Academic literature on the topic 'Placental insufficiency/ mortality'

Chronic placental insufficiency remains a major cause of perinatal morbidity and mortality. In this regard, prediction of this pregnancy complications becomes particularly relevant. Currently, the frequency of pregnancy as result of assisted reproductive technology (ART) increases among the population. Pregnancies after ART administration compare to naturally occurred are accompanied by a higher risk of miscarriage as well as the formation of placental insufficiency. Older women with endocrine and physical disorder participate in the ART programs most frequently. The aim of our study was to investigate the course of pregnancy, after ART administration, selection groups threatened by the development of placental insufficiency. 261 medical records of women with singleton pregnancies after ART have been studied. It was the main group. 167 women had a chronic placental insufficiency. There were allocated two groups of pregnant women: group I – 86 patients with placental insufficiency and preeclampsia, group II – 81 women with placental insufficiency indeed. The comparison group consisted of 30 women without infertility with a normal singleton pregnancy. The development of placental insufficiency in the main group (after ART) depends on a large causes of somatic pathology due to age of pregnant women as well. Therefore, patients after ART have to allocate in the high risk group of developing preeclampsia and placental insufficiency.

According to literature, intrauterine growth retardation complicates about 5% of pregnancies and is usually caused by chronic placental insufficiency. This article reviews literature data on modern views on the issue. Special attention is paid to the role of melatonin in chronic placental insufficiency and intrauterine growth. Examples of experimental studies demonstrate successful pregnancy course and functional fetal development in animals with melatonin treatment. The data obtained by other researchers on the effect of melatonin on pregnancy, in particular, on chronic placental insufficiency in women, are analyzed. Also in this review, we suggest that melatonin, which is a powerful antioxidant, can reduce morbidity and mortality associated with intrauterine growth retardation.

Intrauterine growth restriction (IUGR) is a major cause of perinatal death and neonatal morbidity and mortality. There are numerous causes of IUGR. Glucocorticoid-induced IUGR is highly relevant because administration of synthetic glucocorticoids, principally dexamethasone, to women threatened by premature labor is widely used in clinical practice. Fetal growth is directly related to placental growth and development. In this report, we analyzed the effect of dexamethasone on placental development in the rat. Dexamethasone administered between days 13 and 20 of pregnancy not only induced IUGR but also decreased placental mass by approximately 50%. Impaired placental development was associated with dysregulated placental prolactin (PRL) family and insulin-like growth factor-II (IGF-II) gene expression. Furthermore, there was a significant decrease in the activation of Akt/protein kinase B in the junctional zone of the placenta, as assessed by the phosphorylation status of Akt and the pro-apoptotic protein BAD, a downstream target of the Akt signaling pathway. Such changes are consistent with increases in indices of apoptosis, including increased cleavage of poly(ADP-ribose) polymerase (PARP) in the junctional zone of the placenta of dexamethasone-treated rats. In summary, dexamethasone-induced IUGR is associated with placental insufficiency, including dysregulated placental hormone/cytokine gene expression and down-regulation of the IGF-II/Akt signaling pathway resulting in increases in indices of placental apoptosis.

Intrauterine growth restriction (IUGR) is associated with fetal mortality and morbidity. One of the most common causes of IUGR is placental insufficiency, including placental vascular defects, and mitochondrial dysfunction. In addition, a high level of oxidative stress induces placental vascular lesions. Here, we evaluated the oxidative stress status, mitochondrial function, angiogenesis, and nutrient transporters in placentae of piglets with different birth weights: <500 g (L), 500–600 g (LM), 600–700 g (M), and >700 g (H). Results showed that placentae from the L group had higher oxidative damage, lower adenosine triphosphate and citrate synthase levels, and lower vascular density, compared to those from the other groups. Protein expression of angiogenic markers, including vascular endothelial cadherin, vascular endothelial growth factor A, and platelet endothelial cell adhesion molecule-1, was the lowest in the L group placentae compared to the other groups. In addition, the protein levels of glucose transporters GLUT1 and GLUT3 were downregulated in the L group, compared to the other groups. Furthermore, oxidative stress induced by H2O2 inhibited tube formation and migration in porcine vascular endothelial cells. Collectively, placentae for lower birth weight neonates are vulnerable to oxidative damage, mitochondrial dysfunction, and impaired angiogenesis.

Preeclampsia is a multisystemic pregnancy disorder and a major cause of maternal and neonatal morbidity and mortality worldwide. The exact pathophysiology of preeclampsia remains unclear; however, it is speculated that the various pathologies can be attributed to impaired vascular remodelling and elevated oxidative stress within the placenta. Oxidative stress plays a key role in cell ageing, and the persistent presence of elevated oxidative stress precipitates cellular senescence and mitochondrial dysfunction, resulting in premature ageing of the placenta. Premature ageing of the placenta is associated with placental insufficiency, which reduces the functional capacity of this critical organ and leads to abnormal pregnancy outcomes. The changes brought about by oxidative insults are irreversible and often lead to deleterious modifications in macromolecules such as lipids and proteins, DNA mutations, and alteration of mitochondrial functioning and dynamics. In this review, we have summarized the current knowledge of placental ageing in the aetiology of adverse pregnancy outcomes and discussed the hallmarks of ageing which could be potential markers for preeclampsia and fetal growth restriction.

Fetal growth restriction is one of the most common obstetrical complications resulting in significant perinatal morbidity and mortality. The most frequent etiology of human singleton fetal growth restriction is placental insufficiency, which occurs secondary to reduced utero-placental perfusion, abnormal placentation, impaired trophoblast invasion and spiral artery remodeling, resulting in altered nutrient and oxygen transport. Two nutrient-sensing proteins involved in placental development and glucose and amino acid transport are mechanistic target of rapamycin (mTOR) and O-linked N-acetylglucosamine transferase (OGT), which are both regulated by availability of oxygen. Impairment in either of these pathways is associated with fetal growth restriction and accompanied by cellular stress in the forms of hypoxia, oxidative and endoplasmic reticulum (ER) stress, metabolic dysfunction and nutrient starvation in the placenta. Recent evidence has emerged regarding the potential impact of nutrient sensors on fetal stress response, which occurs in a sexual dysmorphic manner, indicating a potential element of genetic gender susceptibility to fetal growth restriction. In this mini review, we focus on the known role of mTOR and OGT in placental development, nutrient regulation and response to cellular stress in human fetal growth restriction with supporting evidence from rodent models.

Placental insufficiency (PI) and its complications are multifactorial conditions that cause perinatal morbidity and mortality. Since the urokinase system is involved in placentation, it should have a role in PI pathogenesis. The aim of this work was to study the associations between single nucleotide polymorphisms (SNPs) of genes coding for protein components of the urokinase system and PI, as well as investigate their effect on the expression of these proteins in the placenta and placental structure. We examined 114 women with uncomplicated pregnancy and delivery, 48 female patients with pre-eclampsia and/or intrauterine growth restriction (IUGR), and 95 newborns, (pre-eclampsia and/or IUGR: n = 60; uncomplicated pregnancy and delivery: n = 35). Maternal and fetal DNAs were genotyped using real-time PCR. Placenta fragments were subjected to morphometry and immunohistochemistry. We discovered the associations between PI and the maternal C allele of rs4065 (PI group: СС-СТ 64.1%, TT 35.9%; controls: СС-СТ 25.6%, TT 74.49%; OR (95%CI): 6.83 (2.63–17.79)), the maternal A allele of rs2302524 (GG-GA 20.5%, AA 79.5% vs. GG-GA 48.1%, AA 51.9%, OR (95%CI): 0.27 (0.1–0.71)), the fetal C allele of rs4065 (СС-СТ 76.4 %, TT 23.6% vs. СС-СТ 69.6%, TT 30.4%, OR (95%CI): 1.37 (0.45–4.17)), and the fetal C allele of rs344781 (TT-TC 69.1%, СС 30.9% vs. TT-TC 95.7%, СС 4.3%, OR (95% CI): 5.02 (1.07–23.6)). The multivariate analysis confirmed the significance of the fetal rs4065 genotype. In patients with PI, uPA expression was lower (ME (95%CI): 116.45 (100.5; 128.74) vs. 126.09 (113.76; 139.19); р < 0.05). No associations were established between SNPs and protein expression. The degree of vascularization depended on the maternal rs4065 genotype (the stroma-to-vessel ratio for the CC genotype was 0.17 (0.15; 0.19); for the CT genotype, 0.18 (0.15; 0.21) and for the TT genotype, 0.23 (0.2; 0.27); p < 0.05). We conclude that high placental uPA and the presence of the fetal TT rs4065 genotype are protective against the risk of PI.

Fetal growth restriction (FGR) is an adverse pregnancy outcome associated with significant perinatal and paediatric morbidity and mortality, and an increased risk of chronic disease later in adult life. One of the key causes of adverse pregnancy outcome is fetal growth restriction (FGR). While a number of maternal, fetal, and environmental factors are known causes of FGR, the majority of FGR cases remain idiopathic. These idiopathic FGR pregnancies are frequently associated with placental insufficiency, possibly as a result of placental maldevelopment. Understanding the molecular mechanisms of abnormal placental development in idiopathic FGR is, therefore, of increasing importance. Here, we review our understanding of transcriptional control of normal placental development and abnormal placental development associated with human idiopathic FGR. We also assess the potential for understanding transcriptional control as a means for revealing new molecular targets for the detection, diagnosis, and clinical management of idiopathic FGR.

Placental dysfunction can lead to fetal growth restriction which is associated with perinatal morbidity and mortality. Fetal growth restriction increases the risk of obesity and diabetes later in life. Placental O-GlcNAc transferase (OGT) has been identified as a marker and a mediator of placental insufficiency in the setting of prenatal stress, however, its role in the fetal programming of metabolism and glucose homeostasis remains unknown. We aim to determine the long-term metabolic outcomes of offspring with a reduction in placental OGT. Mice with a partial reduction and a full knockout of placenta-specific OGT were generated utilizing the Cre-Lox system. Glucose homeostasis and metabolic parameters were assessed on a normal chow and a high-fat diet in both male and female adult offspring. A reduction in placental OGT did not demonstrate differences in the metabolic parameters or glucose homeostasis compared to the controls on a standard chow. The high-fat diet provided a metabolic challenge that revealed a decrease in body weight gain (p = 0.02) and an improved insulin tolerance (p = 0.03) for offspring with a partially reduced placental OGT but not when OGT was fully knocked out. Changes in body weight were not associated with changes in energy homeostasis. Offspring with a partial reduction in placental OGT demonstrated increased hepatic Akt phosphorylation in response to insulin treatment (p = 0.02). A partial reduction in placental OGT was protective from weight gain and insulin intolerance when faced with the metabolic challenge of a high-fat diet. This appears to be, in part, due to increased hepatic insulin signaling. The findings of this study contribute to the greater understanding of fetal metabolic programming and the effect of placental OGT on peripheral insulin sensitivity and provides a target for future investigation and clinical applications.

Chronic fetal growth restriction is associated with both increased perinatal mortality and impaired neurodevelopment. Although it is a much more important cause of fetal neurological damage than intrapartum birth asphyxia, it is more difficult to treat, since the main intervention, timed delivery, carries its own risks. Since it is associated with a range of circulatory changes, which may also cause fetal damage, understanding these may improve management. In this article we review these fetal circulatory changes and assess their significance for predicting perinatal and long term neurodevelopmental outcome. We describe the Doppler assessment techniques, their clinical role in prediction of adverse outcome and the pathogenesis of brain injury in the preterm growth restricted fetus.

Objetivo: A finalidade deste estudo foi avaliar o Doppler venoso em gestações gemelares monocoriônicas (MC) com insuficiência placentária e a relação do fluxo sanguíneo venoso com a acidemia no nascimento ou óbito fetal. Método: Estudo prospectivo que incluiu 18 gestações gemelares MC com insuficiência placentária. Os critérios de inclusão foram: gestação gemelar MC e diamniótica, dopplervelocimetria da artéria umbilical (AU) alterada, membranas integras e ausência de defeitos congênitos fetais. Casos que apresentassem a síndrome de transfusão feto- fetal foram excluídos. Os seguintes parâmetros de Doppler foram avaliados: índice de pulsatilidade (IP) da AU, índice de pulsatilidade para veias (IPV) do ducto venoso (DV), IP e velocidade sistólica máxima (Vmax) da artéria cerebral média (ACM), a média da velocidade máxima (TAMxV) da veia umbilical (VU) e a TAMxV da veia portal esquerda (VPE). Os parâmetros dopplervelocimétricos foram transformados em escore zeta (desvios padrão da média) ou múltiplos da mediana (MoM), de acordo com os valores de referência. Amostras de sangue do cordão umbilical foram obtidas imediatamente após o parto para a mensuração do pH da artéria umbilical no nascimento. Resultado: O pH < 7,20 ocorreu em nove recém nascidos (25%), pH< 7,15 em quatro (11,1%) e em quatro (11,1%) casos houve óbito intrauterino. Os escores zeta da TAMxV da VU e da VPE foram significativamente menores no grupo com pH < 7,2 ou óbito intrauterino (respectivamente: -1,79 vs. - 1,22, p=0,006; -2,26 vs. -1,13, p=0,04). Nos casos com pH< 7,15 ou óbito intrauterino a pulsação da VU foi mais frequente (50% vs. 10,7%, p=0,03) e a TAMxV da VU foi significativamente mais baixa (-1,89 vs. -1,26, p= 0,003). A análise de regressão logística demonstrou que o escore zeta da TAMxV da VU prediz significativamente acidemia com pH< 7,20 ou óbito intrauterino (p=0,019). O parâmetro de Doppler que prediz significativamente pH< 7,15 ou óbito intrauterino foi a pulsação da VU (p=0,023). Conclusão: Os parâmetros de Doppler da VU podem predizer a acidemia no nascimento ou o óbito fetal em gestações gemelares MC complicadas por insuficiência placentária
Objectives: The aim of this study was to investigate fetal venous Doppler in monochorionic (MC) twin pregnancies complicated by placental insufficiency and the relationship between fetal venous flow and acidemia at birth or intrauterine fetal death. Methods: This was a prospective study of 18 MC twin pregnancies with placental insufficiency. Inclusion criteria were MC diamniotic twin pregnancies, abnormal umbilical artery (UA) Doppler, intact membranes, and absence of fetal congenital abnormalities. The twin-to-twin transfusion syndrome cases were excluded. The following Doppler measurements were studied: UA pulsatility index (PI), ductus venosus (DV) pulsatility index for veins (PIV), middle cerebral artery (MCA) PI and peak systolic velocity (PSV), intra-abdominal umbilical vein (UV) timeaveraged maximum velocity (TAMxV), and left portal vein (LPV) TAMxV. Doppler parameters were transformed into z-scores (SD values from the mean) or multiples of median (MoM) according to normative references. Blood samples were obtained from the umbilical cord immediately after delivery to measure the pH of the umbilical artery at birth. Results: pH<7.20 occurred in 9 newborns (25%), pH<7.15 in 4 (11.1%), and intrauterine fetal death in 4 (11.1%). The UV-TAMxV and the LPVTAMxV z-scores were significantly lower in the group presenting pH <7.20 or intrauterine fetal death (respectively: -1.79 vs. -1.22, p=0.006; -2.26 vs. -1.13, p=0.04). In cases with pH <7.15 or intrauterine fetal death, UV pulsations were more frequent (50% vs. 10.7%, p=0.03) and the UV-TAMxV z-score was significantly lower (-1.89 vs. -1.26, p=0.003). Logistic regression demonstrated that the UVTAMxV z-score significantly predicted pH at birth <7.20 or intrauterine fetal death (p=0.019). The Doppler parameter which independently predicted pH < 7.15 or intrauterine fetal death was the presence of pulsation in the umbilical vein (p=0.023). Conclusion: UV Doppler parameters may predict acidemia at birth or intrauterine fetal death in MC twins complicated by placental insufficiency