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Dynamics of Submicroscopic Plasmodium falciparum Infections Throughout Pregnancy: A Preconception Cohort Study in Benin.

Clin Infect Dis. 2019 Sep 12. pii: ciz748. doi: 10.1093/cid/ciz748. [Epub ahead of print]

BACKGROUND:

In the context of global malaria elimination efforts, special attention is being paid to submicroscopic Plasmodium falciparum infections. In pregnant, sub-Saharan African women, such infections are more prevalent than microscopic infections, and are thought to have adverse effects on both mothers’ and newborns’ health. However, no study has studied the dynamics and determinants of these infections throughout pregnancy. Retard de Croissance Intra-uterin et Paludisme (RECIPAL), a preconception cohort study carried out in Benin between 2014 and 2017, represented a unique opportunity to assess this issue.

METHODS:

We used data from 273 pregnant Beninese women who were followed-up from preconception to delivery. We studied the dynamics of and factors influencing submicroscopic (and microscopic) P. falciparum infections during the 3 trimesters of pregnancy, using an ordinal logistic mixed model.

RESULTS:

The incidence rate of submicroscopic P. falciparum infections during pregnancy was 12.7 per 100 person-months (95% confidence interval [CI] 10.8-14.9), compared to 6.7 per 100 person-months (95% CI 5.5-8.1) for microscopic infections. The prevalences were highest in the first trimester for both submicroscopic and microscopic infections. After adjustment for potential confounding factors, we found that those of young age and those with a submicroscopic P. falciparum infection prior to pregnancy were at significantly higher risks of submicroscopic and microscopic infections throughout pregnancy, with a more pronounced effect in the first trimester of pregnancy.

CONCLUSIONS:

The first trimester of pregnancy is a particularly high-risk period for P. falciparum infection during pregnancy, especially for the youngest women. Malaria prevention tools covering the preconception period and early pregnancy are urgently needed to better protect pregnant women and their newborns.

Gut microbiota from infant with cow’s milk allergy promotes clinical and immune features of atopy in a murine model.

Allergy. 2019 Sep;74(9):1790-1793. doi: 10.1111/all.13787. Epub 2019 Apr 30.

Letter to the Editor

Physical Violence During Pregnancy in France: Frequency and Impact on the Health of Expectant Mothers and New-Borns.

Matern Child Health J. 2019 Aug;23(8):1108-1116. doi: 10.1007/s10995-019-02747-y.

Objectives

Even during pregnancy women may suffer from violence. We estimated the prevalence of physical abuse during pregnancy, we analyzed the main risk factors and described the relationship between physical violence, psychological wellbeing and pregnancy outcome.

Methods

We used a national representative sample of births, in all public and private maternity units, in 2016 in France. Women were interviewed after delivery, on their living conditions and occurrence of physical violence at least once during pregnancy. The study of risk factors and pregnancy outcome was done with multivariable logistic regressions.

Results

Of 12,330 women included in the analysis 1.8% (95% CI 1.6-2.0) had been exposed to physical violence during pregnancy. Risk of violence was associated with the couple situation [women without a partner or in couple not cohabiting (OR 2.89, 95% CI 1.96-4.26)], household income (less than 3000 euros monthly), and state medical assistance coverage. Physical violence was more prevalent in case of a history of induced abortion or cannabis use during pregnancy. Psychological distress was more frequent with than without physical violence (e.g., 62% vs. 24% had a sadness period during pregnancy, p < 0.001). The risk of spontaneous preterm birth and transfer of the newborn to a neonatal intensive care unit were significantly higher among women experiencing physical violence during pregnancy compared to other women.

Conclusions for Practice

Main factors associated with increased risk of violence during pregnancy were socio-economics. The identification by caregivers of women exposed to violence during pregnancy needs to be improved to develop preventive and care strategies.

Long-term cardiovascular disorders in the STOX1 mouse model of preeclampsia

Sci Rep. 2019; 9: 11918. Published online 2019 Aug 15. doi: 10.1038/s41598-019-48427-3. PMCID: PMC6695383.

AbstrAct:

Adverse long-term cardiovascular (CV) consequences of PE are well established in women. However, the mechanism responsible for that risk remains unknown. Here, we mated wild-type female mice of the FVB/N strain to STOX1A-overexpressing mice to mimic severe PE and investigated the long-term consequences on the maternal cardiovascular system. Ultrasonography parameters were analyzed in mice before pregnancy and at 3 and 6 months post-pregnancy. At 6 months post-pregnancy, cardiac stress test induced by dobutamine injection revealed an abnormal ultrasonography doppler profile in mice with previous PE. Eight months post-pregnancy, the heart, endothelial cells (ECs) and plasma of females were analyzed and compared to controls. The heart of mice with PE showed left-ventricular hypertrophy associated with altered histology (fibrosis). Transcriptomic analysis revealed the deregulation of 1149 genes in purified ECs and of 165 genes in the hearts, many being involved in heart hypertrophy. In ECs, the upregulated genes were associated with inflammation and cellular stress. Systems biology analysis identified interleukin 6 (IL-6) as a hub gene connecting these pathways. Plasma profiling of 33 cytokines showed that, 8 of them (cxcl13, cxcl16, cxcl11, IL-16, IL-10, IL-2, IL-4 and Ccl1) allowed to discriminate mice with previous PE from controls. Thus, PE triggers female long-term CV consequences on the STOX1 mouse model.

Qualitative and quantitative analysis of the uptake of lipoplexes by villous placenta explants.

Int J Pharm. 2019 Aug 15;567:118479. doi: 10.1016/j.ijpharm.2019.118479. Epub 2019 Jun 27.

Abstract

Controlled distribution of a drug by its association to a nanocarrier is a promising approach for the treatment of pregnancy disorders such as preeclampsia. For this application, tracking both the nanocarrier and the drug is necessary to ensure the safety of both the mother and the foetus. This study reports a method to visualize and quantify the uptake of liposomal formulations in placental tissue using florescent labelling and appropriate analytical tools. Lipoplexes were labelled with a fluorescent lipid, DOPE-NBD while the encapsulated siRNA was fluorescently labelled with rhodamine. Lipoplexes were incubated with villous placenta explants, explants were imaged with confocal microscopy, then DOPE-NBD was extracted from the explant and quantified by HPLC. Qualitative evaluation by confocal microscopy showed the presence of lipoplexes and siRNA into the outer layer of the placental explants, the syncytiotrophoblast. For quantitative evaluation, an HPLC method for the quantification of fluorescent lipid DOPE-NBD in placental tissue was developed and validated. The developed method was applied to quantify the DOPE-NBD uptake in the placental tissue. Increased amounts of DOPE-NBD were detected in placental explants when increasing the incubation concentration of lipoplexes. This study provides a method to evaluate the interactions between liposomal formulation and the placental barrier.

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.