Prenatal RSV Infection Linked to Fetal Inflammation, Poorer Growth

Prenatal infection with common respiratory viruses transmitted from the mother was associated with poorer growth, a prospective cohort study found.

Postnatal weight change significantly correlated with maternal blood respiratory syncytial virus (RSV) copy numbers and titers of SARS-CoV-2 in blood from both mother and baby, reported Giovanni Piedimonte, MD, of Tulane University School of Medicine in New Orleans, and co-authors.

Vertical transmission from the mother in utero was twice as likely for RSV as for SARS-CoV-2 (25.2% vs 11.9%, P=0.019), according to the multi-site study published in the American Journal of Respiratory and Critical Care Medicine.

Intrauterine exposure to RSV was linked to fetal inflammation, with several inflammatory mediators detected in cord blood at delivery.

Cord blood concentrations of inflammatory mediators like CXCL5 and macrophage inflammatory protein independently and significantly predicted birth weight. Neonatal weight loss before hospital discharge was significantly predicted by cord blood RSV copy number and concentrations of inflammatory markers SCF-R, vascular endothelial growth factor, IL-1 receptor type 2, and acute-phase reactant c-reactive protein.

This study “highlights the potential importance of even subtle events occurring in pregnant women (e.g., apparently inconsequential head colds) for the future development and well-being of the offspring,” the researchers said.

Maternal infection doesn’t just risk passing replicating viral particles to the fetus, but — especially within critical developmental windows — may damage the fetus by “activation of maternal inflammation and immunity, transfer of soluble inflammatory mediators, mobilization of cellular effectors, or by impairing placental function and limiting the passage of nutrients and other factors essential for fetal growth,” they wrote.

The findings emphasize the importance of the new RSV vaccine for use in pregnant persons and monoclonal antibody for infants, Piedimonte and colleagues suggested, which “promise to usher in a new era when the prevalence of respiratory disease will be significantly reduced by primary prophylaxis.”

Dean Blumberg, MD, of the University of California Davis, commented that if the results are replicated in further studies, it “would suggest another reason to be careful of getting an infection during pregnancy.”

“Obviously, everybody’s nervous about everything during pregnancy — taking medications, or being exposed to potential infections,” he continued. “But, this would be another reason to be extra careful — making sure that everybody’s up to date on immunizations, both the mother and their contacts, to avoid infection, to avoid any adverse outcomes.”

Ashish Premkumar, MD, PhD, of the University of Chicago, told MedPage Today that the potential effects of these inflammatory responses is documented in similar cases, for example, bacterial infections in the setting of chorioamnionitis.

Fetal exposure to that inflammation “can have ramifications for the neonate in the long term — we get this more pronounced for preterm neonates,” who were excluded from Piedimonte’s study, Premkumar noted. He encouraged more research on factors such as gestational age during infection.

The study included cases at two hospitals in the New Orleans area from October 2020 through June 2022 in which pregnant adults at 12 weeks or more with a singleton gestation reported two or more respiratory symptoms, tested positive for COVID-19 during the course of pregnancy, or both, and delivered at 34 weeks or later.

Initially, 287 de-identified blood samples, with an additional 121 cord blood samples drawn immediately after delivery. A total of 103 mother-baby dyads were tested utilizing droplet digital (dd)PCR for RSV and 101 dyads had ddPCR data for SARS-CoV-2.

Nearly 60% of the maternal or newborn blood samples turned up viral RNA for either RSV, SARS-CoV-2, or both. The rest of the dyads with no evidence of infection were used as negative controls. Dual infection with both RSV and SARS-CoV-2 was present in 6.8% of mothers, 5.8% of newborns, and 1.9% of paired dyads.

The study didn’t turn up significant differences among the groups for neonatal clinical outcomes, such as respiratory distress or symptoms, supplemental oxygen requirement, NICU admission, or length of stay.

Maternal demographics seemed to have little impact on the findings, save a slightly higher amount of white patients compared to non-white patients in the SARS-CoV-2 analysis.

The researchers noted that there was a slight risk of false positives from possible contamination of cord blood samples during collection. Other potential limitations included the study’s sample size as well as multiple comparisons without creating families of soluble factors tested for in the blood samples.