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APPROVEDReviewed and approved by the Chamgap Editorial Team (2026-08-18). The draft was written by AI, the existence of all 1 cited sources was verified at the original page, and the verdict passed blind grading and adversarial audit. Methodology v0.7.
Verdict No. 2833 · Search date 2026-08-18 · Methodology v0.7

Preterm formula powder used to fortify human milk,
does it really help with Noninferiority to commercial human milk fortifier for in-hospital weight-gain velocity in very-low-birth-weight preterm infants?

30-Second Summary
C
Evidence Grade C · 50 · Safety caution
Preterm formula powder was noninferior for in-hospital weight-gain velocity, while rare safety and long-term development remain uncertain
NEC occurred in 0 versus 3 infants, late-onset sepsis in 15% versus 16%, and feed intolerance was lower with formula powder, but 123 infants cannot exclude uncommon serious harms.
What the
research shows
The grade is C with 50 points. In a 123-infant single-center Indian trial, in-hospital weight-gain velocity was 15.7 versus 16.3 g/kg/day, difference -0.5 g/kg/day (95% CI -1.9 to 0.7). The lower bound remained above the prespecified -2 g/kg/day margin, but growth velocity is a surrogate rather than a clinical event or long-term developmental outcome.
What the
ads claim
This was a resource-constrained Indian single-center trial. Korean NICUs generally use commercial human milk fortifier as standard care, so different product composition, sterile preparation, micronutrient supplementation, and infection-control systems limit direct transfer.
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Useful facts when choosing a product

  • The formula-powder arm also received calcium, phosphorus, iron, vitamin D, and multivitamins; the HMF arm received vitamin D.
  • The available products used were Dexolac Special Care and PreNAN.
  • Extrauterine growth restriction at 40 weeks was 73% versus 81%; long-term neurodevelopment was not measured.
Gap Measurement · Verdict 2833 · C 50
What advertising claims
What independent, higher-quality research supports
△ GAP
01

What the research actually shows

One level-3 neonatal unit in Delhi randomized 123 infants born at no more than 34 weeks and weighing under 1,500 g, 60 versus 63; 59 versus 63 entered the primary analysis. Limitation 1: noninferiority design. Which listed item: noninferiority design. Was it avoidable: yes - superiority could test increased growth, but investigators chose whether the low-cost substitute was no more than 2 g/kg/day worse. Limitation 2: small study. Which listed item: small study, total below 200; actual total was 123. Was it avoidable: yes - multicenter recruitment above 200 could improve precision for growth and uncommon harms. Short term under 12 weeks was not separately counted because discharge growth was the target endpoint. Open-label subjective outcome was not applicable because calibrated scales measured objective weight. Active comparator only was unavoidable because withholding standard fortification would inadequately meet these infants' nutritional needs. The article states that no external funding was received and does not report product provision; no external funding is not public funding.

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Why this is classified as C (50)

The trial met a prespecified 2 g/kg/day margin, but the primary endpoint was a growth surrogate, and evidence comes from one 123-infant noninferiority trial without confirmed public funding. This gives C with 50 points.

Counterpoint. Formula powder is not interchangeable with HMF as a product. The intervention included separate micronutrient supplementation and specific preparation, and equivalence for rare serious harms or development was not shown.

Rejudgment record. Article and registry cross-check — Surrogate growth velocity, one 123-infant noninferiority trial, the prespecified -2 g/kg/day margin, no external funding, and safety events

Scoring profile behind this grade
EndpointSSurrogate marker - laboratory or imaging measures
ReplicationR1Single confirmatory trial
IndependenceI1Mixed funding sources
Effect sizeE+Meets the clinically important threshold

The scoring table and the verdict agree (C).

Sub-claim grades by effect

This ingredient is marketed for several effects. A single overall grade blends strong and weak claims together, so each effect is graded separately here. The overall grade reflects the strongest disconfirming or core claim.

Effect (sub-claim)GradeBasis
Noninferiority for in-hospital weight-gain velocityCThe -1.9 lower bound remained above the -2 g/kg/day margin.
Reduced feed intoleranceCRates were 1.4 versus 6.8 per 1,000 patient-days, a secondary outcome in a small open-label trial.
Safety for necrotizing enterocolitis and sepsis?Few events and wide intervals prevent a firm safety conclusion.

Cross-check — Codex and Claude

This verdict was drafted by Codex through literature review and source-existence checks, cross-checked through blind grading and adversarial audit, and settled by reapplying the methodology boundary rules. Cases with split grades were resolved through rejudgment.
03

Evidence Table

StudyDesignSampleFundingEndpointResultWeight
Study 1Single-center open-label randomized noninferiority trial in India63No external funding; no trial-product provision reportedIn-hospital weight-gain velocity in g/kg/day until discharge or 40 weeks' postmenstrual age15.7 versus 16.3 g/kg/day; difference -0.5 (95% CI -1.9 to 0.7); noninferiority margin -2 g/kg/daySingle small surrogate-endpoint noninferiority evidence
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Receipt — 1 References

All 1 cited sources were verified for existence at the original page (as of 2026-08-18).

Chinnappan A, Sharma A, Agarwal R, Thukral A, Deorari A, Sankar MJ. Fortification of Breast Milk With Preterm Formula Powder vs Human Milk Fortifier in Preterm Neonates: A Randomized Noninferiority Trial. JAMA Pediatr. 2021;175(8):790-796. PMID: 33970187. DOI: 10.1001/jamapediatrics.2021.0678.
checked
Draft and rewrite: Codex (AI) · Verification: Codex blind grading and adversarial audit · Final adjudication: Claude
Reviewed and approved: Chamgap Editorial Team · Approval date: 2026-08-18 · Corrections: none

Cite this verdict

Preterm Formula Powder for In-Hospital Weight Gain in Very-Low-Birth-Weight Preterm Infants - Benefit Evidence Grade C card
[Chamgap] Preterm Formula Powder for In-Hospital Weight Gain in Very-Low-Birth-Weight Preterm Infants - Benefit — Evidence Grade C·50. 1 cited sources checked. Source: https://chamgap.com/en/verdicts/general/preterm-formula-powder-in-hospital-weight-gain-vlbw-preterm-infants/ · CC BY 4.0

CC BY 4.0 — free to use with attribution; do not distort grades, numbers, or verdict meaning.

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What this document does and does not do

Chamgap is an information source. It reports what research has and has not confirmed; it does not tell readers what to take or buy. That decision belongs to readers and, when needed, medical or legal professionals. This verdict reflects literature available up to the search date and may change as new research appears. Nothing here is medical advice.