Effect of molecular hydrogen on uterine inflammation during preterm labour
Nakano T, Kotani T, Imai K, Iitani Y, Ushida T, Tsuda H, Li H, Iwase A, Toyokuni S, Kikkawa F. · Biomedical Reports. 2018;8(5):454-460.
What kind of evidence is this?
Preclinical
Randomized controlled pregnant-mouse prevention experiment
Women’s health
H₂-rich water
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Methods at a glance
Thirty-eight pregnant ICR mice in an acute lipopolysaccharide model of inflammation-associated preterm labour.
For uterine/serum outcomes, control, LPS and H₂-water plus LPS groups had n=6 each. For delivery timing, separate LPS and H₂-water plus LPS groups had n=10 each; no delivery-timing control group was used.
Pretreatment began 24 hours before LPS; uterine/serum outcomes were collected six hours after LPS, and delivery was monitored hourly.
H₂-rich drinking water began 24 hours before LPS administration on embryonic day 15.5 and continued until sacrifice or delivery assessment; mice drank approximately 200 mL/kg/day.
H₂ dissolved in drinking water — H₂ only, not Brown's gas.
Donated water was stored above 0.4 mM and delivered through degassing-resistant glass bottles; drinking-water H₂ was maintained above 0.2 mM and replaced every 24 hours.
Not applicable — drinking water, not gas inhalation.
No O₂ was co-delivered as part of the intervention.
LPS-exposed mice receiving ordinary water and, for molecular outcomes, a PBS-injected control group.
Outcomes and reported result
Time to delivery, preterm-birth proportion, progesterone, uterine inflammatory cytokine transcripts, contractile-associated proteins, Mmp3, Et1 and Cox2 protein.
H₂ water delayed mean delivery after LPS and changed several inflammatory/contractile markers. It did not significantly reduce preterm birth within 24 hours (90% vs 60%, p=0.303), Il8 was unchanged versus LPS, and the Mmp3 reduction was not significant (p=0.055). The authors concluded that prevention of acute-inflammation preterm birth was weak/ineffective despite molecular effects.
The complete free PMC article was checked for both cohorts, randomization, H₂ source/concentration/intake, timing, positive and null outcomes, stated limitations, donation, funding and conflict declaration.
A reported association, difference or mechanism is not automatically a clinical benefit. Null findings, outcome type, study design and precision all matter.
Cautions and applicability
Small mouse cohorts, preventive treatment before acute LPS exposure, no delivery-timing control arm, no neonatal clinical outcomes and many molecular comparisons. Blue Mercury donated the H₂ water; Japanese public grants funded the study, and authors declared no competing interests.
Acute LPS-associated preterm labour in mice; it does not establish prevention or treatment of human preterm birth.
Not reported in this record.
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No single-study GRADE certainty rating is assigned. Certainty is assessed by important outcome across a complete eligible evidence set, not by attaching a final grade to one source.
Sources and record status
PMID: 29732148 · DOI: 10.3892/br.2018.1082
Free full article in PubMed Central.
Complete PMC article and PubMed metadata; full-text extraction checked 9 August 2026.
2026-08-10