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While pregnancy increases the risk for severe COVID19, the clinical and immunological implications of COVID19 on maternal-fetal health remain unknown. Here, we present the clinical and immunological landscapes of 93 COVID19 mothers and 45 of their SARS-CoV-2-exposed infants through comprehensive serum proteomics profiling for >1400 cytokines of their peripheral and cord blood specimens. Prenatal SARS-CoV-2 infection triggers NF-κB-dependent proinflammatory immune activation. Pregnant women with severe COVID19 show increased inflammation and unique IFNλ antiviral signaling, with elevated levels of IFNL1 and IFNLR1. Furthermore, SARS-CoV-2 infection re-shapes maternal immunity at delivery altering the expression of pregnancy complication-associated cytokines, inducing MMP7, MDK, ESM1, and reducing BGN and CD209. Finally, COVID19-exposed infants exhibit induction of T cell-associated cytokines (IL33, NFATC3 and CCL21), while some undergo IL-1β/IL-18/CASP1 axis-driven neonatal respiratory distress despite birth at term. Our findings demonstrate COVID19-induced immune rewiring in both mothers and neonates, warranting long-term clinical follow-up to mitigate potential health risks.

Objective This study aimed to describe two cases of acute respiratory distress syndrome (ARDS) secondary to novel coronavirus disease 2019 (COVID-19) in pregnant women requiring extracorporeal membrane oxygenation (ECMO), and resulting in premature delivery. Study Design The clinical course of two women hospitalized with ARDS due to COVID-19 care in our intensive care (ICU) is summarized; both participants provided consent to be included in this case series. Results Both women recovered with no clinical sequelae. Neonatal outcomes were within the realm of expected for prematurity with the exception of coagulopathy. There was no vertical transmission to the neonates. Conclusion This case series highlights that ECMO is a feasible treatment in the pregnant woman with severe COVID-19 and that delivery can be performed safely on ECMO with no additional risk to the fetus. While ECMO carries its natural risks, it should be considered a viable option during pregnancy and the postpartum period. Key Points

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Background Since its commercial release in 2011 cell-free DNA screening has been rapidly adopted as a routine prenatal genetic test. However, little is known about its performance in actual clinical practice. Objective To investigate factors associated with the accuracy of abnormal autosomal cell- free DNA results. Study Design Retrospective cohort study of 121 patients with abnormal cell-free DNA results from a referral maternal-fetal medicine practice from March 2013 to July 2015. Patients were included if cell-free DNA results for trisomy 21, trisomy 18, trisomy 13, or microdeletions (if reported by the laboratory) were positive or non-reportable. The primary outcome was confirmed aneuploidy or microarray abnormality on either prenatal or postnatal karyotype or microarray. Secondary outcomes were identifiable associations with in vitro fertilization, twins, ultrasound findings, testing platform, and testing laboratory. Kruskal-Wallis or Fisher’s exact tests were used as appropriate. Results 121 patients had abnormal cell-free DNA results for for trisomy 21, trisomy 18, trisomy 13, and/or microdeletions. 105 patients had abnormal cell-free DNA results for for trisomy 21, trisomy 18, trisomy 13. Of these, 92 (87.6%) were positive and 13 (12.4%) were non-reportable. The results of the 92 positive cell-free DNA were for trisomy 21 (48, 52.2%), trisomy 18 (22, 23.9%), trisomy 13 (17, 18.5%), triploidy (2, 2.2%), and positive for >1 parameter (3, 3.3%). Overall, the positive predictive value of cell-free DNA was 73.5% (61/83, 95% confidence interval (CI) 63% to 82%) for all trisomies (by chromosome: trisomy 21, 83.0% (39/47, CI 69% to 92%, trisomy 18, 65.0% (13/20, CI 41% to 84%), and trisomy 13, 43.8% (7/16, CI 21% to 70%). Abnormal cell-free DNA results were associated with positive serum screening (by group: trisomy 21 17/48, 70.8%; trisomy 18 7/22, 77.8%; trisomy 13 3/17, 37.5%; non-reportable 2/13, 16.7%; p=0.004), and abnormal first trimester ultrasound (trisomy 21 25/45, 55.6%; trisomy 18 13/20, 65%; trisomy 13 6/14, 42.9%; non-reportable 1/13, 7.7%; p=0.003). There was no association between false positive rates and testing platform, but there was a difference between the four laboratories (p=0.018). Twenty-six patients had positive (n=9) or non-reportable (n=17) microdeletion results. Seven of nine screens positive for microdeletions underwent confirmatory testing; all were false positives. Conclusions The positive predictive value of 73.5% for cell-free DNA screening for autosomal aneuploidy is lower than reported. The positive predictive value for microdeletion testing was 0%. Diagnostic testing is needed to confirm abnormal cell-free DNA results for aneuploidy and microdeletions.