Prenatal Infection by Respiratory Viruses Is Associated With Immuno-Inflammatory Responses in the Fetus

Am J Respir Crit Care Med. 2023 Dec 5. doi: 10.1164/rccm.202308-1461OC. Online ahead of print.

Abstract

Rationale: Respiratory viral infections can be transmitted from pregnant women to their offspring, but frequency, mechanisms, and postnatal outcomes remain unclear.

Objectives: This prospective cohort study compared frequencies of transplacental transmission of respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), analyzed the concentrations of inflammatory mediators in maternal and fetal blood, and assessed clinical consequences.

Methods: 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.

Results: From October 2020 to June 2022, droplet digital (dd)PCR was used to test blood mononuclear cells of 103 mother-baby dyads. Twice more newborns in our sample were vertically infected with RSV compared to SARS-CoV-2 (25.2% (26/103) versus 11.9% (12/101), p = 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 in utero compared to the control dyads group. Prenatal infection was associated with significantly lower birth weight and postnatal weight growth.

Conclusions: 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. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Keywords: Coronavirus Disease 2019 (COVID-19); Developmental Origins of Health and Disease (DOHaD); Fetal Inflammation; Maternal Immune Activation; Vertical Transmission.