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.
Keywords
newborn infant - infection - primary immunodeficiency - phenotype - genetic - single-gene
