In Utero COVID-19 Exposure Associated With Respiratory Distress Among Infants


Although the risk of respiratory distress among infants exposed to SARS-CoV-2 is high, the odds of developing the condition decreased by 67% among neonates born to vaccinated mothers.

A new study found the risk of developing respiratory distress (RD) among SARS-CoV-2 exposed uninfected (SEU) full-term neonates to be uniquely high. However, the study also found that maternal vaccination reduced the incidence of the condition. Findings from the UCLA-led study were published in Nature Communications.1

Although prior research has examined links between RD and SEU neonates, the associations have often been attributed to well-studied risk factors like maternal hypoxia and multiorgan failure that cause premature delivery. Addressing a gap in the relevant literature, investigators noted that these previously cited factors do not apply to cases of RD among infants born at full term.

Using information about the clinical features of RD in SEU infants, the effect of maternal vaccination on infant RD, and proteomic measures to identify unique proteins expressed in SEU infants, investigators explored the impact of in utero COVID-19 exposure on the development of RD among full-term neonates.

“We found unusually high rates of respiratory distress shortly after birth in the full-term babies born to mothers who had COVID-19 during pregnancy,” said Karin Nielsen, MD, senior study author and professor of pediatrics in the division of pediatric infectious diseases at the David Geffen School of Medicine at UCLA in a press release.2 “The mothers had not been vaccinated prior to acquiring COVID, indicating that vaccination protects against this complication.”

In total, 221 pregnant persons with COVID-19 and 199 COVID-19 exposed infants were included for analysis in the longitudinal cohort study conducted between April 2020 and August 2022. Among 151 (68%) mothers that were unvaccinated, 16% (23) experienced severe or critical disease, whereas only 4% (3) of vaccinated mothers experienced severe or critical disease, demonstrating the protection that vaccination grants against disease severity.

Although none of the infants tested positive for SARS-CoV-2 at birth, 17% (34) were diagnosed with RD. Maternal vaccination before COVID-19 infection was associated with a significantly lower rate of respiratory distress in infants; among the 34 infants born with RD, only 15% (5) were born to vaccinated mothers (P = .012). In contrast, 41% (63) of infants without RD were born to vaccinated mothers.

Study results also demonstrated that the prevalence of severe or critical COVID-19 in mothers was significantly higher among infants with RD (21%) compared to those without RD (6%) (P = .009). Investigators noted that when pregnant patients received at least 1 mRNA vaccine dose prior to SARS-CoV-2 infection, the odds of developing RD among neonates decreased by 67% (OR: 0.33, 95% CI: 0.10–0.96).

Proteomic evaluation found that exposure to SARS-CoV-2 activated an “inflammatory cascade” that dysregulated the ciliary function pathway and amplified immunoglobulin E production among neonates.1

Whereas prior research has studied the link between premature infants and RD, current results offer insight into how the condition presents at a later gestational age.

“Not only do our results show higher rates of respiratory distress in SARS-CoV-2 exposed uninfected infants when compared to the general population, but we observed more cases of respiratory distress at later gestational ages than anticipated, when neonates should presumably have more mature lung anatomy,” said investigators.

In light of study findings demonstrating the benefit of COVID-19 vaccination on the health of both mother and infant, investigators emphasized the importance of public health interventions as they contribute to improved well-being among the parties.

“Our findings can help inform the mechanisms by which maternal SARS-CoV-2 infection during pregnancy may impact fetal development and neonatal outcomes,” investigators wrote. “Moreover, our study highlights the importance of public health interventions and vaccination efforts that target pregnant individuals due to the potential for lasting effects on the health of both the mother and the infant.”

1. Man, O.M., Azamor, T., Cambou, M.C. et al. Respiratory distress in SARS-CoV-2 exposed uninfected neonates followed in the COVID Outcomes in Mother-Infant Pairs (COMP) Study. Nat Commun 15, 399 (2024).
2. Infants born to COVID-infected mothers have triple the risk of developing respiratory diseases. News release. EurekAlert. January 24, 2024. Accessed January 25, 2024.
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