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Novel Approaches to the Study of Neonatal Infections
Alessandro Borghesi1, Mauro Stronati1, Riccardo Castagnoli1
1Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Insights
Understanding neonatal infection requires exploring immune immaturity and pathogen virulence. Maternal antibodies offer protection, but further research into infant immunity, genetics, and microbiome is crucial for personalized prevention strategies.
Area of Science:
- Neonatal immunology
- Infectious disease pathogenesis
- Pediatric infectious diseases
Background:
- Neonatal infection pathogenesis is not fully understood, with immune immaturity and virulence factors only partially explaining varied responses.
- Epidemiological studies stratifying infants by risk have aided preventive strategies.
- Maternal antibodies, like anti-group B streptococcal antibodies, are vital for neonatal protection.
Purpose of the Study:
- To investigate the cellular and molecular differences in neonatal immune responses contributing to individual susceptibility and resistance to common pathogens.
- To elucidate the interplay between infant genetics, immune background, microbiome, maternal factors, and pathogen characteristics.
- To identify specific infant cohorts for targeted research methodologies.
Main Methods:
- Utilizing precise phenotyping and clinical heterogeneity analysis of neonatal infections.
- Investigating term and preterm infants based on underlying mechanisms (single-gene vs. multifactorial predisposition).
- Integrating novel technologies: genotyping, exome/genome sequencing, microbiome analysis, and metabolome studies.
Main Results:
- Maternal antibodies play a significant role in protecting newborns against specific infections like group B streptococcal sepsis.
- Individual differences in protective responses are influenced by a complex interplay of host and pathogen factors.
- Current understanding is incomplete, necessitating further investigation into host-pathogen molecular interactions.
Conclusions:
- Further research is essential to define the immune differences underlying susceptibility and resistance in neonates.
- A comprehensive approach integrating host genetics, microbiome, maternal factors, and pathogen characteristics is needed.
- Advanced technologies can provide deeper insights into the unexplained bases of neonatal infection susceptibility.
Abstract:
The pathogenesis of neonatal infection is incompletely understood. Neonatal immune immaturity and the microbial factors of virulence only partially explain the interindividual differences in the protective responses to the most common neonatal pathogens. Stratification of infants into high- and low-risk groups through epidemiological studies has been invaluable in designing preventive strategies and reducing the burden of neonatal infection. The discovery of the role of maternal antibodies (Abs) as, for instance, anti-capsular polysaccharide group B streptococcal (GBS) Abs, in protecting newborn infants against neonatal GBS sepsis, has been a milestone in the unraveling of the molecular underpinnings of susceptibility to infection in the neonatal age. Future work should aim at defining the cellular and molecular differences in the neonatal immune responses that account for individual susceptibility and resistance to common neonatal pathogens. The interplay between the genetic and immune backgrounds of the infant, changes in the infant's microbiome, maternal factors, and the pathogen's characteristics needs to be accurately described through human studies. Precise phenotyping and dissection of the clinical heterogeneity of neonatal infection should identify cohorts that can be studied through different study methodologies. Term and preterm infants should be investigated according to the most likely underlying mechanism, single-gene disorders and multifactorial predisposition, respectively. Novel technologies, including genotyping studies, exome and genome sequencing, analysis of the microbiome, and the study of the metabolome, are nowadays established and available and can be integrated to gain a better insight into the unexplained bases of individual susceptibility to neonatal infections.
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