Open research questions in Neonatal and Maternal Infections

What the literature leaves open

• The impact of the COVID-19 pandemic on GBS epidemiology is poorly understood. There is a need for studies investigating the temporal trends in GBS colonization, serotypes, and antimicrobial susceptibility.

  Temporal trends in Group B Streptococcus colonization, serotype distribution, and antimicrobial resistance among pregnant women in the Brazilian Amazon across the COVID-19 pandemic, 2018–2023 · 2026 · DOI

• Limited understanding of the genetic lineages associated with transmission clusters.

  Contribution of nosocomial transmission to Klebsiella pneumoniae neonatal sepsis in Africa and South Asia: An observational study of infection clusters inferred from pathogen genomics and temporal data · 2026 · DOI

• The fraction of K. pneumoniae neonatal sepsis attributable to nosocomial transmission is unknown. The genetic lineages associated with transmission clusters are not well characterized.

  Contribution of nosocomial transmission to Klebsiella pneumoniae neonatal sepsis in Africa and South Asia: An observational study of infection clusters inferred from pathogen genomics and temporal data · 2026 · DOI

• Further research is needed to understand the emergence of multidrug-resistant lineages and hypervirulent genomic clones, such as ST283. Research should focus on developing effective preventive measures and strategies to mitigate the threat of invasive GBS infections in nonpregnant adults.

  Descriptive review: global spectrum of invasive group B streptococcal disease in nonpregnant adults: epidemiology, risk factors and clinical presentations · 2026 · DOI

• Collective data on invasive group B streptococcal disease in nonpregnant adults remains fragmented. There is a need for further research on effective preventive measures and strategies.

  Descriptive review: global spectrum of invasive group B streptococcal disease in nonpregnant adults: epidemiology, risk factors and clinical presentations · 2026 · DOI

• Antenatal screening for GBS does not always reflect intrapartum colonization status. There is a need for rapid and accurate detection of GBS during labor. The performance of point-of-care platforms for intrapartum GBS detection under real-world conditions is not well established.

  Intrapartum Molecular Detection of Group B Streptococcus: Real-World Evaluation of Multiple Point-of-Care Platforms and the Potential Role of Lysis Efficiency · 2026 · DOI

• The lack of understanding of how GBS maintains heme homeostasis despite lacking surface-displayed heme acquisition systems. The need to characterize the role of HssS in heme sensing and extraction.

  The bacterial cell membrane acts as a dynamic heme reservoir during group B Streptococcus bloodstream infection · 2026 · DOI

• The implementation of Sepsis-3 in resource-limited settings can be challenging due to the requirement for laboratory measurements. The sensitivity of blood culture is often low, particularly if antibiotics are administered before sample collection. The availability of laboratory diagnostics and antimicrobial susceptibility testing is limited in many Nigerian hospitals.

  Development of Diagnostic Criteria for Early Diagnosis of Gram-Positive and Gram-Negative Bacterial Sepsis: A Review · 2026 · DOI

• The evaluation of the effectiveness of emerging technologies in resource-limited settings. The development of strategies to address the challenges confronting prompt and accurate sepsis diagnosis in Kano and similar environments.

  Development of Diagnostic Criteria for Early Diagnosis of Gram-Positive and Gram-Negative Bacterial Sepsis: A Review · 2026 · DOI

• There is a need for improved diagnostic tools and management strategies for neonatal sepsis. There is a lack of data on the long-term outcomes of neonates with sepsis. There is a need for more effective antimicrobial stewardship programs.

  Recognizing and managing neonatal sepsis · 2026 · DOI

• Routine maternal serum procalcitonin measurement should be incorporated into PPROM management protocols. Large multicenter studies are needed to validate optimal cutoff values across different gestational ages and to establish PCT-guided neonatal surveillance algorithms.

  Maternal Serum Procalcitonin as a Predictor of Early-Onset Neonatal Sepsis in Preterm Premature Rupture of Membranes: A Study in a Tertiary Care Hospital in Bangladesh · 2026 · DOI

• The need to balance antibiotic strength with the need to protect healthy human flora and prevent antibiotic resistance. The difficulty in predicting renal clearance rates in neonates.

  Neonatal digital twins enable personalized antibiotic dosing for treating suspected sepsis · 2026 · DOI

• The current model approximates amikacin clearance as largely dependent on creatinine filtration rate, which would make the model inaccurate for patients on dialysis. The model needs to be validated in real-world neonate cohorts across hospitals. Differences in laboratory testing procedures at different hospital sites can affect physiological parameter measurements.

  Neonatal digital twins enable personalized antibiotic dosing for treating suspected sepsis · 2026 · DOI

• Second, the PSU-NEWS was evaluated only in neonates born at least 35 weeks of gestation and weighing at least 1,800 g; therefore, low-birthweight infants remains uncertain.

  Predictive performance of the PSU-neonatal early warning score in identifying newborns requiring intensive care · 2026 · DOI

• Limited understanding of the epidemiology of gram-negative bloodstream infections in neonatal intensive care units. Limited knowledge of the factors associated with multidrug resistance and 28-day mortality in this population.

  Risk factors for multidrug resistance and mortality in healthcare-associated neonatal gram-negative bloodstream infections · 2026 · DOI

• Clinical and experimental data implicate Ureaplasma exposure in early lung inflammation, impaired alveolar development, and bronchopulmonary dysplasia (BPD), yet the pathogenic events preceding microbial invasion of the amniotic cavity or fetal tissues remain poorly defined.

  Choriodecidual Ureaplasma parvum infection induces fetal lung inflammation prior to intra-amniotic infection in a nonhuman primate model · 2026 · DOI

• The study has a retrospective design. The sample size is limited. The study may be influenced by obstetric and perinatal factors on neonatal outcomes.

  Risk of disseminated tuberculosis and other infections after neonatal Bacillus Calmette–Guérin vaccination in infants with in-utero exposure to tumor necrosis factor-α inhibitors · 2026 · DOI

• There is a lack of data on the safety of BCG vaccination in infants exposed to TNF-α inhibitors in utero. Recent guidelines recommend deferring live attenuated vaccines, such as BCG, until after 6–12 months of age in this population.

  Risk of disseminated tuberculosis and other infections after neonatal Bacillus Calmette–Guérin vaccination in infants with in-utero exposure to tumor necrosis factor-α inhibitors · 2026 · DOI

• The study highlights the need for further research on the correlation between neonatal sepsis and other clinical and epidemiological factors.

  NEONATAL SEPSIS AS AN INDICATOR OF INFECTIOUS BURDEN DURING WARTIME: DATA FROM LVIV REGION (2022–2024) · 2026 · DOI

• There is a need for more data on the frequency of meningitis in neonates with late-onset sepsis. There is a need to identify risk factors for meningitis in this population.

  Frequency of meningitis in late onset sepsis at NESCOM Hospital · 2026 · DOI

• Limited data on the impact of quality improvement-based programs on antibiotic use.

  Implementation of quality improvement principles for antimicrobial stewardship program in the level III B neonatal intensive care unit of a tertiary care public hospital · 2026 · DOI

• Lack of effective antimicrobial stewardship programs in high-burden NICUs. Limited data on the impact of quality improvement-based programs on antibiotic use.

  Implementation of quality improvement principles for antimicrobial stewardship program in the level III B neonatal intensive care unit of a tertiary care public hospital · 2026 · DOI

• Limited treatment options for multidrug-resistant gram-negative infections. Difficulty in empirical treatment selection due to high rates of resistance.

  Risk factors for multidrug resistance and mortality in healthcare-associated neonatal gram-negative bloodstream infections · 2026 · DOI

• Limited resources and infrastructure for healthcare services.

  NEONATAL SEPSIS AS AN INDICATOR OF INFECTIOUS BURDEN DURING WARTIME: DATA FROM LVIV REGION (2022–2024) · 2026 · DOI

• Further investigation of the mechanisms of heme sensing and extraction in GBS. Exploration of the potential for targeting heme sensing and extraction systems as a therapeutic strategy.

  The bacterial cell membrane acts as a dynamic heme reservoir during group B Streptococcus bloodstream infection · 2026 · DOI

Most-cited papers in Neonatal and Maternal Infections

• The immunopathogenesis of sepsis · Nature · 2002 · 2,112 citations
• Late-Onset Sepsis in Very Low Birth Weight Neonates: The Experience of the NICHD Neonatal Research Network · PEDIATRICS · 2002 · 1,832 citations
• Neurodevelopmental and Growth Impairment Among Extremely Low-Birth-Weight Infants With Neonatal Infection · JAMA · 2004 · 1,274 citations
• Early Onset Neonatal Sepsis: The Burden of Group B Streptococcal and E. coli Disease Continues · PEDIATRICS · 2011 · 920 citations
• Prolonged Duration of Initial Empirical Antibiotic Treatment Is Associated With Increased Rates of Necrotizing Enterocolitis and Death for Extremely Low Birth Weight Infants · PEDIATRICS · 2008 · 827 citations
• Management of Neonates With Suspected or Proven Early-Onset Bacterial Sepsis · PEDIATRICS · 2012 · 603 citations
• The neonatal blood count in health and disease.I. Reference values for neutrophilic cells · The Journal of Pediatrics · 1979 · 591 citations
• Neonatal Candidiasis Among Extremely Low Birth Weight Infants: Risk Factors, Mortality Rates, and Neurodevelopmental Outcomes at 18 to 22 Months · PEDIATRICS · 2006 · 547 citations
• Prolonged Initial Empirical Antibiotic Treatment is Associated with Adverse Outcomes in Premature Infants · The Journal of Pediatrics · 2011 · 544 citations
• Late-onset sepsis in very low birth weight neonates: A report from the National Institute of Child Health and Human Development Neonatal Research Network · The Journal of Pediatrics · 1996 · 515 citations

Most recent work

• Group B Streptococcal Disease · New England Journal of Medicine · 2026
• Maternal immunization against group B Streptococcus: Immune correlates, microbiome trade-offs, and global implementation challenges · Vaccine · 2026
• Predictive and Prognostic Performance of the Phoenix Sepsis Criteria and Phoenix Sepsis Score in PICU Patients With Suspected Infection: A Multicenter Prospective Study · Critical Care Medicine · 2026
• Neonatal Sepsis from 2014 to 2024: The Resurgence of Gram-Negative Rods · The Journal of Pediatrics · 2026
• Penicillin-Binding Proteins in Streptococcus agalactiae and Their Association with Reduced Penicillin Susceptibility: An Overview · Antibiotics · 2026
• Restricting C-Reactive Protein Use in Early-Onset Neonatal Sepsis Reduces Unnecessary Antibiotic Exposure · Antibiotics · 2026
• Gut microbiota immaturity with DL-endopeptidase deficiency links antibiotic use to preterm late-onset sepsis · Cell Host & Microbe · 2026
• A fungal pathobiont promotes Streptococcus vaginal persistence and pathogenesis through physical and metabolic interactions · Cell Host & Microbe · 2026
• Revisiting time to blood culture positivity: can we decrease antibiotic exposure in the NICU? · Journal of Perinatology · 2026
• Duration of Antibiotic Therapy for Gram-Negative Bloodstream Infections in the Neonatal Intensive Care Unit · The Journal of Pediatrics · 2026

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