Major Obstetrical Syndromes Research Articles

Peculiarities of micronutrient metabolism in obese pregnant women (literature review)

Here we summarize uptodate data on the influence of the most significant micro, macroelements, and vitamins, such as magnesium, vitamin D, iron, and folic acid, on the course of pregnancy and childbirth in obese women. The paper considers both domestic and foreign recommendations for correcting nutritional deficiencies to prevent the development of complications from the pregravid stage to the end of lactation. Nowadays, the deficiency of micro-, macroelements and vitamins is an extremely urgent problem, especially in a group of special risk, i.e. overweight and obese women, whose number is steadily growing simultaneously with an increase of the number of pregnant women of 35+ years of age. It is important to consider a woman's body mass index to prescribe the minimum effective dose of the necessary drugs. Timely preventive personalized correction of the micronutrient state can reduce the risks of such major obstetric syndromes as preeclampsia, premature birth, fetal growth retardation, miscarriage, and placental dysfunction.

MiRNAs and Their Gene Targets-A Clue to Differentiate Pregnancies with Small for Gestational Age Newborns, Intrauterine Growth Restriction, and Preeclampsia.

Despite the differences in the clinical manifestations of major obstetric syndromes, such as preeclampsia (PE) and intrauterine growth restriction (IUGR), their pathogenesis is based on the dysregulation of proliferation, differentiation, and invasion of cytotrophoblast cells that occur in the developing placenta, decidual endometrium, and myometrial parts of the spiral arteries. To understand the similarities and differences in the molecular mechanisms of PE and IUGR, samples of the placental bed and placental tissue were analyzed using protein mass spectrometry and the deep sequencing of small RNAs, followed by validation of the data obtained by quantitative RT-PCR in real time. A comparison of the transcriptome and proteomic profiles in the samples made it possible to conclude that the main changes in the molecular profile in IUGR occur in the placental bed, in contrast to PE, in which the majority of molecular changes occurs in the placenta. In placental bed samples, significant changes in the ratio of miRNA and its potential target gene expression levels were revealed, which were unique for IUGR (miR-30c-5p/VIM, miR-28-3p/VIM, miR-1-3p/ANXA2, miR-30c-5p/FBN1; miR-15b-5p/MYL6), unique for PE (miR-185-3p/FLNA), common for IUGR and PE (miR-30c-5p/YWHAZ and miR-654-3p/FGA), but all associated with abnormality in the hemostatic and vascular systems as well as with an inflammatory process at the fetal‒maternal interface.

Ante and Postnatal Ultrasound Contribution and Near-infrared Spectroscopy (NIRS) Monitoring in Preterm Newborns with Intrauterine Growth Restriction Under 32 Weeks of Gestation

IUGR remains an important health problem in developing countries around the world, being one of the major obstetrical syndromes associated with placental defects, but also one of the topical issues of neonatology, and in particular the association between IUGR and prematurity under 32 weeks of gestation. Neonatal morbidity and mortality remain significant and has an important economic impact. The need for more stringent diagnostic criteria remains a problem. The study proposes to follow the time of extraction of a premature pregnancy IUGR with gestation age �32 weeks, taking into account the centralization of bloodflow as well as IH (hypoxic index) during observation, following the immediate consequences on this new category - as well as their prognosis depending on the associated pathology using cerebral serial Doppler ultrasounds and near-infrared spectroscopy (NIRS).

Characteristics of early pregnancy and prevention of gestational and perinatal complications in women with metabolic syndrome

Introduction. Based on the knowledge of early gestational disorders related to metabolic syndrome (MS), pathogenetically relevant preventive treatment meeting the requirements of perinatal pharmacology can be developed.
 Aim. To reveal clinical and laboratory characteristics of early pregnancy and develop pathogenetically relevant preventive monotherapy for unfavorable gestational and perinatal outcomes in women with metabolic syndrome.
 Material and methods. A total of 230 women were investigated and divided into four groups: Group I consisted of 68 pregnant women with MS who refused any preventive measures; Group II comprised 97 women with MS who received periconceptional preventive monotherapy with dydrogesterone, a progestagen; Group III consisted of 35 healthy primigravidas women with physiological course of gestation; Group IV comprised 30 healthy non-pregnant women. Laboratory testing during IIII trimesters allowed to assess the dynamics demonstrated by markers of lipid spectrum, endothelial dysfunction, apoptosis, decidualization, energy metabolism, and immunomodulation.
 Results. A balance between factors of physiological damage and gestational adaptation in the course of physiological pregnancy has been shown to be of primary significance. In women with MS, embryo-placental dysfunction develops during early pregnancy, and this stage is preceding for major obstetric syndromes. Preventive administration of dydrogesterone in women with MS appeared highly effective: NNT (number needed to treat) was 1.33 (95% CI 0.91.8); OR 5.2 (95% CI 4.65.7).
 Conclusion. Pregestational changes and atherogenic profile of gestational process determine the course of early pregnancy in women with MS with the development of embryo-placental dysfunction and major obstetric syndromes. High efficacy in the prevention of unfavorable gestational and perinatal outcomes was shown by preventive dydrogesterone monotherapy.

The impact of uterine immaturity on obstetrical syndromes during adolescence

Pregnant nulliparous adolescents are at increased risk, inversely proportional to their age, of major obstetric syndromes, including preeclampsia, fetal growth restriction, and preterm birth. Emerging evidence indicates that biological immaturity of the uterus accounts for the increased incidence of obstetrical disorders in very young mothers, possibly compounded by sociodemographic factors associated with teenage pregnancy. The endometrium in most newborns is intrinsically resistant to progesterone signaling, and the rate of transition to a fully responsive tissue likely determines pregnancy outcome during adolescence. In addition to ontogenetic progesterone resistance, other factors appear important for the transition of the immature uterus to a functional organ, including estrogen-dependent growth and tissue-specific conditioning of uterine natural killer cells, which plays a critical role in vascular adaptation during pregnancy. The perivascular space around the spiral arteries is rich in endometrial mesenchymal stem-like cells, and dynamic changes in this niche are essential to accommodate endovascular trophoblast invasion and deep placentation. Here we evaluate the intrinsic (uterine-specific) mechanisms that predispose adolescent mothers to the great obstetrical syndromes and discuss the convergence of extrinsic risk factors that may be amenable to intervention.

Методология профилактики больших акушерских синдромов

Методология профилактики больших акушерских синдромов

591: Maternal total cell free DNA in preeclampsia and IUGR: evidence for differences in maternal and fetal response for abnormal implantation

591: Maternal total cell free DNA in preeclampsia and IUGR: evidence for differences in maternal and fetal response for abnormal implantation

Menstrual preconditioning for the prevention of major obstetrical syndromes in polycystic ovary syndrome

The presence of multiple ovarian cysts, anovulation, and endometrial progesterone resistance in the neonate seems remarkably similar to ovarian and endometrial features of the polycystic ovary syndrome (PCOS) of adolescent and adult women. In fact, in the absence of cyclic menstruations after menarche, the neonatal progesterone resistance is likely to persist and adversely affect young women with PCOS at the time of pregnancy after induction of ovulation, because any persisting defect in progesterone response can interfere with the process of decidualization and trophoblast invasion. The primigravid woman with PCOS therefore is likely to be at risk of defective deep placentation as manifested by the increased risk of major obstetric syndromes. A recent, large epidemiologic study has demonstrated that the risk of preeclampsia and preterm delivery is elevated in the 13- to 15-year old group, although it does not persist in the 16- to 17-year old group. It is proposed therefore that induction of ovulation in the infertile nulligravid woman with PCOS should be preceded by a period of progesterone withdrawal bleedings to achieve full endometrial progesterone response by the time of pregnancy. The cyclic administration of clomiphene citrate for a period to be determined by vascular response may be an appropriate tool to reduce the risk of major obstetric syndromes by menstrual preconditioning.

The perinatal origins of major reproductive disorders in the adolescent: Research avenues

The fetal endometrium becomes responsive to steroid hormones around the fourth month of pregnancy starting with an oestrogenic phase, which is followed late in pregnancy by a secretory phase. Based on post-mortem studies, the endometrium at birth is secretory in only one-third of neonates and proliferative in the remaining cases. Decidual or menstrual changes are rare in fetal endometrium despite high circulating steroid hormone levels, which drop rapidly after birth. Hence, acquisition of progesterone responsiveness appears to be dependent on endometrial maturation and relative immaturity may persist in a majority of girls until the menarche and early adolescence. Two major reproductive disorders have been linked with either advanced or delayed endometrial maturation. First, early-onset endometriosis may be caused by menstruation-like bleeding in the neonate, leading to tubal reflux and ectopic implantation of endometrial stem/progenitor cells. Second, persistence of partial progesterone resistance in adolescent girls may compromise deep placentation and account for the increased risk of major obstetrical syndromes, including preeclampsia, fetal growth retardation and preterm birth. The concept of neonatal origins of common reproductive disorders poses important research challenges but also subsumes potential new preventative strategies.

The potential perinatal origin of placentation disorders in the young primigravida

The fetus is exposed to high plasma concentrations of unbound estrogens and progesterone throughout pregnancy. However, secretory or decidual changes in the fetal uterus occur relatively infrequently before birth, suggesting a variable endometrial progesterone response at the time of birth. Arguably, partial progesterone resistance that persists into adolescent years may compromise the physiological transformation of the spiral arteries and predispose for defective placentation in the case of pregnancy. Decidualization of the endometrial stromal compartment and junctional zone myometrium precedes trophoblast invasion. It represents the first step in the process of spiral artery remodeling needed to establish effective uteroplacental blood flow by midpregnancy. The major obstetric syndromes caused by impaired placental bed spiral artery remodeling are prevalent in teenage pregnancies, including preeclampsia, fetal growth restriction, and spontaneous preterm labor. Preconditioning of the uterus in response to cyclic menstruation during adolescence may be critical to achieve full uterine responsiveness to hormonal cues. Understanding the mechanisms of functional maturation of the uterus during the early reproductive years may yield novel insights into the major obstetric syndromes.

Endometriosis: a life cycle approach?

To improve the still fragmented understanding of endometriosis, a life cycle approach was adopted that revealed unexpected aspects of the natural history of the disease throughout a woman's life. Three age-related stages of endometriosis are distinguished. In premenarcheal and adolescent endometriosis, 2 types can be distinguished: a classic form that can occur before menarche, and a congenital obstructive form that is caused by uterine anomaly and outflow obstruction. The lesions include superficial peritoneal implants, but adhesions and endometrioma can also occur. It is suggested that premenarcheal and possibly adolescent endometriosis develop by activation of resting stem cells shed at the time of neonatal retrograde uterine bleeding. In the adult, endometriosis can be related to uterine preconditioning by cyclic menstruations acting as a priming mechanism for deep placentation. In adult life, the typical lesions are peritoneal, ovarian, and deep or adenomyotic endometriosis. More recently, endometriosis has been associated with endometrial dysfunction and myometrial junctional zone hyperplasia. These uterine changes can be linked with some major obstetrical syndromes. In postmenopause, endometriosis can develop or be reactivated both in the presence or absence of exogenous estrogens and can spread to a variety of organs and structures causing constrictive lesions.

Defective myometrial spiral artery remodelling as a cause of major obstetrical syndromes in endometriosis and adenomyosis

Endometriosis and adenomyosis are characterized by the presence of ectopic endometrium, but are also associated with functional and structural changes in the eutopic endometrium and inner myometrium. Alterations in the inner myometrium occurring in women with endometriosis and adenomyosis may be at the root of a defective remodelling of the myometrial spiral arteries from the onset of decidualization and result in vascular resistance and increased risk of defective deep placentation. The association of major obstetrical syndromes and different types of defective remodelling of the myometrial spiral arteries has been well documented. The possibility of a link between both endometriosis and adenomyosis and some major obstetric syndromes remains controversial because of at least two factors: first, changes of the inner myometrium are frequently present in women with endometriosis but the diagnosis requires high-resolution imaging such as magnetic resonance which is not routinely performed and second, patients with endometriosis are frequently subjected to prolonged hormone suppressive therapy. Indeed, there is evidence that pre-treatment with a Gonadotropin Releasing-Hormone analogue can improve the uterine microenvironment and implantation rate following IVF in infertile patients with endometriosis.

Proteomics of the Amniotic Fluid in Assessment of the Placenta. Relevance for Preterm Birth

Proteomics is the study of expressed proteins and has emerged as a complement to genomic research. The major advantage of proteomics over DNA–RNA based technologies is that it more closely relates to phenotypes and not the source code. Proteomics thus holds the promise of providing a direct insight into the true mechanisms of human diseases. Historically, examination of the placenta has been the first modality to subclassify pathogenetic entities responsible for preterm birth. Because placenta is a key pathophysiological participant in several major obstetrical syndromes (preterm birth, pre-eclampsia, intrauterine growth restriction) identification of relevant biomarkers of placental function can profoundly impact on the prediction of fetal outcome and treatment efficacy. Since proteomics is a young science and studies that associate proteomic patterns with long-term outcome require follow-up of children up to school age, using placental pathological footprints of cellular injury as intermediate outcomes can be useful in the interim. Furthermore, knowledge on the identity of the dysregulated proteins may provide the needed breakthrough insight into novel pathophysiological pathways and unravel possible targets for therapeutical intervention that could not have been envisioned through hypothesis-driven approaches.