JOURNAL CLUB · ARTICLE OF THE WEEK
Routine probiotics and NEC in preterm infants
Imren C, Jongejans V, Onland W, et al. JAMA Netw Open. 2026;9(8):e2631601. doi:10.1001/jamanetworkopen.2026.31601. A multicentre retrospective before-after cohort study.
HALVED NEC
12% TO 5%
NEC roughly halved
NEC fell from 11.9% to 5.3% after implementation (adjusted RR 0.49, 95% CI 0.34-0.70, P<0.001).
Not just a time trend
Interrupted time-series found no evidence that background temporal trends explained the reduction.
Held across severity and gestation
The fall was consistent across medical, surgical and fatal NEC, and among extremely preterm (<28 weeks) infants.
No change in all-cause mortality
All-cause mortality was unchanged (11.7% vs 11.5%; ARR 1.06, 95% CI 0.82-1.39).
A safety signal to watch
Non-NEC mortality rose from 7.2% to 9.6% (ARR 1.42, 95% CI 1.01-1.98), not clearly attributable to probiotics, with 1 case of probiotic-associated sepsis.
WHY THIS MATTERS
- NEC is a devastating, hard-to-predict emergency of the preterm gut
- Probiotics are already widely used, but the evidence has been mixed and strain-dependent
- Regulators (including the US FDA) have warned about probiotic sepsis in preterm infants
- Units need real-world data on whether to adopt routine probiotics
- This study pairs a large cohort with a specific, well-characterised product
STRENGTHS
- Large and multicentre, with a parallel reference cohort
- Interrupted time-series analysis to guard against secular trends
- Adjusted for key confounders, with uniform human-milk feeding
- High protocol adherence (96%) after implementation
- A substantial number of extremely preterm infants, enabling subgroup analysis
LIMITATIONS
- Retrospective before-after design, open to secular and unmeasured confounding
- Exposure was defined by implementation period, not confirmed individual receipt, so it estimates a strategy rather than individual efficacy
- The higher baseline NEC rate may reflect case mix or diagnostic differences
- The rise in non-NEC mortality is unexplained and warrants caution
- A single product and setting; randomised trials are still warranted, especially in the most preterm
Practice implications
NEC is one of the emergencies a special care nursery dreads, so prevention matters. This large Dutch cohort found that routinely implementing a specific multistrain probiotic (B. infantis Bb-02, B. lactis BB-12, S. thermophilus TH-4) roughly halved NEC in very and extremely preterm infants, and the fall held up against background time trends. That is encouraging and consistent with earlier trials of the same formulation. Two cautions temper it: this is a before-after cohort (not a randomised trial), and non-NEC mortality rose for reasons that were not clearly related to probiotics, alongside one case of probiotic-associated sepsis. The practical message is that routine probiotics are a plausible NEC-prevention strategy, but the product, strain and protocol matter and any program needs careful safety monitoring. Probiotic use is a unit-level decision, so follow your own network or state guidance, keep prioritising human milk, and stay alert for probiotic sepsis in the smallest babies.
Would you adopt routine probiotics on the strength of a before-after cohort, or wait for a randomised trial?
How much does the specific strain and product matter when interpreting probiotic evidence?
How should the unexplained rise in non-NEC mortality change your interpretation?
What safety monitoring would you want in place before starting a probiotic program?
JAMA Netw Open 2026NEC
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Take-home message: In a large Dutch cohort of very and extremely preterm infants, routinely implementing a specific multistrain probiotic (B. infantis Bb-02, B. lactis BB-12, S. thermophilus TH-4) was associated with NEC roughly halving (12% to 5%), a reduction that held up against background time trends. All-cause mortality was unchanged. Two cautions: it is a before-after cohort, not a randomised trial, and non-NEC mortality rose for unclear reasons, with one probiotic-associated sepsis. Routine probiotics are a plausible NEC-prevention strategy, but product, strain and safety monitoring matter.
For educational purposes only. Journal club appraisal - figures paraphrased from the published trial; read the full article for complete data. Always align practice to your local guidelines.