Contribution of fetal blood sampling to determining the prognosis of congenital cytomegalovirus infections: a case-cohort study in Switzerland.

BACKGROUND: Cytomegalovirus is responsible for the most common congenital infection, affecting 0.5% to 1.0% of live births in Europe. Congenital cytomegalovirus infection can be diagnosed during pregnancy by viral DNA amplification in the amniotic fluid, but the prognosis of fetuses without severe brain abnormalities remains difficult to establish on the basis of prenatal imaging alone. OBJECTIVE: To identify predictors of moderate to severe symptomatic cytomegalovirus infection among fetal blood parameters and to propose an algorithm on the basis of these parameters and on prenatal imaging that would provide the best positive and negative predictive values. STUDY DESIGN: Fetal blood sampling at 21-28 weeks gestation was performed in fetuses with congenital cytomegalovirus infection confirmed by amniocentesis after maternal infection in the first-trimester or periconceptional period. We compared the levels of hemoglobin, thrombocytes, γ-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, ß2-microglobulin, immunoglobulins G and M, and cytomegalovirus DNA viral loads in amniotic fluid and fetal blood between those with moderate to severe symptomatic infection and those with asymptomatic to mild infection (median follow-up of 36 months for live births). RESULTS: Among 58 fetuses included, 25 (43%) had a moderate to severe symptomatic infection: 16 with severe cerebral abnormalities, 5 with multiple signs or symptoms at birth, 2 with bilateral sensorineural hearing loss, and 2 with neurodevelopmental delay. The values of thrombocytes, aspartate aminotransferase, ß2 microglobulin, Immunoglobulin M, and cytomegalovirus viral loads differed significantly between fetuses with moderate to severe symptomatic infection and those with asymptomatic to mild infection. The optimal strategy to predict moderate to severe symptomatic infection was to first perform fetal brain imaging, followed by fetal blood sampling with the following cutoffs: thrombocytes <120,000/mL, viremia ≥5 log10/mL, and ß2 microglobulin ≥12 mg/L). This recursive algorithm had a negative predictive value of 100% for moderately to severely symptomatic infection. CONCLUSION: The combination of thrombocytes, ß2-microglobulin, and cytomegalovirus viral load in fetal blood can be used for prognosis determination, particularly in cytomegalovirus-infected fetuses without severe brain abnormalities at the time of prenatal diagnosis. Future studies should evaluate whether these parameters remain useful in infected fetuses who have been treated with valacyclovir before fetal blood sampling.

[Venous thromboembolic disease during pregnancy : diagnosis, treatment and follow-up]. / Maladie thromboembolique veineuse et grossesse : diagnostic, traitement et suivi.

Venous thromboembolism is a leading cause of maternal morbidity and mortality with an overall incidence of 1-2 cases per 1000 pregnancies. The purpose of this article is to summarize more recent recommendations for the management of venous thromboembolism during pregnancy and post-partum period.

La maladie thromboembolique veineuse est l'une des principales causes de morbidité et mortalité maternelles avec une incidence globale de 1 à 2 cas pour 1000 grossesses. Le but de cet article est de résumer les recommandations les plus récentes concernant la prise en charge de la maladie thromboembolique veineuse pendant la grossesse et dans le post-partum.

Placental mesenchymal dysplasia: An underdiagnosed placental pathology with various clinical outcomes.

BACKGROUND: Placental mesenchymal dysplasia (PMD) is a rare vascular and connective placental anomaly, which is often associated with severe fetal and/or maternal complications. The diversity of presentation of PMD challenges diagnosis and effective pregnancy management. OBJECTIVE: We aimed to review cases presenting at 7 tertiary centers worldwide over the last decade and to study the occurrence of obstetric and neonatal complications. STUDY DESIGN: Pathology databases from 7 tertiary hospitals were screened for cases of PMD (between 2007-2017). Pregnancy history, outcomes and ultrasound images were then reviewed for each case. RESULTS: Twenty-two cases of PMD were identified. Mean gestational age at diagnosis was 23 weeks (16-39 weeks). Prenatal biochemical screening was abnormal in 8 cases (36%). Of the 12 cases that underwent invasive genetic testing, 4 were abnormal. Six patients (27%) developed maternal complications (preeclampsia/gestational hypertension). Fetal growth restriction was identified in 11 cases (50%) and fetal death in 4 (18%). Four (18%) pregnancies were terminated, 9/14 (64%) delivered preterm and only three (14%) progressed normally. Fourteen babies were born alive; 5 (35%) died in the first sixty-one days after birth, 5 (35%) had transient thrombopenia and 1 (7%) had developmental delay at last follow-up. Our series identified four potential new associations with PMD: placental triploidy mosaicism, CHARGE syndrome, fetal pleuropulmonary blastoma and fetal skeletal dysplasia. CONCLUSIONS: PMD was substantially under-diagnosed before delivery in this cohort. Sonographers, fetal medicine specialists, obstetricians and pathologists should all suspect PMD in cases of an enlarged placenta and should look for fetal abnormalities. Diagnostic genetic testing should be discussed to exclude partial molar pregnancy. Close pregnancy follow-up is indicated due to the high risk of associated fetal or maternal adverse outcomes.

[Nausea and vomiting in pregnancy]. / Nausées et vomissements chez la femme enceinte.

Nausea and vomiting in early pregnancy is a common condition at risk to be minimized by women or care providers. If not treated in the early stages, it can evolve to a severe condition with a morbidity risk for the mother and/or the fetus, and expose to public health consequences. Severe forms of nausea and vomiting and hyperemesis gravidarum are a clinical diagnosis with nonspecific manifestations in addition to biologic and metabolic consequences for mother and/or child. Safe and effective treatments can prevent severe consequences if used in an early stage of symptoms.

Les nausées et vomissements au premier trimestre de grossesse sont des manifestations fréquentes et donc à risque d'être banalisés par les femmes comme par les soignants. Mal contrôlés initialement, ils sont à risque d'évoluer vers une forme sévère, avec une morbidité maternelle et/ou fœtale non négligeable, et impliquer des conséquences en matière de santé publique. Les formes sévères de nausées et vomissements de grossesse (hyper-émèse gravidique) sont des diagnostics cliniques avec des manifestations aspécifiques et des complications biologiques, voire métaboliques, sur la mère comme sur le fœtus. Plusieurs lignes de traitement existent, qui ont montré leur efficacité et leur innocuité. Instaurés précocement, ils préviennent l'évolution vers des formes graves.

Fetal Intra-Peritoneal Transfusion for the Management of Very Early Spontaneous Twin Anemia-Polycythemia Sequence in an Obese Patient With a Whole Anterior Placenta.

Twin anemia-polycythemia sequence (TAPS) is a rare condition in monochorionic twin pregnancies. Small intertwin placental vascular communications allow transfusion, which results in a hemoglobin difference in the twins in the absence of oligohydramnios or polyhydramnios. We report here a case of TAPS diagnosed at 17 weeks' gestation in an obese patient (BMI 42) with a whole anterior placenta. The only possible treatment at this stage of pregnancy was intra-uterine transfusion (IUT), which was repeated weekly until photocoagulation of placental anastomoses was feasible. Fetoscopic laser surgery is the only curative treatment, but is challenging in TAPS because of the absence of polyhydramnios and the presence of minuscule anastomoses. An anterior placenta and high BMI can make the procedure even more challenging. This case report demonstrates that very early and rapidly progressing TAPS with technically complicated conditions (elevated BMI and anterior placenta) can be successfully managed with IUT until laser procedure is achievable.

SCRIB and PUF60 are primary drivers of the multisystemic phenotypes of the 8q24.3 copy-number variant.

Copy-number variants (CNVs) represent a significant interpretative challenge, given that each CNV typically affects the dosage of multiple genes. Here we report on five individuals with coloboma, microcephaly, developmental delay, short stature, and craniofacial, cardiac, and renal defects who harbor overlapping microdeletions on 8q24.3. Fine mapping localized a commonly deleted 78 kb region that contains three genes: SCRIB, NRBP2, and PUF60. In vivo dissection of the CNV showed discrete contributions of the planar cell polarity effector SCRIB and the splicing factor PUF60 to the syndromic phenotype, and the combinatorial suppression of both genes exacerbated some, but not all, phenotypic components. Consistent with these findings, we identified an individual with microcephaly, short stature, intellectual disability, and heart defects with a de novo c.505C>T variant leading to a p.His169Tyr change in PUF60. Functional testing of this allele in vivo and in vitro showed that the mutation perturbs the relative dosage of two PUF60 isoforms and, subsequently, the splicing efficiency of downstream PUF60 targets. These data inform the functions of two genes not associated previously with human genetic disease and demonstrate how CNVs can exhibit complex genetic architecture, with the phenotype being the amalgam of both discrete dosage dysfunction of single transcripts and also of binary genetic interactions.

[Giant pedunculated cavernous hepatic haemangioma: a case report and review of the literature]. / Hémangiome caverneux pédiculé géant du foie: a propos d'un cas et revue de la littérature.

Cavernous hepatic haemangioma is the most frequent benign liver tumour, but the giant pedunculated form is rare because only 17 cases have been described in the literature. We report our experience of one case, and compare it to the 17 other described cases. Age, incidence and size of the lesion were the same as results in the literature. Our patient has had a left hepatic lobectomy because of an uncertain diagnosis. We discuss the diagnosis and the different treatments.

[Recurrent anal abscess and cecal perforation as a first presentation of Behçet's disease]. / Abcès para-anaux récidivants et perforation caecale révélant une maladie de Behçet.

Intestinal involvement during Behçet's disease (entero-Behçet) is rare in Europe (<1%). We report the case of a 33-year-old Chad woman with Behçet's disease revealed by recurrent anal abscess and cecal perforation. We discuss the diagnosis of this atypical presentation and the different therapeutic strategies in severe attacks of Behçet's disease.