Low vitamin D in newborns linked to higher sepsis risk in Guangzhou study

A study of term newborns found that higher vitamin D levels shortly after birth were associated with substantially lower odds of sepsis, but researchers caution that the findings do not prove cause and effect.

A study from Guangzhou has added fresh evidence to the debate over whether vitamin D levels in the first days of life are linked to neonatal sepsis, a dangerous bloodstream infection that can escalate rapidly in newborns. Researchers at Sun Yat-sen University reported in BMC Pediatrics that babies with higher early vitamin D levels were less likely to develop sepsis during their hospital stay, while a companion genetic analysis pointed in the same direction, albeit with more modest force.

The research team reviewed 366 hospitalised babies born between 2018 and 2023 at Sun Yat-sen Memorial Hospital and measured serum 25-hydroxyvitamin D within 72 hours of birth, before any supplementation had been given. That marker, known as 25(OH)D, is the standard way to assess vitamin D status. The study found that the median level was 37.7 nanomoles per litre, below the threshold generally considered adequate in paediatric practice. Nearly four in five infants had levels below 50 nanomoles per litre, with 28.4 per cent classified as deficient and 49.5 per cent as insufficient. That pattern fits with earlier research showing vitamin D shortfalls are common in pregnant women and newborns alike. A systematic review and meta-analysis indexed on PubMed reported that vitamin D deficiency was present in 79.4 per cent of neonates with sepsis and suggested that maternal and neonatal supplementation could help reduce risk.

In the main analysis, the investigators focused on 235 term infants, reflecting the fact that preterm babies face a different risk profile. Among those term newborns, every 10-nanomole-per-litre increase in 25(OH)D was associated with about 30 per cent lower odds of neonatal sepsis after adjustment for other factors. The adjusted odds ratio was 0.70, with a 95 per cent confidence interval of 0.54 to 0.90, and the result was statistically significant. That finding is consistent with earlier studies, including case-control work in term neonates and research into late-onset and early-onset sepsis, both of which found lower vitamin D levels in babies with infection than in healthy controls.

To strengthen the case, the researchers also used Mendelian randomisation, a method that examines whether genetic variants linked to vitamin D status are associated with disease outcomes. Because those variants are fixed at conception, the approach can reduce some of the bias that affects observational studies. In that analysis, genetically predicted higher vitamin D levels were nominally associated with lower odds of streptococcal septicaemia, one of the bacterial causes of neonatal sepsis. The effect was small and the authors were cautious, but the direction matched the clinical data. That is notable because a separate randomised controlled trial in preterm infants with sepsis found vitamin D administration improved sepsis scores and lowered C-reactive protein, a marker of inflammation.

Even so, the findings stop well short of proving that vitamin D deficiency causes sepsis. The study was retrospective, drawn from a single hospital and based on infants who were tested because clinicians ordered vitamin D measurements, which can limit how widely the results apply. The genetic analysis also relied on instruments developed largely in European-ancestry populations, which may not transfer neatly to other groups. Still, the work supports a practical question that merits further testing: whether improving maternal vitamin D status during pregnancy, and ensuring adequate levels in newborns, might help lower the risk of a severe and sometimes deadly infection. For now, the evidence is suggestive rather than definitive, but it adds weight to the idea that a common nutritional deficiency may have consequences beyond bone health.