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Newborns Infected with SARS-CoV-2 in Utero Are at Higher Risk of Respiratory Distress


In a recent Nature Communications study, experts delved into the risks of respiratory distress (RD) in newborns born to mothers with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.


What Are the Effects of Maternal SARS-CoV-2 Infection on the Baby?

Maternal SARS-CoV-2 infection during pregnancy can lead to serious complications for both mother and baby, including stillbirth, prematurity, and maternal health issues. Although the transmission of the virus from mother to child is relatively low, concerns about potential long-term effects on newborns persist.  


Interestingly, RD has been observed not only in infected newborns but also in those exposed to SARS-CoV-2 without being infected. Initial explanations focused on maternal health issues leading to premature birth, a known risk factor for RD. However, recent insights suggest that prenatal exposure might trigger inflammation in the newborn's airways, indicated by specific proteins found in affected infants.  


The impact of maternal coronavirus disease 2019 (COVID-19) vaccination on preventing neonatal RD post-exposure remains uncertain. Hence, additional research is essential to uncover the mechanisms by which prenatal SARS-CoV-2 exposure leads to RD in newborns and to explore potential preventive strategies. As these findings are further studied, it will be critical to understand the intricate links between maternal infection, prenatal exposure, and neonatal respiratory distress. Continued research in this critical area is needed to clarify the role of COVID-19 vaccination in preventing such complications.


About the Study

This study, conducted at the Department of Obstetrics at the University of California, Los Angeles (UCLA) between April 15, 2020, and August 31, 2022, focused on participants aged 16 and older. Recruitment involved screening all women admitted for labor and delivery at UCLA during this period for SARS-CoV-2.  


A total of 221 pregnant individuals and 227 exposed fetuses were part of the study, resulting in 199 live births. The well-being of these maternal-infant pairs was monitored until the infants reached six months of age. Informed consent was obtained from participants or surrogate decision-makers in cases of incapacity.  


To gauge neonatal RD, criteria such as respiratory rate and cyanosis were employed, with premature birth defined as delivery before 37 weeks. The study considered maternal COVID-19 severity, vaccination status, and self-reported race and ethnicity.  


Statistical analyses delved into comparing demographics of infants with and without RD, examining maternal and infant characteristics and pregnancy complications. Key predictors of RD, identified through logistic regression analyses, included maternal vaccination and prematurity. A post-hoc analysis assessed the impact of vaccination on perinatal outcomes.  


Beyond statistical analysis, the researchers conducted proteomic profiling to explore associations between RD and SARS-CoV-2 in a subset of infants. This involved analyzing blood specimens from 52 infants, comparing 45 SARS-CoV-2 exposed unin­fected (SEU) infants with seven control infants born to unexposed healthy mothers. SEU infants were clustered based on RD outcome and gestational age for further analysis.  


In unraveling the intricacies of maternal SARS-CoV-2 infection and its impact on neonatal health, this study employed a comprehensive approach, combining statistical analysis with proteomic profiling to gain a deeper understanding of the factors influencing respiratory distress in newborns.


Study Findings

Diving into the study's findings, approximately half of the participants identified as Black or Hispanic, with 24% being Asian, mixed-race, or belonging to other categories, and 25% identifying as White. Notably, around 13% of participants faced severe or critical COVID-19, with a higher occurrence among unvaccinated mothers.  


The winter of 2020 marked the peak of COVID-19 cases in the cohort, with subsequent smaller peaks aligning with the emergence of the Delta and Omicron SARS-CoV-2 variants. Most mothers were vaccinated before the prevalence of the Alpha variant, leading to notable differences in maternal vaccination status across various viral variants. Importantly, none of the newborns tested positive for SARS-CoV-2 at birth, but 17% were later diagnosed with respiratory distress (RD).  


Among the 34 infants experiencing RD, common discharge diagnoses included respiratory distress syndrome (RDS), transient tachypnea of the newborn, and other infections at 47%, 16%, and 16%, respectively. Although many infants were considered early preterm (born before 34 weeks), most were late preterm or term deliveries. The average time for RD resolution was around 24 days, varying by gestational age.  


Physical examinations revealed nonspecific findings like subcostal or intercostal retractions, abnormal respirations, or grunting. Chest X-ray results commonly showed opacifications, such as interstitial and ground glass opacities, though 8% were described as normal.  


Unadjusted logistic regression models highlighted associations between neonatal RD, maternal disease severity, prematurity, and the lack of maternal COVID-19 immunization. In a proteomic pathway analysis of 52 infants born during the initial pandemic year, those with RD exhibited elevated levels of cytokines and proteins, indicating an upregulated NLRP3 inflammasome-mediated pathway. This included higher levels of specific cytokines like IL-18, CASP1, and IL-1β.  


Preterm infants with RD displayed significant upregulation in biological processes related to inflammation, chemotactic responses, and IL-8 production. The functional networks analysis suggested a predominantly Th2-skewed response, potentially leaning towards hyperimmune responses due to associations with higher IgE production. These findings shed light on the intricate immunological landscape of newborns facing respiratory distress following maternal SARS-CoV-2 exposure.



In conclusion, this study not only sheds light on the immediate clinical implications but also beckons for a deeper dive into the immunological landscape of newborns born to mothers with SARS-CoV-2 exposure. As we continue to probe the intricate links between maternal infection, prenatal exposure, and neonatal respiratory distress, the imperative for ongoing research in this critical area becomes undeniable. Only through sustained efforts can we unlock the full story and potentially pave the way for preventative strategies, ensuring a healthier start for our youngest generation in the face of viral challenges.

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