In January 2024 the University of California Los Angeles (UCLA) shared that results from a study in Nature Communications reveal that infants born full to term to mothers who had been infected with COVID-19 during pregnancy had a three times greater risk of experiencing respiratory distress (RD). The risk was “significantly lower” if mothers who were infected during pregnancy had been vaccinated.
Respiratory distress
The study authors note that SARS-CoV-2 infection during pregnancy has been associated with “adverse maternal and neonatal outcomes”. Although estimates of vertical transmission from mother to child are “low”, they report “growing concern for long-term neonatal consequences”. Furthermore, research has identified cases of infant respiratory distress (RD) among SARS-CoV-2 exposed uninfected (SEU) term neonates.
Previous studies have attributed cases of RD among these SEU neonates to “maternal hypoxia and multiorgan failure”, which increases the risk of premature delivery. However, for infants born at term, the increased cases of RD remain unexplained.
“Our prior analysis suggests that prenatal exposure to SARS-CoV-2 may activate an inflammatory cascade in the newborn airway leading to ciliary beat dysregulation of the airway epithelium.”
Furthermore, inflammasome associated proteins (IL-18, IL-1B, and CASP1) have been identified in SEU term infants with RD, but the “exact mechanism of this pathway has yet to be elucidated”. The study considers that maternal immunisation against COVID-19 has been demonstrated “highly protective” against maternal mortality and morbidity, possibly preventing COVID-19 hospitalisations in infants under 6 months of age.
The study
The research explores the “complex relationship between maternal SARS-CoV-2 infection during pregnancy and infant RD”. The team considered 3 objectives:
- Characterise the clinical features of RD among SEU infants
- Construct a multivariable statistical model to assess the effect of maternal vaccination on infant RD
- Conduct a proteomic ingenuity pathway analysis to identify proteins differently expressed in SEU infants and their biological functions
“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.”
221 mothers were enrolled in the study, of which 151 (68%) were unvaccinated before their infection. Of these, 23 women (16%) experienced severe or critical disease, compared with 3 (4%) of vaccinated mothers. 34 (17%) of the 199 exposed infants that were followed had respiratory distress, a “high frequency” compared to the general population. The team found that of the 34 infants with respiratory distress, only 5 (16%) were born to mothers who had been vaccinated prior to infection, compared to 63 (41%) without the breathing disorder. This suggests that vaccination had a “protective effect”.
Senior author Dr Karin Nielsen, professor of paediatrics at the David Geffen School of Medicine at UCLA, commented that “unusually high rates” of respiratory distress were observed in babies born to mothers who had COVID-19 during pregnancy.
“The mothers had not been vaccinated prior to acquiring COVID, indicating that vaccination protects against this complication.”
How good is the study?
UCLA and the authors recognise the limitations of the study, including a possible skew towards “more severe” illness compared to the general population. On the other hand, because of a “high level of specialised services and medical equipment”, the people in the study may have “higher rates of survival” than other regions.
“While our findings suggest that the magnitude of the effect of in utero COVID-19 exposure on neonatal RD is high, the absolute number of cases remains small and limits the power of our study. Given our small sample size, our results should be interpreted with caution.”
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