# BBG-001 × prevention of NEC, sepsis and death in very preterm infants — three primary outcomes evidence sheet Verdict 2928 · Evidence Check Stored-material review date: Not recorded Original evidence cut-off: 2026-08-26 Review-criteria version: 1.0 Public page/material preparation date: 2026-10-10 Clinical papers were not read directly; existing review summaries were checked. No new clinical-literature search was performed. Unverified does not mean that research is absent or that there is no effect. ## Assessment scope - Population: PiPS prevention in very preterm infants; detailed eligibility and baseline information not read - Ingredient, formulation and route: Historical exposure in a prevention trial of the specific BBG-001 strain; no recommendation for use - Dose: Only the original daily administration condition is preserved; no dosing, duration or procedural guidance is created - Comparator: Placebo; detailed actual concomitant exposures not read - Measured outcome: Distinguish sepsis, Bell stage 2 or greater NEC and death before discharge by their individual definitions and original results within one existing question - Duration: Apart from death before discharge, exact observation windows by event and actual administration duration have not been read in detail - Questions outside this scope: Adding individual or composite events as new units, independent trials or participants; Certifying a null result, confidence interval or nonreporting as an exact zero effect or absence of all harms; Combining BBG-001 prevention with adjunctive IVIG treatment after infection; Transferring effects to other strains, products, durations or populations; Recommendations on neonatal product selection, use, suitability, administration or treatment ## Checklist items ### N01 · Have the original subclaim verdict and the parent values and context been distinguished? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: The selected original claim is 'prevention of NEC, sepsis and death', with subclaim grade D and the note 'All were null.'; the parent is D34 with Good safety status. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Do not fill absent subclaim score, status or axes with parent values. There is no new grade, effect verdict or certification of independence. - Reason for missing information: Do not fill absent subclaim score, status or axes with parent values. There is no new grade, effect verdict or certification of independence. - Required materials and conditions: Separate preservation of the selected claim, grade and note and the parent grade, score and assessment axes - Materials to obtain first: Do not fill absent subclaim score, status or axes with parent values. There is no new grade, effect verdict or certification of independence. - Further research: Link additional materials separately to the selected question and the parent context. - Conditions for verification: Separate preservation of the selected claim, grade and note and the parent grade, score and assessment axes - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01 ### N02 · Have the population and eligibility for prevention in very preterm infants been distinguished from adjunctive treatment? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: PiPS is a BBG-001 trial to prevent NEC, sepsis and death in very preterm infants; it differs from adding IVIG as adjunctive treatment after sepsis. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Detailed gestational-age and birth-weight criteria, baseline risk, recruitment timing and nutrition or antibiotic conditions are absent from the summary. Do not create new eligibility or product-selection instructions. - Reason for missing information: Detailed gestational-age and birth-weight criteria, baseline risk, recruitment timing and nutrition or antibiotic conditions are absent from the summary. Do not create new eligibility or product-selection instructions. - Required materials and conditions: Gestational age, birth, recruitment, eligibility, baseline and denominators - Materials to obtain first: Detailed gestational-age and birth-weight criteria, baseline risk, recruitment timing and nutrition or antibiotic conditions are absent from the summary. Do not create new eligibility or product-selection instructions. - Further research: Obtain original eligibility, baseline, recruitment, timing and concomitant-exposure materials. - Conditions for verification: Gestational age, birth, recruitment, eligibility, baseline and denominators - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01 ### N03 · What are the BBG-001 strain identity, placebo and actual exposure? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: The study condition was daily administration of the specific Bifidobacterium breve BBG-001 strain or placebo. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Do not transfer this to other strains, mixtures or probiotics in general. Detailed dose, formulation, manufacturing criteria, start and stop times and actual adherence are absent from the summary. Do not create intake or use instructions. - Reason for missing information: Do not transfer this to other strains, mixtures or probiotics in general. Detailed dose, formulation, manufacturing criteria, start and stop times and actual adherence are absent from the summary. Do not create intake or use instructions. - Required materials and conditions: Original strain, formulation, quality, control, administration duration and actual exposure - Materials to obtain first: Do not transfer this to other strains, mixtures or probiotics in general. Detailed dose, formulation, manufacturing criteria, start and stop times and actual adherence are absent from the summary. Do not create intake or use instructions. - Further research: Obtain original strain, product, placebo, quality, duration and actual-exposure tables. - Conditions for verification: Original strain, formulation, quality, control, administration duration and actual exposure - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01 ### N04 · Have the 1,315 participants and group denominators for the three outcomes been distinguished? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: The stored summary records 1,315 PiPS participants and the proportions for three events in each group. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Do not newly calculate original group sizes, outcome-specific event counts, denominators or missing-data rates. Do not add participants or events as independent evidence when the same infant appears in different events. - Reason for missing information: Do not newly calculate original group sizes, outcome-specific event counts, denominators or missing-data rates. Do not add participants or events as independent evidence when the same infant appears in different events. - Required materials and conditions: Original allocation, group analyses, missing data and event-specific denominators - Materials to obtain first: Do not newly calculate original group sizes, outcome-specific event counts, denominators or missing-data rates. Do not add participants or events as independent evidence when the same infant appears in different events. - Further research: Obtain original participant flow, group denominators for each outcome, omissions and event mapping. - Conditions for verification: Original allocation, group analyses, missing data and event-specific denominators - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01 ### N05 · Are sepsis, NEC and death before discharge a single composite event? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: The evidence list records sepsis, Bell stage 2 or greater NEC and death before discharge as endpoints. The original grade decision records three co-primary outcomes. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Do not turn the three outcomes into a newly summed composite event or new structural units. Do not arbitrarily change the existing false indicator for splitting co-primary outcomes. - Reason for missing information: Do not turn the three outcomes into a newly summed composite event or new structural units. Do not arbitrarily change the existing false indicator for splitting co-primary outcomes. - Required materials and conditions: Three co-primary outcomes, original definitions, individual people or events and time - Materials to obtain first: Do not turn the three outcomes into a newly summed composite event or new structural units. Do not arbitrarily change the existing false indicator for splitting co-primary outcomes. - Further research: Obtain the original definition of each endpoint, prespecified hierarchy, overlap, denominators and timing. - Conditions for verification: Three co-primary outcomes, original definitions, individual people or events and time - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01 ### N06 · What are the actual sepsis definition, confirmation and observation period? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: The original evidence list records sepsis as a primary outcome. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Do not invent details of culture confirmation, clinical diagnosis, timing criteria, repeated events or sepsis categories. The exact observation window and denominators have not been read. - Reason for missing information: Do not invent details of culture confirmation, clinical diagnosis, timing criteria, repeated events or sepsis categories. The exact observation window and denominators have not been read. - Required materials and conditions: Sepsis definition, testing, confirmation, timing, people or events and denominators - Materials to obtain first: Do not invent details of culture confirmation, clinical diagnosis, timing criteria, repeated events or sepsis categories. The exact observation window and denominators have not been read. - Further research: Obtain original sepsis definition, confirmation, timing, denominators and repeated-event tables. - Conditions for verification: Sepsis definition, testing, confirmation, timing, people or events and denominators - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01 ### N07 · Are the sepsis proportions, adjusted RR, 95% CI and original absolute difference preserved? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: BBG-001 11.2% versus placebo 11.7%, adjusted RR 0.97 (95% CI 0.73~1.29), with an original absolute difference of −0.5%p. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Do not calculate new event counts, RRs, absolute differences, P values or NNTs from the original proportions. Adjustment variables, missing data and model details have not been read. - Reason for missing information: Do not calculate new event counts, RRs, absolute differences, P values or NNTs from the original proportions. Adjustment variables, missing data and model details have not been read. - Required materials and conditions: Original group order, proportions, adjustment model, effect, CI and denominators - Materials to obtain first: Do not calculate new event counts, RRs, absolute differences, P values or NNTs from the original proportions. Adjustment variables, missing data and model details have not been read. - Further research: Obtain original event tables, group denominators, adjustment model, tests and CIs. - Conditions for verification: Original group order, proportions, adjustment model, effect, CI and denominators - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01 ### N08 · What are the definition, classification and verification scope for Bell stage 2 or greater NEC? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: The evidence list records Bell stage 2 or greater NEC. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Do not replace this definition with other stages, suspected diagnosis, surgical NEC or nutritional indicators. Detailed adjudication, observation windows and group denominators have not been read. - Reason for missing information: Do not replace this definition with other stages, suspected diagnosis, surgical NEC or nutritional indicators. Detailed adjudication, observation windows and group denominators have not been read. - Required materials and conditions: Original NEC classification, adjudication, timing and denominators - Materials to obtain first: Do not replace this definition with other stages, suspected diagnosis, surgical NEC or nutritional indicators. Detailed adjudication, observation windows and group denominators have not been read. - Further research: Obtain original Bell definitions, adjudication, results by stage or timing and denominators. - Conditions for verification: Original NEC classification, adjudication, timing and denominators - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01 ### N09 · Have the original NEC proportions, RR, interval and absolute difference been preserved exactly? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: The original main-text NEC result is 9.4% versus 10.0%, RR 0.93, interval 0.68~1.27 and original absolute difference −0.6%p. The 95% CI context in the original reader answer is preserved in the full stored review summary. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Do not arbitrarily fill event counts, new CIs, P values, interval levels or model details absent from the original evidence list. - Reason for missing information: Do not arbitrarily fill event counts, new CIs, P values, interval levels or model details absent from the original evidence list. - Required materials and conditions: Original group proportions, effects, intervals, denominators and tests - Materials to obtain first: Do not arbitrarily fill event counts, new CIs, P values, interval levels or model details absent from the original evidence list. - Further research: Obtain original NEC events, denominators, RR, interval, model and tests. - Conditions for verification: Original group proportions, effects, intervals, denominators and tests - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01 ### N10 · Has death before discharge been distinguished from deaths in other periods or from other causes? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: The evidence list records death before discharge. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Do not extend the pre-discharge outcome to prevention of death at age 2, throughout life or by other causes. Original cause, duration, denominator and follow-up procedures have not been read in detail. - Reason for missing information: Do not extend the pre-discharge outcome to prevention of death at age 2, throughout life or by other causes. Original cause, duration, denominator and follow-up procedures have not been read in detail. - Required materials and conditions: Death definition, time, cause, denominators and follow-up - Materials to obtain first: Do not extend the pre-discharge outcome to prevention of death at age 2, throughout life or by other causes. Original cause, duration, denominator and follow-up procedures have not been read in detail. - Further research: Obtain original death definitions, timing, causes, group denominators and follow-up materials. - Conditions for verification: Death definition, time, cause, denominators and follow-up - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01 ### N11 · Are the original death proportions, RR, interval and absolute difference preserved? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: The original main-text death result is 8.3% versus 8.5%, RR 0.93, interval 0.67~1.30 and original absolute difference −0.2%p. The 95% CI context in the original reader answer is preserved in the stored review summary. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Do not calculate new death counts, RRs, risk differences or P values from the original proportions. Do not mix the death RR with the same RR or CI for NEC. - Reason for missing information: Do not calculate new death counts, RRs, risk differences or P values from the original proportions. Do not mix the death RR with the same RR or CI for NEC. - Required materials and conditions: Original group proportions, original effects, intervals, denominators and tests - Materials to obtain first: Do not calculate new death counts, RRs, risk differences or P values from the original proportions. Do not mix the death RR with the same RR or CI for NEC. - Further research: Obtain original death tables, denominators, effects, intervals, adjustment and tests. - Conditions for verification: Original group proportions, original effects, intervals, denominators and tests - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01 ### N12 · Has the original null result been distinguished from CIs that leave both benefit and harm possible? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: The stored summary records null results for the three primary outcomes and the limitation that CIs leave both potentially meaningful benefit and harm possible. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Do not newly certify a null result as an exact zero effect, equivalence or absence of all harms. There are no new MCIDs, power calculations, sample sizes or hypothetical numerical examples. - Reason for missing information: Do not newly certify a null result as an exact zero effect, equivalence or absence of all harms. There are no new MCIDs, power calculations, sample sizes or hypothetical numerical examples. - Required materials and conditions: Original intervals, precision and clinical importance for each outcome - Materials to obtain first: Do not newly certify a null result as an exact zero effect, equivalence or absence of all harms. There are no new MCIDs, power calculations, sample sizes or hypothetical numerical examples. - Further research: Obtain original effects, precision, clinical boundaries and denominators for each outcome. - Conditions for verification: Original intervals, precision and clinical importance for each outcome - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01 ### N13 · Have cross-colonization, within-group colonization and actual event effects been distinguished? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: The stored summary records BBG-001 colonization in the placebo group and states that prespecified analyses did not explain the null result. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Do not count colonization as clinical prevention efficacy or an independent trial. Do not add cross-colonization as a new axis defect or certify the original analysis as newly reviewed. - Reason for missing information: Do not count colonization as clinical prevention efficacy or an independent trial. Do not add cross-colonization as a new axis defect or certify the original analysis as newly reviewed. - Required materials and conditions: Placebo-group colonization, timing, confirmation, actual exposure and prespecified analyses - Materials to obtain first: Do not count colonization as clinical prevention efficacy or an independent trial. Do not add cross-colonization as a new axis defect or certify the original analysis as newly reviewed. - Further research: Obtain original colonization confirmation, exposure, timing, denominators, prespecified analyses and sensitivity analyses. - Conditions for verification: Placebo-group colonization, timing, confirmation, actual exposure and prespecified analyses - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01 ### N14 · What gaps remain in double blinding, placebo and actual adjudication and analysis procedures? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: The original evidence list describes PiPS as a multicenter double-blind placebo-controlled RCT. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Do not invent detailed allocation concealment, blinding checks, event adjudication or analyst procedures. Do not certify nominal blinding as absence of all bias. - Reason for missing information: Do not invent detailed allocation concealment, blinding checks, event adjudication or analyst procedures. Do not certify nominal blinding as absence of all bias. - Required materials and conditions: Original allocation, concealment, blinding, adjudicators and analysts - Materials to obtain first: Do not invent detailed allocation concealment, blinding checks, event adjudication or analyst procedures. Do not certify nominal blinding as absence of all bias. - Further research: Obtain original allocation, blinding, confirmation, analysis and missing-data procedures. - Conditions for verification: Original allocation, concealment, blinding, adjudicators and analysts - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01 ### N15 · What gaps remain in the prespecified hierarchy, multiple primary outcomes and registration access? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: The registration identifier is ISRCTN05511098, and the stored review summary preserves wording about three co-primary outcomes and prespecified colonization analyses. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Do not newly read registration, full text or plans. Exact alpha, test P values, multiplicity, ITT or missing-data handling and changes have not been read in detail. - Reason for missing information: Do not newly read registration, full text or plans. Exact alpha, test P values, multiplicity, ITT or missing-data handling and changes have not been read in detail. - Required materials and conditions: Original registration, protocol, SAP, multiplicity, changes and analysis population - Materials to obtain first: Do not newly read registration, full text or plans. Exact alpha, test P values, multiplicity, ITT or missing-data handling and changes have not been read in detail. - Further research: Obtain original registration, plans, hierarchy, multiplicity, analysis populations and changes. - Conditions for verification: Original registration, protocol, SAP, multiplicity, changes and analysis population - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01 ### N16 · Have the single PiPS trial, multiple outcomes and related-verdict links been kept from being added as independent evidence? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: NEC, sepsis and death before discharge concern the same PiPS report and infant cohort. Verdict 1503 is a cross-citation of an existing verdict on a different strain combination. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Do not add the three outcomes or related links as new independent trials or participants. The verdict 1503 target and included trials have not been newly read; final independent counts and participant totals are null. - Reason for missing information: Do not add the three outcomes or related links as new independent trials or participants. The verdict 1503 target and included trials have not been newly read; final independent counts and participant totals are null. - Required materials and conditions: Relationships among the same trial, reports, cohort, outcomes and cross-citations - Materials to obtain first: Do not add the three outcomes or related links as new independent trials or participants. The verdict 1503 target and included trials have not been newly read; final independent counts and participant totals are null. - Further research: Link additional reports by original identifiers, participants, outcomes and strain relationships. - Conditions for verification: Relationships among the same trial, reports, cohort, outcomes and cross-citations - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01, R02 ### N17 · Have the original cross-citation of the verdict 1503 strain combination and new direct evidence been separated? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: The stored summary cross-cites verdict 1503, where a Bifidobacterium plus Lactobacillus combination had NEC and total-mortality benefit, B77, in the same preterm prevention indication. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. That verdict and its original trials have not been read or reassessed in this preparation. Do not transfer effects of another combination to BBG-001 or create a direct product-superiority comparison. - Reason for missing information: That verdict and its original trials have not been read or reassessed in this preparation. Do not transfer effects of another combination to BBG-001 or create a direct product-superiority comparison. - Required materials and conditions: Existing related-verdict record, strains, population, trials and denominators - Materials to obtain first: That verdict and its original trials have not been read or reassessed in this preparation. Do not transfer effects of another combination to BBG-001 or create a direct product-superiority comparison. - Further research: Link relevant original materials provided by the user by strain, comparison and cohort. - Conditions for verification: Existing related-verdict record, strains, population, trials and denominators - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01, R02 ### N18 · Have NIHR cash funding, Yakult in-kind provision and study roles each been preserved? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: Preserve the NIHR HTA research funding and Yakult Honsha's free manufacture and transport to the UK of probiotic and placebo products. The stored summary records no company involvement in design, conduct or analysis. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Do not newly certify absence of in-kind provision or complete independence solely from public support. Employee authors and other writing roles have not been separately read; preserve original I1. - Reason for missing information: Do not newly certify absence of in-kind provision or complete independence solely from public support. Employee authors and other writing roles have not been separately read; preserve original I1. - Required materials and conditions: Funding, product or placebo manufacture, transport, affiliations, analysis and study roles - Materials to obtain first: Do not newly certify absence of in-kind provision or complete independence solely from public support. Employee authors and other writing roles have not been separately read; preserve original I1. - Further research: Obtain original disclosures on funding, in-kind provision, affiliations, design, conduct, analysis and writing. - Conditions for verification: Funding, product or placebo manufacture, transport, affiliations, analysis and study roles - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01 ### N19 · Have nonreporting of a probiotic-bacteremia signal and the original event intervals been separated? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: The original safety description states that no major safety signal, including probiotic bacteremia, was reported and that the three primary events did not increase. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Do not turn nonreporting into zero bacteremia events, absence of harm or certification of long-term safety. Preserve as historical both the possibility of harm within the original effect CIs and the original Good safety verdict. - Reason for missing information: Do not turn nonreporting into zero bacteremia events, absence of harm or certification of long-term safety. Preserve as historical both the possibility of harm within the original effect CIs and the original Good safety verdict. - Required materials and conditions: Harm definition, collection, people or events, exposure, denominators and relatedness - Materials to obtain first: Do not turn nonreporting into zero bacteremia events, absence of harm or certification of long-term safety. Preserve as historical both the possibility of harm within the original effect CIs and the original Good safety verdict. - Further research: Obtain original harm collection, group events or people, denominators, relatedness, exposure and CIs. - Conditions for verification: Harm definition, collection, people or events, exposure, denominators and relatedness - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01 ### N20 · What gaps remain in exposure duration, missing data, safety-analysis populations and rare harms? Verification status: Unverified Reading scope: Summary read; external or linked material unread - Current findings: The stored summary preserves daily study-product administration and descriptions of primary events and safety signals. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Do not newly calculate specific administration durations, safety populations, repeated events, rare-harm rates, discontinuation or long-term follow-up. - Reason for missing information: Do not newly calculate specific administration durations, safety populations, repeated events, rare-harm rates, discontinuation or long-term follow-up. - Required materials and conditions: Actual exposure, harm denominators, observation windows, relatedness and discontinuation - Materials to obtain first: Do not newly calculate specific administration durations, safety populations, repeated events, rare-harm rates, discontinuation or long-term follow-up. - Further research: Obtain original exposure, safety-analysis population, discontinuation, missing-data, follow-up and relatedness materials. - Conditions for verification: Actual exposure, harm denominators, observation windows, relatedness and discontinuation - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01 ### N21 · Do gaps remain when applying effects or harms to other populations, strains, combinations or durations? Verification status: Unverified Reading scope: Summary read; external or linked material unread - Current findings: The stored summary distinguishes prevention with the specific BBG-001 strain in very preterm infants from results for other combination products. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Do not treat all probiotics as ineffective or safe, or equate their effects with those of other strains. There are no neonatal product-selection, use or suitability instructions. - Reason for missing information: Do not treat all probiotics as ineffective or safe, or equate their effects with those of other strains. There are no neonatal product-selection, use or suitability instructions. - Required materials and conditions: Direct comparisons and independent relationships by population, strain, formulation and duration - Materials to obtain first: Do not treat all probiotics as ineffective or safe, or equate their effects with those of other strains. There are no neonatal product-selection, use or suitability instructions. - Further research: Obtain direct effect and harm materials by population, strain, combination and duration. - Conditions for verification: Direct comparisons and independent relationships by population, strain, formulation and duration - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01, R02 ### N22 · Are the stored summary, original URLs, registration identifier and access to linked targets distinguished? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: The full stored summary of the designated parent verdict was read for preparation, and the original citation-list URLs and registration identifier are preserved. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. External abstracts, full texts, registration, protocols, SAPs and targets of related-verdict links have not been read. Do not create new URLs or DOIs from identifiers or perform separate link tests. - Reason for missing information: External abstracts, full texts, registration, protocols, SAPs and targets of related-verdict links have not been read. Do not create new URLs or DOIs from identifiers or perform separate link tests. - Required materials and conditions: Reports or cross-citations, URLs, identifiers and access by material - Materials to obtain first: External abstracts, full texts, registration, protocols, SAPs and targets of related-verdict links have not been read. Do not create new URLs or DOIs from identifiers or perform separate link tests. - Further research: Link user-provided original materials to each material type and access status. - Conditions for verification: Reports or cross-citations, URLs, identifiers and access by material - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01, R02 ### N23 · Have the Korean and English manuscripts, original axes, dates, corrections, empty values, candidate history and preparation status been preserved? Verification status: Partly verified Reading scope: Summary read; external or linked material unread - Current findings: Preserve 2026-08-26, empty correction and deliberation values, subclaim grade D and its note, and the actual parent grade, score, safety, assessment axes and Korean and English manuscripts. - Why unverified: Only the relevant information in the stored summary is recorded; detailed original materials and user review remain outstanding. Original verification, funding independence, design-defect and safety descriptions are historical, not certification of the present review. Do not fill absent subclaim fields; original review-pending and preparation-eligible indicators are candidate history. - Reason for missing information: Original verification, funding independence, design-defect and safety descriptions are historical, not certification of the present review. Do not fill absent subclaim fields; original review-pending and preparation-eligible indicators are candidate history. - Required materials and conditions: Distinguish the selected verdict record, complete parent, original languages and history from current preparation - Materials to obtain first: Original verification, funding independence, design-defect and safety descriptions are historical, not certification of the present review. Do not fill absent subclaim fields; original review-pending and preparation-eligible indicators are candidate history. - Further research: Preserve user materials and decisions in full, then link them as separate events. - Conditions for verification: Distinguish the selected verdict record, complete parent, original languages and history from current preparation - Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries - Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Prevention of NEC, sepsis and death - Related sources: R01 ## Evidence and sources ### R01 Costeloe K, et al. Lancet. 2016;387:649-660. PMID: 26628328. [PubMed](https://pubmed.ncbi.nlm.nih.gov/26628328/) Materials actually read: Summary read; external or linked material unread Findings recorded in the summary: Sepsis: BBG-001 11.2% versus placebo 11.7%, absolute difference -0.5%p, adjusted RR 0.97 (95% CI 0.73~1.29); NEC 9.4% versus 10.0%; death 8.3% versus 8.5% Record level: Existing review summary; no comparison with the external original report Independent replication: Three co-primary outcomes in the same PiPS trial and infant cohort; a cross-citation of existing verdict 1503 on a different strain combination, whose linked target and included trials have not been read and which does not certify independent replication of BBG-001; family IDs link relationships and do not certify independent counts; do not newly add events, composite components, sites, cross-citations or the same participants as independent evidence | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | local_summary | Original URL preserved | Summary read | Summary read | Preserved parent verdict summary; report-specific links to the same stored summary copy | | abstract | Original URL preserved | Not read | Not read | External or linked verdict material unread; a URL does not mean reading or review is complete | | fulltext | No separate URL in the original material | Not read | Not read | External or linked verdict material unread; a URL does not mean reading or review is complete | | registration | No separate URL in the original material | Not read | Not read | External or linked verdict material unread; a URL does not mean reading or review is complete | | protocol_sap | No separate URL in the original material | Not read | Not read | External or linked verdict material unread; a URL does not mean reading or review is complete | ### R02 Verdict 1503: Bifidobacterium plus Lactobacillus combination probiotics × prevention of NEC and total mortality in preterm infants (B 77) [Official source](https://chamgap.com/verdicts/gut/bifidobacterium-lactobacillus-probiotics-preterm-nec-mortality/) Materials actually read: Summary read; external or linked material unread Findings recorded in the summary: Outcomes differ by strain and combination within the same indication. Record level: Only the original cross-citation summary is preserved; no new clinical evidence on other strains has been read Independent replication: Three co-primary outcomes in the same PiPS trial and infant cohort; a cross-citation of existing verdict 1503 on a different strain combination, whose linked target and included trials have not been read and which does not certify independent replication of BBG-001; family IDs link relationships and do not certify independent counts; do not newly add events, composite components, sites, cross-citations or the same participants as independent evidence | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | local_summary | Original URL preserved | Summary read | Summary read | Preserved parent verdict summary; report-specific links to the same stored summary copy | | source_link | Original URL preserved | Not read | Not read | External or linked verdict material unread; a URL does not mean reading or review is complete | | fulltext | No separate URL in the original material | Not read | Not read | External or linked verdict material unread; a URL does not mean reading or review is complete | | registration | No separate URL in the original material | Not read | Not read | External or linked verdict material unread; a URL does not mean reading or review is complete | | protocol_sap | No separate URL in the original material | Not read | Not read | External or linked verdict material unread; a URL does not mean reading or review is complete | ## Review criteria and methods These are Chamgap's own application conditions, informed by the relevant sections of official methodological guidance. They do not constitute official assessment-tool certification or a new efficacy score. - M03 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03) · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13 · Clearly record the question, eligibility conditions and reasons for changes, and distinguish variations in interventions. · Existing stored methodological links reused for preparation; no current review, reassessment of methodological content or external-link testing - M04 [Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04) · §4.5, §4.6.1–4.6.3, MECIR C42 · Distinguish studies from reports and link them; do not omit a study solely because results are unreported. · Existing stored methodological links reused for preparation; no current review, reassessment of methodological content or external-link testing - M08 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08) · §8.1–8.2.3, Table 8.2.a · Define the outcome and effect of interest, then examine randomization, deviations, missing data, measurement and selective reporting. · Existing stored methodological links reused for preparation; no current review, reassessment of methodological content or external-link testing - M15 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15) · §15.2.4, §15.3.1–15.3.3 · Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision. · Existing stored methodological links reused for preparation; no current review, reassessment of methodological content or external-link testing - M19 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19) · §19.1.2, §19.2.1–19.2.4 · Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence rates. · Existing stored methodological links reused for preparation; no current review, reassessment of methodological content or external-link testing ## What the statuses mean - Partly verified: Some information exists in the preserved review summary, with detailed original materials still unverified; no certification of a passed review or clinical efficacy - Unverified: Detailed materials for the selected condition could not be established within the stored scope; this does not mean zero effect, zero studies or safety - Review incomplete: Review of existing content incomplete - Met: Use only within the relevant condition's scope after user review; no automatic display in this preparation - Not reported: Distinguish only within materials actually read; do not turn unread external materials into unreported findings - Inaccessible: Not applied during this preparation because actual access was not tested - Not applicable: Use with a reason for non-applicability based on an explicit question boundary - Conflicting data: Judge after actual material comparison; review was not performed during this preparation - Insufficient evidence for the conditions: Do not use as a clinical grade encompassing currently unread materials ## Change history 2026-10-10 · Public page/materials 1.0. Reader pages and materials were prepared from the existing 23 items. No new clinical search, change in verification status or scoring was performed.