deliveryn(AHR:2.7; 95%CI:1.13,6.84), maternal highest systolic blood pressure level ≥160mmHg (AHR: 2.3; 95%CI: 1.02,5.55) and prepartum onset of pregnancy induced hypertension (AHR: 6; 95%CI: 5.3,19.2) were statistically significant in multivariable analysis. The risk of perinatal mortality was high among the mothers with pregnancy induced hypertension compared to those of pregnancy induced hypertension free mother,s and the perinatal mortality rate was high. High parity, low gestational age, low number of antenatal care visits, low birth weight, vaginal delivery, antepartum onset of pregnancy induced hypertension and highest maternal systolic blood pressure level were the independent predictors of perinatal mortality.

Early postpartum dyslipidemia and its potential predictors during pregnancy in women with a history of gestational diabetes mellitus

BackgroundThis study aimed to analyze the incidence of early postpartum dyslipidemia and its potential predictors in women with a history of gestational diabetes mellitus (GDM).MethodsThis was a retrospective study. Five hundred eighty-nine women diagnosed with GDM were enrolled and followed up at 6–12 weeks after delivery. A 75 g oral glucose tolerance test (OGTT) and lipid levels were performed during mid-trimester and the early postpartum period. Participants were divided into the normal lipid group and dyslipidemia group according to postpartum lipid levels. Demographic and metabolic parameters were analyzed. Multiple logistic regression was performed to analyze the potential predictors for early postpartum dyslipidemia. A receiver operating characteristic curve (ROC) was calculated to determine the cut-off values.ResultsA total of 38.5% of the 589 women developed dyslipidemia in early postpartum and 60% of them had normal glucose metabolism. Delivery age, systolic blood pressure (SBP), glycated hemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDL-C) were independent predictors of early postpartum dyslipidemia in women with a history of GDM. The cut-offs of maternal age, SBP, HbA1c values, and LDL-C levels were 35 years, 123 mmHg, 5.1%, and 3.56 mmol/L, respectively. LDL-C achieved a balanced mix of high sensitivity (63.9%) and specificity (69.2%), with the highest area under the receiver operating characteristic curve (AUC) (0.696). When LDL-C was combined with age, SBP, and HbA1c, the AUC reached to 0.733.ConclusionsA lipid metabolism evaluation should be recommended in women with a history of GDM after delivery, particularly those with a maternal age > 35 years, SBP > 123 mmHg before labor, HbA1c value > 5.1%, or LDL-C levels > 3.56 mmol/L in the second trimester of pregnancy.

Dissecting maternal and fetal genetic effects underlying the associations between maternal phenotypes, birth outcomes, and adult phenotypes: A mendelian-randomization and haplotype-based genetic score analysis in 10,734 mother-infant pairs.

Many maternal traits are associated with a neonate's gestational duration, birth weight, and birth length. These birth outcomes are subsequently associated with late-onset health conditions. The causal mechanisms and the relative contributions of maternal and fetal genetic effects behind these observed associations are unresolved. Based on 10,734 mother-infant duos of European ancestry from the UK, Northern Europe, Australia, and North America, we constructed haplotype genetic scores using single-nucleotide polymorphisms (SNPs) known to be associated with adult height, body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), and type 2 diabetes (T2D). Using these scores as genetic instruments, we estimated the maternal and fetal genetic effects underlying the observed associations between maternal phenotypes and pregnancy outcomes. We also used infant-specific birth weight genetic scores as instrument and examined the effects of fetal growth on pregnancy outcomes, maternal BP, and glucose levels during pregnancy. The maternal nontransmitted haplotype score for height was significantly associated with gestational duration (p = 2.2 × 10-4). Both maternal and paternal transmitted height haplotype scores were highly significantly associated with birth weight and length (p < 1 × 10-17). The maternal transmitted BMI scores were associated with birth weight with a significant maternal effect (p = 1.6 × 10-4). Both maternal and paternal transmitted BP scores were negatively associated with birth weight with a significant fetal effect (p = 9.4 × 10-3), whereas BP alleles were significantly associated with gestational duration and preterm birth through maternal effects (p = 3.3 × 10-2 and p = 4.5 × 10-3, respectively). The nontransmitted haplotype score for FPG was strongly associated with birth weight (p = 4.7 × 10-6); however, the glucose-increasing alleles in the fetus were associated with reduced birth weight through a fetal effect (p = 2.2 × 10-3). The haplotype scores for T2D were associated with birth weight in a similar way but with a weaker maternal effect (p = 6.4 × 10-3) and a stronger fetal effect (p = 1.3 × 10-5). The paternal transmitted birth weight score was significantly associated with reduced gestational duration (p = 1.8 × 10-4) and increased maternal systolic BP during pregnancy (p = 2.2 × 10-2). The major limitations of the study include missing and heterogenous phenotype data in some data sets and different instrumental strength of genetic scores for different phenotypic traits. We found that both maternal height and fetal growth are important factors in shaping the duration of gestation: genetically elevated maternal height is associated with longer gestational duration, whereas alleles that increase fetal growth are associated with shorter gestational duration. Fetal growth is influenced by both maternal and fetal effects and can reciprocally influence maternal phenotypes: taller maternal stature, higher maternal BMI, and higher maternal blood glucose are associated with larger birth size through maternal effects; in the fetus, the height- and metabolic-risk-increasing alleles are associated with increased and decreased birth size, respectively; alleles raising birth weight in the fetus are associated with shorter gestational duration and higher maternal BP. These maternal and fetal genetic effects may explain the observed associations between the studied maternal phenotypes and birth outcomes, as well as the life-course associations between these birth outcomes and adult phenotypes.

Magnesium sulfate prophylaxis attenuates the postpartum effects of preeclampsia by promoting M2 macrophage polarization.

Preeclampsia is a complex disorder that is characterized by new onset hypertension and proteinuria at or after 20 weeks of gestation. Preeclampsia is a leading cause of maternal and fetal morbidity and mortality. MgSO4 is commonly used to treat severe preeclampsia, but its mechanism of action is poorly understood, and investigations into the effects of MgSO4 during the postpartum period are lacking. In this study, timed-pregnant Sprague-Dawley rats received low-dose lipopolysaccharide (LPS) on gestational day 14 to induce preeclampsia. Maternal and fetal outcomes and the macrophage profile 1 week after delivery were explored. On postpartum day (PD) 7, the maternal systolic blood pressure and urinary protein level were significantly increased, the number of M1 macrophages was increased and the number of M2 macrophages was decreased in the maternal kidney and brain; the median duration of gestation, the number of live fetuses, and the fetal weight/placenta weight ratio were significantly decreased; and the percentage of growth-restricted pups and fetal mortality were significantly increased in preeclampsia rats compared to normal pregnant control rats. Prophylactic MgSO4 decreased blood pressure at PD7, improved pregnancy outcomes, and promoted the polarization of M2 macrophages in the kidney and of M2 microglia in the brain of preeclampsia rats. These findings confirm that the pathophysiology of preeclampsia involves the dysregulation of the inflammatory response and the activation of M1 macrophages in several target organs during pregnancy. MgSO4 prophylaxis attenuates the postpartum effects of preeclampsia by promoting M2 macrophage polarization in the maternal kidney and brain.

Associations Between Maternal Tocopherol Levels and Pregnancy-Induced Blood Pressure Changes

Abstract Objectives Vitamin E plays different roles in health based on its three isoforms: alpha (α)-tocopherol is anti-inflammatory, gamma (γ)-tocopherol is pro-inflammatory, delta (δ)-tocopherol remains unknown. As inflammation may promote hypertension, the objective of this study is to examine relationships between maternal serum tocopherol levels at time of delivery and pregnancy-related blood pressure (BP) changes. Hypothesis is that increased level of α-tocopherol has favorable effects and γ-tocopherol has adverse effects on maternal BP. Methods An IRB-approved cross-sectional study enrolled mother-infant dyads (n = 342) at time of delivery (Omaha, NE, USA) for collection of electronic health data and maternal blood. High-performance liquid chromatography analyzed serum tocopherol levels. Maternal BP values were collected from 1st and 3rd trimester clinic/hospital visits with changes calculated in systolic BP and mean arterial pressure (MAP = diastolic BP + 1/3(systolic BP – diastolic BP). Mothers were classified as hypertensive if: systolic BP ≥140, diastolic BP ≥ 90, or diagnosis of preeclampsia. Two-sample t-test and Pearson correlation coefficients compared relationships between serum tocopherol levels and BP data. P-value &amp;lt; 0.05 was significant. Results Mean maternal age was 28.5 years, majority (61.4%) Caucasian, 10.4% (n = 29) with hypertension. Mean serum levels: α-tocopherol 15,229 + 5849 mcg/L, γ-tocopherol 1642 + 868 mcg/L, δ-tocopherol 226 + 164 mcg/L, with α: γ ratio 11.5 + 8.7. Mean serum α-tocopherol level was higher in normotensive vs. hypertensive mothers (15,751 vs. 13,819 mcg/L; P = 0.06). Ratio of α: γ demonstrated an inverse correlation with change in maternal systolic BP (r = −0.128; P = 0.03). No other relationships were significant. Conclusions Increasing maternal α-tocopherol and α: γ ratio has favorable association with maintaining normal BP during pregnancy. More research is needed to specifically identify serum thresholds and tocopherol isoform ratios for favorably reducing risk of pregnancy-related hypertension. Funding Sources Department of Pediatrics and the Child Health Research Institute at the University of Nebraska Medical Center and Children's Hospital &amp; Medical Center (Omaha, NE).

Beetroot juice lowers blood pressure and improves endothelial function in pregnant eNOS-/- mice: importance of nitrate-independent effects.

Maternal hypertension is associated with increased rates of pregnancy pathologies, including fetal growth restriction, due at least in part to reductions in nitric oxide (NO) bioavailability and associated vascular dysfunction. Dietary nitrate supplementation, from beetroot juice (BRJ), has been shown to increase NO bioavailability and improve cardiovascular function in both preclinical and clinical studies. This study is the first to investigate effects of dietary nitrate supplementation in a pregnant animal model. Importantly, the effects of nitrate-containing BRJ were compared with both 'placebo' (nitrate-depleted) BRJ as well as water to control for potential nitrate-independent effects. Our data show novel, nitrate-independent effects of BRJ to lower blood pressure and improve vascular function in endothelial nitric oxide synthase knockout (eNOS-/- ) mice. These findings suggest potential beneficial effects of BRJ supplementation in pregnancy, and emphasize the importance of accounting for nitrate-independent effects of BRJ in study design and interpretation. Maternal hypertension is associated with adverse pregnancy outcomes, including fetal growth restriction (FGR), due in part to reductions in nitric oxide (NO) bioavailability. We hypothesized that maternal dietary nitrate administration would increase NO bioavailability to reduce systolic blood pressure (SBP), improve vascular function and increase fetal growth in pregnant endothelial NO synthase knockout (eNOS-/- ) mice, which exhibit hypertension, endothelial dysfunction and FGR. Pregnant wildtype (WT) and eNOS-/- mice were supplemented with nitrate-containing beetroot juice (BRJ+) from gestational day (GD) 12.5. Control mice received an equivalent dose of nitrate-depleted BRJ (BRJ-) or normal drinking water. At GD17.5, maternal SBP was measured; at GD18.5, maternal nitrate/nitrite concentrations, uterine artery (UtA) blood flow and endothelial function were assessed, and pregnancy outcomes were determined. Plasma nitrate concentrations were increased in both WT and eNOS-/- mice supplemented with BRJ+ (P < 0.001), whereas nitrite concentrations were increased only in eNOS-/- mice (P < 0.001). BRJ- did not alter nitrate/nitrite concentrations. SBP was lowered and UtA endothelial function was enhanced in eNOS-/- mice supplemented with either BRJ+ or BRJ-, indicating nitrate-independent effects of BRJ. Improvements in endothelial function in eNOS-/- mice were abrogated in the presence of 25 mm KCl, implicating enhanced EDH signalling in BRJ- treated animals. At GD18.5, eNOS-/- fetuses were significantly smaller than WT animals (P < 0.001), but BRJ supplementation did not affect fetal weight. BRJ may be a beneficial intervention in pregnancies associated with hypertension, endothelial dysfunction and reduced NO bioavailability. Our data showing biological effects of non-nitrate components of BRJ have implications for both interpretation of previous findings and in the design of future clinical trials.

Abstract 41: The Effect Of Maternal Weight On Offspring Blood Pressure At 18 Years Of Age: A Causal Natural-effects Mediation Analysis

Objectives: Examine the relationship between maternal pre-pregnancy body mass index (BMI) and offspring systolic blood pressure (SBP) at 18 yrs old. Methods: We performed multivariate regression and causal mediation analysis within 3700 mother - offspring pairs from a prospective birth cohort. The main exposure was maternal pre-pregnancy BMI categorized as healthy weight, overweight, or obese according to international criteria. The main outcomes were high-normal BP and hypertension defined as SBP between the 90-95 th centile and &gt;95 th centile for height and sex at 18 years, respectively, as per 2017 AAP guidelines. Analyses were adjusted for social class, pre-eclampsia, sex, and maternal tobacco use during pregnancy. The Canadian Pediatric Endocrine Group R Shiny app was used to obtain age-standardized BMI Z-scores and latent class analysis (LCA) was used to quantify the mediating factor of offspring BMIZ trajectories from 7 to 18 yrs. Results: Before pregnancy 14% of women were overweight and 5% were obese. At 18 yrs, SBP (122 ± 12 vs 118 ±11mmHg, p &lt; 0.001), DBP (67 ± 7 vs 63 ± 6mmHg, p &lt; 0.001) and the odds of elevated BP (aOR: 1.6; 95% CI: 1.1-2.3) and hypertension (aOR: 2.1; 95% CI: 1.4-3.1) were higher in offspring from women that were obese prior to pregnancy compared to those that were normal weight. LCA identified five distinct offspring BMIZ trajectories shown in the figure. SBP (125 ± 12 vs 117 ± 10 mmHg, p &lt; 0.001) and the odds of hypertension (aOR: 3.8; 95% CI: 2.8-5.1) at 18 years were significantly higher in offspring with sustained high BMIZ (teal) compared to sustained low normal BMIZ (green). Casual mediation analysis revealed that maternal BMI directly (OR: 1.14; 95% CI: 1.03-1.25) and indirectly through offspring BMIZ trajectories (OR: 1.12; 95% CI: 1.08-1.15) increased offspring SBP at 18 years of age. Conclusion: Maternal obesity prior to pregnancy is associated with an increased risk of hypertension in offspring at 18 yrs of age, partly mediated by an elevated BMIZ score trajectory throughout childhood and adolescence.

Bolus norepinephrine and phenylephrine for maternal hypotension during elective cesarean section with spinal anesthesia: a randomized, double-blinded study

Background:In recent years, norepinephrine has attracted increasing attention for the management of maternal hypotension during elective cesarean section with spinal anesthesia. Intermittent bolus is a widely used administration paradigm for vasopressors in obstetric anesthesia in China. Thus, in this randomized, double-blinded study, we compared the efficacy and safety of equivalent bolus norepinephrine and phenylephrine for rescuing maternal post-spinal hypotension.Methods:In a tertiary women's hospital in Nanjing, China, 102 women were allocated with computer derived randomized number to receive prophylactic 8 μg norepinephrine (group N; n = 52) or 100 μg phenylephrine (group P; n = 50) immediately post-spinal anesthesia, followed by an extra bolus of the same dosage until delivery whenever maternal systolic blood pressure became lower than 80% of the baseline. Our primary outcome was standardized maternal cardiac output (CO) reading from spinal anesthesia until delivery analyzed by a two-step method. Other hemodynamic parameters related to vasopressor efficacy and safety were considered as secondary outcomes. Maternal side effects and neonatal outcomes were collected as well.Results:Compared to group P, women in group N had a higher CO (standardized CO 5.8 ± 0.9 vs. 5.3 ± 1.0 L/min, t = 2.37, P = 0.02) and stroke volume (SV, standardized SV 73.6 ± 17.2 vs. 60.0 ± 13.3 mL, t = 4.52, P < 0.001), and a lower total peripheral resistance (875 ± 174 vs. 996 ± 182 dyne·s/cm5, t = 3.44, P < 0.001). Furthermore, the incidence of bradycardia was lower in group N than in group P (2% vs. 14%, P = 0.023), along with an overall higher standardized heart rate (78.8 ± 11.6 vs. 75.0 ± 7.3 beats/min, P = 0.049). Other hemodynamics, as well as maternal side effects and neonatal outcomes, were similar in two groups (P > 0.05).Conclusions:Compared to equivalent phenylephrine, intermittent bolus norepinephrine provides a greater CO for management of maternal hypotension during elective cesarean section with spinal anesthesia; however, no obvious maternal or neonatal clinical advantages were observed for norepinephrine.

Differential DNA Methylation in Placenta Associated With Maternal Blood Pressure During Pregnancy.

Abnormal blood pressure during pregnancy is associated with impaired fetal growth, predisposing the offspring to cardiometabolic abnormalities over the life-course. Placental DNA methylation may be the regulatory pathway through which maternal blood pressure influences fetal and adult health outcomes. Epigenome-wide association study of 301 participants with placenta sample examined associations between DNA methylation and millimetre of mercury increases in systolic and diastolic blood pressure in each trimester. Findings were further examined using gene expression, gene pathway, and functional annotation analyses. Cytosine-(phosphate)-guanine (CpGs) known to be associated with cardiometabolic traits were evaluated. Increased maternal systolic and diastolic blood pressure were associated with methylation of 3 CpGs in the first, 6 CpGs in the second, and 15 CpGs in the third trimester at 5% false discovery rate (P values ranging from 6.6×10-15 to 2.3×10-7). Several CpGs were enriched in pathways including cardiovascular-metabolic development (P=1.0×10-45). Increased systolic and diastolic blood pressure were associated with increased CpG methylation and gene expression at COL12A1, a collagen family gene known for regulatory functions in the heart. Out of 304 previously reported CpGs known to be associated with cardiometabolic traits, 36 placental CpGs were associated with systolic and diastolic blood pressure in our data. The present study provides the first evidence for associations between placental DNA methylation and increased maternal blood pressure during pregnancy at genes implicated in cardiometabolic diseases. Identification of blood pressure-associated methylated sites in the placenta may provide clues to early origins of cardiometabolic dysfunction and inform guidelines for early prevention. Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00912132.

Abstract 445: Monitoring the Hemodynamic Status During Three Trimesters of Pregnancy and Non-pregnancy Periods

Pregnancy is an important stage in women and is associated with delicate cardiovascular adaptation from non-pregnancy to pregnancy. Maternal hemodynamic changes are made to provide sufficient nutrients and oxygen to support the normal growth of the developing fetus. This study was designed to assess maternal hemodynamic status during three trimesters of pregnancy and non-pregnancy periods. Total 326 women (84 pregnant women and 242 age-matched non-pregnant women of childbearing age) between the ages of 20 and 44 participated in this non-invasive observational study. In this cross-sectional study, enrolled participants underwent blood pressure and radial pressure pulse measurements. In order to compare the hemodynamic status of different subjects, we recorded the systolic and diastolic blood pressure and calculated the first five harmonic amplitudes(C1~C5) and phases(P1~P5) of radial pulse wave using Fourier transform method. Compared with non-pregnant women, the maternal systolic and diastolic blood pressures were lower, and heart rate, C2, C4, and P1 were higher in pregnant women (Table 1). Those hemodynamic changes may be due to decreased arterial stiffness and peripheral arterial vasodilatation in pregnancy. In summary, a series of changes in maternal hemodynamic status can be observed during the trimesters of pregnancy, including lowering blood pressure and increasing harmonics of radial pulse. This study demonstrates the feasibility of non-invasive monitoring of the hemodynamic status of pregnant women, which could be used for early detection of pregnancy disorder.

Transient Tachypnea of Newborns Is Associated With Maternal Spinal Hypotension During Elective Cesarean Delivery: A Retrospective Cohort Study.

The risk for transient tachypnea of newborns, a common cause of respiratory distress in the neonatal period, is 2- to 6-fold higher during elective cesarean delivery compared to vaginal delivery. Here, we evaluated the association between transient tachypnea of newborns and the degree and duration of predelivery maternal hypotension during spinal anesthesia for elective cesarean delivery. Demographic data, details of anesthetic management, blood pressure measurements, and vasopressor requirement preceding delivery were compared between transient tachypnea newborns (n = 30) and healthy neonates (n = 151) with normal respiratory function born via elective cesarean delivery between July 2015 and February 2016. The degree and duration of hypotension were assessed using area under the curve for systolic blood pressure (SBP) ≤90 mm Hg and area under the curve for mean arterial pressure ≤65 mm Hg. After adjusting for confounders, multivariable logistic regression was used to evaluate the association between area under the curve for SBP and transient tachypnea of newborns. The median area under the curve for SBP was higher in cases of transient tachypnea of newborns (0.94; interquartile range, 0-28.7 mm Hg*min) compared to healthy controls (0; interquartile range, 0-3.30 mm Hg*min; P = .001). Similarly, median area under the curve for mean arterial pressure was also higher in cases of transient tachypnea of newborns (0; interquartile range, 0-18.6 mm Hg*min) compared to controls (0; interquartile range, 0-1.1 mm Hg*min; P = .01). Mothers of transient tachypnea newborns received significantly higher amounts of phenylephrine and ephedrine compared to controls (P = .001 and 0.01, respectively). Hence, the total vasopressor dose given to mothers in the transient tachypnea of newborn group was much higher than for the control group (P = .001). In the multivariable logistic regression, area under the curve for SBP was significantly associated with transient tachypnea of newborns (odds ratio, 1.02; 95% CI, 1.01-1.04, P = .005) after adjusting for gravidity and the type of anesthetic (spinal versus combined spinal epidural). Our results suggest that the degree and duration of maternal SBP <90 mm Hg after neuraxial anesthesia during elective cesarean delivery are associated with transient tachypnea of newborns. Future prospective studies should further explore the effects of maternal hypotension, its prevention, and treatment for transient tachypnea of newborns.

Placental Growth Factor as an Indicator of Maternal Cardiovascular Risk After Pregnancy.

Angiogenic placental growth factor (PlGF) concentrations rise during pregnancy, peaking at the end of midpregnancy. Low PlGF concentrations during pregnancy are associated with pregnancy complications with recognized later-life cardiovascular risk. We hypothesized that low PlGF concentrations, especially in midpregnancy, identify not only a subset of women at risk for pregnancy complications but also women with greater cardiovascular risk factor burden after pregnancy regardless of pregnancy outcome. In a population-based prospective cohort study of 5475 women, we computed gestational age-adjusted multiples of the medians of early pregnancy and midpregnancy PlGF concentrations. Information on pregnancy complications (preeclampsia, small for gestational age, and spontaneous preterm birth) was obtained from hospital registries. Six years after pregnancy, we measured maternal systolic and diastolic blood pressures, cardiac structure (aortic root diameter, left atrial diameter, left ventricular mass, and fractional shortening), carotid-femoral pulse wave velocity, and central retinal arteriolar and venular calibers. Blood pressure was also measured 9 years after pregnancy. Women were on average 29.8 (SD, 5.2) years of age in pregnancy, were mostly European (55.2%), and 14.8% developed a pregnancy complication. Quartile analysis showed that especially women with midpregnancy PlGF in the lowest quartile (the low-PlGF subset) had a larger aortic root diameter (0.40 mm [95% CI, 0.08-0.73]), left atrial diameter (0.34 mm [95% CI, -0.09 to 0.78]), left ventricular mass (4.6 g [95% CI, 1.1-8.1]), and systolic blood pressure (2.3 mm Hg [95% CI, 0.93-3.6]) 6 years after pregnancy than women with the highest PlGF. Linear regression analysis showed that higher midpregnancy PlGF concentrations were associated with a smaller aortic root diameter (-0.24 mm [95% CI, -0.39 to -0.10]), smaller left atrial diameter (-0.75 mm [95% CI, -0.95 to -0.56]), lower left ventricular mass (-3.9 g [95% CI, -5.5 to -2.3]), and lower systolic blood pressure (-1.1 mm Hg [95% CI, -1.7 to -0.46]). These differences persisted after the exclusion of women with complicated pregnancies. Women with low PlGF in midpregnancy have a greater aortic root diameter, left atrial diameter, and left ventricular mass and higher systolic blood pressure 6 and 9 years after pregnancy compared to women with higher PlGF, including women with uncomplicated pregnancies. The pathophysiological implications of lower PlGF concentrations in midpregnancy might provide insight into the identification of pathways contributing to greater cardiovascular risk factor burden.

African Green Monkeys Born to Mothers with Hypertensive Pregnancy Disorders have Higher Blood Pressures and Altered Water Balance in Early Adolescence

Hypertensive pregnancy disorders are a leading cause of maternal and fetal mortality worldwide. Preeclampsia (PE), or de novo maternal hypertension, is associated with high incidences of preterm birth. Lower birth weight and exposure to hypertension (HTN) in utero have been shown to increase the risk of HTN and cardiovascular disease later in life. The African Green Monkey (AGM; Chlorocebus aethiops sabaeus) spontaneously develops gestational hypertension (GH) with pathophysiological similarities to PE, including proteinuria and fetal growth restriction. The AGM also spontaneously develops chronic HTN not associated with pregnancy. We tested the hypothesis that GH and chronic HTN in pregnancy will developmentally program offspring to HTN in adolescence. Male and female juvenile AGMs between the ages of 1 and 2 years were single housed. After a 1‐week acclimation, urine excretion and water intake were measured daily for 3 consecutive days. Blood pressure was measured by forearm plethysmography and fasting blood glucose was assessed. Juvenile AGMs were characterized by maternal systolic blood pressure (SBP) during pregnancy: normotensive (NP; SBP &lt; 120 mmHg throughout pregnancy); hypertensive (HP; SBP &gt; 140 mmHg before, during, and after pregnancy); and gestational hypertensive (GHP; SBP &lt; 120 mmHg before and &gt; 140 mmHg in the second half of pregnancy). Juvenile growth rate was based on body weight from birth to 1–2 years of age. Juvenile growth rates were reduced for GHP and HP compared to NP (NP 1303 g/year; GHP 1083 g/year; HP 946 g/year; p &lt; 0.05). Although animals born to GHP and HP have hindered growth from birth through early adolescence, growth within the first 2 weeks postpartum was greater in GHP animals (34 g/week) compared to NP (15 g/week) and HP (14.6 g/week). Juvenile SBP was higher for HP offspring compared to NP (HP 131.3 ± 11.7 mmHg, n = 3; NP 100.2 ± 9.1 mmHg, n = 5; p &lt; 0.05) but not GHP offspring (GHP 103.4 ± 6.4 mmHg, n = 7; p &gt; 0.05). Diastolic blood pressure (DBP) was higher for HP animals compared to both NP and GHP (HP 67.3 ± 5.7 mmHg, n = 3; NP 45.4 ± 4.4 mmHg, n = 5; GHP 50.7 ± 3.7 mmHg, n = 7; p &lt; 0.05). Fasting glucose tended to be higher in GHP AGM offspring compared to NP and HP, (GHP 111.6 ± 12.1 mg/dL, n = 7; NP 75.4 ± 14.3 mg/dL, n = 5; HP 75.7 ± 18.5 mg/dL, n = 3; p = 0.07). Water intake was similar between NP and GHP (NP 457.5 ± 43.9 ml/day, n = 4; GHP 425.0 ± 13.1 ml/day; p &gt; 0.05). Urine flow was lower in GHP animals compared to NP (NP 146.3 ± 52.0 ml/day vs GHP 77.5 ± 28.2 ml/day, p &lt; 0.05). Thus, adolescent AGMs born to GH pregnancies may have dysregulation of water balance, favoring water retention. This suggests in utero developmental programming may contribute to increased blood pressures later in life. In conclusion, HTN in AGM pregnancy adversely impacts offspring into early adolescence. These insults include hindered growth and susceptibility to HTN. In pregnancy‐induced hypertension, offspring display altered water homeostasis in early adolescence. Continued studies of these NP, HP and GHP offspring will include long‐term blood pressure and heart rate measurements, regulation of sodium and potassium balance, and the further phenotyping of over 50 additional offspring from 2018 births.Support or Funding InformationAHA 17PRE33670127This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Norepinephrine versus phenylephrine infusion for prophylaxis against post-spinal anaesthesia hypotension during elective caesarean delivery: A randomised controlled trial

BackgroundProphylactic vasopressors are fundamental during caesarean delivery under spinal anaesthesia. The aim of this work is to compare the efficacy and safety of phenylephrine and norepinephrine when used in variable infusion rate during caesarean delivery. MethodsA randomised, double-blinded, controlled trial was conducted including mothers scheduled for elective caesarean delivery under spinal anaesthesia. Participants were allocated to two groups norepinephrine group (n = 60), and phenylephrine group (n = 63). Participants received prophylactic vasopressors after spinal block at rate started at 0.05 mcg/kg/min and 0.75 mcg/kg/min respectively. The rate of vasopressor infusion was manually adjusted according to maternal systolic blood pressure. Both groups were compared according to incidence of post-spinal hypotension (the primary outcome), incidence of bradycardia, incidence of reactive hypertension, systolic blood pressure, heart rate, rescue vasopressor consumption, number of physician interventions, and neonatal outcomes. ResultsOne hundred and twenty-three mothers were available for final analysis. Both groups were comparable in the incidence of post-spinal hypotension (32% versus 30%, P = 0.8). The number of physician intervention was lower in norepinephrine group. The incidence of bradycardia and the incidence of reactive hypertension were potentially lower in norepinephrine group without reaching statistical significance, (13% vs. 21%, P = 0.3) and (12% vs. 24%, P = 0.1). Rescue vasopressor consumption, and neonatal outcomes were comparable between both groups. ConclusionWhen given in a manually adjusted infusion, norepinephrine effectively maintained maternal SBP during caesarean delivery under spinal anaesthesia with lower number of physician interventions, and likely less incidence of reactive hypertension and bradycardia compared to phenylephrine.

Maternal Blood Pressure, Cord Glucocorticoids, and Child Neurodevelopment at 2 Years of Age: A Birth Cohort Study.

Pregnancy hypertensive disorders have impaired neurodevelopment in offspring. We aimed to explore the association of normal range maternal blood pressure (BP) with child neurodevelopment, as well as the possible role of placental 11-beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2) therein. Among 1,008 mother-child pairs recruited in Wuhan, China, in 2013-2015, we measured maternal third-trimester BP (systolic BP (SBP) and diastolic BP (DBP)) and cord glucocorticoids (cortisol and cortisone), a marker reflecting placental 11β-HSD2 activity. We evaluated child neurodevelopment using the Bayley Scales of Infant Development (BSID) with obtaining the Mental and Psychomotor Development Index (MDI and PDI). Multiple regression and mediation analysis were performed to estimate the effect. Each 5 mm Hg increase in maternal third-trimester SBP was associated with 1.54 points decrease in MDI (95% confidence interval (CI) = -2.60, -0.48) and 1.23 points decrease in PDI (95% CI = -2.14, -0.31); similar association was observed between DBP and BSID (adjusted β = -1.32; 95% CI = -2.53, -0.10 for MDI and -1.37; 95% CI = -2.42, -0.33 for PDI). Also, we found significant associations between cord cortisol/cortisone ratio and PDI (adjusted β = 2.95; 95% CI = 0.91, 4.99), as well as between maternal BP and cord cortisol/cortisone ratio (adjusted β = -0.03; 95% CI = -0.06, -0.01 for both SBP and DBP). Mediation analysis revealed that cord cortisol/cortisone ratio explained 6.29% of the association between SBP and PDI, and 6.85% between DBP and PDI. Increased maternal normal range BP may affect child neurodevelopment. Furthermore, placental 11β-HSD2 activity might be involved in the process.

Comparative Study between the Effect of Nifedipine, Ritodrine and Magnesium Sulphate Therapy on Doppler Indices of Fetal Umbilical and Middle Cerebral Arteries in Patients with Preterm Labour

Background: Spontaneous preterm labor (SPTL) and preterm birth (PTB), is the single most important cause of perinatal mortality and morbidity in high-income countries despite the enormous efforts over the past several decades. Preterm labor is defined as regular, painful, frequent uterine contractions causing a progressive effacement and dilatation of the cervix occurring before 37 completed weeks of gestation. Many drug therapies were used as tocolytics in cases of preterm labor, however none of them proved to be the best. The present study was performed to compare three of the used drugs for tocolysis to assess their efficacy and side effects on the mother and fetus. Aim: The aim of this study is to compare the effect of oral nifedipine, intravenous ritodrine infusion and magnesium sulfate infusion used as tocolytics in cases of preterm labour on Doppler parameters of fetal umbilical and middle cerebral artery and to evaluate their effects on the mother and the fetus in order to choose the safest and the most effective drug. Methodology: This study was held in the period from December 2014 to october 2015 on 90 patients attended and admitted from the Casualty Unit of the Obstetric Department In Elsayed Glal University Hospital with preterm labor pains , intact membranes, singleton pregnancy between 28 and completed 34 weeks gestation. All patients had been dated accurately with a gestational age based on the last menstrual period and if available a corresponding second trimester ultrasound report performed before 20 weeks gestation. Treatment continued until contractions stopped for 24 hours, maximum doses were attained without response; unacceptable side effects occurred or labor proceeded. Successful treatment was defined as cessation of contractions observed for 24 hours and no further cervical changes. Patients with successful treatment were put under observation for another 24 hours without additional treatment then discharged on no maintenance therapy. Results: Maternal tachycardia, palpitation and dyspnea were more common in the ritodrine group with (p-value = 0.000). The present study showed increase in umbilical artery PI after treatment in the magnesium sulfate group only which was statistically significant (P value = 0.016). The study showed statistically significant increase in middle cerebral artery PI after treatment in magnesium sulfate group with a P value=0.000 and statistically significant decrease in middle cerebral artery with nifedipine group with P value=0.027. When comparing the cerebroplacental ratio before and after treatment in the three groups; the study showed significant increase in cerebroplacental ratio after treatment in the magnesium sulfate group with P value = 0.000, which is statistically significant. This suggests that nifedipine could be used as a safer alternative to ritodrine and magnesium sulfate. Conclusion: In our study, nifedipine therapy was not associated with a significant change in maternal systolic and diastolic blood pressure after 24h, with minor insignificant effect on maternal heart rate. Fetal heart rate was not affected after therapy. Fetal Doppler study found no clinically significant effect on the pulsatility index (PI) of umbilical and middle cerebral artery, while with magnesium sulfate therapy there was increase in cerebro- placental ratio 24hr after treatment, these findings ensure safety of the drugs on the maternal and fetal aspects.

A critical approach to research on brain markers of hypnosis and suggestibility

Because it induces a state of reduced awareness and deep relaxation, hypnosis is thought to be efficient at relieving stress and anxiety. This study examined whether hypnosis may alter the pattern and time evolution of maternal and fetal stress. Here we report a 23-yrs-old primigravida woman at 31-weeks’ gestation who underwent daily sessions of hypnosis during one week. An A (baseline)-B (intervention) – A′ (return to baseline) design was used. Each study phase lasted one week. The State Anxiety Inventory (SAI) was completed daily. Uterine contractions as well as maternal and fetal heart rate were recorded over 24-h periods in each of the study phase. Uterine contractions and maternal systolic blood pressure showed clear reductions during the hypnosis phase. In addition, a statistically significant declining trend in anxiety scores was observed during the hypnosis phase, and anxiety re-increased in the return-to-baseline phase (p < 0.05). Coefficient of variation of maternal heart rate was found to be considerably lower during the hypnosis phase. Our results suggest that a short-lived hypnosis intervention (combined with standard care) holds sufficient promise for antenatal stress relief to justify testing its efficacy in larger groups of pregnant women.

A randomized controlled trial of a web-based education intervention for women with gestational diabetes mellitus

ObjectiveThis study aimed to investigate changes in maternal body mass index (BMI), blood pressure and glycemic level and infant birthweight using an online educational program compared to standard clinic-based GDM education. DesignA preliminary randomized controlled trial of the online intervention was conducted in Melbourne, Australia between 2014 and 2015. A total of 110 women were randomized to (1) the control group and received standard clinic-based GDM education; or (2) the intervention group and received standard care plus the web-based education program. Data were collected at two time points: baseline and 12 weeks postpartum. Infant birthweight was also recorded. Chi-squared test, independent t-test and paired t-test were used to compare outcomes. ParticipantsPregnant women with newly diagnosed GDM, in the Western region of Melbourne, Australia. FindingsStatistically significant differences were reported between intervention and control groups in maternal weight and glycemia post-intervention (p < 0.05). More women in the intervention group than in the control group reported weight loss post-intervention (90.4% vs 48.3%, p < 0.001), and were considered a healthy weight (BMI = 18.5, 24.9kg/m2) at 12 weeks postpartum (44.2% vs 31%). More women in the intervention group had attended for follow up OGTT at 12 weeks postpartum (96.2% vs 70.7%, p < 0.001). Comparing measures pre- and post-intervention in the intervention group, maternal BMI was lower [(28.60 ± 7.93) vs (29.60 ± 8.32); p = 0.000], maternal systolic blood pressure was increased but within normal range [(108.19 ± 11.80) vs (107.29 ± 12.13); p = 0.001], and maternal glycemic level returned to within normal limits [(4.86 ± 0.42) vs (8.80 ± 2.50); p = 0.026]. Most women in both groups gave birth to normal birthweight infants (92.3% and 94.8%). These findings are offset by differences in the groups at baseline. Key conclusionsFindings suggest that the education intervention had a positive impact on women’s postpartum weight and attendance at OGTT by 12 weeks postpartum. No effect was found on maternal blood pressure or infant birthweight. Further studies with matched intervention and control groups are needed to achieve more definitive conclusions.

Is infant arterial stiffness associated with maternal blood pressure in pregnancy? Findings from a UK birth cohort (Baby VIP study).

BackgroundIn adults, arterial stiffness measured by pulse wave velocity (PWV) is regarded as a predictor of cardiovascular disease. Infant vascular development depends on factors related to pregnancy, including maternal blood pressure (BP). This study assessed the association between maternal BP in pregnancy and infant brachio-femoral PWV at age 2–6 weeks.MethodsThe Baby Vascular health and Iron in Pregnancy (Baby VIP) study is a birth cohort which measured PWV and heart rate (HR) in 284 babies in Leeds, UK, at 2–6 weeks after birth. Maternal BP measurements at 12 and 36 weeks gestation was collected from antenatal clinical records. Multivariable linear regression models assessed associations between maternal systolic and diastolic BPs, and BP change from booking to 36 weeks, with infant PWV adjusting for covariables at both mother and baby level.ResultsThere was no evidence of an association between infant PWV and maternal systolic BP at booking (adjusted regression coefficient -0.01 m/s per 10mmHg, 95% CI -0.11, 0.14, p = 0.84) or at 36 weeks (adjusted regression coefficient 0.00 m/s per 10mmHg, 95% CI -0.12, 0.11, p = 0.95). Change between 12 and 36 weeks gestation of more than 30 mmHg in systolic BP or 15 mmHg in diastolic BP was also not associated with infant PWV. There was an inverse relationship between infant HR and infant PWV (regression coefficient -0.14 m/s per 10 bpm, 95% CI -0.22, -0.05, p<0.01).ConclusionsThis study has shown no evidence of association between infant PWV at 2–6 weeks of age and maternal BP in early or late pregnancy. Infant HR was inversely associated with infant PWV. Further studies are required to determine the predictors of infant PWV as well as the importance and long term implications of PWV measurements in infants.

Long non-coding HOTTIP regulates preeclampsia by inhibiting RND3.

Preeclampsia (PE) is an important disease affecting maternal and neonatal pregnancy. Long non-coding RNA plays an important role in preeclampsia. This study aims to explore the role of HOXA distal transcript antisense RNA (HOTTIP) in preeclampsia. The expression of HOTTIP in placentas of preeclampsia and normal pregnancy was detected by polymerase chain reaction (PCR). The difference of clinical data between high expression HOTTIP group and low expression HOTTIP group was compared to explore the relationship between HOTTIP and the progress of preeclampsia. Cell proliferation and cell cycle were detected after overexpression and interference with HOTTIP. Western blot was finally used for detecting protein expression. By analyzing the clinical data, we found that systolic blood pressure, diastolic blood pressure, and urinary protein in preeclampsia patients were significantly higher than those in normal pregnant women. The birth weight of fetuses was significantly lower than that of normal pregnant women. Through PCR results, we found that the expression of HOTTIP in patients with preeclampsia was significantly lower, and the maternal systolic blood pressure, diastolic blood pressure and urinary protein in the low expression HOTTIP group were significantly higher than that in the high expression group. Fetal birth weight was significantly lower than the high expression group. After overexpression and interference with HOTTIP, it was found that overexpression of HOTTIP significantly increased the proliferation of trophoblast cells and markedly accelerated the cycle. Interfering with HOTTIP, trophoblast cell proliferation was significantly reduced and cell cycle was arrested. By Western blotting, we found that HOTTIP regulated the progression of preeclampsia via Rho family GTPase 3(RND3). HOTTIP was lowly expressed in preeclampsia and was able to suppress the progression of preeclampsia.