Placental Blood Samples Research Articles

Comparative performance of microscopy, rapid diagnostic tests, and multiplex real-time PCR for detection of malaria parasites among pregnant women in northwest Ethiopia

BackgroundLow malaria parasitaemia is a diagnostic challenge in pregnancy, leading to false negative microscopy and rapid diagnostic test (RDT) results. However, these submicroscopic or subpatent infections could cause adverse pregnancy outcomes. Thus, evaluating the diagnostic performance of microscopy, RDT, and multiplex qPCR in pregnancy is vital for informed decisions.MethodsA total of 835 peripheral blood and 372 placental blood samples were collected from 835 pregnant women attending first antenatal care or admitted for delivery at selected health facilities in northwest Ethiopia between November 2021 and July 2022. In multiplex qPCR, all microscopy and/or RDT positive samples were extracted and amplified individually, whereas all samples negative by both RDT and microscopy were extracted after pooling ten samples together and tested for Plasmodium genus. The diagnostic performance of microscopy, RDT, and multiplex qPCR in pregnancy was compared and evaluated against each other.ResultsUsing multiplex qPCR as a reference test, microscopy had a sensitivity of 73.8% (95% confidence interval (CI): 65.9–80.7) and 62.2% (95% CI: 46.5–76.2) to detect Plasmodium parasites in peripheral and placental blood samples, respectively, with a 100% (95% CI: 98.9–100) specificity in both samples. Similarly, the RDT had a sensitivity of 67.6% (95% CI: 59.3–75.1) and a specificity of 96.5% (95% CI: 94.9–97.8) for Plasmodium infection diagnosis in peripheral blood and a sensitivity of 62.2% (95% CI: 46.5–76.2) and a specificity of 98.8% (95% CI: 96.9–99.7) in placental blood samples. Considering microscopy as a reference test, multiplex qPCR showed a sensitivity of 100% (95% CI: 96.6–100) and a specificity of 94.8% (95% CI: 93.0–96.3) to diagnose Plasmodium infections in both peripheral and placental blood samples. Pooled multiplex qPCR detected 34 peripheral and 12 placental blood Plasmodium infections from microscopy and RDT negative samples. The pooled assay obviated about half of the reactions and its testing costs. Microscopy showed almost perfect agreement (κ = 0.823) with multiplex qPCR for detecting malaria parasites in pregnancy, whereas the RDT showed a substantial agreement (κ = 0.684).ConclusionMultiplex qPCR had a better performance for Plasmodium infection diagnosis in pregnancy compared to microscopy and RDT. Pooled multiplex qPCR could be a sensitive and resource-efficient strategy for epidemiological surveillance of Plasmodium infections in pregnancy.

Parasitic Effects on the Congenital Transmission of Trypanosoma cruzi in Mother-Newborn Pairs.

Maternal parasitemia and placental parasite load were examined in mother-newborn pairs to determine their effect on the congenital transmission of Trypanosoma cruzi. Parasitemia was qualitatively assessed in mothers and newborns by the microhematocrit test; parasite load was determined in the placental tissues of transmitting and non-transmitting mothers by the detection of T. cruzi DNA and by histology. Compared to transmitter mothers, the frequency and prevalence of parasitemia were found to be increased in non-transmitter mothers; however, the frequency and prevalence of parasite load were higher among the transmitter mothers than among their non-transmitter counterparts. Additionally, serum levels of interferon (IFN)-γ were measured by an enzyme-linked immunosorbent assay (ELISA) in peripheral, placental, and cord blood samples. Median values of IFN-γ were significantly increased in the cord blood of uninfected newborns. The median IFN-γ values of transmitter and non-transmitter mothers were not significantly different; however, non-transmitter mothers had the highest total IFN-γ production among the group of mothers. Collectively, the results of this study suggest that the anti-T. cruzi immune response occurring in the placenta and cord is under the influence of the cytokines from the mother's blood and results in the control of parasitemia in uninfected newborns.

284 Supranutritional Mineral Supplementation During Pregnancy Alters Placental Blood Flow and Calf Mineral Concentrations

Abstract Fetal development is dependent on maternal nutrient status, and the maternal-fetal connection is mediated by the placenta. There are well-established nutrient requirements for gestating cattle aimed at promoting the health of dam and fetus; however, there is limited information on the impact of supranutritional nutrient availability on placental function and calf development. This study evaluated the effect of supranutritional mineral administration during gestation on uterine artery blood flow and calf mineral status. Angus and SimAngus cows (n = 52) were bred via artificial insemination. At d 60 of gestation, cows were assigned to treatment groups; an injectable group (INJ, n = 26) receiving a single subcutaneous mineral injection and access to free-choice trace minerals and a control group (CON; n = 26) having access to free-choice trace minerals. Liver mineral content was analyzed in a subset of cows (CON n = 10; INJ n = 6) at d 60 and 209 ± 1 of gestation. At d 139.5 ± 0.5 and 209 ±1 of gestation, uterine artery measurements were collected using Color Doppler ultrasonography. Placental cotyledons, liver tissue, and blood samples were collected from a subset of animals at calving (n = 11; CON, n = 5; INJ, n = 6). Analysis revealed a TRT*day interaction at d 139.5 ± 0.5 for circulating Co concentrations which were greater (P = 0.05) and Se tended to be greater in INJ cows (P = 0.09) compared with CON cows. Circulating Zn concentrations tended to be decreased at d 209 ± 1 (P = 0.06) in INJ cows compared with the CON cows. Circulating Cu tended to be increased (P = 0.09) and Mn was decreased (P = 0.04) in INJ cows throughout the study. Hepatic Fe concentrations were decreased in INJ cows (P = 0.01) at d 209 ± 1. At d 139.5 ± 0.5, non-gravid uterine artery area, diameter, and circumference were increased in the INJ cows (P < 0.006 ). Additionally, pulsatility index of the gravid uterine artery tended to be increased (P = 0.09) in the INJ cows. Blood and liver samples were collected from calves (CON n = 24; INJ n = 26) at 4 to 8 d post-calving to assess mineral concentrations. INJ calves had greater liver Se (P = 0.001), decreased Fe (P = 0.04), and tended to have increased Zn (P = 0.09) and Mn (P = 0.08) concentrations compared with CON calves. Finally, INJ calves tended to have greater serum Se concentrations (P = 0.09) compared with CON calves. Trace minerals have roles in immune function and impact overall calf health. These results indicate that supranutritional trace mineral administration during early gestation alters placental blood flow and improves calf mineral availability. This supplementation protocol may provide the opportunity to improve the health of future calf crops.

Chemokine modulation in microscopic and submicroscopic Plasmodium falciparum malaria infection in women at delivery in Yaoundé, Cameroon.

In pregnancy-associated malaria, chemokines such as CXCL-4, CXCL-13, CXCL-16, and CCL-24 play critical roles in leucocyte trafficking to tissue sites in the infected placenta where inflammatory reactions are active. However, how plasma levels of these chemokines associate with Plasmodium falciparum placental malaria and pregnancy outcomes remains not well understood. The present study analyzed the plasma levels of CXCL-4, CXCL-13, CXCL-16, and CCL-24 chemokines in matched peripheral, placental and cord blood in relation with placental malaria (PM), and with submicroscopic parasitaemia. This was a retrospective case-control study (1:3 ratio) involving samples from 134 women (34 PM+ and 100 PM-) enrolled at delivery at the Marie Reine Health Center in Yaoundé, Cameroon between June 2013 and October 2018. Samples were collected just after delivery and used to diagnose microscopic and submicroscopic Plasmodium falciparum infections. Submicroscopic infections were detected by reverse transcription LAMP whereas chemokine levels were determined by Magnetic Luminex Screening Assay. Overall, PM was associated with increased plasma levels of CXCL-13 and CXCL-16 and low levels of CXCL-4 and CCL-24 in both peripheral and placental blood (0.0002 ≤ p ≤ 0.042). Similarly, CCL-24 levels in peripheral and placental blood samples were significantly lower in submicroscopically infected women compared to healthy controls (p = 0.04 and 0.02, respectively). Maternal hemoglobin levels increased with peripheral plasma levels of CXCL-4 (p = 0.005), CXCL-16 (p = 0.03), and CCL-24 (p = 0.002) while birth weight was lower for babies born from women with high levels of peripheral CXCL-13 (p = 0.0006) and low levels of cord CXCL-4 and CCL-24 (p = 0.02 and 0.08, respectively). Together the data suggest that low levels of CXCL-4 and CCL-24 coupled with high plasma levels of CXCL-13 and for a lesser extend CXCL-16 represent signatures of PM in the study population. These findings are relevant for understanding the immunopathogenesis of PM and developing new therapeutic or preventive strategies against severe PM outcomes.

Factors associated with birth asphyxia among term singleton births at two referral hospitals in Northern Uganda: a cross sectional study

BackgroundBirth asphyxia is one of the leading causes of neonatal mortality worldwide. In Uganda, it accounts for 28.9% of all neonatal deaths. With a view to inform policy and practice interventions to reduce adverse neonatal outcomes, we aimed to determine the prevalence and factors associated with birth asphyxia at two referral hospitals in Northern Uganda.MethodsThis was a cross-sectional study, involving women who gave birth at two referral hospitals. Women in labour were consecutively enrolled by the research assistants, who also attended the births and determined Apgar scores. Data on socio-demographic characteristics, pregnancy history and care during labour, were obtained using a structured questionnaire. Participants were tested for; i) malaria (peripheral and placental blood samples), ii) syphilis, iii) white blood cell counts (WBC), and iv) haemoglobin levels. The prevalence of birth asphyxia was determined as the number of newborns with Apgar scores < 7 at 5 min out of the total population of study participants. Factors independently associated with birth asphyxia were determined using multivariable logistic regression analysis and a p-value < 0.05 was considered statistically significant.ResultsA total of 2,930 mother-newborn pairs were included, and the prevalence of birth asphyxia was 154 [5.3% (95% confidence interval: 4.5- 6.1)]. Factors associated with birth asphyxia were; maternal age ≤ 19 years [adjusted odds ratio (aOR) 1.92 (1.27–2.91)], syphilis infection [aOR 2.45(1.08–5.57)], and a high white blood cell count [aOR 2.26 (1.26–4.06)], while employment [aOR 0.43 (0.22–0.83)] was protective. Additionally, referral [aOR1.75 (1.10–2.79)], induction/augmentation of labour [aOR 2.70 (1.62–4.50)], prolonged labour [aOR 1.88 (1.25–2.83)], obstructed labour [aOR 3.40 (1.70–6.83)], malpresentation/ malposition [aOR 3.00 (1.44–6.27)] and assisted vaginal delivery [aOR 5.54 (2.30–13.30)] were associated with birth asphyxia. Male newborns [aOR 1.92 (1.28–2.88)] and those with a low birth weight [aOR 2.20 (1.07–4.50)], were also more likely to develop birth asphyxia.ConclusionThe prevalence of birth asphyxia was 5.3%. In addition to the known intrapartum complications, teenage motherhood, syphilis and a raised white blood cell count were associated with birth asphyxia. This indicates that for sustained reduction of birth asphyxia, appropriate management of maternal infections and improved intrapartum quality of care are essential.

Hsa_circ_0008726 regulates the proliferation, migration, and invasion of trophoblast cells in preeclampsia through modulating the miR-1290-LHX6 signaling pathway.

BackgroundPreeclampsia (PE) is a serious complication of pregnancy, with a global incidence of about 2%–8%. It is one of the important causes of morbidity and mortality among the pregnant women and perinatal infants. Circular RNA (circRNA) has been confirmed to play an important regulatory role in PE. This study aimed to evaluate the role of hsa_circ_0008726 in the occurrence and development of PE.MethodsThe expression of hsa_circ_0008726 in PE placental tissue and blood was detected by qRT‐PCR. CCK‐8, wound closure, and Transwell assay were used to measure cell proliferation, migration, and invasion. Bioinformatics prediction, Western blotting, and dual‐luciferase reporter gene detection were used to explore the mechanism of hsa_circ_0008726 in HTR8/SVneo cells.ResultsThe expression level of circ_0008726 in the placental tissue and blood samples of PE patients was significantly higher than that of normal controls. The overexpression of circ_0008726 can significantly inhibit the proliferation, migration, and invasion ability of HTR‐8/SVneo cells. While the silence of circ_0008726 showed an opposite effect. Furthermore, hsa_circ_0008726 can modulate the expression of LHX6 by adsorbing miR‐1290.ConclusionHsa_circ_000872 can regulate LHX6 by adsorbing miR‐1290 to inhibit PE progression, thus establishing hsa_circ_000872 as a potential target for predicting and treating PE.

Plasmodium falciparum\xa0multiplicity of infection and pregnancy outcomes in Congolese women from southern Brazzaville, Republic of Congo

BackgroundInvestigating whether the multiplicity of Plasmodium falciparum infection (MOI) is related to pregnancy outcomes, is of interest in sub-Saharan area where malaria is highly endemic. The present study aimed to characterize the genetic diversity of P. falciparum in women at delivery from Southern Brazzaville, and investigate whether the MOI is associated with maternal anaemia, preterm delivery, or low birth weight.MethodsThis was a cross sectional study carried out with samples collected between March 2014 and April 2015 from 371 women recruited at delivery at a Health Centre in southern Brazzaville, Republic of Congo. Matched peripheral, placental, and cord blood collected from each of the women at delivery were used for the detection of P. falciparum microscopic and submicroscopic parasitaemia, and parasite DNA genotyping by nested PCR.ResultsFrom 371 recruited women, 27 were positive to microscopic malaria parasitaemia while 223 women harboured submicroscopic parasitaemia. All msp-1 block 2 family allelic types (K1, MAD20 and RO33) were observed in all the three compartments of blood, with K1 being most abundant. K1 (with 12, 10, and 08 alleles in the peripheral, placental, and cord blood respectively) and MAD20 (with 10, 09, and 06 alleles in the respective blood compartments) were more diverse compared to RO33 (with 06, 06, and 05 alleles in the respective blood compartments). From the 250 women with microscopic and/or submicroscopic parasitaemia, 38.5%, 30.5%, and 18.4% of peripheral, placental and cord blood sample, respectively, harboured more than one parasite clone, and polyclonal infection was more prevalent in the peripheral blood of women with microscopic parasitaemia (54.5%) compared to those with submicroscopic parasitaemia (36.7%) (p = 0.02). The mean multiplicity of genotypes per microscopic and submicroscopic infection in peripheral blood was higher in anemic women (2.00 ± 0.23 and 1.66 ± 0.11, respectively) than in non-anaemic women (1.36 ± 0.15 and 1.45 ± 0.06, respectively) (p = 0.03 and 0.06). In logistic regression, women infected with four or more clones of the parasite were 9.4 times more likely to be anaemic than women harbouring one clone. This association, however, was only observed with the peripheral blood infection. No significant association was found between the MOI and low birth weight or preterm delivery.ConclusionsThese results indicate that the genetic diversity of P. falciparum is high in pregnant women from southern Brazzaville in the Republic of Congo, and the multiplicity of the infection might represent a risk for maternal anaemia.

PLACENTAL MALARIA IN SOME PARTS OF ANAMBRA SOUTH-EASTERN NIGERIA

In the study conducted to determine the prevalence of placental malaria burden in Anambra State, Nigeria, venous and placenta blood samples were collected from 254 pregnant women screened in a cross-sectional hospital – based survey. Malaria parasitaemia was diagnosed by microscopy while anaemia was defined as haemoglobin concentration &lt;12g/l. Malaria species were typed using thin film parasite morphology and count. Of the 254 placental blood sample tested 131 (51.6%) samples were positive for malaria parasite. Age was significantly associated with malaria infection (P=0.0001). The intensity of the malaria infection showed a very strong association with marital status, educational level, fever and anaemia (P=0.0001, respectively). Age, educational status, fever and anaemia were significantly associated with placental malaria. Advocacy and pubic enlightenment on control measures and adequate coverage into hinter land on expectant mother to ensure adherence, acceptance and compliance to control measure.

Congenital Malaria in Newborns Delivered to Malaria-infected Mothers in the Hilly Region of Northern India: Is it Deadly?

Malaria is endemic in many states of India. Though there are reports of maternal and congenital malaria from endemic areas, however, there remains a paucity of data from hilly terrains. The present study evaluated the prevalence, clinical and microbiological spectrum of maternal and congenital malaria at a tertiary health care facility in Northern India over a period of 18 months. In this observational study, mothers along with their newborns were evaluated for malaria by maternal, placental, and cord blood smear examination and rapid point-of-care diagnostic serological tests. Positive cases were confirmed by polymerase chain reaction. Mother-newborn duos were followed up till discharge from the hospital. A total of 843 mothers delivered during the study period and were screened along with their newborns and placentae. A total of Ten (1.18%) mothers had evidence of malarial parasitemia (Plasmodium vivax, n=7 and Pl. falciparum, n=3), however, none of the placental and cord blood samples were positive for malaria. Overall, 127 (15.1%) neonates required admission in neonatal intensive care unit for various morbidities. Incidence of small for gestational age (SGA) was high (n=210; 24.9%). Multivariate logistic regression analysis demonstrated maternal malaria to be an independent contributor for SGA [Odds Ratio (95% Confidence Interval), 10.7 (2.06 - 49.72)]. However, only 2% variance of SGA could be explained by maternal malaria alone. We report an encouragingly lower incidence of maternal malaria in mothers attending for delivery and a 'Zero' incidence for placental and congenital malaria during the study period as compared to national data (upto 7.4% in non-immune mothers), although maternal malaria could be a causative factor for SGA.

Prevalence of Malaria and Associated Factors among Delivering Mothers in Northwest Ethiopia.

Background Malaria is one of the leading causes of morbidity and mortality especially in pregnant women and under-five-year-old children. However, data on the prevalence among delivering mothers, potential fetal transmission, and associated birth outcomes is lacking in Ethiopia. Objective To assess the prevalence of Plasmodium infection from peripheral, placental, and cord blood samples among delivering mothers in Kuch health center, Northwest Ethiopia. Methods An institution-based cross-sectional study was conducted among 218 delivering mothers from February to May 2021 in Kuch health center. Data on sociodemographic characteristics and clinical and obstetric history of mothers were collected using a structured questionnaire. Giemsa stained blood films from maternal capillary and placental and umbilical cord blood were examined for plasmodium infection. Data were analyzed using Statistical Package for the Social Sciences version 23 software package. Results The prevalence of maternal, placental, and umbilical cord malaria was 6.4% (14/218), 2.3% (5/218), and 0.5% (1/218), respectively. Plasmodium falciparum and Plasmodium vivax accounted 3.7% (8/218) and 2.8% (6/218), respectively, in maternal peripheral blood but only Plasmodium falciparum was detected in placental and umbilical cord blood samples. Maternal malaria had significant association with primigravida (χ2 = 12.611, p = 0.002) and low birth weight (χ2 = 8.381, p = 0.004). Placental malaria was also significantly associated with low birth weight (χ2 = 32.255, p ≤ 0.001). Conclusion The prevalence of malaria among delivering mothers was considerable. Maternal peripheral malaria had a significant association with gravidity and birth weight. Placental and umbilical cord malaria also had a significant association with birth weight. Pregnant mothers should be examined for malaria and receive appropriate treatment to prevent adverse birth outcomes.

Elevated expression of galectin-3, thioredoxin and thioredoxin interacting protein in preeclampsia.

Preeclampsia (PE) is a pregnancy-related syndrome characterized by the onset of hypertension and proteinuria that can lead to end-organ dysfunction. Galectin-3 (Gal-3) is involved in cell growth, differentiation, inflammation and fibrosis. Thioredoxin (TXN) acts as antioxidant enzyme in several cellular processes, regulating inflammation and inhibiting apoptosis. TXNIP is an endogenous inhibitor of TXN. We evaluated changes in the inflammatory response of Gal-3, TXN, and TXNIP at the level of maternal blood, placenta, and umbilical cord blood of women with PE. Ten women with PE and 20 with normal pregnancy (NP) were recruited during admission for delivery. Blood samples were obtained from parturients and umbilical cords, and placental tissue for analysis. Gal-3 and TXNIP mRNA expression were higher in maternal plasma in PE group compared to NP and were lower in cord blood plasma and placentas in the PE group. In the PE group, TXN/TXNIP mRNA ratio was higher in cord blood plasma (2.07) compared to maternal plasma (1.09). TXN/TXNIP placental protein ratio was similar between PE (0.89) and NP (0.79). ELISA demonstrated that Gal-3 levels in maternal serum were significantly higher in the PE vs. the NP group. Pro-inflammatory changes were expressed by high Gal-3 and TXNIP mRNA in maternal blood of PE women, but not in their placental and cord blood samples. These findings may imply that the placenta has a role in protecting the fetus from the damages of inflammatory response, which is more common in PE than in NP.

MicroRNA signatures associated with fetal growth restriction: a systematic review.

Placental-origin microRNA (miRNA) profiles can be useful toward early diagnosis and management of fetal growth restriction (FGR) and associated complications. We conducted a systematic review to identify case-control studies that have examined miRNA signatures associated with human FGR. We systematically searched PubMed and ScienceDirect databases for relevant articles and manually searched reference lists of the relevant articles till May 18th, 2021. Of the 2133 studies identified, 21 were included. FGR-associated upregulation of miR-210 and miR-424 and downregulation of a placenta-specific miRNA cluster miRNA located on C19MC (miR-518b, miR-519d) and miR-221-3p was reported by >1 included studies. Analysis of the target genes of these miRNA as well as pathway analysis pointed to the involvement of angiogenesis and growth signaling pathways, such as the phosphatidylinositol 3-kinase- protein kinase B (PI3K-Akt) pathway. Only 3 out of the 21 included studies reported FGR-associated miRNAs in matched placental and maternal blood samples. We conclude that FGR-associated placental miRNAs could be utilized to inform clinical practice towards early diagnosis of FGR, provided enough evidence from studies on matched placental and maternal blood samples become available.Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42019136762.

Asemptomatik gebe kadınlarda COVID-19 taraması: Hangisi daha iyi; rektal mi orofaringeal / nazofaringeal sürüntü mü?

Aim: The aim of the study was to evaluate the incidence of asymptomatic COVID-19 disease in pregnant women withrectal and oropharyngeal/nasopharyngeal swab to compare the efficacy of two samples.Material and Method: This prospective cohort study included 234 asymptomatic pregnant women who had undergoneplanned cesarean section between May 7 and September 24, 2020 in obstetrics unit of a tertiary care center, in Ankara,Turkey. The oropharyngeal/nasopharyngeal swab, rectal swab, placental, amniotic fluid, and cord blood samples wereobtained from all participants. The placental, amniotic fluid, and cord blood samples were tested when any of theoropharyngeal/nasopharyngeal or rectal samples were positive. The real-time reverse transcriptase-polymerase chainreaction (RT-PCR) test was performed to detect SARS-CoV-2 virus in the samples.Results: The incidence of the asymptomatic COVID-19 disease was 0.42% (1/234) in the study population. One of 234oropharyngeal/nasopharyngeal swabs was positive, while none of the rectal swabs including the one positive withoropharyngeal/nasopharyngeal swab were positive for SARS-CoV-2 virus. The RT-PCR test results of the placental,amniotic fluid, and cord blood samples of the COVID-positive case were negative.Conclusion: The incidence of asymptomatic COVID-19 disease in pregnant women who had undergone elective cesareandelivery was low, in Ankara, Turkey. In asymptomatic pregnant women, oropharyngeal/nasopharyngeal swab was foundto be more useful in detecting COVID-19 disease compared to rectal swab. No evidence was found about the intrauterinetransmission of asymptomatic disease.

MicroRNA-3935 promotes human trophoblast cell epithelial-mesenchymal transition through tumor necrosis factor receptor-associated factor 6/regulator of G protein signaling 2 axis

BackgroundInsufficient migration and invasion during trophoblast epithelial-mesenchymal transition (EMT) results in the occurrence and development of preeclampsia (PE), and our previous study has screened 52 miRNAs, whose expression levels are altered in the placental samples from PE patients, compared with the normal group. Among those, miR-3935 is one of the miRNAs being most significantly down-regulated, indicating its involvement in PE. However, the exact effect and molecular mechanisms remain unknown.MethodsIn the present study, we investigate the roles and underlying mechanisms of miR-3935 in trophoblast EMT by use of the human extra-villous trophoblast cell line HTR-8/SVneo as well as human placental tissues and maternal blood samples obtained from 15 women with normal pregnancies and 15 women with PE. Experimental methods include transfection, quantitative reverse transcription-PCR (qRT-PCR), western blot, immunofluorescence staining, dual-luciferase assays, in vitro invasion and migration assays, RNA-Seq analysis, bisulfite sequencing and immunohistochemistry staining.ResultsMiR-3935 expression is significantly decreased in both placentas and peripheral blood specimens of PE, and functionally, miR-3935 promotes EMT of trophoblast cells. Mechanistically, TRAF6 is identified to be a direct target of miR-3935 and TRAF6 exerts its negative effect on EMT of trophoblast cells by inhibition of RGS2, which down-regulates the methylation status of promoter of CDH1 gene that encodes E-Cadherin protein through induction of ALKBH1, resulting in increase of E-Cadherin and subsequently insufficient trophoblast EMT.ConclusionsTogether these results uncover a hitherto uncharacterized role of miR-3935/TRAF6/RGS2 axis in the function of human trophoblasts, which may pinpoint the molecular pathogenesis of PE and may be a prognostic biomarker and therapeutic target for such obstetrical diseases as PE.

A blueprint for prioritising preventable stillbirths in low- to middle-income settings.

In this issue, Goldenberg et al present a large and thorough evaluation of stillbirths delivered between 2018 and 2020 in study hospitals in India and Pakistan. For stillborn singletons ≥ 20 weeks' gestation (n=872; 357 from India, 515 from Pakistan), a detailed review of demographics, prenatal complications, and medical history was undertaken and combined with histologic placental examination, surface photographic evaluation of the fetus, and an extensive infectious workup of over 75 known viral, bacterial or parasitic pathogens from placental and cord blood samples.

Predictors of placental malaria in Upper West Regional Hospital-Ghana

BackgroundPlacental malaria (PM) poses life-threatening complications to pregnant women as they are at increased risk of maternal and perinatal morbidity and mortality associated with malaria. This study examined the factors associated with placental malaria in the Upper West Regional Hospital (UWR).MethodsA cross-sectional hospital-based study was carried out among pregnant women delivering at Upper West Regional Hospital. A cross-sectional screening survey was conducted from January 2019 to April 2019. Three hundred eligible mothers were consecutively recruited. A record review of their maternal and child history was assessed using a checklist. Placental blood samples were taken for microscopy to determine placental malaria parasitemia. Logistic regression analysis was done to determine the factors associated with placental malaria at 95 % confidence level.ResultsThe proportion of mothers with placental malaria was 7 % (21/300), (95 % CI, 4.3–10.5 %). Plasmodium falciparum was the only species identified in those with PM. Majority of the women 66.7 % (14/21) with placental malaria had parasite density in the range 501 to 5,000 parasites/µL. Obstetric and health service factors that were significantly associated with placental malaria were gravidity and antenatal care (ANC) attendance. Primigravida (aOR = 3.48, 95 %CI = 1.01–12.01) and having less than 4 ANC attendance (aOR = 9.78, 95 %CI = 2.89–33.11) were found to be significantly associated with placental malaria.ConclusionsThe proportion of women with PM was relatively low. Primigravid mothers reporting less than 4 ANC visits had the highest risk of placental malaria. Expectant mothers should be encouraged to attend at least 4 ANC visits prior to delivery.

Suitability of Placental Blood Samples of Newborns for Pre-Transfusion Testing.

Objective: To show concordance between heel stick and placental blood sample pairs for newborns' pre-transfusion testing and to validate placental blood's tube and gel methodology.Methods: Placental samples were collected for pre-transfusion testing at birth from 78 singleton and twin newborns admitted to our Mother–Baby Unit to compare with the results of heel stick samples taken from same newborns. Gestational age ≥35 weeks, weight ≥2,000 g. The study was approved by the Institutional Review Board (IRB). Informed consent was obtained from newborn parents. ABO blood group, Rhesus factor (Rh), direct antiglobulin test (DAT), and antibody screen were performed. Ortho ProVue Analyzer was used for tube and gel methods. McNemar's test for paired categorical data was performed.Results: One hundred percent concordance in 78 pairs for ABO and Rh. Seventy-four pairs were tested for antibodies, 72 were both negative, 1 was both positive, and 1 gave discordant result. Ninety-nine percent concordance, p = 0.999. Sixty-five pairs were both DAT negative, seven were both DAT positive, and six gave discordant results. Ninety-two percent concordance, p = 0.68. Placental blood gave identical results comparing tube with gel methods.Conclusions: Placental blood is suitable for pre-transfusion testing and can replace heel sticks. Placental blood tube and gel methods are validated.

Suitability of Placental Blood Sample of Newborns for Pre-Transfusion Testing

Suitability of Placental Blood Sample of Newborns for Pre-Transfusion Testing

374 Thioredoxin, thioredoxin interacting protein and galectin-3 in preeclampsia

Preeclampsia (PE) is a pregnancy-related syndrome characterized by the onset of hypertension and proteinuria and may lead to end-organ dysfunction. Thioredoxin (TXN), acts as antioxidant enzyme in several cellular processes, regulating inflammation, promoting cell proliferation and inhibiting apoptosis. TXNIP is an endogenous inhibitor of TXN. Galectin-3 involves in cell growth, differentiation, inflammation, and fibrosis. We evaluated changes in the inflammatory response of TXNIP, TXN, and Galectin-3 at the level of maternal serum, placenta, and umbilical blood of women with preeclampsia, compared to normal pregnancies (NP). 10 women with PE and 15 with NP were recruited during admission for delivery. Blood samples were obtained from parturients and umbilical cords, as well as placental tissue for mRNA and protein extraction. We evaluated changes in the inflammatory response of TXNIP, TXN, and Galectin-3 at the level of maternal serum, placenta, and umbilical blood of women with preeclampsia, compared to normal pregnancies (NP). TXNIP and Gal-3 mRNA expression were higher in PE maternal serum mRNA compared to NP. TXNIP and Gal-3 mRNA expression were lower in PE placentas and cord blood compared to PE maternal serum mRNA expression. TXN/TXNIP mRNA ratio had high absolute values in placental and cord blood (2.06 and 1.06, respectively), compared to maternal ratio (0.304). TXN/TXNIP placental protein ratio had similar values between PE and NP (1.04 and 1.01). Gal-3 protein was higher in PE placentas compare to NP (3.79±0.66; P<0.0001). We revealed that patients with preeclmapsia had Pro-inflammatory changes that are expressed by high Gal-3 expression and a low TXN/TXNIP mRNA ratio in maternal blood of women with PE, but not in their placental and umbilical cord blood samples. These findings imply that the placenta may have a role in protecting the fetus from the damages of oxidation and the inflammatory response, which are more common in preeclampsia than in normal pregnancies.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

LncRNA PROX1-AS1 mediates the migration and invasion of placental trophoblast cells via the miR-211-5p/caspase-9 axis

ABSTRACT Preeclampsia (PE) is a potentially fatal pregnancy complication; however, its pathogenesis remains unclear. Long non-coding RNAs (lncRNAs) are associated with occurrence and progression of PE. Therefore, this study aimed to explore the function of the lncRNA prospero homeobox 1-antisense RNA 1 (PROX1-AS1) and elucidate its underlying molecular mechanism of action. We found that the expression levels of PROX1-AS1 were elevated in both the placental tissues and blood samples of the patients with PE. Moreover, the results of the flow cytometry and transwell assay showed that the knockdown of PROX1-AS1 inhibited the apoptosis and promoted the migration and invasion of HTR-8/SVneo cells. We also assessed the interactions between PROX1-AS1, caspase-9, and microRNA (miR)-211-5p via dual-luciferase reporter and RNA pull-down analyses. The data indicated that PROX1-AS1 acted as a sponge for miR-211-5p to regulate the expression of caspase-9. Moreover, the expression of miR-211-5p was reduced in PE and negatively related to PROX1-AS1, while that of caspase-9 was increased in PE and negatively regulated by miR-211-5p. Furthermore, inhibition of miR-211-5p rescued the facilitation of cell apoptosis, migration and invasion induced by the knockdown of PROX1-AS1. We also found that caspase-9 improved the apoptosis rate, and suppressed the cell migration and invasion induced by the overexpression of miR-211-5p. In conclusion, the knockdown of PROX1-AS1 promoted the cell morbidity of the trophoblast cells by modulating the miR-211-5p/caspase-9 axis, which may alleviate the progression of PE. This novel regulatory network may contribute to the pathogenesis and progression of PE.