Publications

Abstract

Background: Safety data about rilpivirine use during pregnancy remain scarce, and rilpivirine plasma concentrations are reduced during second/third trimesters, with a potential risk of viral breakthroughs. Thus, French guidelines recommend switching to rilpivirine-free combinations (RFCs) during pregnancy.

Objectives: To describe the characteristics of women initiating pregnancy while on rilpivirine and to compare the outcomes for virologically suppressed subjects continuing rilpivirine until delivery versus switching to an RFC.

Methods: In the ANRS-EPF French Perinatal cohort, we included women on rilpivirine at conception in 2010-18. Pregnancy outcomes were compared between patients continuing versus interrupting rilpivirine. In women with documented viral suppression (<50 copies/mL) before 14 weeks of gestation (WG) while on rilpivirine, we compared the probability of viral rebound (≥50 copies/mL) during pregnancy between subjects continuing rilpivirine versus those switching to RFC.

Results: Among 247 women included, 88.7% had viral suppression at the beginning of pregnancy. Overall, 184 women (74.5%) switched to an RFC (mostly PI/ritonavir-based regimens) at a median gestational age of 8.0 WG. Plasma HIV-1 RNA nearest delivery was <50 copies/mL in 95.6% of women. Among 69 women with documented viral suppression before 14 WG, the risk of viral rebound was higher when switching to RFCs than when continuing rilpivirine (20.0% versus 0.0%, P = 0.046). Delivery outcomes were similar between groups (overall birth defects, 3.8/100 live births; pregnancy losses, 2.0%; preterm deliveries, 10.6%). No HIV transmission occurred.

Conclusions: In virologically suppressed women initiating pregnancy, continuing rilpivirine was associated with better virological outcome than changing regimen. We did not observe a higher risk of adverse pregnancy outcomes.

Hum Reprod Update. 2020 Apr 29:dmaa014. doi: 10.1093/humupd/dmaa014. Epub ahead of print. PMID: 32347305.

Abstract

Background

Haem oxygenases (HO) catabolise haem, which is the prosthetic group of numerous haemoproteins. Thus, multiple primary cellular pathways and functions rely on haem availability. HO exists in two isoforms, both expressed in the placenta, namely HO-1 and HO-2, the first being inducible. Haem oxygenases, particularly HO-1, have garnered specific interest in the field of physiological and pathological placental function. These enzymes mediate haem degradation by cleaving the alpha methene bridge to produce biliverdin, which is subsequently converted to bilirubin, carbon monoxide and iron. HO-1 has anti-inflammatory and antioxidant activities.

Search methods

An initial literature analysis was performed using PubMed on 3 October 2018 using key terms such as ‘haem oxygenase and pregnancy’, ‘haem oxygenase and placenta’, ‘HO-1 and pregnancy’, ‘HO-1 and placenta’, ‘HO and placenta’, ‘HO and pregnancy’, ‘genetic variant and HO’, ‘CO and pregnancy’, ‘CO and placenta’, ‘Bilirubin and pregnancy’, ‘Iron and pregnancy’ and ‘PPAR and Haem’, selecting consensus conferences, recommendations, meta-analyses, practical recommendations and reviews. A second literature analysis was performed, including notable miscarriages, foetal loss and diabetes mellitus, on 20 December 2019. The three authors studied the publications independently to decipher whether they should be included in the manuscript.

Objective and rationale

This review aimed to summarise current pieces of knowledge of haem oxygenase location, function and regulation in the placenta, either in healthy pregnancies or those associated with miscarriages and foetal loss, pre-eclampsia, foetal growth restriction and diabetes mellitus.

Outcomes

HO-1 exerts some protective effects on the placentation, probably by a combination of factors, including its interrelation with the PGC-1α/PPAR pathway and the sFlt1/PlGF balance, and through its primary metabolites, notably carbon monoxide and bilirubin. Its protective role has been highlighted in numerous pregnancy conditions, including pre-eclampsia, foetal growth restriction, gestational diabetes mellitus and miscarriages.

Wider implications

HO-1 is a crucial enzyme in physiological and pathological placentation. This protective enzyme is currently considered a potential therapeutic target in various pregnancy diseases.

Seminars in Fetal and Neonatal Medicine. 2020 Jun;25(3):101109. doi: 10.1016/j.siny.2020.101109. Epub 2020 Apr 8.

Abstract

We summarise rates of survival and neurodevelopmental impairment in very (<32 weeks’ gestation) and extremely (<28 weeks’ gestation) preterm infants using data from recent meta-analyses. Methodological issues that require consideration when comparing international data are highlighted using examples of population-based or multi-centre cohorts of children born extremely preterm. The impact of baseline population, outcome definition, gestational age assessment, age at neurodevelopmental assessment, year of birth and follow-up rates are discussed. The impact of the intensity of perinatal care and of post-discharge management on survival and neurodevelopmental outcomes is also discussed. There is a future need for harmonisation of data collection and for more accurate and standardised reporting of neurodevelopmental outcomes in very preterm children.

PPAR Res. 2020 Apr 1;2020:9210748. doi: 10.1155/2020/9210748. eCollection 2020. PMID: 32308672

Abstract

Trophoblasts, as the cells that make up the main part of the placenta, undergo cell differentiation processes such as invasion, migration, and fusion. Abnormalities in these processes can lead to a series of gestational diseases whose underlying mechanisms are still unclear. One protein that has proven to be essential in placentation is the peroxisome proliferator-activated receptor γ (PPARγ), which is expressed in the nuclei of extravillous cytotrophoblasts (EVCTs) in the first trimester and villous cytotrophoblasts (VCTs) throughout pregnancy. Here, we aimed to explore the genome-wide effects of PPARγ on EVCTs and VCTs via treatment with the PPARγ-agonist rosiglitazone. EVCTs and VCTs were purified from human chorionic villi, cultured in vitro, and treated with rosiglitazone. The transcriptomes of both types of cells were then quantified using microarray profiling. Differentially expressed genes (DEGs) were filtered and submitted for gene ontology (GO) annotation and pathway analysis with ClueGO. The online tool STRING was used to predict PPARγ and DEG protein interactions, while iRegulon was used to predict the binding sites for PPARγ and DEG promoters. GO and pathway terms were compared between EVCTs and VCTs with clusterProfiler. Visualizations were prepared in Cytoscape. From our microarray data, 139 DEGs were detected in rosiglitazone-treated EVCTs (RT-EVCTs) and 197 DEGs in rosiglitazone-treated VCTs (RT-VCTs). Downstream annotation analysis revealed the similarities and differences between RT-EVCTs and RT-VCTs with respect to the biological processes, molecular functions, cellular components, and KEGG pathways affected by the treatment, as well as predicted binding sites for both protein-protein interactions and transcription factor-target gene interactions. These results provide a broad perspective of PPARγ-activated processes in trophoblasts; further analysis of the transcriptomic signatures of RT-EVCTs and RT-VCTs should open new avenues for future research and contribute to the discovery of possible drug-targeted genes or pathways in the human placenta.

Abstract

Introduction: The objective of this study is to investigate factors associated with risks of perinatal death in a disadvantaged, high-migrant French district with mortality rates above the national average.

Material and methods: The study design is a perinatal audit in 2014 in all 11 maternity units in the Seine-Saint-Denis district (25 037 births). The data come from medical chart abstraction, maternal interviews and peer assessor confidential review of deaths. A representative sample of live births in the same district, from the 2010 French Perinatal Survey, was used for comparisons (n = 429). The main outcome measures were stillbirth and neonatal death (0-27 days) at ≥22 weeks of gestation.

Results: The audit included 218 women and 227 deaths (156 stillbirths, 71 neonatal deaths); 75 women were interviewed. In addition to primiparity and multiple pregnancy, overweight and obesity increased mortality risks (50% of cases, adjusted odds ratios [aOR] 1.7, 95% confidence interval [CI] 1.1-2.8, and aOR 1.9 [95% CI 1.1-3.2], respectively) as did the presence of preexisting medical/obstetric conditions (28.6% of cases, aOR 3.2, 95% CI 2.0-5.3). Problems accessing or complying with care were noted in 25% of medical records and recounted in 50% of interviews. Assessors identified suboptimal factors in 73.2% of deaths and judged 33.9% to be possibly or probably preventable. Care not adapted to risk factors and poor healthcare coordination were frequent suboptimal factors. Possibly preventable deaths were higher (P < .05) for women with gestational diabetes or hypertension (44.6%) than women without (29.0%).

Conclusions: Preventive actions to improve healthcare referral and coordination, especially for overweight and obese women and women with medical and obstetrical risk factors, could reduce perinatal mortality in disadvantaged areas.

Ultrasound Obstet Gynecol. 2020 Mar 25. doi: 10.1002/uog.22025.

Abstract

Objective

To investigate the association of absent or reversed end diastolic flow (ARED) in umbilical artery Doppler ultrasound with poor neurological outcome at age 2 after very preterm birth associated with suspected fetal growth restriction (FGR) or maternal hypertensive disorders.

Methods

The study population included all very preterm singletons born because of suspected FGR or maternal hypertensive disorders included in EPIPAGE-2, a prospective, nationwide, population-based cohort of preterm births in France in 2011. We analyzed the association of ARED in the umbilical artery with severe or moderate neuromotor or sensory disabilities, and with an Age and Stages Questionnaire (ASQ) score below the threshold at age 2. ASQ is used to identify children at risk of developmental delay needing reinforced follow-up and further evaluation. We performed univariate and two-level multivariable logistic regression analyses.

Results

The analysis included 484 children followed up at 2 years of age for whom prenatal umbilical Doppler ultrasound was available. Among them, 8 (1.5%) had severe or moderate neuromotor or sensory disabilities, and 156 (43.9%) had an ASQ score below the threshold. Compared to normal or reduced end diastolic flow in the umbilical artery (n=305), ARED (n=179) was associated with either severe or moderate neuromotor or sensory disabilities (adjusted OR 11.3, 95% CI 1.4-93.4) but not with an ASQ score below the threshold (adjusted aOR 1.2, 95% CI 0.8-1.9).

Conclusion

Among children born before 32 weeks of gestation because of suspected fetal growth restriction or hypertensive disorder who survived until age 2, prenatal ARED in the umbilical artery was associated with more frequent moderate or severe neuromotor or sensory disabilities. This article is protected by copyright. All rights reserved.

Scientific Reports (2020), 10:5215. https://doi.org/10.1038/s41598-020-62032-9

Abstract

We investigated the extent to which pre-pregnancy obesity mediates the association between maternal place of birth and severe pre-eclampsia in the PreCARE cohort of pregnant women in Paris (n = 9,579).
Adjusted path analysis logistic regression models were used to assess the role of pre-pregnancy obesity as a mediator in the association between maternal place of birth and the development of severe pre-eclampsia. We calculated 1. adjusted odds ratios and 95% confidence intervals for the total exposure-outcome association and for the direct and indirect/obesity-mediated components 2. the indirect/obesity-mediated effect.
Ninety-five (0.99%) women developed severe pre-eclampsia, 47.6% were non-European immigrants, 16.3% were born in Sub-Saharan Africa, and 12.6% were obese (BMI > = 30 kg/m2). Women experiencing severe pre-eclampsia were more likely to be from Sub-
Saharan Africa (p = 0.023) and be obese (p = 0.048). Mothers from Sub-Saharan Africa had an increased risk of severe pre-eclampsia compared to European-born mothers (aOR 2.53, 95% CI 1.39–4.58) and the obesity-mediated indirect effect was 18% of the total risk (aOR 1.18, 95%CI 1.03–1.35).
In conclusion, Sub-Saharan African immigrant women have a two-fold higher risk of developing severe pre-eclampsia as compared to European-born women, one-fifth of which is mediated by pre-pregnancy obesity. Our results quantify the potential benefit of decreasing obesity among at-risk women.

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.

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.

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.