Can Prenatal Ultrasound Predict Adverse Neonatal Outcomes in SARS-CoV-2 Affected Pregnancies?

BACKGROUND: Based on available data, at least one ultrasound assessment of pregnancies recovering from SARS-CoV-2 infection is recommended. Reports, however, on prenatal imaging findings and potential associations with neonatal outcomes following SARS-CoV-2 infection in pregnancy have been inconclusive. OBJECTIVE: We aim to describe the sonographic characteristics of pregnancies after confirmed SARS-CoV-2 infection and assess the association of prenatal ultrasound (US) findings with adverse neonatal outcomes (ANO). STUDY DESIGN: This is an observational prospective cohort study of pregnancies diagnosed with SARS-CoV-2 by reverse transcription polymerase chain reaction between March 2020 and May 2021. Prenatal US evaluation was performed at least once after diagnosis of infection with the following parameters measured: standard fetal biometric measurements, umbilical and middle cerebral artery Dopplers, placental thickness, amniotic fluid volume, and anatomic survey for infection-associated findings. The primary outcome was composite ANO, defined as one or more of the following: preterm birth, NICU admission, small for gestational age (SGA), respiratory distress, intrauterine fetal demise, neonatal demise, or other neonatal complications. Secondary outcomes were sonographic findings stratified by trimester of infection and severity of SARS-CoV-2 infection. Prenatal US findings were compared with neonatal outcomes, severity of infection, and trimester of infection. RESULTS: A total 103 SARS-CoV-2 affected mother-infant pairs with prenatal US evaluation were identified; 3 cases were excluded due to known major fetal anomalies. Of the 100 included cases, neonatal outcomes were available in 92 pregnancies (97 infants); of these, 28 (29%) had a composite ANO. Twenty-three (23%) had at least one abnormal prenatal US finding. The most common abnormalities seen on US were placentomegaly (11/23, 47.8%) and fetal growth restriction (FGR) (8/23, 34.8%). FGR was associated with a higher rate of a composite ANO (25% vs 1.5%; aOR: 22.67; 95% 95% CI, 2.63-194.91; p<0.001), even when SGA was removed from the composite ANO. Cochran-Mantel Haensel test controlling for possible FGR confounders continued to show this association (relative risk, 3.7; 95% confidence interval, 2.6-5.9; p<0.001). Median estimated fetal weight (EFW) and birthweight were lower in patients with a composite ANO (p<0.001). Infection in the third trimester was associated with lower median percentile of EFW (p=0.019). An association between placentomegaly and third trimester SARS CoV-2 infection was noted (p=0.045). CONCLUSION: In our study of SARS-CoV-2 affected maternal-infant pairs, rates of FGR were comparable to the general population. However, composite ANO rates were high. Pregnancies with FGR after SARS-CoV-2 infection were associated with an increased risk for ANO and may require close surveillance.

Longitudinal Evaluation of Antibody Persistence in Mother-Infant Dyads Following SARS-CoV-2 Infection in Pregnancy.

BACKGROUND: There are limited data on how COVID-19 severity, timing of infection, and subsequent vaccination impact transplacental transfer and persistence of maternal and infant antibodies. METHODS: In a longitudinal cohort of pregnant women with PCR-confirmed SARS-CoV-2 infection, maternal/infant sera were collected at enrollment, delivery/birth, and 6 months. Anti-SARS-CoV-2 spike IgG, IgM and IgA were measured by ELISA. RESULTS: 256 pregnant women and 135 infants were enrolled; 148 maternal and 122 neonatal specimens were collected at delivery/birth; 45 maternal and 48 infant specimens were collected at 6 months. Sixty-eight percent of women produced all anti-SARS-CoV-2 isotypes at delivery (IgG, IgM, IgA); 96% had at least one isotype. Symptomatic disease, and vaccination prior to delivery, were associated with higher maternal IgG at L&D. Detectable IgG in infants dropped from 78% at birth to 52% at 6 months. In the multivariate analysis evaluating factors associated with detectable IgG in infants at delivery, significant predictors were 3rd trimester infection (OR 4.0), mild/moderate disease (OR 4.8), severe/critical disease (OR 6.3), and maternal vaccination prior to delivery (OR 18.8). No factors were significant in the multivariate analysis at 6 months postpartum. CONCLUSIONS: Vaccination in pregnancy post-COVID-19 recovery is a strategy for boosting antibodies in mother-infant dyads.

Neutralizing Monoclonal Antibodies for Coronavirus Disease 2019 (COVID-19) in Pregnancy: A Case Series.

OBJECTIVE: To describe outcomes associated with monoclonal antibody use in pregnant persons with mild-to-moderate coronavirus disease 2019 (COVID-19). METHODS: We present a retrospective case series of pregnant patients who received anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibody infusions at a single center from April 1, 2021, through October 16, 2021. Pregnant patients who had a positive SARS-CoV-2 polymerase chain reaction (PCR) test result and mild-to-moderate COVID-19 symptoms were eligible for monoclonal antibody infusion. Exclusion criteria for administration included need for supplemental oxygen, hospitalization due to COVID-19, and positive SARS-CoV-2 PCR test result more than 7 days before screening. All patients received either bamlanivimab plus etesevimab or casirivimab plus imdevimab based on availability and dosing instructions of the product and emerging resistance patterns in the community. RESULTS: During the study period, monoclonal antibody infusions were administered to 450 individuals at our institution, of whom 15 were pregnant. Of the 15 pregnant persons receiving monoclonal antibody, six (40%) had full-vaccination status at the time of infusion. Two individuals (13%, CI 0-31%) experienced systemic reactions during the infusion, both resulting in temporary changes in the fetal heart rate tracing that recovered with maternal and intrauterine resuscitative efforts. One patient delivered after infusion for worsening maternal and fetal status; the remainder of the patients did not require admission for COVID-19. CONCLUSION: In this case series, pregnant persons who received anti-SARS-CoV-2 monoclonal antibody infusions had generally favorable outcomes.

Neuromotor repertoires in infants exposed to maternal COVID-19 during pregnancy: a cohort study.

OBJECTIVE: To evaluate neuromotor repertoires and developmental milestones in infants exposed to antenatal COVID-19. DESIGN: Longitudinal cohort study. SETTING: Hospital-based study in Los Angeles, USA and Rio de Janeiro, Brazil between March 2020 and December 2021. PARTICIPANTS: Infants born to mothers with COVID-19 during pregnancy and prepandemic control infants from the Graz University Database. INTERVENTIONS: General movement assessment (GMA) videos between 3 and 5 months post-term age were collected and clinical assessments/developmental milestones evaluated at 6-8 months of age. Cases were matched by gestational age, gender and post-term age to prepandemic neurotypical unexposed controls from the database. MAIN OUTCOME MEASURES: Motor Optimality Scores Revised (MOS-R) at 3-5 months. Presence of developmental delay (DD) at 6-8 months. RESULTS: 239 infants were enrolled; 124 cases (83 in the USA/41 in Brazil) and 115 controls. GMA was assessed in 115 cases and 115 controls; 25% were preterm. Median MOS-R in cases was 23 (IQR 21-24, range 9-28) vs 25 (IQR 24-26, range 20-28) in controls, p<0.001. Sixteen infants (14%) had MOS-R scores <20 vs zero controls, p<0.001. At 6-8 months, 13 of 109 case infants (12%) failed to attain developmental milestones; all 115 control infants had normal development. The timing of maternal infection in pregnancy (first, second or third trimester) or COVID-19 disease severity (NIH categories asymptomatic, mild/moderate or severe/critical) was not associated with suboptimal MOS-R or DD. Maternal fever in pregnancy was associated with DD (OR 3.7; 95% CI 1.12 to 12.60) but not suboptimal MOS-R (OR 0.25; 95% CI 0.04 to 0.96). CONCLUSIONS: Compared with prepandemic controls, infants exposed to antenatal COVID-19 more frequently had suboptimal neuromotor development.

Severe COVID-19 in pregnancy has a distinct serum profile, including greater complement activation and dysregulation of serum lipids.

BACKGROUND: Pregnancies complicated by Coronavirus Disease 2019 (COVID-19) are at an increased risk of severe morbidity due to physiologic changes in immunologic, cardiovascular, and respiratory function. There is little is known about how severity of COVID-19 changes protein and metabolite expression in pregnancy. OBJECTIVE: This study aims to investigate the pathophysiology behind various clinical trajectories in pregnant patients diagnosed with COVID-19 using multi-omics profiling. STUDY DESIGN: This is a prospective cohort study of 30 pregnant patients at a single tertiary care center. Participants were categorized by severity of COVID-19 disease (control, asymptomatic, mild/moderate, or severe). Maternal serum samples underwent LC-MS-based multiomics analysis for profiling of proteins, lipids, electrolytes, and metabolites. Linear regression models were used to assess how disease severity related to analyte levels. Reactome pathway enrichment analysis was conducted on differential analytes. RESULTS: Of 30 participants, 25 had confirmed diagnosis of COVID-19 (6 asymptomatic (one post-infection), 13 mild/moderate (all post-infection), 6 severe), and 5 participants were controls. Severe COVID-19 was associated with distinct profiles demonstrating significant proteomic and lipidomic signatures which were enriched for annotations related to complement and antibody activity. (FDR < 0.05). Downregulated analytes were not significantly enriched but consisted of annotation terms related to lipoprotein activity (FDR > 0.2). Post-infection mild/moderate COVID-19 did not have significantly altered serum protein, metabolite, or lipid metabolite levels compared to controls. CONCLUSIONS: Pregnancies with severe COVID-19 demonstrate greater inflammation and complement activation and dysregulation of serum lipids. This altered multiomic expression provides insight into the pathophysiology of severe COVID-19 in pregnancy and may serve as potential indicators for adverse pregnancy outcomes.

The systemic inflammatory landscape of COVID-19 in pregnancy: Extensive serum proteomic profiling of mother-infant dyads with in utero SARS-CoV-2.

While pregnancy increases the risk for severe COVID-19, the clinical and immunological implications of COVID-19 on maternal-fetal health remain unknown. Here, we present the clinical and immunological landscapes of 93 COVID-19 mothers and 45 of their SARS-CoV-2-exposed infants through comprehensive serum proteomics profiling for >1,400 cytokines of their peripheral and cord blood specimens. Prenatal SARS-CoV-2 infection triggers NF-κB-dependent proinflammatory immune activation. Pregnant women with severe COVID-19 show increased inflammation and unique IFN-λ 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, and ESM1 and reducing BGN and CD209. Finally, COVID-19-exposed infants exhibit induction of T cell-associated cytokines (IL33, NFATC3, and CCL21), while some undergo IL-1ß/IL-18/CASP1 axis-driven neonatal respiratory distress despite birth at term. Our findings demonstrate COVID-19-induced immune rewiring in both mothers and neonates, warranting long-term clinical follow-up to mitigate potential health risks.

Evaluation of Respiratory Emissions During Labor and Delivery: Potential Implications for Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

OBJECTIVE: To characterize respiratory emissions produced during labor and vaginal delivery vis-à-vis the potential for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Observational study of three women who tested negative for SARS-CoV-2 and had uncomplicated vaginal deliveries. Using background-oriented schlieren imaging, we evaluated the propagation of respiratory emissions produced during the labor course and delivery. The primary outcome was the speed and propagation of breath over time, calculated through processed images collected throughout labor and delivery. RESULTS: In early labor with regular breathing, the speed of the breath was 1.37 meters/s (range 1.20-1.55 meters/s). The breath appeared to propagate faster with a cough during early labor at a speed of 1.69 meters/s (range 1.22-2.27 meters/s). During the second stage of labor with Valsalva and forced expiration, the propagation speed was 1.79 meters/s (range 1.71-1.86 meters/s). CONCLUSION: Labor and vaginal delivery increase the propagation of respiratory emissions that may increase risk of respiratory transmission of SARS-CoV-2.

Complicated Monochorionic-Diamniotic Twins in a Pregnant Woman with COVID-19 in the Second Trimester.

OBJECTIVE: A majority of studies evaluating the risk of vertical transmission and adverse outcomes in pregnancies with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are mostly based on third-trimester infections. There is limited data available on pregnancy sequelae of maternal infection in the first or second trimester. STUDY DESIGN: We present a patient with monochorionic-diamniotic twins that develops coronavirus disease 2019 infection at 15 weeks of gestation. The pregnancy is further complicated by stage II twin-twin transfusion syndrome. She undergoes laser ablation, which is complicated by development of a subchorionic hematoma. The patient then develops Escherichia coli bacteremia, resulting in septic shock and preterm labor followed by previable delivery at 21 weeks of gestation. Amniotic fluid and placenta were negative for SARS-CoV-2 by real-time polymerase chain reaction. CONCLUSION: This case of SARS-CoV-2 argues against transplacental transmission after a second-trimester infection but brings attention to the possible downstream complications that may arise following early infection. KEY POINTS: · Vertical transmission of SARS-CoV-2 is not evident after a second-trimester infection.. · Antepartum coronavirus disease 2019 may cause vascular placental changes and placental insufficiency.. · SARS-CoV-2 is associated with a maternal hypercoagulable state with adverse perinatal outcomes..

Maternal-Neonatal Dyad Outcomes of Maternal COVID-19 Requiring Extracorporeal Membrane Support: A Case Series.

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: · COVID-19 may present with a more severe course in pregnancy.. · ECMO may be used in pregnant woman with severe COVID-19.. · Delivery can be performed on ECMO without added fetal risk..