{
  "abstract": "Probiotics may reduce the risk of necrotizing enterocolitis (NEC), late-onset sepsis (LOS), and mortality in preterm infants. However, their efficacy in extremely preterm infants (gestational age < 28 weeks) is still regularly questioned due to limited data and safety concerns. In Dutch Neonatal Intensive Care Units (NICUs), a three-strain probiotic product (ProPrems®; Bifidobacterium infantis Bb-02, Bifidobacterium lactis BB-12, and Streptococcus thermophilus TH-4) was implemented as standard of care from 2021 onwards. This study evaluates the clinical effects of these probiotics in extremely preterm infants. Pre- and postimplementation cohorts of extremely preterm infants from 6 Dutch NICUs (2018-2023) were compared. Clinical data from the first 29 days of life were collected. Incidence of NEC (modified Bell's stage ≥ IIA), LOS, and mortality were compared with logistic regression; growth velocity with linear regression; and time to full enteral feeds (tFEF) with survival analyses. In total, 481 extremely preterm infants (212 pre-, 269 post-implementation) were included. After implementation, the adjusted odds ratio was 0.49 (0.25-0.99; p = 0.049) for NEC; 0.87 (0.59-1.28; p = 0.49) for LOS; and 0.67 (0.35-1.27; p = 0.22) for all-cause mortality. Furthermore, tFEF decreased by 2 days (p < 0.001) and probiotic use was associated with an increase in growth velocity of 1.8 g/kg/day (p < 0.001). One infant (0.4%) developed probiotic-associated sepsis.Conclusion\n\nThis multicenter pre-postimplementation study showed that multi-strain probiotic administration was associated with lower NEC incidence, shorter tFEF, and greater growth velocity in extremely preterm infants during the first four weeks of life. Probiotic-associated sepsis was rare. These results support continued use of probiotics in this vulnerable population.What is known\n\n• Certain probiotic strains effectively reduce incidence of necrotizing enterocolitis (NEC) in preterm infants, but the efficacy and safety for extremely preterm infants (GA < 28 weeks) remain under debate.What is new\n\n• This study shows that a multi-strain probiotic supplement was associated with lower NEC incidence, shorter time to full enteral feeds, and greater early postnatal growth in a Dutch multicenter cohort of extremely preterm infants. • The incidence of probiotic-associated sepsis in extremely preterm infants was very low in our cohort with just 1 case (0.4%), consistent with the rare occurrence reported previously.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, Amsterdam, Netherlands. a.j.vanwesemael@amsterdamumc.nl.",
    "Amsterdam Reproduction and Development Research Institute, Amsterdam UMC, Amsterdam, Netherlands. a.j.vanwesemael@amsterdamumc.nl.",
    "Amsterdam Gastroenterology Endocrinology & Metabolism Research Institute, Amsterdam UMC, Amsterdam, Netherlands. a.j.vanwesemael@amsterdamumc.nl.",
    "Department of Neonatology, Maxima Medical Centre, Veldhoven, Netherlands. a.j.vanwesemael@amsterdamumc.nl.",
    "Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, Amsterdam, Netherlands.",
    "Amsterdam Reproduction and Development Research Institute, Amsterdam UMC, Amsterdam, Netherlands.",
    "Amsterdam Gastroenterology Endocrinology & Metabolism Research Institute, Amsterdam UMC, Amsterdam, Netherlands.",
    "Department of Pediatrics, Catharina Hospital, Eindhoven, Netherlands.",
    "Department of Neonatal and Pediatric Intensive Care, Division of Neonatology, Sophia Children's Hospital, Erasmus MC, Rotterdam, Netherlands.",
    "Department of Pediatrics - Neonatology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.",
    "Department of Neonatology, MosaKids Children's Hospital, Maastricht UMC, Maastricht, Netherlands.",
    "Department of Neonatology, Beatrix Children's Hospital, UMC Groningen, Groningen, Netherlands.",
    "Department of Neonatology, Amalia Children's Hospital, Radboud UMC, Nijmegen, Netherlands.",
    "Department of Neonatology, Maxima Medical Centre, Veldhoven, Netherlands.",
    "Department of Electrical Engineering, Technical University Eindhoven, Eindhoven, Netherlands."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "A J van Wesemael",
      "orcid": "0009-0007-6957-3850"
    },
    {
      "affs": [
        4,
        5,
        6
      ],
      "name": "R R de Kroon",
      "orcid": "0000-0002-7971-3120"
    },
    {
      "affs": [
        7
      ],
      "name": "L M H E van Eijk",
      "orcid": "0009-0008-3347-0064"
    },
    {
      "affs": [
        4,
        5,
        6
      ],
      "name": "N M Frerichs",
      "orcid": "0000-0002-3568-863X"
    },
    {
      "affs": [
        8
      ],
      "name": "M J Vermeulen",
      "orcid": "0000-0001-9686-8186"
    },
    {
      "affs": [
        5,
        6,
        9
      ],
      "name": "C H P van den Akker",
      "orcid": "0000-0002-5494-730X"
    },
    {
      "affs": [
        10
      ],
      "name": "M M A Raets",
      "orcid": "0000-0002-5298-7594"
    },
    {
      "affs": [
        11
      ],
      "name": "C V Hulzebos",
      "orcid": "0000-0002-8159-7501"
    },
    {
      "affs": [
        12
      ],
      "name": "W P de Boode",
      "orcid": "0000-0003-3194-7005"
    },
    {
      "affs": [
        5,
        9
      ],
      "name": "A H van Kaam",
      "orcid": "0000-0003-4030-7085"
    },
    {
      "affs": [
        4,
        5,
        6
      ],
      "name": "T G J de Meij",
      "orcid": "0000-0002-7556-5896"
    },
    {
      "affs": [
        13,
        14
      ],
      "name": "H J Niemarkt",
      "orcid": "0000-0002-0844-7208"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4k43h5dvvjbbr.bib",
  "cited_by": 0,
  "doi": "10.1007/s00431-026-07560-8",
  "fulltext_url": "https://europepmc.org/articles/PMC13722641",
  "id": "4k43h5dvvjbbr",
  "issns": [
    "0340-6199",
    "1432-1076"
  ],
  "landing_url": "https://europepmc.org/article/MED/42963493",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2916|Infant Nutrition and Health"
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  "openalex": "W7224795811",
  "pdf_url": "https://europepmc.org/articles/PMC13722641?pdf=render",
  "pmcid": "PMC13722641",
  "pmid": "42963493",
  "published": "2026-10-31",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4k43h5dvvjbbr.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T03:21:21Z",
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    {
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      "native_id": "PMC13722641",
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      "url": "https://doi.org/10.1007/s00431-026-07560-8"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "journal-openalex:F27",
      "subfield": "general"
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  ],
  "title": "Clinical effects of multi-strain probiotics in extremely preterm infants: a multicenter pre-post implementation study in the Netherlands.",
  "title_text": "Clinical effects of multi-strain probiotics in extremely preterm infants: a multicenter pre-post implementation study in the Netherlands.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T12:21:25Z",
  "url": "https://research.draconitic.com/paper/4k43h5dvvjbbr",
  "venue": "European journal of pediatrics",
  "versions": []
}