Early antibiotic exposure and vaccine immune responses in preterm infants: potential sex-specific differences.
Early antibiotic exposure in preterm infants may impair their immune response to vaccines, especially in girls, highlighting the need for careful consideration of antibiotic use in this population.
Where it sits
this study against the rest of the l-carnitine (levocarnitine) corpusSummary and findings
This study investigated the effect of early antibiotic exposure on vaccine titers in 69 preterm infants (<32 weeks gestational age) at a corrected age of four months. Infants were divided into two groups: 35 with antibiotic exposure during the first postnatal week and 34 without. Results indicated reduced antibody titers in antibiotic-exposed infants, particularly pronounced in girls.
Abstract
Neonatal sepsis represents a major risk in preterm infant care, resulting in widespread early-life antibiotic exposure. While the latter has been linked to immune maturation in term-born neonates, its impact on preterm immune development remains unclear. The aim of this prospective observational study was to investigate the effect of early antibiotic exposure on vaccine titers at a corrected age of four months. To achieve this, blood and stool samples were analyzed from 69 preterm infants (<32 weeks gestational age; 35 with 34 without antibiotic exposure during the first postnatal week) at postnatal day 14 and again at four months corrected age. We assessed vaccine-induced antibody titers against <i>Bordetella pertussis</i> and <i>Haemophilus influenza</i>e, immune cell profiles (flow cytometry), gut microbiome composition (16S rRNA sequencing), and plasma amino acid and acylcarnitine levels (tandem mass spectrometry). Preterm infants exposed to early antibiotics showed reduced antibody titers following vaccination, with differences appearing more pronounced in girls. Antibiotic-exposed girls displayed increased monocytes and myeloid-derived suppressor cells (MDSCs), both of which inversely correlated with antibody titers. Early antibiotic exposure was associated with differences in microbial community types at postnatal day 14, with <i>Klebsiella</i>-dominated and <i>Bifidobacteria</i>-lacking communities occurring more frequently in antibiotic-exposed infants. Antibiotic-exposed girls exhibited distinct metabolomic alterations, including elevated levels of two unsaturated fatty acids that negatively correlated with monocyte and MDSC abundance. Our findings suggest that early antibiotic exposure impairs vaccine responses in preterm infants and indicates a potentially sex-specific susceptibility. Antibiotic-driven changes in the microbiome and metabolome may sustain suppressive innate immune cell populations, which may in turn weaken adaptive responses to vaccination.
Background
This paper addresses the impact of early antibiotic exposure on immune responses in preterm infants, a population at high risk for neonatal sepsis. Prior research has linked early antibiotic use to immune maturation in term infants, but its effects on preterm infants remain unclear. Understanding these effects is crucial for optimizing vaccination strategies in vulnerable populations.
Methods
This prospective observational study included 69 preterm infants with gestational ages less than 32 weeks. The infants were divided into two groups based on antibiotic exposure during the first postnatal week. Blood and stool samples were collected at postnatal day 14 and again at four months corrected age to assess vaccine-induced antibody titers, immune cell profiles, gut microbiome composition, and plasma metabolomics.
Results
Antibiotic-exposed preterm infants exhibited reduced vaccine-induced antibody titers compared to those without exposure. The study found that these differences were more pronounced in female infants. Additionally, antibiotic exposure was associated with increased levels of monocytes and MDSCs, which inversely correlated with antibody titers.
Interpretation
These findings suggest that early antibiotic exposure may impair vaccine responses in preterm infants, particularly in girls. While the study shows statistically significant differences, the clinical significance of these findings remains to be established. Limitations include the observational nature of the study and the small sample size, which may affect the robustness of the conclusions drawn.
Key findings
- Reduced antibody titers observed in antibiotic-exposed infants compared to those without exposure.
- Differences in antibody titers were more pronounced in girls.
- Antibiotic-exposed girls showed increased monocytes and myeloid-derived suppressor cells (MDSCs), which inversely correlated with antibody titers.
- Klebsiella-dominated and Bifidobacteria-lacking microbial communities were more frequent in antibiotic-exposed infants.
- Antibiotic-exposed girls exhibited elevated levels of two unsaturated fatty acids that negatively correlated with monocyte and MDSC abundance.
Limitations
- Observational study design limits causal inferences.
- Small sample size (n=69) may affect generalizability.
- Potential confounding factors not controlled for.
- Single-site study may limit external validity.
- Short follow-up duration may not capture long-term effects.