Impact of variants of SARS-CoV-2 on obstetrical and neonatal outcomes

International audienceBackground: SARS-CoV-2 can lead to several types of complications during pregnancy. Variant surges are associated with different severities of disease. Few studies have compared the clinical consequences of specific variants on obstetrical and neonatal outcomes. Our goal was to evaluate and compare disease severity in pregnant women and obstetrical or neonatal complications between variants of SARS-CoV-2 that have circulated in France over a two-year period (2020-2022).Method: This retrospective cohort study included all pregnant women with a confirmed SARS-CoV-2 infection (positive naso-pharyngeal RT-PCR test) from March 12, 2020 to January 31, 2022, in three tertiary maternal referral obstetric units in the Paris metropolitan area, France. We collected clinical and laboratory data for mothers and newborns from patients' medical records. Variant identification was either available following sequencing or extrapolated from epidemiological data.Results: There were 234/501 (47%) Wild Type (WT), 127/501 (25%) Alpha, 98/501 (20%) Delta, and 42/501 (8%) Omicron. No significative difference was found regarding two composite adverse outcomes. There were significantly more hospitalizations for severe pneumopathy in Delta variant than WT, Alpha and Omicron respectively (63% vs 26%, 35% and 6%, pConclusion: Although the Delta variant was associated with more severe disease in pregnant women, we found no difference regarding neonatal and obstetrical outcomes. Neonatal and obstetrical specific severity may be due to mechanisms other than maternal ventilatory and general infection

Developmental phenotype in Phelan-McDermid (22q13.3 deletion) syndrome: A systematic and prospective study in 34 children

Background: Phelan- McDermid syndrome (PMS) or 22q13.3 deletion syndrome is characterized by global developmental delay, cognitive deficits, and behaviour in the autism spectrum. Knowledge about developmental and behavioural characteristics of this rare chromosomal disorder is still limited despite a rapid growing number of diagnoses. Our aim was to study a new and relatively large cohort to further characterize the developmental phenotype of children with PMS. Methods: We performed a descriptive study of children with a 22q13.3 deletion including SHANK3, aged 8 to 178 months, who were systematically (n = 34) and longitudinally (n = 29) assessed with standardized instruments: Bayley Scales of Infant and Toddler Development, third edition; Wechsler Preschool and Primary Scale of Intelligence, third edition; and Vineland Screener for Social and Adaptive Behavior. Results: Maximal developmental functioning ranged from 34 to 52 months depending on the developmental domain. In general, children performed poorest in the domain of language and best on the domain of motor (young children) or cognitive development (older children). At the individual level, 25 % scored better for receptive and 18 % for expressive language, whereas 22 % scored better for fine and 33 % for gross motor function. Developmental quotients were higher in younger children and decreased with age for all developmental domains, with 38 % of the children showing no improvement of cognitive developmental functioning. Almost all children (33/34) had significant deficits in adaptive behaviour. Children with very small deletions, covering only the SHANK3, ACR, and RABL2B genes, had a more favourable developmental phenotype. Conclusions: Cognitive, motor, and especially language development were significantly impaired in all children with PMS but also highly variable and unpredictable. In addition, deficits in adaptive behaviour further hampered their cognitive development. Therefore, cognitive and behavioural characteristics should be evaluated and followed in each child with PMS to adapt supportive and therapeutic strategies to individual needs. Further research evaluating the relationship between deletion characteristics and the developmental phenotype is warranted to improve counselling of parents

Hofbauer Cells and COVID-19 in Pregnancy Molecular Pathology Analysis of Villous Macrophages, Endothelial Cells, and Placental Findings From 22 Placentas Infected by SARS-CoV-2 With and Without Fetal Transmission

Context.-SARS-CoV-2 can undergo maternal-fetal transmission, heightening interest in the placental pathology findings from this infection. Transplacental SARS-CoV-2 transmission is typically accompanied by chronic histiocytic intervillositis together with necrosis and positivity of syncytiotrophoblast for SARS-CoV-2. Hofbauer cells are placental macrophages that have been involved in viral diseases, including HIV and Zika virus, but their involvement in SARS-CoV-2 is unknown. Objective.-To determine whether SARS-CoV-2 can extend beyond the syncytiotrophoblast to enter Hofbauer cells, endothelium, and other villous stromal cells in infected placentas of liveborn and stillborn infants. Design.-Case-based retrospective analysis by 29 perinatal and molecular pathology specialists of placental findings from a preselected cohort of 22 SARS-CoV-2- infected placentas delivered to pregnant women testing positive for SARS-CoV-2 from 7 countries. Molecular pathology methods were used to investigate viral involvement of Hofbauer cells, villous capillary endothelium, syncytiotrophoblast, and other fetal-derived cells. Results.-Chronic histiocytic intervillositis and trophoblast necrosis were present in all 22 placentas (100%). SARS-CoV-2 was identified in Hofbauer cells from 4 of 22 placentas (18.2%). Villous capillary endothelial staining was positive in 2 of 22 cases (9.1%), both of which also had viral positivity in Hofbauer cells. Syncytiotrophoblast staining occurred in 21 of 22 placentas (95.5%). Hofbauer cell hyperplasia was present in 3 of 22 placentas (13.6%). In the 7 cases having documented transplacental infection of the fetus, 2 (28.6%) occurred in placentas with Hofbauer cell staining positive for SARS-CoV-2. Conclusions.-SARS-CoV-2 can extend beyond the trophoblast into the villous stroma, involving Hofbauer cells and capillary endothelial cells, in a small number of infected placentas. Most cases of SARS-CoV-2 transplacental fetal infection occur without Hofbauer cell involvement. (Arch Pathol Lab Med. 2021;145:1328-1340 ; doi: 10.5858/arpa.2021-0296-SA)OV