Viral Infections During Pregnancy: The Big Challenge Threatening Maternal and Fetal Health

Abstract

Viral infections during pregnancy are associated with adverse pregnancy outcomes, including maternal and fetal mortality, pregnancy loss, premature labor, and congenital anomalies. Mammalian gestation encounters an immunological paradox wherein the placenta balances the tolerance of an allogeneic fetus with protection against pathogens. Viruses cannot easily transmit from mother to fetus due to physical and immunological barriers at the maternal-fetal interface posing a restricted threat to the fetus and newborns. Despite this, the unknown strategies utilized by certain viruses could weaken the placental barrier to trigger severe maternal and fetal health issues especially through vertical transmission, which was not fully understood until now. In this review, we summarize diverse aspects of the major viral infections relevant to pregnancy, including the characteristics of pathogenesis, related maternal-fetal complications, and the underlying molecular and cellular mechanisms of vertical transmission. We highlight the fundamental signatures of complex placental defense mechanisms, which will prepare us to fight the next emerging and re-emerging infectious disease in the pregnancy population.

Keywords: Congenital infection; Hepatitis B virus; Human immunodeficiency virus; Influenza A virus; Severe acute respiratory syndrome coronavirus 2; Trophoblasts; Zika virus.

Figure 1

Viral infections during pregnancy and the corresponding maternal-fetal outcomes. Viral infections throughout the entire course of pregnancy can lead to diverse pregnancy complications such as maternal death, pregnancy loss, and preterm birth. Fetal and neonatal anomalies relevant to viral infections during pregnancy, especially the ones causing vertical transmission, can cause IUGR, stillbirth, microcephaly, motor disorders, and other neurodevelopmental disorders. Additionally, the offspring with prenatal exposure to maternal infectious diseases also encounter lifelong health issues.

Figure 2

Placental defense mechanisms against viral infections. The human placenta exploits disparate cellular and molecular mechanisms of antiviral defense, which encompasses the physical or anatomical defenses, constitutive release of antimicrobial immunomodulators, autophagy and FcRn mediated antibodies transplacental transfer. CCL2: C-C motif chemokine ligand 2; CTB: Cytotrophoblast; ECs: Endothelial cells; EVT: Extravillous trophoblast; FcRn: The neonatal fragment crystallizable receptor; HBCs: Hofbauer cells; HBV: Hepatitis B virus; HIV: Human immunodeficiency virus; IAV: Influenza A virus; IFNλ: Interferon λ; IgG: Immunoglobulin G; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; STB: Syncytiotrophoblast; TORCH: Toxoplasma, Others, Rubella, Cytomegalovirus, and Herpes simplex virus; ZIKV: Zika virus.