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Hydraulic fracturing and active coarsening position the lumen of the mouse blastocyst

Science. 2019 Aug 2;365(6452):465-468. doi: 10.1126/science.aaw7709.

Abstract

During mouse pre-implantation development, the formation of the blastocoel, a fluid-filled lumen, breaks the radial symmetry of the blastocyst. The factors that control the formation and positioning of this basolateral lumen remain obscure. We found that accumulation of pressurized fluid fractures cell-cell contacts into hundreds of micrometer-size lumens. These microlumens eventually discharge their volumes into a single dominant lumen, which we model as a process akin to Ostwald ripening, underlying the coarsening of foams. Using chimeric mutant embryos, we tuned the hydraulic fracturing of cell-cell contacts and steered the coarsening of microlumens, allowing us to successfully manipulate the final position of the lumen. We conclude that hydraulic fracturing of cell-cell contacts followed by contractility-directed coarsening of microlumens sets the first axis of symmetry of the mouse embryo.

Does the availability of influenza vaccine at prenatal care visits and of immediate vaccination improve vaccination coverage of pregnant women?

PLoS One. 2019 Aug 1;14(8):e0220705. doi: 10.1371/journal.pone.0220705. eCollection 2019.

INTRODUCTION:

Although vaccination against influenza is recommended for pregnant women in France because it exposes them to a risk of death and severe respiratory complications, their vaccination coverage in 2016 was estimated at 7%. This study’s principal objective was to assess the association between the availability of influenza vaccination at prenatal care visits and vaccination coverage.

MATERIAL AND METHODS:

This multicenter survey took place in 3 Paris-area public hospital (AP-HP) maternity wards (A, B, and C). Only maternity ward A offered the vaccine and vaccination without charge at prenatal visits. Data were collected from parturients during 10 days in January 2017 by a self-administered anonymous questionnaire.

RESULTS:

Data from 248 women showed overall vaccination coverage of 19.4% (48/248): 35.4% (46/130) in maternity unit A, 2.7% (2/75) in B, and 0% (0/43) in C (P<0.01). After adjustment for socio-demographic characteristics, women at maternity ward A were significantly more likely to be vaccinated than those at B and C (aOR 25.52, 95%CI [5.76-113.10]). Other factors significantly associated with higher vaccination coverage were the mother’s French birth (aOR 2.37 CI [1.03-5.46]) and previous influenza vaccination (aOR 3.13, 95%CI [1.25-7.86]). Vaccinated women generally considered they had received adequate information (aOR 4.15 CI [2.10-8.22]), principally from the professional providing their prenatal care. Nonvaccination was attributed to the absence of an offer of vaccination (81.5%), fear of fetal side effects (59.5%), and inadequate information (51.4%).

CONCLUSION:

Our results show that availability of influenza vaccination, free of charge, at prenatal consultations at the maternity ward increases vaccination coverage significantly.

Maternity staff immunization coverage against pertussis and maternal vaccination practices: Results of a 2017 cross-sectional survey in five public maternity hospitals.

Abstract

Objectives: To conduct an audit of vaccination practices against pertussis in maternity wards to assess immunization practices targeting women, knowledge and awareness among health professionals and their involvement in the vaccination process, and to estimate their vaccine coverage.

Materials and methods: 2017 cross-sectional descriptive survey using a data collection sheet of immunization practices targeting women and an anonymous questionnaire for health professionals whose vaccine coverage had been documented by the occupational health service.

Results: Five public maternity wards participated: one had a vaccination policy for women; 426 of 822 health professionals completed the questionnaire, 76% (from 50% of all residents to 83% of nurses) declared their vaccination status as up to date. Staff files in occupational health services showed that 69% of 822 health professionals received at least one vaccine booster during adulthood (57% less than 10 years before the survey); documented vaccination coverage rates ranged from 75% for residents to 91% for senior physicians. Occupational physicians and family physicians respectively performed 41% and 34% of vaccinations. While knowledge regarding vaccines was good, only 47% of health professionals declared prescribing them and 18% declared administering the anti-pertussis vaccine « often » or « very often ».

Conclusions: Updated data is needed to confirm the reported increase as participating centers are not representative of all birth centers. The active role of health professionals in vaccination-based pertussis prevention needs to be reinforced.

Study characteristics impacted the pragmatism of randomized controlled trial published in nursing: a meta-epidemiological study.

Abstract

Objectives: The objective of this study was to examine the impact of study characteristics on the score of the pragmatism/explanatory continuum of randomized controlled trials (RCTs) published in nursing journals using the PRagmatic Explanatory Continuum Indicator Summary (PRECIS)-2 tool.

Study design and setting: RCTs concerning five themes of nursing care indexed in the PubMed and CINAHL databases published from 2002 to 2005 and 2012 to 2015 were selected by title/abstract. A sample of 400 was randomly selected and evaluated with the PRECIS-2 tool and reading grid.

Results: The median PRECIS score was 32 of a possible 45 [28; 36] corresponding to a medium level of pragmatism. Studies with « medication » as an intervention had a more explanatory PRECIS score than studies with other intervention types (P = 0.015). Studies with « placebo » and « no usual care » as comparators had a more explanatory PRECIS score (P = 0.0027). The pragmatism/explanatory level was unaffected by impact factor (P = 0.42), h-index of the first and last author (P = 0.27 and P = 0.25, respectively), funding (P = 0.32), blinding (P = 0.41), sample size (P = 0.22), and time (P = 0.11).

Conclusion: This study highlights the pragmatism/explanatory level of nursing RCTs, the impact of the field of the article, and the comparator type on the pragmatism of these studies. Further studies are needed to confirm the astonishing result that blinding resulted in no significant difference in the PRECIS score.

IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise

Science. 2019 Jul 12;365(6449):176-180. doi: 10.1126/science.aaw7733. PMID: 31296770.

Abstract

Elevated levels of type I interferon (IFN) during pregnancy are associated with intrauterine growth retardation, preterm birth, and fetal demise through mechanisms that are not well understood. A critical step of placental development is the fusion of trophoblast cells into a multinucleated syncytiotrophoblast (ST) layer. Fusion is mediated by syncytins, proteins deriving from ancestral endogenous retroviral envelopes. Using cultures of human trophoblasts or mouse cells, we show that IFN-induced transmembrane proteins (IFITMs), a family of restriction factors blocking the entry step of many viruses, impair ST formation and inhibit syncytin-mediated fusion. Moreover, the IFN inducer polyinosinic: polycytidylic acid promotes fetal resorption and placental abnormalities in wild-type but not in Ifitm-deleted mice. Thus, excessive levels of IFITMs may mediate the pregnancy complications observed during congenital infections and other IFN-induced pathologies.

The impact of neonatal unit policies on breast milk feeding at discharge of moderate preterm infants: The EPIPAGE-2 cohort study.

The impact of neonatal unit policies on breast milk feeding at discharge of moderate preterm infants: The EPIPAGE-2 cohort study – PubMed

Abstract

Facilitating factors and barriers to breast milk feeding (BMF) for preterm infants have been mainly studied in very preterm populations, but little is known about moderate preterm infants. We aimed to analyze hospital unit characteristics and BMF policies associated with BMF at discharge for infants born at 32 to 34 weeks’ gestation. EPIPAGE-2, a French national cohort of preterm births, included 883 infants born at 32 to 34 weeks’ gestation. We investigated kangaroo care in the first 24 hr, early involvement of parents in feeding support, volume of the unit, BMF information given to mothers hospitalized for threatened preterm delivery, protocols for BMF, presence of a professional trained in human lactation, unit training in neurodevelopmental care, and regional BMF initiation rates in the general population. Multilevel logistic regression analysis was used to investigate associations between unit policies and BMF at discharge, adjusted for individual characteristics and estimating odds ratios (ORs) and 95% confidence intervals (CIs). Overall, 59% (490/828) of infants received BMF at discharge (27% to 87% between units). Rates of BMF at discharge were higher with kangaroo care (adjusted OR 2.03 [95% CI 1.01, 4.10]), early involvement of parents in feeding support (1.94 [1.23, 3.04]), unit training in a neurodevelopmental care programme (2.57 [1.18, 5.60]), and in regions with a high level of BMF initiation in the general population (1.85 [1.05, 3.28]). Creating synergies by interventions at the unit and population level may reduce the variability in BMF rates at discharge for moderate preterm infants.

VEGF (Vascular Endothelial Growth Factor) Functionalized Magnetic Beads in a Microfluidic Device to Improve the Angiogenic Balance in Preeclampsia.

Hypertension. 2019 Jul;74(1):145-153. doi: 10.1161/HYPERTENSIONAHA.118.12380. Epub 2019 May 13.

Abstract

Preeclampsia is a hypertensive pregnancy disease associated with a massive increase in sFlt-1 (soluble form of the vascular endothelial growth factor 1) in the maternal circulation, responsible for angiogenic imbalance and endothelial dysfunction. Pilot studies suggest that extracorporeal apheresis may reduce circulating sFlt-1 and prolong pregnancy. Nonspecific apheresis systems have potential adverse effects because of the capture of many other molecules. Our concept is based on a specific and competitive apheresis approach using VEGF (vascular endothelial growth factor) functionalized magnetic beads to capture sFlt-1 while releasing endogenous PlGF (placental growth factor) to restore a physiological angiogenic balance. Magnetic beads were functionalized with VEGF to capture sFlt-1. Experiments were performed using PBS, conditioned media from human trophoblastic cells, and human plasma. The proof of concept was validated in dynamic conditions in a microfluidic device as an approach mimicking real apheresis. Magnetic beads were functionalized with VEGF and characterized to evaluate their surface ligand density and recognition capabilities. VEGF-coated magnetic beads proved to be an efficient support in capturing sFlt-1 and releasing PlGF. In static conditions, sFlt-1 concentration decreased by 33±13%, whereas PlGF concentration increased by 27±10%. In dynamic conditions, the performances were improved, with 40% reduction of sFlt-1 and up to 2-fold increase of free PlGF. The sFlt-1/PlGF ratio was reduced by 63% in the plasma of preeclamptic patients. Apheresis was also associated with VEGF release. A ligand-based approach using VEGF-coated beads is an effective approach to the capture of sFlt-1 and the release of endogenous PlGF. It offers new perspectives for the treatment of preeclampsia.

Differential rates of cesarean delivery by maternal geographical origin: a cohort study in France.

BMC Pregnancy and Childbirth (2019) 19:217. https://doi.org/10.1186/s12884-019-2364-x.

Background

In many Western countries, higher rates of cesarean have been described among migrant women compared to natives of receiving countries. We aimed to estimate this difference comparing women originating from France and Sub-Saharan Africa (SSA), identify the clinical situations explaining most of this difference and assess whether maternal origin was independently associated with cesarean risk.

Methods

The PreCARE prospective multicenter cohort study was conducted in 2010–2012 in the north Paris area. Our sample was restricted to 1500 women originating from Sub-Saharan Africa and 2206 from France. Profiles of cesarean section by maternal origin were described by the Robson classification. Independent associations between maternal origin and 1) cesarean before labor versus trial of labor, then 2) intrapartum cesarean versus vaginal delivery were assessed by logistic regression models to adjust for other maternal and pregnancy characteristics.

Results

Rates of cesarean for women originating from France and SSA were 17 and 31%. The Robson 5A category “unique uterine scar, single cephalic ≥37 weeks” was the main contributor to this difference. Within this category, SSA origin was associated with cesarean before labor after adjustment for medical risk factors (adjusted odds ratio [aOR] = 2.30 [1.12–4.71]) but no more significant when adjusting on social deprivation (aOR = 1.45 [0.63–3.31]). SSA origin was associated with cesarean during labor after adjustment for both medical and social factors (aOR = 2.95 [1.35–6.44]).

Conclusions

The wide difference in cesarean rates between SSA and French native women is mainly explained by the Robson 5A category. Within this group, medical factors alone do not explain the increased risk of cesarean in SSA women.

High level of soluble human leukocyte antigen (HLA)-G at beginning of pregnancy as predictor of risk of malaria during infancy

Sci Rep. 2019 Jun 24;9(1):9160. doi: 10.1038/s41598-019-45688-w.

Abstract

Placental malaria has been associated with an immune tolerance phenomenon and a higher susceptibility to malaria infection during infancy. HLA-G is involved in fetal maternal immune tolerance by inhibiting maternal immunity. During infections HLA-G can be involved in immune escape of pathogens by creating a tolerogenic environment. Recent studies have shown an association between the risk of malaria and HLA-G at both genetic and protein levels. Moreover, women with placental malaria have a higher probability of giving birth to children exhibiting high sHLA-G, independently of their own level during pregnancy. Our aim was to explore the association between the level of maternal soluble HLA-G and the risk of malaria infection in their newborns. Here, 400 pregnant women and their children were actively followed-up during 24 months. The results show a significant association between the level of sHLA-G at the first antenatal visit and the time to first malaria infection during infancy adjusted to the risk of exposure to vector bites (aHR = 1.02, 95%CI [1.01-1.03], p = 0.014). The level of sHLA-G is a significant predictor of the occurrence of malaria infection during infancy consistent with the hypothesis that mother sHLA-G could be a biomarker of malaria susceptibility in children.

The Role of Epigenetics in Placental Development and the Etiology of Preeclampsia

Int J Mol Sci. 2019 Jun; 20(11): 2837. Published online 2019 Jun 11. doi: 10.3390/ijms20112837.

Abstract

In this review, we comprehensively present the function of epigenetic regulations in normal placental development as well as in a prominent disease of placental origin, preeclampsia (PE). We describe current progress concerning the impact of DNA methylation, non-coding RNA (with a special emphasis on long non-coding RNA (lncRNA) and microRNA (miRNA)) and more marginally histone post-translational modifications, in the processes leading to normal and abnormal placental function. We also explore the potential use of epigenetic marks circulating in the maternal blood flow as putative biomarkers able to prognosticate the onset of PE, as well as classifying it according to its severity. The correlation between epigenetic marks and impacts on gene expression is systematically evaluated for the different epigenetic marks analyzed.