[Ventilatory management of SARS-CoV-2 acute respiratory failure]. / Prise en charge ventilatoire de l'insuffisance respiratoire aiguë à SARS-CoV-2.

COVID-19 pneumonia presents several particularities in its clinical presentation (cytokine storm, silent hypoxemia, thrombo-embolic risk) and may lead to a number of acute respiratory distress syndrome (ARDS) phenotypes. While the optimal oxygenation strategy in cases of hypoxemic acute respiratory failure (ARF) is still under debate, ventilatory management of COVID-19-related ARF has confirmed the efficacy of high-flow oxygen therapy and restored interest in other ventilatory approaches such as continuous positive airway pressure (CPAP) and noninvasive ventilation involving a helmet, which due to patient overflow are sometimes implemented outside of critical care units. However, further studies are still needed to determine which patients should be given which oxygenation technique, and under which conditions they require invasive mechanical ventilation, given that delayed initiation potentially burdens prognosis. During invasive mechanical ventilation, ventral decubitus and extracorporeal membrane oxygenation have become increasingly prevalent. While innovative therapies such as awake prone position or lung transplantation have likewise been developed, their indications, modalities and efficacy remain to be determined.

Role of chromosomal imbalances in the pathogenesis of DSD: A retrospective analysis of 115 prenatal samples.

Differences of sex development (DSDs) are a group of congenital conditions characterized by a discrepancy between chromosomal, gonadal, and genital sex development of an individual, with significant impact on medical, psychological and reproductive life. The genetic heterogeneity of DSDs complicates the diagnosis and almost half of the patients remains undiagnosed. In this context, chromosomal imbalances in syndromic DSD patients may help to identify new genes implicated in DSDs. In this study, we aimed at describing the burden of chromosomal imbalances including submicroscopic ones (copy number variants or CNVs) in a cohort of prenatal syndromic DSD patients, and review their role in DSDs. Our patients carried at least one pathogenic or likely pathogenic chromosomal imbalance/CNV or low-level mosaicism for aneuploidy. Almost half of the cases resulted from an unbalanced chromosomal rearrangement. Chromosome 9p/q, 4p/q, 3q and 11q anomalies were more frequently observed. Review of the literature confirmed the causative role of CNVs in DSDs, either in disruption of known DSD-causing genes (SOX9, NR0B1, NR5A1, AR, ATRX, …) or as a tool to suspect new genes in DSDs (HOXD cluster, ADCY2, EMX2, CAMK1D, …). Recurrent CNVs of regulatory elements without coding sequence content (i.e. duplications/deletions upstream of SOX3 or SOX9) confirm detection of CNVs as a mean to explore our non-coding genome. Thus, CNV detection remains a powerful tool to explore undiagnosed DSDs, either through routine techniques or through emerging technologies such as long-read whole genome sequencing or optical genome mapping.

Perinatal grief following neonatal comfort care for lethal fetal condition.

BACKGROUND: The objective of the study was to assess perinatal grief experienced after continuing pregnancy and comfort care in women diagnosed with lethal fetal condition compared with termination of pregnancy for fetal anomaly (TOPFA). METHODS: This was a retrospective observational study which included women who chose to continue their pregnancy after the diagnosis of lethal fetal condition with comfort care support at birth at the Prenatal Diagnosis Center of Rennes Hospital from January 2007 to January 2017. Women were matched with controls who underwent TOPFA for the same type of fetal anomaly, gestational age at diagnosis and year. Women were evaluated by a questionnaire including the Perinatal Grief Scale. RESULTS: There were 28 patients in the continuing pregnancy group matched with 56 patients in the TOPFA group. Interval between fetal loss and completion of questionnaire was 6±3 years. Perinatal grief score was similar at 61±22 vs 58±18 (p = 0.729) in the continuing pregnancy and TOPFA groups, respectively. Women in the TOPFA group expressed more guilt. The cesarean-section rate in the continuing pregnancy group was 25%. CONCLUSION: Perinatal grief experienced by women opting for continuing pregnancy and comfort care after diagnosis of a potentially lethal fetal anomaly is not more severe than for those choosing TOPFA.

Diagnostic yield of chromosomal microarray analysis in fetuses with isolated increased nuchal translucency: a French multicenter study.

OBJECTIVE: To determine the frequency and nature of copy number variants (CNVs) identified by chromosomal microarray analysis (CMA) in a large cohort of fetuses with isolated increased nuchal translucency thickness (NT) ≥ 3.5 mm. METHODS: This was a retrospective, multicenter study, including 11 French hospitals, of data from the period between April 2012 and December 2015. In total, 720 fetuses were analyzed by rapid aneuploidy test and the fetuses identified as euploid underwent CMA. CNVs detected were evaluated for clinical significance and classified into five groups: pathogenic CNVs; benign CNVs; CNVs predisposing to neurodevelopmental disorders; variants of uncertain significance (VOUS); and CNVs not related to the phenotype (i.e. incidental findings). RESULTS: In 121 (16.8%) fetuses, an aneuploidy involving chromosome 13, 18 or 21 was detected by rapid aneuploidy test and the remaining 599 fetuses were euploid. Among these, 53 (8.8%) had a CNV detected by CMA: 16/599 (2.7%) were considered to be pathogenic, including 11/599 (1.8%) that were cryptic (not visible by karyotyping); 7/599 (1.2%) were CNVs predisposing to neurodevelopmental disorders; and 8/599 (1.3%) were VOUS. Additionally, there was one (0.2%) CNV that was unrelated to the reason for referral diagnosis (i.e. an incidental finding) and the remaining 21 were benign CNVs, without clinical consequence. Interestingly, we identified five genomic imbalances of the 1q21.1 or 15q11.2 regions known to be associated with congenital heart defects. CONCLUSION: Our study demonstrates the benefit of CMA in the etiological diagnosis of fetuses with isolated increased NT. It is worth noting that most (69%) of the detected pathogenic CNVs were cryptic. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

[Antenatal palliative plan following diagnosis of fetal lethal condition: Rennes Teaching Hospital experience]. / Projet palliatif anténatal après diagnostic de malformation fœtale létale : expérience du CHU de Rennes de 2006 à 2012.

OBJECTIVES: To study the pregnancies followed at Rennes University Hospital from 2006 to 2012, after prenatal diagnosis of lethal fetal condition and prenatal project of palliative care at birth consisting of comfort care emphasizing parent-child encounters and bonding. MATERIAL AND METHODS: Retrospective study of 20 pregnancies with diagnosis of lethal fetal condition where parents accepted antenatally the proposal or sought for palliative care at birth. RESULTS: Diagnosis was made at a median age of 20 weeks gestation (12-33). Birth occurred at 37.4 WG, 6 caesarean sections were performed for maternal conditions. Six cases of hypoplastic left heart syndrome (HLHS) share common characteristics: good Apgar score, prolonged survival (26hours to 159days) transfer to neonatology ward (6) or later at home (4). In four multiple pregnancies, the choice of SP mainly contributed to protect healthy twins during pregnancy. In birth room, there was no need for invasive procedure or drugs. Death: one occurred during labor, 8 in birth room before H2, others in neonatal ward before d4 (excluding HLHS). CONCLUSION: These data will enable better antenatal preparation of both teams and parents. Lifetime, however short, allowed parents to meet with their child alive this permitting collection of memory traces and bonding.

[Termination of pregnancy without feticide: A French national survey]. / L'interruption médicale de grossesse sans fœticide : une enquête nationale.

PURPOSE: Termination of pregnancy without feticide (TOPWF) is poorly known in France and far less practiced than palliative care after term birth of a child having a lethal pathology. Few teams consider it and its practice remains confidential. This survey tries to describe it. MATERIAL AND METHODS: A national survey was realized in 2014 using a questionnaire sent to 50 centers of prenatal diagnosis depending on a perinatal diagnosis center in France. RESULTS: Thirty-one centers answered the questionnaire. Seven teams shared their experience of TOPWF after 22-24 weeks gestation (WG). This practice concerned fetuses affected by "lethal" pathologies. The absence of feticide followed a parental request or a proposal of the medical team, after individual discussion in a multidisciplinary meeting. All the children born alive after TOPWF benefited of palliative care. The 24 other centers having answered our investigation performed systematically the feticide beyond 22-24 WG. They so wished "to protect" the fetus, the parents and the nursing team. A majority of these teams faced parental demands of abstention of feticide but few of them answered it favorably. CONCLUSION: A robust "palliative culture" seems essential to allow the nursing team to consider the development of TOPWF.

[Very preterm births (22-26 WG): from the decision to the implement of palliative care in the delivery room. Experience of Rennes University Hospital (France)]. / Naissances très prématurées (22 à 26 SA) : de la décision à la mise en œuvre des soins palliatifs en salle de naissance. Expérience du CHU de Rennes (France).

OBJECTIVES: After the establishment of a palliative care protocol (PC) in the delivery room, study how the postnatal management decision was taken and in particular how PC was developed. MATERIAL AND METHODS: Retrospective analysis of births between 22 and 25+6 WG, in Rennes University Hospital, during 21 months. RESULTS: Twenty-seven women meeting the criteria gave birth to 32 live children. Decision making (intensive care or PC) was fast but shared with the parents, mainly on the criterion of the term. The delivery was vaginal for 24 children. Thirteen children were resuscitated. Nineteen children received comfort care, their life was less than 3 hours, 18/19 were supported by their parents. CONCLUSION: The management of these births is consistent with current recommendations, decisions are individualized but often informally. The secondary prognostic criteria could be better taken into account. Obstetrical and pediatric management is consistent. The PC protocol is fairly well used but the collective decisions should be more formally organized and transcribed more accurately in the records, the requirements for analgesics should be based on clinical assessments.

[Severe hypoplastic left heart syndrome: palliative care after prenatal diagnosis]. / Hypoplasies sévères du ventricule gauche: soins palliatifs après un diagnostic prénatal.

We analyzed 16 cases of hypoplastic left heart syndrome (HLHS) submitted to the multidisciplinary center at Rennes Teaching Hospital from 2006 to 2010 for prenatal diagnosis. The information given to parents at the moment of choice is capital for them to make their own decision: in our team the real choice for parents stands between termination of pregnancy (TOP) and palliative care (PC). The Norwood procedure is rarely proposed to parents in France and it is performed in very few centers. Heart transplant is never proposed nor done at this age. The objectives of our study were to understand the reasons for the choice of PC, take stock of our experience of PC, and relate the benefits but also the disadvantages of PC. Over the 16 patients whose fetus had HLHS, 9 requested TOP, while 7 others wanted to live their pregnancy and meet their child at birth, therefore requesting neonatal PC. No family asked for the Norwood procedure. Four children died within the first days (D1, D2, D4, D9), 2 others died at 5 and 7 months, 1 child was operated on for coarctation of the aorta (unknown before birth) and is still alive 1.5 years later. Maternal motivations to continue the pregnancy were clearly described for 2 of the 7 cases: religious prohibition of TOP in 1 case, negative experiences of previous abortions in the second case. In another case, the parents hesitated between PC and Norwood surgery. For the other women, the reasons were less clearly expressed. In our series, HLHS is the first indication for PC from prenatal diagnosis (7/16 cases in the same period) while in the literature, heart diseases are the second cause of TOP after the neurological causes. The overrepresentation of this pathology in the families who opt for PC may be due to the unconscious image that both professionals and families have of HLHS: severity of an inevitably fatal disease, rapid postnatal death, and no suffering. Our study may change this view: a child was in fact carrying a curable defect which was discovered 12 days after birth, 2 children died at 5 and 7 months, and 5 of 6 children had major analgesics at the end of life. Nevertheless, the families were supported and followed by the PC network, except 1 who ruptured all contacts in a context of presumed intense suffering, but the other 6 do not regret their choice despite the difficulties.

Diagnosis of fetal urinary tract malformations: prenatal management and postnatal outcome.

OBJECTIVE: To evaluate prenatal management and to define the criteria of gravity for accurate assessment of the renal and overall prognosis of fetuses presenting malformations of the urinary tract. METHODS: We carried out a retrospective study of 127 cases of urinary tract malformation. We carried out descriptive statistical and univariate analyses as a function of severity criteria and the outcome of pregnancy. RESULTS: One-third of fetuses presented associated extrarenal malformations and 10% of the karyotypes were abnormal. There were more abortions in case of decrease in amniotic fluid volume (p < 0.001), extent of renal damage (p < 0.05), presence of associated extrarenal malformations (p < 0.05), early diagnosis of the malformation (p < 0.001) and presence of chromosomal syndrome (p = 0.01). In our study, there was an excellent correlation between prenatal data and pathological findings for the fetus following abortions for medical reasons or obtained during the surveillance of live-born children. Fetal biochemistry made very little contribution. CONCLUSION: In cases of urinary tract malformation, this work confirms the need for regular and frequent ultrasound scans, checking for the echographic factors indicative of gravity and for adapted karyotyping. It also demonstrates that pluridisciplinary management is necessary for the prenatal evaluation of renal and overall fetal prognosis.

[Acute pancreatitis induced by major hypertriglyceridemia during pregnancy. A case report]. / Pancréatite aiguë secondaire à une hypertriglycéridémie majeure au cours de la grossesse. A propos d'un cas.

A parturient in the 37th week of gestation is referred to the obstetrical emergency ward for an acute abdominal pain with vomiting and fever. Few hours after her admission, a caesarean section is performed for acute fetal distress. It gave birth to a 3940 g healthy newborn. An abundant and milky peritoneal fluid is noted during the C-section related to a major hypertriglyceridemia (84,47 g/L) which induced an acute pancreatitis explaining the early symptoms. The patient is then hospitalized in surgical reanimation: heparin and a low fat diet led to a quick decrease of triglyceridemia and the healing of the acute pancreatitis. We review the most recent literature about acute pancreatitis during pregnancy, especially induced by hypertriglyceridemia, and the different management option: heparin, parenteral nutrition or plasmapheresis.

[Antenatal metastatic neuroblastoma: prognostic criteria. A case report]. / Le neuroblastome métastatique anténatal: critères pronostiques. A propos d'un cas.

Neuroblastoma, the most common malignant tumor in the neonatal period is metastatic in 25 to 50% of cases. While the prognosis of antenatal neuroblastoma is often considered as favorable, included in the most common metastatic stage (Stage IV S), it can lead to fetal or neonatal death. We report a case of a fetus with a stage IV neuroblastoma who died in utero. The most important prognostic factor is tumor stage, making sonographic detection of metastasis essential. Nevertheless, accurate staging remains difficult by sonography. When metastatic neuroblastoma is suspected, sonographic survey has to be reinforced, and if serious criteria such as massive hepatomegaly, placentomegally or hydrops appear, delivery must be considered.

[Intravenous beta-2-adrenergic agonists for tocolytic therapy in pre-eclampsia: two cases of acute pulmonary edema]. / Bêta 2-mimétiques intraveineux pour tocolyse au cours de la prééclampsie: deux cas d'oedème aigu du poumon.

Two cases of pulmonary oedema during beta 2-adrenergic agonist therapy in pre-eclampsia pregnant patients are reported. In our first case, the pulmonary oedema was exceptionally severe, because the patient (twins at 26 SA) had to be intubated and ventilated, but the caesarean section was performed only 6 weeks later. These two clinical observations underline the fact that B2 adrenergic agonist are not indicated for the treatment of preeclampsy. Furthermore they suggest that such patients should be rapidly admitted to intensive care units.

[Markers of infection and inflammation in the amniotic fluid: therapeutic contribution of amniocentesis]. / Marqueurs de l'infection et de l'inflammation dans le liquide amniotique: intérêt de l'amniocentèse dans la prise en charge.

A part of preterm labor with intact membranes seems to be related to amniotic infection or local inflammatory process. In these cases, amniotic fluid is collected by amniocentesis for bacteriological studies: amniotic cultures are positive in 10% and polymerase chain reaction (PCR) in 40-50%. Interleukin 6 (IL6) concentrations are elevated in cases with amniotic infection and in some cases with negative cultures. IL6 amniotic concentrations are predictive of premature delivery and neonatal morbidity. Matrix metalloproteinases (MMP) are endogenous enzymes implicated in membrane weakening. Amniotic concentrations of these enzymes seem to be predictive of premature delivery and neonatal prognosis. Furthermore, at the time of genetic amniocentesis, IL6 and MMP concentrations are markers for preterm delivery. In the second half of gestation, amniocentesis is a safe procedure complicated in less than 1% of cases, although specific evaluation in cases of premature labor is missing. Nevertheless, as long as there is no evidence of any benefit in this procedure, there is no indication for amniocentesis in premature labor with intact membranes in general practice.

Uterine rupture during pregnancy following myomectomy via coelioscopy.

A 33-year-old woman underwent a myomectomy via coelioscopy and then showed 5 years later a uterine rupture at the 32nd week of amenorrhea. The rupture was diagnosed after the echography, while there was no peritoneal maternal patency nor foetal consequence. After a cesarean and an uterine repair, the recovery of the mother was satisfactory but the newborn was to die at the 6th week of life. This obstetrical complication raises the problem of myomectomy via coelioscopy in young women, whose indications are being discussed.