The relationship between impaired uteroplacental blood flow and blood pressure level in pregnant women with chronic and gestational hypertension

Aim. To assess the relationship between impaired uteroplacental blood flow and different levels of blood pressure in pregnant women with chronic and gestational hypertension at different stages of pregnancy with the determination of the optimal systolic blood pressure. Methods. We conducted a prospective cohort study between 2018 and 2019. The study enrolled pregnant women aged 18 to 45 years: 55 women with chronic and gestational hypertension each, as well as 80 healthy pregnant women as control. The groups were formed by the continuous method, in which all pregnant women with arterial hypertension were included in the study until the required number of subjects was obtained. Follow-up was conducted at different gestation periods (1416, 2022, 2830, 3436 weeks) until delivery. Independent groups were compared by using the Student's t-test, the Pearsons 2 test, the MannWhitney U test, the KruskalWallis H test. Results. Comparison of the groups revealed differences in blood pressure levels at different gestation periods. In chronic hypertension compared with gestational hypertension, there was an increase in the impairment of the uteroplacental blood flow in pregnant women, indicating an unfavorable prognosis. The study of impaired uteroplacental blood flow among pregnant women with various forms of arterial hypertension revealed an increase in pregnant women with chronic arterial hypertension compared with gestational (p=0.04), indicating an unfavorable prognosis. In chronic arterial hypertension, the impairment of uteroplacental blood flow was the least for systolic pressures up to 120 mm Hg (up to 0.9%) at 1416 and 2022 weeks of gestation, and for 130139 mm Hg (from 1.8 to 2.7%) in later pregnancy. In gestational hypertension, the least or no impairment rate of uteroplacental blood flow was determined for blood pressures up to 129 mm Hg at all stages of pregnancy compared with chronic hypertension. Conclusion. The optimal systolic blood pressure in chronic hypertension reducing the risk of impaired uteroplacental blood flow in pregnant women is 129 mm Hg before 20th week of pregnancy and 130139 mm Hg in later (2030 weeks); in gestational hypertension, blood pressure reduction to 129 mm Hg is recommended at all stage of gestation.

ANALYSIS OF ANAMNESIS FEATURES IN PREGNANT WOMEN WITH PLACENTAL DYSFUNCTION

The article examines the analysis of the anamnesis of pregnant women with placental dysfunction, the results of the studies made it possible to conclude that with impaired uteroplacental blood flow from 18-22 weeks, showed a high level of development of late gestosis (84.7%). Timely treatment of placental insufficiency and prophylaxis of late gestosis made it possible to reduce the incidence of complications.

248 Maternal Nutrient Restriction During Mid-gestation Decreases Uteroplacental Release and Fetal Uptake of Essential Amino Acids in Sheep

To examine the effects of maternal nutrient restriction on net uteroplacental flux during mid-gestation, 14 singleton ewes (48.2 ± 4.0 kg body weight) were fed 100% (control; CON; n = 7) or 60% of nutrient requirements (restricted; RES; n = 7) from day 50–90 (mid-gestation). On day 90, uteroplacental blood flow was measured via Doppler ultrasonography and blood samples were collected from the femoral artery, uterine vein, umbilical artery, and umbilical vein. Blood vessel glucose and amino acids (AA) concentrations were measured and arterial-venous (uterine, AV; fetal, va) differences and net fluxes were calculated. Data were analyzed using the GLM procedure of SAS for effects of treatment. Nutrient restriction during mid-gestation did not influence (P ≥ 0.17) uterine or umbilical blood flows. Uterine AV and fetal va differences of total, essential, and nonessential AA were not influenced (P > 0.10) by nutrient restriction. Nutrient restriction decreased (P ≤ 0.05) uterine and uteroplacental release of total AA and tended to decrease (P = 0.07) total AA uptake by the fetus. Uteroplacental release and fetal uptake of essential AA were decreased (P = 0.03) with RES by 53.4% and 45%, respectively. Uterine and uteroplacental release of nonessential AA were decreased (P = 0.03) with RES but, fetal uptake was not affected (P = 0.14). Nutrient restriction decreased (P ≤ 0.04) fetal uptake of methionine, phenylalanine, threonine, and valine and tended to decrease (P ≤ 0.10) fetal uptake of isoleucine, leucine, and tryptophan. Umbilical artery glucose concentrations were 32% lesser (P = 0.01) with RES and RES tended to increase (P = 0.08) fetal glucose uptake. Nutrient restriction during mid-gestation altered uteroplacental and fetal flux of AA in the current study. The results may indicate that fetal metabolism shifts to adapt to reduced AA supply which results in greater glucose utilization.

Uteroplacental Circulation in Normal Pregnancy and Preeclampsia: Functional Adaptation and Maladaptation

Uteroplacental blood flow increases as pregnancy advances. Adequate supply of nutrients and oxygen carried by uteroplacental blood flow is essential for the well-being of the mother and growth/development of the fetus. The uteroplacental hemodynamic change is accomplished primarily through uterine vascular adaptation, involving hormonal regulation of myogenic tone, vasoreactivity, release of vasoactive factors and others, in addition to the remodeling of spiral arteries. In preeclampsia, hormonal and angiogenic imbalance, proinflammatory cytokines and autoantibodies cause dysfunction of both endothelium and vascular smooth muscle cells of the uteroplacental vasculature. Consequently, the vascular dysfunction leads to increased vascular resistance and reduced blood flow in the uteroplacental circulation. In this article, the (mal)adaptation of uteroplacental vascular function in normal pregnancy and preeclampsia and underlying mechanisms are reviewed.

Assessment of Sub-endometrial Blood Flow Parameters Following Oral Dydrogesterone versus Micronized Vaginal Progesterone in Women with Idiopathic Recurrent Miscarriage

Background: Recurrent pregnancy loss is an important reproductive health issue, affecting 2%–5% of couples. An unsupportive endometrium, leading to abnormal implantation, is considered to be one of the key factors contributing to idiopathic recurrent spontaneous miscarriage (IRSM). The aim of this work was to evaluate differences in uteroplacental blood flow and pregnancy outcome in women with idiopathic recurrent spontaneous miscarriage (IRSM) following administration of micronized vaginal progesterone versus oral dydrogesteron. Materials and Methods: This prospective, randomized-controlled study comprised 90 pregnant women who came to outpatient clinic of obstetrics .All women had a singleton pregnancy with active cardiac pulsations at gestational age between 5-8 weeks Pregnant women in the study group were randomly distributed into: Group {A}: 30 pregnant women received 10 mg of oral dydrogesterone (Duphaston; Abbott Company) twice daily.Group {B}: 30 pregnant women received 200 mg micronized vaginal progesterone (Prontogest) twice-daily. Control group:30 pregnant women without history of recurrent miscarriage served as controls and they received folic acid as placebo. Results: comparing the Doppler indices before progesterone supplementation, the mean resistance index (RI) was statistically significant less in the control group compared with both study groups (A&B) (P=0.012, P=0.005 respectively) .Moreover, pulsatility index (PI) was statistically significant less in the control group compared with both study groups (A&B) (P=0.026, P=0.05 respectively) .Paralleled to that, the S/D ratio was statistically significant less in control group compared with both group A &B (P=0.43, & P=0.019respectively) .In addition, the mean PSV was significantly higher in control group compared to group B (P=0.047) and was higher in control group than group A with nearly significant P value. Conclusion: Considerable improvement in uteroplacental blood flow parameters of pregnant women with IRSM is evident with progesterone supplementation.

Antenatal Markers Related to Fetal Growth Restriction Can Predict Childhood Systolic Blood Pressure

Background: Being born small for gestational age (SGA) is linked with higher systolic blood pressure (SBP). Fetuses with growth restriction (FGR) may be either SGA or appropriate size for gestational age at birth. However, it is not known which factors contributing to size at birth influence the relationship with SBP. Aim. To determine whether antenatal markers of FGR can predict the upper quartile of childhood SBP. Methods: Brachial SBP was measured for 75 children aged 3-6 years from the Manchester BabyGRO Study, using a Tensiomed®Arteriograph with a child-sized cuff. SBP quartiles were generated. Participants were born to mothers who had attended a specialised clinic, following identification of higher FGR risk based on abnormal maternal serology (pregnancy associated plasma protein-A, β-human chorionic gonadotrophin, α-fetoprotein, Inhibin-A). Antenatal ultrasound data at 23 weeks gestation were obtained. Uterine artery Doppler (UtAD) notching was assigned a rank (0=absent, 1=unilateral, 2=bilateral). Random forest (RF) is a machine learning approach that generates many independent, uncorrelated decision trees based on multiple variables. This was used to determine the relative importance of antenatal variables in prediction of upper quartile of childhood SBP. Variables included in the model were maternal body mass index (BMI), parity, ethnicity (black/white/asian/mixed), maternal SBP and diastolic BP (DBP), maternal serology relating to FGR risk, UtAD pulsatility index, resistance index and notching rank (all measures of uteroplacental blood flow resistance), placental size measurements, 23 week estimated fetal weight (EFW) centile, ∆23w EFW-birthweight centile and birthweight SDS. A receiver operating characteristic (ROC) curve was generated, providing an area under the curve (AUC). A variable of importance (VIP) score was calculated for each marker that was significant in the model. All analyses were conducted in R (version 3.6). Results: RF analysis demonstrated antenatal markers relating to FGR risk predict the upper quartile of childhood SBP with an AUC 0.97. The top five ranked variables were maternal DBP (VIP score 14.0), birthweight SDS (11.5), parity (9.9), notching rank (9.5) and ∆23w EFW-birthweight centile (9.1). Conclusion: Maternal and antenatal markers, as well as birthweight SDS are linked with the upper quartile of SBP at 3-6 years. Antenatal markers were within the top five ranked and could help identify those babies at risk of higher SBP in childhood.

Hemodynamic Consequences of Incomplete Uterine Spiral Artery Transformation in Human Pregnancy, with Implications for Placental Dysfunction and Preeclampsia.

Normal human pregnancy requires a dramatic increase in uteroplacental blood flow which is achieved by a transformation in the geometry of uterine spiral arteries, a key element in this blood supply system. The transformation is mediated by trophoblast invasion directed at converting a portion of the spiral artery into an open funnel, thereby greatly reducing resistance to flow. The converted portion lies within the depth of the decidua and part of the myometrium. Insufficient depth of trophoblast invasion in early pregnancy predisposes to inadequate perfusion of the developing placenta andfetus and may lead to preeclampsia, fetal growth restriction and preterm delivery, sometimes referred to as the "Great Obstetrical Syndromes". We examine the hemodynamic consequences of spiral artery transformation in human pregnancy and the relationship between the degree of transformation and the corresponding change in flow rate and resistance to flow. We identify two key variables in determining the hemodynamic change: the longitudinal converted fraction of the spiral artery and the relative downstream diameterof the open funnel. Our results indicate that there is a critical threshold in the value of the converted fraction required to achieve the marked increase in uteroplacental blood flow in normal pregnancy. This finding validates common clinical observations that the depth of trophoblast invasion reflects the "adequacy" of the increase in uteroplacental blood supply required in normal human pregnancy. Our results provide a quantitative measure of that adequacy and may serve as a future diagnostic marker for high-risk pregnancy.

Review article: Nutritional effects on fetal development during gestation in ruminants

Intrauterine growth retardation is a massive problem in animal production as it influencesthe body composition, carcass quality, and impairs health. This condition can lead to areduction in neonatal survival, growth, feed efficiency utilisation, and future production bythe animals. Pregnancy may negatively influence maternal nutritional status because ofincreased uteroplacental blood flow, nutrient mobilisation, and transfer of nutrients from thedam to the fetus. The critical factor for fetal survival and health is an adequate nutrient andoxygen supply to the dam during gestation. This ability is dependent on her nutritionalsupply, body size, body composition, and metabolism during pregnancy. The placenta is aunique organ of reproduction that helps in the exchange of nutrients, respiratory gases andexcretory waste between the mother and offspring. Maternal nutrition restriction inembryonic, placenta and fetal stages of pregnancy can result in metabolic compromise,cardiovascular, renal and adipose tissue dysfunction. The major effects of nutritionalchallenges on fetoplacental growth and development appear to occur when the placenta israpidly developing. Poor nutrition caused by inadequate, excess or imbalanced nutrientintake has been shown to adversely affect subsequent reproductive performance (delayedpuberty, luteal inadequacy, reduced follicular reserve, reduced ovulation, and conceptionrates). Proteins, carbohydrates, fats, minerals and vitamins are key components in animalfeeds that are required for a daily maintenance diet. Amino acids serve as building blocks forproteins and essential precursors for the synthesis of different physiologicalmolecules–hormones, neurotransmitters, nitric oxide, creatine, glutathione, carnitine, andpolyamines.