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Infection par le SARS-CoV-2 chez les femmes enceintes : état des connaissances et proposition de prise en charge par CNGOF

SARS-CoV-2 Infection During Pregnancy. Information and Proposal of Management Care. CNGOF

Gynecol Obstet Fertil Senol. 2020 May;48(5):436-443. doi: 10.1016/j.gofs.2020.03.014.

Résumé

Un nouveau coronavirus (SARS-CoV-2) mis en évidence en fin d’année 2019 en Chine se diffuse à travers tous les continents. Le plus souvent à l’origine d’un syndrome infectieux sans gravité, associant à différents degrés des symptômes bénins (fièvre, toux, myalgies, céphalées et éventuels troubles digestifs) le SARS-Covid-2 peut être à l’origine de pathologies pulmonaires graves et parfois de décès. Les données sur les conséquences pendant la grossesse sont limitées. Les premières données chinoises publiées semblent montrer que les symptômes chez la femme enceinte sont les mêmes que ceux de la population générale. mais il y a un risque qu’il y ai plus de formes graves. Il n’y a pas de cas de transmission maternofœtale intra utérine mais des cas de nouveau-nés infectés précocement font penser qu’il pourrait y avoir transmission verticale per-partum ou néonatale. Une prématurité induite et des cas de détresses respiratoires chez les nouveau-nés de mères infectées ont été décrits. La grossesse est connue comme une période plus à risque pour les conséquences des infections respiratoires, comme pour la grippe, il parait donc important de dépister le Covid-19 en présence de symptômes et de surveiller de façon rapprochée les femmes enceintes infectées. Dans ce contexte d’épidémie de SARS-Covid-2, les sociétés savantes de gynécologie-obstétrique, d’infectiologie et de néonatalogie ont proposé un protocole français de prise en charge des cas possibles et avérés de SARS-Covid-2 chez la femme enceinte. Ces propositions peuvent évoluer de façon quotidienne avec l’avancée de l’épidémie et des connaissances chez la femme enceinte.

Abstract

A new coronavirus (SARS-CoV-2) highlighted at the end of 2019 in China is spreading across all continents. Most often at the origin of a mild infectious syndrome, associating mild symptoms (fever, cough, myalgia, headache and possible digestive disorders) to different degrees, SARS-Covid-2 can cause serious pulmonary pathologies and sometimes death. Data on the consequences during pregnancy are limited. The first Chinese data published seem to show that the symptoms in pregnant women are the same as those of the general population. There are no cases of intrauterine maternal-fetal transmission, but cases of newborns infected early suggest that there could be vertical perpartum or neonatal transmission. Induced prematurity and cases of respiratory distress in newborns of infected mothers have been described. Pregnancy is known as a period at higher risk for the consequences of respiratory infections, as for influenza, so it seems important to screen for Covid-19 in the presence of symptoms and to monitor closely pregnant women. In this context of the SARS-Covid-2 epidemic, the societies of gynecology-obstetrics, infectious diseases and neonatalogy have proposed a French protocol for the management of possible and proven cases of SARS-Covid-2 in pregnant women. These proposals may evolve on a daily basis with the advancement of the epidemic and knowledge in pregnant women. Subsequently, an in-depth analysis of cases in pregnant women will be necessary in order to improve knowledge on the subject.

Severe maternal morbidity by mode of delivery in women with twin pregnancy and planned vaginal delivery.

Abstract

Planned vaginal delivery in twin pregnancies has three potential outcomes: vaginal or cesarean delivery of both twins, or cesarean for the second twin. Our objective was to assess the association between delivery mode and severe acute maternal morbidity (SAMM) in women with twin pregnancies and planned vaginal deliveries. We limited this planned secondary analysis of the JUMODA cohort, a national prospective population-based study of twin deliveries, to women with planned vaginal delivery at or after 24 weeks of gestation who gave birth to two live fetuses at hospital. The association between delivery mode and SAMM was estimated from multivariate Poisson regression models. Of 5,055 women with planned vaginal delivery, 4,007 (79.3%) delivered both twins vaginally, 134 (2.6%) had cesarean for the second twin and 914 (18.1%) cesarean for both twins. Compared to vaginal delivery of both twins, the risk of SAMM was significantly higher after cesarean for the second twin (9.0% versus 4.5%; aRR 2.22, 95% CI 1.27-3.88) and for both twins (9.4% versus 4.5%, aRR 1.56, 95% CI 1.16-2.10). In twin pregnancies with planned vaginal delivery, cesarean deliveries for the second twin and for both twins are associated with higher risks of SAMM than vaginal delivery.

Conflict of interest statement

The authors declare no competing interests.

Exploring the Molecular Aetiology of Preeclampsia by Massive Parallel Sequencing of DNA.

Abstract

Purpose of review: This manuscript aims to review (for the first time) studies describing NGS sequencing of preeclampsia (PE) women’s DNA.

Recent findings: Describing markers for the early detection of PE is an essential task because, although associated molecular dysfunction begins early on during pregnancy, the disease’s clinical signs usually appear late in pregnancy. Although several biochemical biomarkers have been proposed, their use in clinical environments is still limited, thereby encouraging research into PE’s genetic origin. Hundreds of genes involved in numerous implantation- and placentation-related biological processes may be coherent candidates for PE aetiology. Next-generation sequencing (NGS) offers new technical possibilities for PE studying, as it enables large genomic regions to be analysed at affordable cost. This technique has facilitated the description of genes contributing to the molecular origin of a significant amount of monogenic and complex diseases. Regarding PE, NGS of DNA has been used in familial and isolated cases, thereby enabling new genes potentially related to the phenotype to be proposed. For a better understanding of NGS, technical aspects, applications and limitations are presented initially. Thereafter, NGS studies of DNA in familial and non-familial cases are described, including pitfalls and positive findings. The information given here should enable scientists and clinicians to analyse and design new studies permitting the identification of novel clinically useful molecular PE markers.

Maternal and Perinatal Morbidity and Mortality Associated With Anemia in Pregnancy.

Comment : No abstract available

Risk factors for bronchiolitis hospitalization in infants: A French nationwide retrospective cohort study over four consecutive seasons (2009-2013).

PLoS One. 2020 Mar 6;15(3):e0229766. doi: 10.1371/journal.pone.0229766. eCollection 2020.

Objectives

Large studies are needed to update risk factors of bronchiolitis hospitalization. We performed a nationwide analysis of hospitalization rates for bronchiolitis over four consecutive bronchiolitis seasons to identify underlying medical disorders at risk of bronchiolitis hospitalization and assess their frequency.

Methods

Data were retrieved from the French National Hospital Discharge database. Of all infants discharged alive from maternity wards from January 2008 to December 2013 in France (N = 3,884,791), we identified four consecutive cohorts at risk of bronchiolitis during the seasons of 2009-2010 to 2012-2013. The main outcome was bronchiolitis hospitalization during a season. Individual risk factors were collected.

Results

Among infants, 6.0% were preterm and 2.0% had ≥1 chronic condition including 0.2% bronchopulmonary dysplasia (BPD) and 0.2% hemodynamically significant congenital heart disease (HS-CHD). Bronchiolitis hospitalization rates varied between seasons (min: 1.26% in 2010-2011; max: 1.48% in 2012-2013; p<0.001). Except omphalocele, the following conditions were associated with an increased risk for bronchiolitis hospitalization: solid organ (9.052; 95% CI, 4.664-17.567) and stem cell transplants (6.012; 95% CI, 3.441-10.503), muscular dystrophy (4.002; 95% CI, 3.1095-5.152), cardiomyopathy (3.407; 95% CI, 2.613-4.442), HS-CHD (3.404; 95% CI, 3.153-3.675), congenital lung disease and/or bronchial abnormalities, Down syndrome, congenital tracheoesophageal fistula, diaphragmatic hernia, pulmonary hypertension, chromosomal abnormalities other than Down syndrome, hemodynamically non-significant CHD, congenital abnormalities of nervous system, cystic fibrosis, cleft palate, cardiovascular disease occurring during perinatal period, and BPD.

Conclusion

Besides prematurity, BPD, and HS-CHD, eighteen underlying conditions were associated with a significant increased risk for bronchiolitis hospitalization in a nationwide population.

Risk factors and high-risk subgroups of severe acute maternal morbidity in twin pregnancy: A population-based study

PLoS One. 2020 Feb 28;15(2):e0229612. doi: 10.1371/journal.pone.0229612. PMID: 32109258; PMCID: PMC7048407.

Abstract

Objective: To determine risk factors of severe acute maternal morbidity in women with twin pregnancies and identify subgroups at high risk.

Methods: In a prospective, population-based study of twin deliveries, the JUMODA cohort, all women with twin pregnancies at or after 22 weeks of gestation were recruited in 176 French hospitals. Severe acute maternal morbidity was a composite criterion. We determined its risk factors by multilevel multivariate Poisson regression modeling and identified high-risk subgroups by classification and regression tree (CART) analysis, in two steps: first considering only characteristics known at the beginning of pregnancy and then adding factors arising during its course.

Results: Among the 8,823 women with twin pregnancies, 542 (6.1%, 95% confidence interval (CI) 5.6-6.6) developed severe acute maternal morbidity. Risk factors for severe maternal morbidity identified at the beginning of pregnancy were maternal birth in sub-Saharan Africa (adjusted relative risk (aRR) 1.6, 95% CI 1.1-2.3), preexisting insulin-treated diabetes (aRR 2.2, 95% CI 1.1-4.4), nulliparity (aRR 1.6, 95% CI 1.3-2.0), IVF with autologous oocytes (aRR, 1.3, 95% CI, 1.0-1.6), and oocyte donation (aRR 2.0, 95% CI 1.4-2.8); CART analysis identified nulliparous women with oocyte donation as the subgroup at highest risk (SAMM rate: 14.7%, 95% CI, 10.3-19.1). At the end of pregnancy, additional risk factors identified were placenta praevia (aRR 3.5, 95% CI 2.3-5.3), non-severe preeclampsia (aRR 2.5, 95% CI 1.9-3.2), and macrosomia for either twin (aRR 1.7, 95% CI 1.3-2.1); CART analysis identified women with both oocyte donation and non-severe preeclampsia (SAMM rate: 28.9%, 95% CI, 19.9-37.9) and sub-Saharan nulliparous women with non-severe preeclampsia (SAMM rate: 26.9%, 95% CI, 9.9-43.9) as the two subgroups at highest risk.

Conclusion: In woman with twin pregnancy, rates of severe acute maternal morbidity vary between subgroups from 4.6% to 14.7% and from 3.8% to 28.9% at the beginning and at the end of pregnancy respectively, depending on the combined presence of risk factors.

Decision-making based on sFlt-1/PlGF ratios: are immunoassay results interchangeable for diagnosis or prognosis of preeclampsia?

Letter to the Editor: No abstract available

Schistosoma haematobium infection modulates Plasmodium falciparum parasite density and antimalarial antibody responses.

Abstract

Aims: Schistosomiasis and malaria are endemic in sub-Saharan Africa where Schistosoma haematobium (Sh) and Plasmodium falciparum (Pf) coinfections are thus frequent. We explored the effect of Sh infection on antibody responses directed to Pf merozoite antigens and on malaria susceptibility in Beninese children.

Methods and results: A total of 268 children were followed during a malaria transmission season. Detection of Pf infection was performed by microscopy and rapid diagnostic tests. Sh infection was determined in urine by microscopy. Antimalarial antibody, cytokine and HLA-G concentrations were quantified by ELISA. The expression of HLA-G receptors by immune cells was assessed by flow cytometry. Children infected by Sh had higher concentrations of IgG1 directed to MSP3 and GLURPR0 , IgG2 directed to GLURPR0 and IgG3 directed to MSP3, GLURPR0 and GLURPR2 and have lower Pf densities than those uninfected by Sh. No difference in cytokine and HLA-G concentrations was observed between Sh egg carriers and non-carriers.

Conclusion: Schistosoma haematobium modulates host immune responses directed to Pf antigens. The absence of immune downregulation usually observed during helminth infections is surprising in our study. We hypothesize that the stage of Sh development could partly explain the immune pathways leading to increased antibody levels that favour better control of Pf parasitemia.

Placental overexpression of soluble CORIN in preeclampsia

Am J Pathol.2020 Feb 18. pii:S0002-9440(20)30079-1. doi: 10.1016/j.ajpath.2019.12.012

Abstract

Preeclampsia (PE) is a hypertensive disease of pregnancy associated with substantial maternal and fetalmorbidity and mortality. CORIN is a transmembrane type II serine protease expressed in cardiomyocytes thatconverts pro-atrial natriuretic peptide (pro-ANP) into ANP, a cardiac hormone that regulates blood pressure. High levels of soluble CORIN have been reported inpreeclampsiaand are supposed to be cardiac in origin. Wehypothesized that during pregnancy soluble CORIN is released by the syncytiotrophoblast and that increasedlevels of soluble CORIN in preeclampsia originate from placenta. Three hundred and ninety-five patients (181PE patients and 194 controls) were analyzed. High levels of soluble CORIN were confirmed in maternal bloodfrom preeclamptic pregnancies compared to controls. Differentiated primary villous cytotrophoblasts showedthat CORIN was expressed (mRNA and protein levels) and secreted by trophoblastic cells, mostly by thesyncytiotrophoblast . Finally, placental explants demonstrated a significant increase in CORIN production and secretion in PE cases compared to controls. This study demonstrates that CORIN is secreted by trophoblasticcells and that high levels of soluble CORIN in preeclampsia have a placental origin.

Impact of Supraphysiological Estradiol Serum Levels on Birth Weight in Singletons Born After Fresh Embryo Transfer.

Abstract

In assisted reproductive technology, high estradiol (E2) levels at trigger may increase the risk of low birth weight (LBW). Our objective was to investigate the impact of supra-physiological E2 levels at trigger, on the rate of LBW in singleton pregnancies following fresh embryo transfers (ET), in a center that typically employs the ‘freeze-all’ strategy in case of high E2 levels, to prevent ovarian hyper stimulation syndrome risk. A cohort study was conducted in a university hospital between November 2012 and January 2017. The main inclusion criterion was having a live birth (LB) singleton (≥ 24 weeks of gestation) after a fresh-ET. Four groups were defined according to the E2 level at trigger, as quartiles of the entire patient population. The main measured outcome was the rate of LBW. 497 fresh-ET led to LB. Mean E2 level was 1608.4 ± 945.5 pg/ml. The groups were allocated as follows: 124LB in the Group E2 < 25 percentile(p) (1106.5 pg/ml), 124LB in the Group E2 [25p-50p] (1106.5-1439 pg/ml), 124LB in the Group E2[50p-75p] (1440-1915 pg/ml), and 125LB in the Group E2 > 75p (>1915 pg/ml). There was no significant difference in the rate of LBW (Group E2 < 25p, n = 8/124, (6.5%); Group E2[25p-50p], n = 15/124, (12.1%); Group E2 [50p-75p], n = 13/124, (10.4%); and Group E2 > 75p, n = 10/12, (8.1%); (p = 0.43)). After multivariate analysis, E2 level at trigger was not significantly correlated to the rate of LBW. In our cohort, E2 level on the day of hCG trigger was not associated with increased odds of LBW after fresh embryo transfers.