High-Grade Fetal Vascular Malperfusion Is Associated With Diffuse Chorionic Hemosiderosis

Introduction Diffuse chorionic hemosiderosis (DCH) is an abnormality of the placental membranes characterized by the deposition of iron pigment. It is usually secondary to recurrent venous bleeding in early pregnancy. In many papers, it is associated with pre-term delivery. Fetal vascular malperfusion (FVM) is an abnormality of the feto-placental circulation that may be seen at any stage of gestation, but most often in the third trimester. It may be graded as low grade (LGFVM) or high grade (HGFVM). No link has been identified in the placental literature between DCH and FVM, but we have noted the 2 co-existing in placentas submitted for analysis. This study explored a possible association of these 2 entities. Methods Laboratory records were searched for singleton cases coded as DCH based on diagnosis on H&E stain over a 6-year period. Of 4478 placentas reported, 66 cases were coded as DCH (1.5%). These were classified as showing HGFVM, LGFVM, or no FVM. Controls (n = 132) were gestational age-matched cases without DCH. Cord length, coiling, insertion, or other abnormalities were noted. Membranes were classified as normal or circumvallate. Results were analyzed using Graphpad. Results Gestation ranged between 16 and 41 weeks gestation. 14/66 (21%) cases of DCH showed HGFVM and 2/66 (3%) showed LGFVM. 16/132 (12%) controls showed HGFVM and 21/132 (15.9%) had LGFVM. Where FVM is present, high-grade FVM is significantly associated with DCH versus controls ( P < .0031 Fischer’s Test). Discussion HGFVM occurs significantly more often in placentas with DCH than in controls. Both FVM and DCH are associated with adverse perinatal outcomes, and a possible relationship between the 2 remains to be clarified.

Chorioamnionitis has no impact on immunohistochemical expression of IL-6 in placental membranes of the late preterm delivery regardless of the membrane status

Objectives To compare the immunohistochemical expression of IL-6 in placental membranes of late preterm delivery in women with histologically proven chorioamnionitis with and without preterm premature rupture of membranes (PPROM). Methods Fetal membranes were collected from 60 women who had late preterm delivery with histologic chorioamnionitis with and without PPROM (30 in each group). Immunohistochemistry for IL-6 was performed on formalin fixed and paraffin-embedded sections. The two groups were matched for age, body mass index and parity. SPSS Version 17.0 was used for statistical analysis. Results There was no difference in immunohistochemical expression of IL-6 in placental membranes of women with histologic chorioamnionitis regardless of the membrane status. Conclusions Chorioamnionitis has no impact on immunohistochemical expression of IL-6 in placental membranes of women with late preterm delivery despite the clinical presentation.

The Inflammatory Milieu of Amniotic Fluid Increases with Chorio-Deciduitis Grade in Inflammation-Restricted to Choriodecidua, but Not Amnionitis, of Extra-Placental Membranes

No information exists about whether intra-amniotic inflammatory response increases with a chorio-deciduitis grade in the context of both inflammation-restricted to chorio-decidua and amnionitis of extra-placental membranes among spontaneous preterm births. The objective of current study is to examine this issue. A study population included 195 singleton pregnant women with chorio-deciduitis, and who spontaneously delivered at preterm (21.6~35.7 weeks) within 7 days of amniocentesis. We examined intra-amniotic inflammatory response according to the chorio-deciduitis grade in the context of inflammation restricted to chorio-decidua and amnionitis of extra-placental membranes. Intra-amniotic inflammatory response was measured by MMP-8 concentration (ng/mL) and WBC-count (cells/mm3) in amniotic-fluid (AF). Inflammation restricted to chorio-decidua and amnionitis were present in 47.7% (93/195) and 52.3% (102/195) of cases, respectively. Median AF MMP-8 concentration and WBC-count significantly increased with chorio-deciduitis grade in the context of inflammation restricted to chorio-decidua. However, there was no significant difference in median AF MMP-8 concentration and WBC-count between chorio-deciduitis grade-1 and grade-2 in the context of amnionitis. The inflammatory milieu of AF increases with chorio-deciduitis grade in inflammation-restricted to chorio-decidua, but not amnionitis, of extra-placental membranes. This finding suggests that a chorio-deciduitis grade may have little effect on the intensification of intra-amniotic inflammatory response in the context of amnionitis of extra-placental membranes.

Integrin Adhesion Complex Organization in Sheep Myometrium Reflects Changing Mechanical Forces during Pregnancy and Postpartum

Cells respond to extracellular mechanical forces through the assembly of integrin adhesion complexes (IACs) that provide a scaffold through which cells sense and transduce responses to those forces. IACs are composed of transmembrane integrin receptors that bind to extracellular matrix (ECM) proteins externally and connect with the actomyosin cytoskeleton internally. Myometrial smooth muscle cells respond to forces that arise due to increases in fetal growth/weight, placental fluid volumes, and blood flow. As a result, the uterus transforms into an organ that can forcefully expel the fetus and placental membranes during parturition. While earlier studies focused on IAC expression in the myometrial compartment of rodents and humans to explore pregnancy-associated responses, the present study examines IAC assembly in ovine myometrium where mechanical forces are expected to be amplified in a manner similar to humans. Results indicate that the ITGA5 and ITGB1 heterodimers associate with the ECM protein FN1 externally, and with VCL and TLN1 internally, to form IACs in myometrial cells during the first trimester of pregnancy. These IACs become increasingly ordered until parturition. This ordered structure is lost by one day postpartum; however, the abundance of the integrin proteins remains elevated for at least two weeks postpartum. Implications of the present study are that sheep are similar to humans regarding the assembly of IACs in the pregnant myometrium and suggest that IACs may form much earlier in human gestation than was previously implied by the rat model. Results highlight the continued value of the sheep model as a flagship gynecological model for understanding parturition in humans.

MICROBIAL LANDSCAPE OF THE NEONATAL INTENSIVE CARE UNIT: A RETROSPECTIVE ANALYSIS

Objective. To investigate the structure, antenatal and intranatal risk factors and results of treatment of neonatal sepsis.Materials and methods. This study used analysis of 137 case histories of newborns from 2015 to 2019. We evaluated maternal risk factors, intrapartum asphyxia, duration of treatment, number of days on mechanical ventilation, the presence of sepsis, necrotic enterocolitis, mortality.Results and discussion. Most children were over 2500 g (69.3%). In infants with a birth weight lower than 1500 g were 10.9%. 70.8% of newborns received in the first 24 hours after birth. From the moment of admission to the department, among all infected children was 71%, mortality was 14%. In children under 29 weeks of gestation, the risk of developing sepsis is 17.2 times higher. (р˂0.001) In children under 1 kg of weight, the risk of manifestation of sepsis is 42.2 times higher. (р˂0.001)The maternal colonization have the risk of developing a child’s infection is 4.36 times higher. (р˂0.001)With a diagnosis of sepsis most infants were more than 2.5 kg and mortality remained significantly high 31.6-36.8% in all weight groups (0.00001), depending on birth weight.The majority of the applicants were children over 37 weeks, but mortality was significantly higher in the group from 29-37 weeks (0.00001), depending on the term of gestation.Among the studied mothers, up to 53% were maternal colonization and in this group the mortality of children was significantly higher than 23% (p=0.020).However, in the group of children where there were signs of ascending infection of the placenta (there were 25%) mortality was still significantly higher by 1.4 times, 32% (p=0,008).Conclusions. The risk of developing neonatal sepsis was increased in ascending infection (clinical chorioamnionitis) in 6.65 times, (р˂0.001), the presence of a coagulase-negative culture by 5.83 (р˂0.011) and invasive respiratory therapy by 18.52 times. (р˂0.002) Mortality rates are affected by gestational age OR=13.81 (р˂0.001), birth weight 1-1.5 kg OR=13.15 (р˂0.001), 1.5-2.5 kg OR=2.86 (р=0.043), maternal factors (vaginal colonization, ascending infection) OR=3,22 (р˂0.023), infection of placental membranes OR=4,32 (р˂0.008), the presence of sepsis OR=15,56 (р˂0.001), necrotic enterocolitis OR=8,06 (р˂0.001) and CoNS OR=4,98 (р˂0.033).

Food and Drug Administration’s Position on Commonly Injected Biologic Materials in Orthopaedic Surgery

The use of biologically based therapies is becoming a popular less-invasive therapy for relieving pain and promoting tissue regeneration. The most commonly used biologics are autologous adipose-derived products, bone marrow aspirations, and platelet-rich plasma (PRP). Birth tissue is a common allogenic source of biologics, including umbilical cord, placental membranes, and amniotic fluid. Injected biologics, depending on the indication and how they are processed, formulated, delivered, and promoted, can be subject to different regulatory pathways. The aim of this review is to provide an overview of these products and procedures and educate the musculoskeletal community about the relevant current Food and Drug Administration (FDA) regulations.

Luteal phase pregnancy after mirena coil insertion for intrauterine septum resection

This report is of an unusual case of an intrauterine singleton pregnancy with a Mirena Coil (IUS) in situ following an elective hysteroscopic intrauterine septum resection for treatment of primary subfertility in a 27-year-old female. The patient elected to continue with the pregnancy and underwent additional monitoring via ultrasound. A caesarean section was undertaken at 39-weeks gestation and a healthy male infant was born. The Mirena coil was recovered intraoperative and was visualised in the placental membranes. Pregnancy occurring with Mirena coil insertion as an adjunct to hysteroscopic septum resection in our case is an unusual clinical scenario with no management recommendations and limited recorded outcomes. Therefore, this case demonstrates potential management of such a case and learning points for intrauterine septum excision in the context of primary subfertility.

Loss of ITGB3 in ovine conceptuses decreases conceptus expression of NOS3 and SPP1: implications for the developing placental vasculature†

During the peri-implantation period of pregnancy in sheep, there is an initial period of loose apposition of the elongating conceptuses (embryos and associated placental membranes) to the endometrial luminal epithelium (LE) that is followed by adhesion of the conceptus trophectoderm to the endometrial LE for implantation. Integrins and maternal extracellular matrix (ECM) molecules are major contributors to stable adhesion at implantation, and the β3 integrin subunit (ITGB3) is implicated in the adhesion cascade for implantation in several species including the sheep. We blocked mRNA translation for trophectoderm-expressed ITGB3 by infusing morpholino antisense oligonucleotides into the uterine lumen of pregnant ewes on Day 9 to assess effects on conceptus elongation, and on Day 16 to assess effects on early placental development in sheep. Results indicate that sheep conceptuses elongate and implant to the uterine wall in the absence of ITGB3 expression by the conceptuses; however, loss of ITGB3 in conceptuses decreased the growth of embryos to Day 24 of gestation, and decreased expression of secreted phosphoprotein 1 (SPP1) and nitric oxide synthase 3 (NOS3). Abundant SPP1 was localized around the blood vessels in the placental allantoic membrane in normal sheep pregnancies. We hypothesize that NOS3 and SPP1 positively influence the development of the vasculature within the allantois, and that decreased expression of NOS3 and SPP1, in response to knockdown of ITGB3 in conceptuses, alters development of the vasculature in the allantois required to transport nutrients from the endometrium to support growth and development of the embryo.

410 Steroids Regulate SLC2A1 and SLC2A3 to Deliver Glucose into Trophectoderm for Metabolism via Glycolysis

The conceptuses (embryo/fetus and placental membranes) of pigs require energy to support elongation and implantation, and amounts of glucose and fructose increase in the uterine lumen during the peri-implantation period. Conceptuses from Day 16 of pregnancy were incubated with either 14C-glucose or 14C-fructose and amounts of radiolabeled CO2 released from the conceptuses measured to determine rates of oxidation of glucose and fructose. Both glucose and fructose transport into conceptuses, and glucose is preferentially metabolized in the presence of fructose, while fructose is actively metabolized in the absence of glucose and to a lesser extent in the presence of glucose. Endometrial and placental expression of glucose transporters SLC2A1, SLC2A2, SCL2A3 and SLC2A4 were determined. SLC2A1 mRNA and protein, and SLC2A4 mRNA were abundant in the uterine luminal epithelium of pregnant compared to cycling gilts, and increased in response to progesterone and conceptus-secreted estrogen. SLC2A2 mRNA was expressed weakly by conceptus trophectoderm on Day 15 of pregnancy, while SLC2A3 mRNA was abundant in trophectoderm/chorion throughout pregnancy. Therefore, glucose can be transported into the uterine lumen by SLC2A1, and then into conceptuses by SLC2A3. On Day 60 of gestation, the cell-specific expression of these transporters was more complex, suggesting that glucose and fructose transporters are precisely regulated in a spatial-temporal pattern along the uterine-placental interface of pigs to maximize hexose sugar transport to the pig conceptus/placenta.