Beyond TORCH: A narrative review of the impact of antenatal and perinatal infections on the risk of disability.

Infections and inflammation during pregnancy or early life can alter child neurodevelopment and increase the risk for structural brain abnormalities and mental health disorders. There is strong evidence that TORCH infections (i.e., Treponema pallidum, Toxoplasma gondii, rubella virus, cytomegalovirus, herpes virus) alter fetal neurodevelopment across multiple developmental domains and contribute to motor and cognitive disabilities. However, the impact of a broader range of viral and bacterial infections on fetal development and disability is less well understood. We performed a literature review of human studies to identify gaps in the link between maternal infections, inflammation, and several neurodevelopmental domains. We found strong and moderate evidence respectively for a higher risk of motor and cognitive delays and disabilities in offspring exposed to a range of non-TORCH pathogens during fetal life. In contrast, there is little evidence for an increased risk of language and sensory disabilities. While guidelines for TORCH infection prevention during pregnancy are common, further consideration for prevention of non-TORCH infections during pregnancy for fetal neuroprotection may be warranted.

Common pathways targeted by viral hemorrhagic fever viruses to infect the placenta and increase the risk of stillbirth.

Viral hemorrhagic fevers (VHF) are endemic to Africa, South America and Asia and contribute to significant maternal and fetal morbidity and mortality. Viruses causing VHFs are typically zoonotic, spreading to humans through livestock, wildlife, or mosquito vectors. Some of the most lethal VHF viruses also impart a high-risk of stillbirth including ebolaviruses, Marburg virus (MARV), Lassa virus (LASV), and Rift Valley Fever Virus (RVFV). Large outbreaks and epidemics are common, though the impact on the mother, fetus and placenta is understudied from a public health, clinical and basic science perspective. Notably, these viruses utilize ubiquitous cellular surface entry receptors critical for normal placental function to enable viral invasion into multiple key cell types of the placenta and set the stage for maternal-fetal transmission and stillbirth. We employ insights from molecular virology and viral immunology to discuss how trophoblast expression of viral entry receptors for VHF viruses may increase the risk for viral transmission to the fetus and stillbirth. As the frequency of VHF outbreaks is expected to increase with worsening climate change, understanding the pathogenesis of VHF-related diseases in the placenta is paramount to predicting the impact of emerging viruses on the placenta and perinatal outcomes.

Virulence, phenotype and genotype characteristics of invasive group B Streptococcus isolates obtained from Swedish pregnant women and neonates.

Group B streptococci (GBS) are bacteria that can cause preterm birth and invasive neonatal disease. Heterogeneous expression of virulence factors enables GBS to exist as both commensal bacteria and to become highly invasive. A molecular epidemiological study comparing GBS bacterial traits, genotype and host characteristics may indicate whether it is possible to predict the risk of perinatal invasive GBS disease and more accurately target intrapartum antibiotic prophylaxis. A total of 229 invasive GBS isolates from Swedish pregnant women or neonates were assessed for virulence and phenotypic traits: hemolysis zone, hemolytic pigment (Granada agar), Streptococcus B Carrot Broth (SBCB) assay, CAMP factor, and hyaluronidase activity. Genes regulating hemolytic pigment synthesis (covR/covS, abx1, stk1, stp1) were sequenced. Of the virulence factors and phenotypes assessed, a Granada pigment or SBCB score ≥ 2 captured more than 90% of EOD isolates with excellent inter-rater reliability. High enzyme activity of hyaluronidase was observed in 16% (36/229) of the invasive GBS isolates and notably, in one case of stillbirth. Hyaluronidase activity was also significantly higher in GBS isolates obtained from pregnant/postpartum individuals versus the stillbirth or neonatal invasive isolates (p < 0.001). Sequencing analysis found that abx1 (g.T106I), stk1 (g.T211N), stp1 (g.K469R) and covS (g.V343M) variants were present significantly more often in the higher (Granada pigment score ≥ 2) versus lower pigmented isolates (p < 0.001, each variant). Among the 203 higher Granada pigment scoring isolates, 22 (10.8%) isolates had 3 of the four sequence variants and 10 (4.9%) had 2 of the four sequence variants. Although heterogeneity in GBS virulence factor expression was observed, the vast majority were more highly pigmented and contained several common sequence variants in genes regulating pigment synthesis. High activity of hyaluronidase may increase risk for stillbirth and invasive disease in pregnant or postpartum individuals. Our findings suggest that testing for GBS pigmentation and hyaluronidase may, albeit imperfectly, identify pregnant people at risk for invasive disease and represent a step towards a personalized medical approach for the administration of intrapartum antibiotic prophylaxis.