RESUMEN
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.
RESUMEN
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.