Maternal Blood Pressure Research Articles

COMPARATIVE ANALYSIS OF SERUM MAGNESIUM & ZINC LEVELS AND THEIR ASSOCIATIONS WITH PRETERM LABOUR

Background: Preterm is dened as babies born alive before 37 weeks of pregnanc, it occurs when there is a regular contraction of uterus which results in opening of cervix after 20 weeks and before 37 weeks of gestation. preterm labour is spontaneous but it can also be due to a biochemical changes in body functions at the cellular level of trace elements such as magnesium and zinc. The main objective of this study is to nd the association of hypomagnesaemia and low zinc levels in preterm delivered women and to compare the maternal serum magnesium and zinc levels between Preterm and Term delivered mothers. Methods: A Comparative study was done in the Department of Biochemistry, Andhra Medical College, Visakhapatnam. Atotal of 126 women who were admitted to the labour room at Department of Obstetrics and gynaecology, King George Hospital, Visakhapatnam were selected for this study. All the subjects were divided into two groups as Preterm Consists of 63 women with spontaneous preterm labour delivered between 28- 37 weeks and Term Consists of 63 Women with Term labour after 37 weeks. Results: Women with Preterm labour had a signicantly low serum magnesium level with a mean serum magnesium level of 1.8 mg/dl with SD of 0.38 whereas the patients with Term labour had a mean serum magnesium level of 2.09 mg/dl with SD of 0.50 and also low zinc levels in Preterm labour with mean zinc levels of 51.28 µg/dl with SD 10.9 whereas patients with Term labour had mean serum zinc levels of 56.5 µg/dl with SD 9.7. The difference of serum magnesium and zinc levels observed between the study population and control population is independent of factors like maternal age, parity, gestational age, Blood pressure and socioeconomic status. In this study there is non signicant weak correlation was found between Demographic data and parametric data. Conclusions:Serum magnesium and zinc levels can be used as predictors for preterm labour. Spontaneous preterm delivery can be avoided by early assessment of maternal magnesium and zinc status and also by simple oral supplementation of magnesium and zinc which might provide an easy and inexpensive means to decrease the problems related to preterm labour. There is a further scope for research on serum magnesium and zinc levels based on gestational age.

Selenium status in term neonates, according to birth weight and gestational age, in relation to maternal hypertensive pathology.

Pregnancy represents a state of increased oxidative stress and antioxidants, in which selenium (Se) plays a pivotal role, contribute to maintain the oxidative balance. If antioxidant defenses are depleted, placental function is disrupted, resulting in pregnancy complications, including pregnancy-induced hypertension (PIH). Little is known about fetal selenium status in concomitant relation to maternal PIH, gestational age (GA) and birthweight (BW). We examined over a 3-year period the serum (SeS) and urine selenium (SeU) status in term neonates from normotensive (nonPIH) and hypertensive (PIH) mothers as clinical markers of oxidative stress. In this retrospective observational study, 72 neonates with maternal PIH were matched for GA and BW to 72 neonates of normotensive mothers. Four groups were obtained, based on maternal PIH and BW relative to GA (appropriate-for-gestational-age-AGA, small-for-gestational-age-SGA): nonPIH-AGA (control group), nonPIH-SGA, PIH-AGA, and PIH-SGA. The results showed significant differences (p < 0.001) in selenium levels among the study groups: SeS - 44.85 ± 7.56 μg/L in nonPIH-AGA, 39.62 ± 11.42 μg/L in nonPIH-SGA, 40.01 ± 10.07 μg/L in PIH-AGA, and 25.39 ± 8.99 μg/L in PIH-SGA; SeU - 27.98 ± 7.99 μg/L in nonPIH-AGA, 22.85 ± 9.48 μg/L in nonPIH-SGA, 23.44 ± 6.73 μg/L in PIH-AGA, and 13.05 ± 5.86 μg/L in PIH-SGA. Selenium depletion was more common in neonates born from hypertensive mothers and those born small for gestational age. Though moderate in intensity, selenium levels were positively correlated with BW (0.319 for SeS, 0.397 for SeU) and negatively correlated with maternal systolic blood pressure (-0.313 for SeS, -0.324 for SeU). The main independent effects on SeS and SeU of each maternal blood pressure and birth weight turned out statistically significant. In interaction, a more pronounced effect was reached in PIH-SGA neonates. Selenium status seemed to reflect the negative impact that PIH exerts in neonates during intrauterine development. Clinical markers of selenium status could thus be of great value for tracking responses of individuals to selenium supplementation as part of health improvement and harm mitigation approaches.

Transcriptomics-Based Subphenotyping of the Human Placenta Enabled by Weighted Correlation Network Analysis in Early-Onset Preeclampsia With and Without Fetal Growth Restriction.

Placental disorders contribute to pregnancy complications, including preeclampsia and fetal growth restriction (FGR), but debate regarding their specific pathobiology persists. Our objective was to apply transcriptomics with weighted gene correlation network analysis to further clarify the placental dysfunction in these conditions. We performed RNA sequencing with weighted gene correlation network analysis using human placental samples (n=30), separated into villous tissue and decidua basalis, and clinically grouped as follows: (1) early-onset preeclampsia (EOPE)+FGR (n=7); (2) normotensive, nonanomalous preterm FGR (n=5); (2) EOPE without FGR (n=8); (4) spontaneous idiopathic preterm birth (n=5) matched for gestational age; and (5) uncomplicated term births (n=5). Our data was compared with RNA sequencing data sets from public databases (GSE114691, GSE148241, and PRJEB30656; n=130 samples). We identified 14 correlated gene modules in our specimens, of which most were significantly correlated with birthweight and maternal blood pressure. Of the 3 network modules consistently predictive of EOPE±FGR across data sets, we prioritized a coexpression gene group enriched for hypoxia-response and metabolic pathways for further investigation. Cluster analysis based on transcripts from this module and the glycolysis/gluconeogenesis metabolic pathway consistently distinguished a subset of EOPE±FGR samples with an expression signature suggesting modified tissue bioenergetics. We demonstrated that the expression ratios of LDHA/LDHB and PDK1/GOT1 could be used as surrogate indices for the larger panels of genes in identifying this subgroup. We provide novel evidence for a molecular subphenotype consistent with a glycolytic metabolic shift that occurs more frequently but not universally in placental specimens of EOPE±FGR.

The role of the PLGF in the management of pregnancies complicated with fetal microsomia.

To explore the contribution of maternal and fetal parameters in predicting the time interval between diagnosis and development of adverse events leading to delivery in singleton pregnancies complicated with fetal microsomia. Prospective study on singleton pregnancies referred to a tertiary center because of suspicion of fetal smallness in the third trimester. The study cohort included cases with fetal abdominal circumference (AC) ≤ 10th centile or estimated fetal weight ≤ 10th centile or umbilical artery pulsatitlity index ≥ 90th centile. Development of pre-eclampsia, fetal demise, and fetal deterioration diagnosed by fetal Doppler studies or fetal heart rate monitoring and leading to delivery were considered as adverse events. Maternal demographics, obstetric history, blood pressure, serum PLGF, and fetal Doppler studies were explored as predictors of the time interval between the first visit to the clinic and the diagnosis of complications. In 59 women, the median incubation period from presentation to the clinic to an adverse event was 6, 2weeks, whereas half of the pregnancies (52.5%) did not develop any adverse event. PLGF was the strongest predictor of adverse events. Both PLGF in raw values and PLGF MOM had equally good predictive ability (AUC 0.82 and 0.78 respectively). Optimal cut-off points were 177.7pg/ml for PLGF raw values (sensitivity 83% and specificity 66.7%) and 0.277 MoM (sensitivity 76% and specificity 86.7%). On multiple Cox regression analysis, maternal systolic blood pressure, PLGF, fetal increased umbilical artery PI, and reduced CP ratio were independently associated with adverse events. Half of the pregnancies with low PLGF and only one in ten with high PLGF were delivered within two weeks after the initial visit. Half of the pregnancies carrying a small fetus in the third trimester will not develop maternal or fetal complications. PLGF is a strong predictor of adverse events that can be used to customize antenatal care.

Potential impact of ambient temperature on maternal blood pressure and hypertensive disorders of pregnancy: A nationwide multicenter study based on the China birth cohort

Limited evidence exists regarding the association between ambient temperature and blood pressure (BP) level of pregnant women. To investigate the associations of ambient temperature with maternal BP and hypertensive disorders of pregnancy (HDP), we studied 105,063 participants in 38 centers of 17 provinces from November 2017 to December 2021. BP was measured with standardized automated digital sphygmomanometers. Ambient temperature was classified into five classes as very hot, moderate hot, mild, moderate cold, and very cold. Generalized linear mixed models were used to investigate the ambient temperature-BP/HDP associations, controlling for multiple covariates. No significant associations of first-trimester ambient temperature with maternal BP and HDP prevalence were observed. Compared with mild temperature, second-trimester very cold and second-trimester moderate cold were statistically associated with the increase of 1.239 mmHg (95% CI: 0.908, 1.569) and 0.428 mmHg (95% CI: 0.099, 0.757) for second-trimester systolic blood pressure (SBP), respectively. Similar trends were also observed in the association between second-trimester cold exposure and second-trimester diastolic blood pressure (DBP), in the association between second-trimester cold exposure and third-trimester SBP/DBP as well as in the association between third-trimester cold exposure and third-trimester SBP/DBP although some estimates were not statistically significant. Furthermore, in the second and third trimester, very cold [second trimester: adjusted odds ratio (aOR) = 1.298; third trimester: aOR = 1.236) and moderate cold (second trimester: aOR = 1.208; third trimester: aOR = 1.146) exposures also increased the odds of HDP, and these associations were stronger among participants aged ≥35 years or from North China. The second and third trimesters are the critical exposure windows for ambient temperature exposure-BP/HDP associations. During this period, exposure to cold ambient temperature was associated with elevated BP as well as increased HDP prevalence among most Chinese pregnant women, those aged ≥35 years or from North China being more vulnerable.

THE EFFECT OF RAMADAN FASTING ON PREGNANCY OUTCOMES DURING THE SECOND AND THIRD TRIMESTER

Background &#x0D; Fasting during pregnancy has always been considered a debatable condition. Some Muslim women do not fast during pregnancy for their children’s health; however, they feel uncomfortable because of their religious beliefs. On the other hand, some pregnant mothers prefer to fast despite their anxiety about their children’s health, and they fast during pregnancy.&#x0D; Objectives &#x0D; To evaluate Ramadan fasting effects in the second and third trimesters of pregnancy on maternal health, fetal growth and early neonatal outcome.&#x0D; Patients and Methods&#x0D; An observational case-control study carried out in Sulaymaniyah City/Kurdistan region/Iraq within a period between April to October 2021, involving 220 healthy pregnant women presented one week before and within the first week of Ramadan in their second or third trimester of pregnancy, they are grouped into two groups (fasting and non-fasting) according to their choice. Both groups followed 4-8 weeks after the first visit and at the delivery time.&#x0D; The parameters observed in the first and second visits were maternal age, weight, residency, maternal job, maternal blood pressure, haemoglobin (Hb), random blood glucose (RBS), gestational age measured by ultrasound, amniotic fluid index (AFI), fetal growth measured by ultrasound.&#x0D; The mode of delivery with an indication of cesarean section(C/S) was recorded in addition to the above parameters at the time of delivery. In addition, birth weight and 5 minutes APGAR score were also recorded.&#x0D; Results&#x0D; Of 220 women, 77 were not fasting, and 143 were fasting. About 87 women presented in the second trimester (57 cases were fasting), while 133 women presented in the third trimester (86 cases were fasting), and no significant changes in the evaluated parameters were observed. There was no significant difference between the fasting and non-fasting groups. Three babies from the fasting group were delivered during the preterm period, while two were delivered preterm in the non-fasting group. This study recorded neither intrauterine fetal death (IUFD) nor stillbirth. No significant difference in APGAR scores at 5 minutes and birth weight was observed between the two groups. &#x0D; Conclusion&#x0D; Ramadan fasting does not increase the risk of maternal, fetal and early neonatal complications. Most Muslim pregnant women do not recognize their right to be excused from fasting Ramadan by the Islamic religion, and they have a high rate of fasting with very strong desire and happiness.

Maternal Risk of Cardiovascular Disease Is Associated With Higher BMI Among Preschool-Aged Children: A Cross-Sectional Study.

Childhood obesity is an ongoing concern in the United States. Higher weight status in early childhood is associated with higher weight status at older ages. The Maternal Obesity Matters (MOMs) Study investigated associations between maternal risk of cardiovascular disease (CVD) and child BMI z-scores (BMIz) among preschool-aged children. This cross-sectional exploratory study included mothers and their 3- to 5-year-old children in Colorado, United States. Maternal nonfasting blood samples, blood pressure, and maternal and child anthropometrics were collected. Maternal CVD risk was assessed on a scale of 0-5 using five health measures. Multivariate regression tested associations between maternal CVD risk and child BMIz. Each 1-point increase in maternal CVD risk was associated with a 0.18 increase in child BMIz, controlling for maternal employment. Intervening upon maternal health may be an important strategy for addressing childhood obesity.

Dietary Calcium and Lead Interact to Modify Maternal Blood Pressure, Erythropoiesis, and Fetal and Neonatal Growth in Rats during Pregnancy and Lactation

We studied the effects of dietary calcium and lead exposure on lead toxicity, fetal and neonatal growth, erythropoiesis and blood pressure during pregnancy and lactation in rats. Pregnant Sprague-Dawley rats (n = 43) were randomly assigned to one of six treatment groups of 7–8 rats each. Half of the rats were fed diets of low (0.1%), normal (0.5%) or high (2.5%) calcium as calcium carbonate and exposed to 250 mg/L of lead in their drinking water for the duration of the pregnancy and for 1 wk of lactation. Three control groups were fed the same diets without lead exposure. Pups were studied at 1 d and 1 wk of age. Maternal and fetal blood and organ samples from the groups fed the low calcium diet had the highest lead concentrations, whereas the lowest lead concentrations were found in the groups fed the high calcium diet. Dam and pup hemoglobin concentrations, hematocrits, and body weights and lengths were reduced by lead exposure and by the high calcium diet. The latter also reduced organ iron concentrations and prevented lead-induced increases in free erythrocyte protoporphyrin. Dam systolic blood pressures during the third trimester of gestation were significantly higher in rats exposed to lead and fed the low calcium diet than in rats in the other five treatment groups. The results demonstrate that dietary calcium and lead exposure interact in rats to influence maternal blood pressure, erythropoiesis, and fetal and neonatal growth during pregnancy and lactation.

Household disorder and blood pressure in mother-child dyads: A brief report.

High blood pressure (BP) is the leading risk factor for cardiovascular disease (CVD). Although factors outside the home, such as crime and noise, have been associated with high BP in women and children, it is unknown if disorder within the home (household disorder) influences BP. We tested the hypothesis that women and children with more household disorder would have higher BP, independent of age, race, sodium intake, and body mass index (BMI). This study was a secondary analysis of data from mother-child dyads (n = 216). Mothers were 87% African American, 34 ± 5 years old, with BMI 33.59 ± 9.43 kg/m². Children were 7 ± 2 (range: 4-10) years of age with BMI z score 0.60 ± 2.07. Household disorder was measured by the Confusion Hubbub and Order Scale. Mother-child dyads were assessed for weight, height, BP (adults), BP percentile (children), energy intake, and sodium intake. The relationship between household disorder and BP was evaluated using Pearson's partial correlation coefficients. In fully adjusted models, household disorder was positively associated with systolic BP for mothers (r = 0.15, p < .05) and tended to be positively associated with diastolic BP (r = 0.11, p = .10). For the children, household disorder was not associated with systolic or diastolic BP percentile. This study's results suggest that household disorder is positively associated with higher BP in adult women, but not their children. Nevertheless, these data suggest that interventions to address household disorder could benefit maternal BP and potentially improve long-term CVD outcomes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Maternal heart rate variability patterns associated with maternal hypotension and non-reassuring fetal heart rate patterns following initiation of combined spinal-epidural labor analgesia: a prospective observational trial

BackgroundWe evaluated whether baseline maternal heart rate variability (HRV), including the Analgesia Nociception Index (ANI), is associated with maternal hypotension and fetal heart rate (FHR) abnormalities following combined spinal-epidural (CSE) labor analgesia. MethodsLaboring women were enrolled in this prospective observational study. The primary endpoint was maternal hypotension. The secondary endpoint was FHR abnormalities within 30 min following CSE analgesia initiated with intrathecal plain bupivacaine 1.0 mg and fentanyl 20 µg. The maternal ANI, electrocardiogram, blood pressure, heart rate, oxygen saturation, and FHR tracings were recorded 15 min before and 30 min after CSE. Parturients were grouped based on presence of hypotension and FHR abnormalities. Patient demographics and HRV metrics were compared. Receiver operating characteristics (ROC) curves were constructed for the prediction of hypotension and FHR abnormalities. ResultsNo significant intergroup differences were detected in patient characteristics. Several baseline HRV metrics and ANI differed significantly between the normotensive (n = 50) and hypotensive (n = 31) groups and between parturients showing FHR abnormalities (n = 19) and those showing reassuring FHR traces (n = 62). The area under the ROC curve (AUC) for predicting hypotension of the baseline low-frequency (LF)/high-frequency (HF) ratio was 0.677 (95% CI 0.55 to 0.80), and that of the ANI was 0.858 (95% CI 0.78 to 0.94). For predicting non-reassuring FHR patterns, the AUC of the LF/HF ratio was 0.77 (95% CI 0.65 to 0.89), and that of the ANI was 0.833 (95% CI 0.72 to 0.94). ConclusionsThe ANI can predict the propensity for maternal hypotension and non-reassuring FHR patterns following CSE.

NLRP3 inhibition improves maternal hypertension, inflammation, and vascular dysfunction in response to placental ischemia.

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder with end-organ damage that presents after 20 wk of gestation. PE pathophysiology often includes vascular dysfunction and increased inflammation that continues to damage patient health even after PE resolves. Currently, there is no cure for PE beyond delivery of the fetal-placental unit. Previous clinical studies have identified elevated placental NLRP3 expression in patients with PE and suggest NLRP3 as a potential therapeutic target. In this study, we examined the effect of NLRP3 inhibition on PE pathophysiology in the reduced uterine perfusion pressure (RUPP) model rat using MCC950 (20 mg/kg/day) or esomeprazole (3.5 mg/kg/day). We hypothesized that increased NLRP3 in response to placental ischemia impairs anti-inflammatory IL-33 signaling to induce T-helper 17 cell (TH17) and cytolytic NK cell (cNK) activation, which is known to mediate oxidative stress and vascular dysfunction leading to maternal HTN and intrauterine growth restriction. RUPP rats had significantly higher placental NLRP3 expression, maternal blood pressure, fetal reabsorption rate, vascular resistance, oxidative stress, cNKs and TH17s, and decreased IL-33 compared with normal pregnant (NP) rats. NLRP3 inhibition, with either treatment, significantly reduced placental NLRP3 expression, maternal blood pressure, fetal reabsorption rates, vascular resistance, oxidative stress, cNK, and TH17 populations in RUPP rats. Based on our findings, NLRP3 inhibition reduces PE pathophysiology and esomeprazole may be a potential therapeutic for PE treatment.

Obesity and gestational diabetes independently and collectively induce specific effects on placental structure, inflammation and endocrine function in a cohort of South African women.

Maternal obesity and gestational diabetes mellitus (GDM) are associated with insulin resistance and health risks for mother and offspring. Obesity is also characterized by low-grade inflammation, which in turn, impacts insulin sensitivity. The placenta secretes inflammatory cytokines and hormones that influence maternal glucose and insulin handling. However, little is known about the effect of maternal obesity, GDM and their interaction, on placental morphology, hormones and inflammatory cytokines. In a South African cohort of non-obese and obese pregnant women with and without GDM, this study examined placental morphology using stereology, placental hormone and cytokine expression using real-time PCR, western blotting and immunohistochemistry, and circulating TNFα and IL-6 concentrations using ELISA. Placental expression of endocrine and growth factor genes was not altered by obesity or GDM. However, LEPTIN gene expression was diminished, syncytiotrophoblast TNFα immunostaining elevated and stromal and fetal vessel IL-6 staining reduced in the placenta of obese women in a manner that was partly influenced by GDM status. Placental TNFα protein abundance and maternal circulating TNFα concentrations were reduced in GDM. Both maternal obesity and, to a lesser extent, GDM were accompanied by specific changes in placental morphometry. Maternal blood pressure and weight gain and infant ponderal index were also modified by obesity and/or GDM. Thus, obesity and GDM have specific impacts on placental morphology and endocrine and inflammatory states that may relate to pregnancy outcomes. These findings may contribute to developing placenta-targeted treatments that improve mother and offspring outcomes, which is particularly relevant given increasing rates of obesity and GDM worldwide. KEY POINTS: Rates of maternal obesity and gestational diabetes (GDM) are increasing worldwide, including in low-middle income countries (LMIC). Despite this, much of the work in the field is conducted in higher-income countries. In a well-characterised cohort of South African women, this study shows that obesity and GDM have specific impacts on placental structure, hormone production and inflammatory profile. Moreover, such placental changes were associated with pregnancy and neonatal outcomes in women who were obese and/or with GDM. The identification of specific changes in the placenta may help in the design of diagnostic and therapeutic approaches to improve pregnancy and neonatal outcomes with particular significant benefit in LMICs.

Effects of Fetal Images Produced in Virtual Reality on Maternal-Fetal Attachment: Randomized Controlled Trial

Maternal-fetal attachment (MFA) has been reported to be associated with the postpartum mother-infant relationship. Seeing the fetus through ultrasound might influence MFA, and the effect could be increased by more realistic images, such as those generated in virtual reality (VR). The aim was to determine the effect of fetal images generated in VR on MFA and depressive symptoms through a prenatal-coaching mobile app. This 2-arm parallel randomized controlled trial involved a total of 80 pregnant women. Eligible women were randomly assigned to either a mobile app-only group (n=40) or an app plus VR group (n=40). The VR group experienced their own baby's images generated in VR based on images obtained from fetal ultrasonography. The prenatal-coaching mobile app recommended health behavior for the pregnant women according to gestational age, provided feedback on entered data for maternal weight, blood pressure, and glucose levels, and included a private diary service for fetal ultrasound images. Both groups received the same app, but the VR group also viewed fetal images produced in VR; these images were stored in the app. All participants filled out questionnaires to assess MFA, depressive symptoms, and other basic medical information. The questionnaires were filled out again after the interventions. Basic demographic data were comparable between the 2 groups. Most of the assessments showed comparable results for the 2 groups, but the mean score to assess interaction with the fetus was significantly higher for the VR group than the control group (0.4 vs 0.1, P=.004). The proportion of participants with an increased score for this category after the intervention was significantly higher in the VR group than the control group (43% vs 13%, P=.005). The feedback questionnaire revealed that scores for the degree of perception of fetal appearance all increased after the intervention in the VR group. The use of a mobile app with fetal images in VR significantly increased maternal interaction with the fetus. ClinicalTrials.gov NCT04942197; https://clinicaltrials.gov/ct2/show/NCT04942197.

Statins in pre-eclampsia or fetal growth restriction: A systematic review and meta-analysis on maternal blood pressure and fetal growth across species.

Several human randomised controlled trials (RCTs) are investigating the effects of statins on pre-eclampsia (PE) and fetal growth restriction (FGR). This cross-species meta-analysis summarises the preclinical evidence of statin use for PE and FGR. Evaluate the effects of statins on maternal blood pressure (MBP) and birthweight (BW) in pregnancies complicated by PE or FGR. PubMed and Embase.com were searched on 10 May 2022 using 'statins' and 'pregnancy'. We included RCTs and cohorts with matched control groups as well as animal studies. The main outcomes were MBP in mmHg and BW in grams. The standardised mean difference (SMD) with a 95% confidence interval (CI) was calculated. Subgroup analyses on species, statin, dose, timing and route of administration were performed if subgroups included at least three studies. Our data included one human and 12 animal studies. Prenatal administration of statins significantly reduced MBP during pregnancy (SMD -2.49 mmHg [95% CI -4.26 to -0.71], p= 0.01). There was no significant effect of statins on BW (SMD 0.69 [95% CI -0.65 to 2.03], p= 0.28). Our subgroup analyses showed no effect on MBP of different doses, species or route of administration. Our cross-species meta-analyses demonstrate that statins only reduce maternal blood pressure in rodent pregnancies complicated by pre-eclampsia or fetal growth restriction and have no effect on birthweight across species. The broad confidence intervals, inconsistent direction of the observed effects across the studies and large risk of bias lead us to conclude that a solid base for further human RCTs is lacking.

Ionizable Lipid Nanoparticles for In Vivo mRNA Delivery to the Placenta during Pregnancy.

Ionizable lipid nanoparticles (LNPs) are the most clinically advanced nonviral platform for mRNA delivery. While they have been explored for applications including vaccines and gene editing, LNPs have not been investigated for placental insufficiency during pregnancy. Placental insufficiency is caused by inadequate blood flow in the placenta, which results in increased maternal blood pressure and restricted fetal growth. Therefore, improving vasodilation in the placenta can benefit both maternal and fetal health. Here, we engineered ionizable LNPs for mRNA delivery to the placenta with applications in mediating placental vasodilation. We designed a library of ionizable lipids to formulate LNPs for mRNA delivery to placental cells and identified a lead LNP that enables in vivo mRNA delivery to trophoblasts, endothelial cells, and immune cells in the placenta. Delivery of this top LNP formulation encapsulated with VEGF-A mRNA engendered placental vasodilation, demonstrating the potential of mRNA LNPs for protein replacement therapy during pregnancy to treat placental disorders.

Late Pregnant Dahl Salt-Sensitive Rats from Charles River Laboratories Do Not Exhibit Superimposed Preeclampsia.

Healthy pregnancy is characterized by a reduction in total peripheral vascular resistance which produces a decrease in maternal blood pressure. Failure of this normal maternal adaptation to pregnancy results in hypertensive disorders of pregnancy, which are dangerous for both the mother and fetus. Recently, it has been proposed that Dahl salt-sensitive (SS) rats are a model of spontaneous superimposed preeclampsia when maintained on a normal salt diet. Since these reports are from animals that are derived from sources that are not commercially available, the purpose of this study was to evaluate the blood pressure and pregnancy outcomes of SS rats from a commercial vendor. Mean arterial blood pressure was measured by indwelling femoral catheter in anesthetized SS virgin and SS day 21 late pregnant rats from Charles River Laboratories (CRL). Fetal outcomes from SS rats and control Sprague-Dawley (SD) rats were also measured. All rats were euthanized by exsanguination under anesthesia and tissues weighed. Virgin SS rats were found to have normal mean arterial blood pressure (102 ± 2mmHg), and late pregnant SS rats had the normal decrease in maternal blood pressure. SS rats were also found to have normal pregnancy outcomes. These results suggest that SS rats from CRL are not a model of superimposed preeclampsia. Further studies will be aimed at determining the differences between the blood pressure phenotype and pregnancy outcomes of existing colonies of SS rats in order to elucidate the mechanisms permitting the development of preeclampsia in certain colonies of this strain.

Ephedrine Infusion with Rescue Ephedrine Boluses versus Rescue Boluses alone for Preventing Hypotension during Spinal Anesthesia for Cesarean Delivery.

Background: Maternal hypotension is an unwanted consequence of the physiologic onset of spinal blockade, and causes both maternal and fetal effects. Maternal symptoms include nausea, vomiting, and a sense of ‘‘impending doom’’ from inadequate cerebral perfusion. Inadequate treatment of hypotension can ultimately end with the loss of consciousness and cardiovascular collapse.&#x0D; Materials and methods: We included 80 full term parturient (ASA I or II) with uncomplicated pregnancies. The patients were prospectively randomized into two groups. 80 patients received 1000 mL NaCl 0,9 % solution before the initiation of spinal anesthesia. Maternal systolic blood pressure was measured every 1 minutes (for first 10 minutes) and then every 3 minutes. One group received ephedrine infusion (1 mg/min) with rescue ephedrine boluses (10 mg), (usually defined as a maternal blood pressure ˂ 30% above baseline), (40 patients) and the other received rescue boluses alone (10 mg) , (usually defined as a maternal blood pressure ˂ 30% above baseline), (40 patients).&#x0D; Results: Gr 1 (Ephedrine infusion with rescue ephedrine boluses). The incidence of hypotension was at 8 patients (8/40 [20%]),(when an absolute value of less than 90 mmHg).&#x0D; Gr 2 (rescue boluses ephedrine alone). The incidence of hypotension was at 32 patients (32/40 [80%]), (when an absolute value of less than 90 mmHg).&#x0D; Group 2 had a higher incidence of hypotension compared with group 1 (32/40 [80%]) vs (8/40 [20%]).&#x0D; Neonatal outcomes were not different between the 2 groups.&#x0D; Conclusion: Prophylactic variable rate ephedrine infusion and rescue ephedrine bolus dosing is more effective than relying on rescue ephedrine bolus dosing with respect to limiting clinician workload and maternal symptoms during spinal anesthesia for cesarean delivery.Maternal hypotension

The impact of a neonatal sleep intervention on sleep quality in the postpartum period

To determine the impact of a novel neonatal sleep intervention on maternal sleep quality in the postpartum period in individuals with a hypertensive disorder of pregnancy (HDP) and assess the relationship between maternal sleep quality and blood pressure. In this single institution pilot randomized controlled trial, 110 individuals with a HDP were randomized to receive a neonatal sleep intervention, a SNOO smart bassinet, plus usual care of safe sleep education (n=54) or usual care alone (n=56). Individuals were included if they were 18+ years old, had a singleton term live birth of a non-anomalous infant without a prolonged neonatal intensive care unit stay, and had a new HDP without prior chronic hypertension. Remote follow-up visits conducted at 6 weeks postpartum included vital signs and subjective sleep quality questionnaires including the Pittsburgh Sleep Quality Index (PSQI), Patient-Reported Outcomes Measurement Information System Sleep Disturbance (PROMIS-SD) questionnaire, and the Epworth Sleepiness Scale (ESS). Maternal sleep quality was a prespecified secondary outcome of this trial. Clinical and demographic characteristics were similar between arms (Table 1). Follow-up sleep data was available for 82 (75%) participants at 6 weeks (mean of 41.8±4.8 days) postpartum, with a higher follow rate in the SNOO arm (89% vs 61%) (Table 2). PSQI, PROMIS-SD, and ESS scores were similar between the two groups (p>0.05). The majority (88%) noted poor subjective sleep quality with PSQI score >5. There was no significant correlation between blood pressure and sleep quality (p>0.05) at 6 weeks postpartum. Use of the SNOO bassinet as a neonatal sleep intervention did not result in improved maternal subjective sleep quality at 6 weeks postpartum in our cohort of individuals with HDP. Self-reported sleep quality was not associated with blood pressure in this cohort of individuals with HDP.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The impact of a neonatal sleep intervention on maternal mood in the postpartum period

To determine the impact of a novel neonatal sleep intervention on maternal mood in the postpartum period in individuals with a hypertensive disorder of pregnancy (HDP) and assess the relationship between maternal mood and blood pressure.

Placental Fatty Acid Metabolism and Transport in a Rat Model of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a form of heightened insulin resistance triggered during gestation. This study examines how insulin resistance alters placental long-chain polyunsaturated fatty acid (LCPUFA) transport and metabolism in a rat model of lean GDM. Pregnant Sprague Dawley rats were administered with S961, an insulin receptor antagonist (30 nmol/kg s.c. daily), or vehicle from gestational day (GD) 7 to 20. Daily maternal body weight, food, and water intake were measured. Blood pressure assessment and glucose tolerance test were done on GD20. Fetal plasma and placenta were collected on GD20 and processed for fatty acid measurement using LC-mass spectrometry. The expression of fatty acid metabolism-related genes in the placenta was assessed using RT2 Profiler PCR arrays. The results were validated by qRT-PCR. Blockade of insulin receptors with S961 in pregnant rats resulted in glucose intolerance with increased fasting glucose and insulin levels. Maternal body weight gain and food and water intake were not affected; however, S961 significantly increased maternal blood pressure and heart rate. The placenta n3 and n6 LCPUFA concentrations were significantly decreased by 8% and 11%, respectively, but their levels in the fetal plasma were increased by 15% and 4%. RT2 profiler arrays revealed that placental expressions of 10 genes related to fatty acid β-oxidation (Acaa1a, Acadm, Acot2, Acox2, Acsbg1, Acsl4, Acsm5, Cpt1b, Eci2, Ehhadh) and 3 genes related to fatty acid transport pathway (Fabp2, Fabp3, Slc27a3) were significantly upregulated. In summary, lack of insulin action increased the expression of genes related to placental fatty acid β-oxidation and transport with an increased transfer of LCPUFA to the fetus. The increased lipid levels routed toward the fetus may lead to fat adiposity and later-life metabolic dysfunction.