Prenatal Infection by Respiratory Viruses Is Associated with Immunoinflammatory Responses in the Fetus.

Abstract

<b>Rationale:</b> Respiratory viral infections can be transmitted from pregnant women to their offspring, but frequency, mechanisms, and postnatal outcomes remain unclear. <b>Objectives:</b> The aims of this prospective cohort study were to compare the frequencies of transplacental transmission of respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), analyze the concentrations of inflammatory mediators in maternal and fetal blood, and assess clinical consequences. <b>Methods:</b> We recruited pregnant women who developed upper respiratory infections or tested positive for SARS-CoV-2. Maternal and cord blood samples were collected at delivery. Study questionnaires and electronic medical records were used to document demographic and medical information. <b>Measurements and Main Results:</b> From October 2020 to June 2022, droplet digital PCR was used to test blood mononuclear cells from 103 mother-baby dyads. Twice more newborns in our sample were vertically infected with RSV compared with SARS-CoV-2 (25.2% [26 of 103] vs. 11.9% [12 of 101]; <i>P</i> = 0.019). Multiplex ELISA measured significantly increased concentrations of several inflammatory cytokines and chemokines in maternal and cord blood from newborns, with evidence of viral exposure <i>in utero</i> compared with control dyads. Prenatal infection was associated with significantly lower birth weight and postnatal weight growth. <b>Conclusions:</b> Data suggest a higher frequency of vertical transmission for RSV than SARS-CoV-2. Intrauterine exposure is associated with fetal inflammation driven by soluble inflammatory mediators, with expression profiles dependent on the virus type and affecting the rate of viral transmission. Virus-induced inflammation may have pathological consequences already in the first days of life, as shown by its effects on birth weight and postnatal weight growth.