Multi-country studies assessing the quality of maternal and newborn care (QMNC) during the COVID-19 pandemic, as defined by WHO Standards, are lacking.
Women who gave birth in 12 countries of the WHO ...European Region from March 1, 2020 - March 15, 2021 answered an online questionnaire, including 40 WHO Standard-based Quality Measures.
21,027 mothers were included in the analysis. Among those who experienced labour (N=18,063), 41·8% (26·1%- 63·5%) experienced difficulties in accessing antenatal care, 62% (12·6%-99·0%) were not allowed a companion of choice, 31·1% (16·5%-56·9%) received inadequate breastfeeding support, 34·4% (5·2%-64·8%) reported that health workers were not always using protective personal equipment, and 31·8% (17·8%-53·1%) rated the health workers’ number as “insufficient”. Episiotomy was performed in 20·1% (6·1%-66·0%) of spontaneous vaginal births and fundal pressure applied in 41·2% (11·5% -100%) of instrumental vaginal births. In addition, 23·9% women felt they were not treated with dignity (12·8%-59·8%), 12·5% (7·0%-23·4%) suffered abuse, and 2·4% (0·1%-26·2%) made informal payments. Most findings were significantly worse among women with prelabour caesarean birth (N=2,964). Multivariate analyses confirmed significant differences among countries, with Croatia, Romania, Serbia showing significant lower QMNC Indexes and Luxemburg showing a significantly higher QMNC Index than the total sample. Younger women and those with operative births also reported significantly lower QMNC Indexes.
Mothers reports revealed large inequities in QMNC across countries of the WHO European Region. Quality improvement initiatives to reduce these inequities and promote evidence-based, patient-centred respectful care for all mothers and newborns during the COVID-19 pandemic and beyond are urgently needed.
The study was financially supported by the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy.
ClinicalTrials.gov Identifier: NCT04847336
Photochemical internalization (PCI) is a technology for inducing release of endocytosed antigens into the cell cytosol
a light-induced process. Preclinical experiments have shown that PCI improves ...MHC class I antigen presentation, resulting in strongly enhanced CD8+ T-cell responses to polypeptide antigens. In PCI vaccination a mixture of the photosensitizing compound fimaporfin, vaccine antigens, and an adjuvant is administered intradermally followed by illumination of the vaccination site. This work describes an open label, phase I study in healthy volunteers, to assess the safety, tolerability, and immune response to PCI vaccination in combination with the adjuvant poly-ICLC (Hiltonol) (ClinicalTrials.gov Identifier: NCT02947854).
The primary objective of the study was to assess the safety and local tolerance of PCI mediated vaccination, and to identify a safe fimaporfin dose for later clinical studies. A secondary objective was to analyze the immunological responses to the vaccination. Each subject received 3 doses of HPV16 E7 peptide antigens and two doses of Keyhole Limpet Hemocyanin (KLH) protein. A control group received Hiltonol and vaccine antigens only, whereas the PCI groups in addition received fimaporfin + light. Local and systemic adverse effects were assessed by standard criteria, and cellular and humoral immune responses were analyzed by ELISpot, flow cytometry, and ELISA assays.
96 healthy volunteers were vaccinated with fimaporfin doses of 0.75-50 µg. Doses below 17.5 µg were safe and tolerable, higher doses exhibited local tolerability issues in some study subjects, mainly erythema, and pain during illumination. There were few, and only mild and expected systemic adverse events. The employment of PCI increased the number of subjects exhibiting a T-cell response to the HPV peptide vaccine about 10-fold over what was achieved with the antigen/Hiltonol combination without PCI. Moreover, the use of PCI seemed to result in a more consistent and multifunctional CD8+ T-cell response. An enhancement of the humoral immune response to KLH vaccination was also observed.
Using PCI in combination with Hiltonol for intradermal vaccination is safe at fimaporfin doses below 17.5 µg, and gives encouraging immune responses to peptide and protein based vaccination.
Kudoa thyrsites is a myxosporean parasite (Cnidaria, Myxozoa) that infects the skeletal and cardiac muscle of Northeast Atlantic (NEA) mackerel (Scomber scombrus). Heavy infections are associated ...with post-mortem myoliquefaction of the host skeletal muscle which reduces the quality of the fish product. The biological infection characteristics of the parasite in NEA mackerel are poorly known. This study examined the distribution of K. thyrsites in various organs of NEA mackerel from the northern North Sea, and elucidates the relationship between density of infection, developmental stage and parasite distribution in the musculature, and the extent of visible flesh myoliquefaction. Quantitative polymerase chain reaction (qPCR) data showed that K. thyrsites is unevenly distributed in the somatic musculature of the fish host, with highest density in the anterior ventral muscle sections-the belly flaps. A weak positive correlation was observed between the level of myoliquefaction and the parasite density in the fish host muscle. This relationship was also reflected by the amount and distribution of parasite developmental stages seen during histological examinations. Histological findings indicate an association between the dispersion of free myxospores and the level of myoliquefaction of the fish host muscle. Visceral organs were also found infected using qPCR, although at lower densities compared to the musculature.
Effective priming and activation of tumor-specific CD8+ cytotoxic T lymphocytes (CTLs) is crucial for realizing the potential of therapeutic cancer vaccination. This requires cytosolic antigens that ...feed into the MHC class I presentation pathway, which is not efficiently achieved with most current vaccination technologies. Photochemical internalization (PCI) provides an emerging technology to route endocytosed material to the cytosol of cells, based on light-induced disruption of endosomal membranes using a photosensitizing compound. Here, we investigated the potential of PCI as a novel, minimally invasive, and well-tolerated vaccination technology to induce priming of cancer-specific CTL responses to peptide antigens. We show that PCI effectively promotes delivery of peptide antigens to the cytosol of antigen-presenting cells (APCs)
. This resulted in a 30-fold increase in MHC class I/peptide complex formation and surface presentation, and a subsequent 30- to 100-fold more efficient activation of antigen-specific CTLs compared to using the peptide alone. The effect was found to be highly dependent on the dose of the PCI treatment, where optimal doses promoted maturation of immature dendritic cells, thus also providing an adjuvant effect. The effect of PCI was confirmed
by the successful induction of antigen-specific CTL responses to cancer antigens in C57BL/6 mice following
peptide vaccination using PCI technology. We thus show new and strong evidence that PCI technology holds great potential as a novel strategy for improving the outcome of peptide vaccines aimed at triggering cancer-specific CD8+ CTL responses.
ObjectivesDevelop and validate a WHO Standards-based online questionnaire to measure the quality of maternal and newborn care (QMNC) around the time of childbirth from the health workers’ ...perspective.DesignMixed-methods study.SettingSix countries of the WHO European Region.Participants and methodsThe questionnaire is based on lessons learnt in previous studies, and was developed in three sequential phases: (1) WHO Quality Measures were prioritised and content, construct and face validity were assessed through a Delphi involving a multidisciplinary board of experts from 11 countries of the WHO European Region; (2) translation/back translation of the English version was conducted following The Professional Society for Health Economics and Outcomes Research guidelines; (3) internal consistency, intrarater reliability and acceptability were assessed among 600 health workers in six countries.ResultsThe questionnaire included 40 items based on WHO Standards Quality Measures, equally divided into four domains: provision of care, experience of care, availability of human and physical resources, organisational changes due to COVID-19; and its organised in six sections. It was translated/back translated in 12 languages: Bosnian, Croatian, French, German, Italian, Norwegian, Portuguese, Romanian, Russian, Slovenian, Spanish and Swedish. The Cronbach’s alpha values were ≥0.70 for each questionnaire section where questions were hypothesised to be interrelated, indicating good internal consistence. Cohen K or Gwet’s AC1 values were ≥0.60, suggesting good intrarater reliability, except for one question. Acceptability was good with only 1.70% of health workers requesting minimal changes in question wording.ConclusionsFindings suggest that the questionnaire has good content, construct, face validity, internal consistency, intrarater reliability and acceptability in six countries of the WHO European Region. Future studies may further explore the questionnaire’s use in other countries, and how to translate evidence generated by this tool into policies to improve the QMNC.Trail registration number NCT04847336
Maternal alloimmunization against human platelet antigen (HPA)-1a has been implied to mediate both reduced birth weight and chronic placental inflammation. Fetal growth restriction is associated with ...different types of chronic inflammation in the placenta, mainly chronic histiocytic intervillositis and chronic villitis. The aim of this prospective study was to do a systematic examination of placentas from HPA-1a alloimmunized pregnancies, with focus on the histopathological and immunohistochemical diagnosis of variants of chronic inflammation.
In a Polish-Norwegian study, 48 placentas were examined. The histopathology of placentas from 27 HPA-1a immunized women was compared with 21 placentas from non-immunized HPA-1a negative women (controls). In the group of alloimmunized women, ten received antenatal intravenous immunoglobulin G (IVIg). Tissue sections from formalin fixed paraffin embedded placental tissue were stained with hematoxylin and eosin and microscopically examined with focus on various types of chronic placental inflammations.
Chronic histiocytic intervillositis was observed in 40.7% of placentas from HPA-1a alloimmunized pregnancies, compared to none in the control group (p = 0.001). Chronic villitis of unknown etiology was more frequently found in the alloimmunized group, however this difference was not statistically significant. Maternal administration of IVIg did not seem to protect against chronic inflammatory lesions.
Placentas with detectable maternal anti-HPA-1a antibodies are associated with highly increased risk of low-grade chronic histiocytic intervillositis.
•CHIV found in 40 % of HPA-1a alloimmunized pregnancies.•Immunohistochemistry shows T8-cells involved in destruction of fetal capillaries.•Worse clinical outcome in alloimmunized pregnancies with CHIV.•Antenatal IVIg did not seem to prevent chronic inflammatory lesions.
Cesarean section rates remain high in Georgia. As a cesarean section in the first pregnancy generally lead to a cesarean section in subsequent pregnancies, primiparous women should be targeted for ...prevention strategies. The aim of the study was to assess factors associated with cesarean section among primiparous women. The study comprised 17,065 primiparous women with singleton, cephalic deliveries at 37–43 weeks of gestation registered in the Georgian Birth Registry in 2017. The main outcome was cesarean section. Descriptive statistics and logistic regression analysis were used to identify factors associated with cesarean section. The proportion of cesarean section was 37.1% with regional variations from 14.2% to 57.4%. Increased maternal age, obesity and having a baby weighing ≥4000 g were all associated with higher odds of cesarean section. Of serious concern for newborn wellbeing is the high proportion of cesarean section at 37–38 weeks of gestation. Further research should focus on organizational and economical aspects of maternity care to uncover the underlying causes of the high cesarean section rate in Georgia.
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding disorder caused by maternal antibodies against paternal human platelet antigens (HPAs) on fetal platelets. Antibodies against ...HPA-1a are accountable for the majority of FNAIT cases. We have previously shown that high levels of maternal anti-HPA-1a antibodies are associated with clinically significant reduced birth weight in newborn boys. Chronic inflammatory placental lesions are associated with increased risk of reduced birth weight and have previously been reported in connection with FNAIT pregnancies. The HPA-1a epitope is located on integrin β3 that is associated with integrin αIIb (the fibrinogen receptor) on platelets and megakaryocytes. Integrin β3 is also associated with integrin αV forming the αVβ3 integrin heterodimer, the vitronectin receptor, which is expressed on various cell types, including trophoblast cells. It is therefore thinkable that maternal anti-HPA-1a antibodies present during early pregnancy may affect placenta function through binding to the HPA-1a antigen epitope on invasive throphoblasts. The aim of the study was to examine whether interaction of a human anti-HPA-1a monoclonal antibody (mAb) with HPA-1a on trophoblast cells affect adhesion, migration and invasion of extravillous trophoblast cells.
An in vitro model with human anti-HPA-1a mAb, clone 26.4, and the first trimester extravillous trophoblast cell line HTR8/SVneo was employed. The xCELLigence system was utilized to assess the possible effect of anti-HPA-1a mAb on adhesion and migration of HTR8/SVneo cells. Specially designed chambers precoated with Matrigel were used to assess the effect on the invasive capacity of cells.
We found that human anti-HPA-1a mAb 26.4 partially inhibits adhesion and migratory capacity of HTR8/SVneo cells.
Our findings suggest that anti-HPA-1a antibodies may affect trophoblast functions crucial for normal placental development. Future studies including primary throphoblast cells and polyclonal anti-HPA-1a antibodies are needed to confirm these results.
Introduction: Maternal alloimmunization against human platelet antigen (HPA)-1a has been implied to mediate both reduced birth weight and chronic placental inflammation. Fetal growth restriction is ...associated with different types of chronic inflammation in the placenta, mainly chronic histiocytic intervillositis and chronic villitis. The aim of this prospective study was to do a systematic examination of placentas from HPA-1a alloimmunized pregnancies, with focus on the histopathological and immunohistochemical diagnosis of variants of chronic inflammation.
Material and methods: In a Polish-Norwegian study, 48 placentas were examined. The histopathology of placentas from 27 HPA-1a immunized women was compared with 21 placentas from non-immunized HPA-1a negative women (controls). In the group of alloimmunized women, ten received antenatal intravenous immunoglobulin G (IVIg). Tissue sections from formalin fixed paraffin embedded placental tissue were stained with hematoxylin and eosin and microscopically examined with focus on various types of chronic placental inflammations.
Results: Chronic histiocytic intervillositis was observed in 40.7% of placentas from HPA-1a alloimmunized pregnancies, compared to none in the control group (p = 0.001). Chronic villitis of unknown etiology was more frequently found in the alloimmunized group, however this difference was not statistically significant. Maternal administration of IVIg did not seem to protect against chronic inflammatory lesions. Discussion: Placentas with detectable maternal anti-HPA-1a antibodies are associated with highly increased risk of low-grade chronic histiocytic intervillositis.