# WHO ACTION-I trial Study · id `maternal:action-i-trial` · Maternal & Newborn Atlas · release `15708f235d73cd42` (public) > General information from published sources, not medical advice, and not reviewed by clinicians. Check the cited source before relying on anything here. The atlas's own text and curation may be reused under Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0, https://creativecommons.org/licenses/by-nc/4.0/): credit the atlas, and do not use it commercially. See the atlas About page. Text quoted from a source stays under that source's own terms, given as the source's reuse\_basis. The atlas's reuse terms do not cover it. The downloads list each quotation with its source in third\_party\_quotations. Also called: ACTION-I; WHO ACTION-I Trial Browse, life stage: Pregnancy; Newborn ## In plain language A trial in 29 hospitals in Bangladesh, India, Kenya, Nigeria and Pakistan. Pregnant women who were likely to give birth early received either a dexamethasone steroid injection or a dummy injection, to see whether the steroid lowered newborn deaths. The trial stopped early because deaths among the babies were lower in the dexamethasone group. ## Technical summary Multicountry, multicentre, individually randomized, parallel-group, double-blind, placebo-controlled trial (ACTRN12617000476336; CTRI/2017/04/008326). 2852 women and their 3070 fetuses were randomized; registry targets were 6018 (ANZCTR) and 6120 (CTRI, via ICTRP). Entry: gestational age 26 weeks 0 days to 33 weeks 6 days with birth planned or expected within 48 hours. Intramuscular dexamethasone 6 mg every 12 hours for up to four doses against identical placebo. Primary outcomes: neonatal death, stillbirth or neonatal death, and possible maternal bacterial infection, tested for non-inferiority with a margin of 1.25 on the relative scale. The data safety monitoring board recommended stopping after the second interim analysis, and recruitment stopped on 21 November 2019. The registries differ on first enrolment: the ICTRP view of the CTRI record lists 2017-06-01 (read as day-month-year), the same date as ANZCTR's anticipated first enrolment, while ANZCTR's actual first enrolment is 2017-12-24 and the manuscript says women were randomized from December 2017. Sponsor: WHO. The manuscript names the Gates Foundation as primary funder with additional support from WHO departments; the PubMed abstract credits both. ## Key facts - Design: Multicountry, multicentre, individually randomized (1:1, site-stratified), parallel-group, double-blind, placebo-controlled trial of intramuscular dexamethasone against identical placebo, given to women at risk of imminent preterm birth in 29 secondary- and tertiary-level hospitals. Women were randomized from December 2017 through November 2019. The sources describe the block design differently, and this is not reconciled: the manuscript says "balanced permuted blocks of size 10", while the CTRI record read through ICTRP describes permuted blocks of variable size. - Phase: Phase 3 - Enrolled: 2852 women (randomized count; Antenatal Dexamethasone for Early Preterm Birth in Low-Resource Countries, snapshot `maternal:pubmed-33095526-2026-10-11`, retrieved 2026-10-11); 3070 fetuses (randomized count; Antenatal Dexamethasone for Early Preterm Birth in Low-Resource Countries, snapshot `maternal:pubmed-33095526-2026-10-11`, retrieved 2026-10-11); 6018 women (ANZCTR target sample size) (planned count; The WHO ACTION-I (Antenatal CorticosTeroids for Improving Outcomes in preterm Newborns) Trial, snapshot `maternal:anzctr-actrn12617000476336-2026-10-11`, retrieved 2026-10-11); 6120 participants (CTRI target sample size via ICTRP; the unit is not named) (planned count; Improving newborn survival in preterm birth, snapshot `maternal:ictrp-ctri-2017-04-008326-2026-10-11`, retrieved 2026-10-11); 2852 participants (ANZCTR final sample size under accrual; the unit is not named) (enrolled count; The WHO ACTION-I (Antenatal CorticosTeroids for Improving Outcomes in preterm Newborns) Trial, snapshot `maternal:anzctr-actrn12617000476336-2026-10-11`, retrieved 2026-10-11) - Started: 2017-12-24 (actual) (The WHO ACTION-I (Antenatal CorticosTeroids for Improving Outcomes in preterm Newborns) Trial, snapshot `maternal:anzctr-actrn12617000476336-2026-10-11`, retrieved 2026-10-11) - Primary completion: Not reported - Completion: Not reported - Countries: Bangladesh; India; Kenya; Nigeria; Pakistan (Antenatal Dexamethasone for Early Preterm Birth in Low-Resource Countries, snapshot `maternal:pmc-pmc7660991-2026-10-11`, retrieved 2026-10-11) - Care setting: Hospital-based care at 29 secondary- and tertiary-level hospitals across six study sites. The hospitals were chosen after a standard assessment so that the WHO conditions for antenatal corticosteroid use could reasonably be met. (Antenatal Dexamethasone for Early Preterm Birth in Low-Resource Countries, snapshot `maternal:pmc-pmc7660991-2026-10-11`, retrieved 2026-10-11) - Registry status: "Stopped early" (Australian New Zealand Clinical Trials Registry, snapshot `maternal:anzctr-actrn12617000476336-2026-10-11`, retrieved 2026-10-11); "Completed" (Clinical Trials Registry - India, read through the WHO ICTRP mirror, snapshot `maternal:ictrp-ctri-2017-04-008326-2026-10-11`, retrieved 2026-10-11). The registries disagree; each status is given as its record states it. - Stopped early: Enrollment stopped early, 2019-11-21. After the second interim analysis the data safety monitoring board recommended stopping the trial for benefit on infant mortality, and recruitment stopped at all sites on this date. ANZCTR records the status as stopped early; the CTRI record, read through ICTRP, says completed. (Antenatal Dexamethasone for Early Preterm Birth in Low-Resource Countries, snapshot `maternal:pmc-pmc7660991-2026-10-11`, retrieved 2026-10-11) ## Claims, with the population each applies to ## Context: Pregnant women at risk of imminent preterm birth at 26w0d to 33w6d, in 29 hospitals in five low-resource countries (ACTION-I) Recipient: Maternal; Population: Pregnant women with a confirmed live fetus, single or multiple pregnancy, who were at risk of preterm birth between 26 weeks 0 days and 33 weeks 6 days of gestation and whose birth was planned or expected within 48 hours. Gestational age came from the earliest ultrasound or one done at admission.; Care setting: Hospital-based: 29 secondary- and tertiary-level hospitals across six study sites. The hospitals were chosen after a standard assessment so that the WHO conditions for antenatal corticosteroid use could reasonably be met.; Geography: Bangladesh, India, Kenya, Nigeria and Pakistan; Life stage: Pregnancy, from randomization to birth, with maternal infection followed to 28 days after birth; Gestational age: 26 weeks 0 days (182 days) to 33 weeks 6 days (237 days); Postnatal age: Not reported; Follow-up: The maternal primary outcome, possible maternal bacterial infection, ran from randomization to 28 days postpartum and was captured during hospital admission only. ### ACTION-I stopped recruiting women early. After the second interim analysis the data safety monitoring board recommended stopping the trial because deaths among infants were lower with dexamethasone, and recruitment stopped at all sites on 21 November 2019. The two registries disagree on the trial's status: ANZCTR records it as stopped early and the CTRI record, read through WHO ICTRP, as completed. - Category: Description - Evidence stage: Evidence stage not applicable - Certainty: Certainty not assessed - Applies to: Recipient: Maternal; Population: Pregnant women with a confirmed live fetus, single or multiple pregnancy, who were at risk of preterm birth between 26 weeks 0 days and 33 weeks 6 days of gestation and whose birth was planned or expected within 48 hours. Gestational age came from the earliest ultrasound or one done at admission.; Care setting: Hospital-based: 29 secondary- and tertiary-level hospitals across six study sites. The hospitals were chosen after a standard assessment so that the WHO conditions for antenatal corticosteroid use could reasonably be met.; Geography: Bangladesh, India, Kenya, Nigeria and Pakistan; Life stage: Pregnancy, from randomization to birth, with maternal infection followed to 28 days after birth; Gestational age: 26 weeks 0 days (182 days) to 33 weeks 6 days (237 days); Postnatal age: Not reported; Follow-up: The maternal primary outcome, possible maternal bacterial infection, ran from randomization to 28 days postpartum and was captured during hospital admission only. - Limitations: The registry disagreement is recorded, not reconciled. The CTRI view is a WHO ICTRP mirror refreshed in November 2021, and the primary CTRI record could not be read. - Last checked: Not recorded - Source problem: a cited source is unknown, not verified. Check the sources before relying on this claim. - Sources: 1. Supports: Antenatal Dexamethasone for Early Preterm Birth in Low-Resource Countries (Publication, edition Version of record not fetched (HTTP 403 on 2026-10-11). The abstract comes from PubMed and the bibliographic data from Crossref. Full-text facts come from the PMC Author Final Manuscript PMC7660991. Tables and figures were read in that manuscript and not checked against the version of record. PubMed lists comments and letters on the article but no erratum or retraction.) Locator: Abstract, RESULTS, sentence 2. Retrieved 2026-10-11T19:10:30Z. Source state: Current. Snapshot hash: adb2579c89c865461eb3f3ace681a011868a4f43b15a028d7178d08ad0d7057e. How it applies: Abstract of the primary report. 2. Supports: Antenatal Dexamethasone for Early Preterm Birth in Low-Resource Countries (Publication, edition Version of record not fetched (HTTP 403 on 2026-10-11). The abstract comes from PubMed and the bibliographic data from Crossref. Full-text facts come from the PMC Author Final Manuscript PMC7660991. Tables and figures were read in that manuscript and not checked against the version of record. PubMed lists comments and letters on the article but no erratum or retraction.) Locator: Methods, Statistical analysis, para 3: board recommendation. Retrieved 2026-10-11T19:10:31Z. Source state: Current. Snapshot hash: 8c795f040d84bf82311862509bdde4ea0f243d2933f596c1bd4f80ebdae14b26. How it applies: Author Final Manuscript (CC BY); not checked against the version of record. 3. Supports: Antenatal Dexamethasone for Early Preterm Birth in Low-Resource Countries (Publication, edition Version of record not fetched (HTTP 403 on 2026-10-11). The abstract comes from PubMed and the bibliographic data from Crossref. Full-text facts come from the PMC Author Final Manuscript PMC7660991. Tables and figures were read in that manuscript and not checked against the version of record. PubMed lists comments and letters on the article but no erratum or retraction.) Locator: Methods, Statistical analysis, para 3: recruitment stop. Retrieved 2026-10-11T19:10:31Z. Source state: Current. Snapshot hash: 8c795f040d84bf82311862509bdde4ea0f243d2933f596c1bd4f80ebdae14b26. How it applies: Author Final Manuscript (CC BY); not checked against the version of record. 4. Supports: The WHO ACTION-I (Antenatal CorticosTeroids for Improving Outcomes in preterm Newborns) Trial (Registry, edition Record as last updated 2021-03-22 (22/03/2021 on the page). Registered 2017-03-31 (31/03/2017) and marked as prospectively registered. Dates on the page are day/month/year.) Locator: Recruitment, Reason for early stopping. Retrieved 2026-10-11T19:10:33Z. Source state: Current. Snapshot hash: d43f7def2bdadf8c303488d8b03f6500f3786ed227e6232872ca447906b69d98. How it applies: ANZCTR record as last updated 2021-03-22. 5. Opposes: Improving newborn survival in preterm birth (Registry, edition WHO ICTRP mirror, refreshed 2021-11-24 (24 November 2021). Registered 2017-04-10, read as day-month-year because the CTRI number contains 2017/04; ICTRP marks it as prospectively registered. The primary CTRI record could not be read on 2026-10-11: the http request did not connect and the https request returned a short error page.) Locator: Main record fields. Retrieved 2026-10-11T19:10:34Z. Source state: Unknown, not verified. Snapshot hash: f80b7fcc0c2ca4a7ed56c92219e38fce42bacec3a4baef8335ed9806e6635485. How it applies: ICTRP mirror of CTRI gives the status as completed. ## Study findings Findings are grouped by the claim they support. Each group keeps its own population and follow-up, and each finding keeps its own denominator and time window. Not reported is not zero. ### In the ACTION-I trial, pregnant women at risk of imminent preterm birth, from 26 weeks 0 days to 33 weeks 6 days of pregnancy, received either dexamethasone or a dummy injection. Fewer of their liveborn babies died in the first 28 days of life in the dexamethasone group: 278 of 1417 (19.6%) against 331 of 1406 (23.5%) in the placebo group (relative risk 0.84, 95% CI 0.72 to 0.97). The medicine was given to the mother, and the outcome counted here is the baby's. Claim `maternal:claim-action-i-neonatal-death`. Applies to: Recipient: Newborn; Population: Liveborn infants of the randomized women. The window of 26 weeks 0 days to 33 weeks 6 days is the mother's gestational age when she entered the trial. It does not limit the infant's gestational age at birth, and the research gives no such limit. Birth occurred before 37 weeks for 90.0% of infants in the dexamethasone group and 90.8% of infants in the placebo group.; Care setting: Hospital-based: 29 secondary- and tertiary-level hospitals across six study sites. The hospitals were chosen after a standard assessment so that the WHO conditions for antenatal corticosteroid use could reasonably be met.; Geography: Bangladesh, India, Kenya, Nigeria and Pakistan; Life stage: Neonatal period, birth to 28 days; Gestational age: Not reported; Postnatal age: 0 days to 0 days; Follow-up: Infants entered the analysis at birth and were followed until 28 days after birth or death, whichever came first. Neonatal death means death of a liveborn within 28 completed days of life. The postnatal age bounds give age at entry, not the length of follow-up. Limitations: One placebo-controlled trial in 29 secondary- and tertiary-level hospitals in five low-resource countries. The hospitals were chosen so that the WHO conditions for steroid use could reasonably be met, so the result does not describe lower-level facilities or the community. The trial stopped early for benefit, short of its planned sample. About 90% of the infants were born before 37 weeks. The authors report that 45% of women received fewer than four doses, and name the difficulty of standardizing care across sites and the use of third-trimester ultrasound to confirm gestational age for many participants as limits. The relative risk is model-based, adjusted for site and for multiple births, with intervals adjusted for multiplicity. Figures come from the PubMed abstract and the Author Final Manuscript; the version of record was not fetched (HTTP 403) and the figures were not checked against it. - Neonatal death, birth to 28 completed days (Primary): Liveborn infants who died by 28 completed days of life (count) 278 infants; reported as "278/1417 (19.6)"; arm Dexamethasone (intervention), no comparator arm; interval Not applicable; denominator 1417 (Liveborn infants in this group, as reported in Table 2 of the Author Final Manuscript; not checked against the version of record.); time window Birth to 28 completed days of life - Neonatal death, birth to 28 completed days (Primary): Liveborn infants who died by 28 completed days of life (count) 331 infants; reported as "331/1406 (23.5)"; arm Identical placebo (control), no comparator arm; interval Not applicable; denominator 1406 (Liveborn infants in this group, as reported in Table 2 of the Author Final Manuscript; not checked against the version of record.); time window Birth to 28 completed days of life - Neonatal death, birth to 28 completed days (Primary): Relative risk, dexamethasone vs placebo, modelled with adjustment for study site and for clustering from multiple births (Table 2 footnote) 0.84 ratio; reported as "0.84 (0.72-0.97)"; arm Dexamethasone (intervention) compared with Identical placebo (control); interval 0.72 to 0.97 (95% confidence interval, adjusted for multiplicity (Table 2 footnote)); denominator Not applicable (basis: Comparison of the two per-arm rows above); time window Birth to 28 completed days of life ## Connected pages - Tests dexamethasone given to the mother before preterm birth: Antenatal corticosteroids (`maternal:antenatal-corticosteroids`) - Enrolled women at risk of imminent preterm birth: Preterm birth (`maternal:preterm-birth`) - Primary outcome: neonatal death by 28 completed days: Neonatal death, birth to 28 completed days (`maternal:outcome-neonatal-death-28d`) - Trial sponsor (manuscript, ICTRP): World Health Organization (`maternal:who`) - Primary funder (manuscript, abstract): Bill & Melinda Gates Foundation (`maternal:gates-foundation`) - Additional support (manuscript); credited as funder in the PubMed abstract: World Health Organization (`maternal:who`) - Primary results, NEJM 2020: ACTION-I primary results, NEJM 2020 (`maternal:pub-action-i-nejm-2020`) ## Provenance Content hash: 2345b168518236d31f82d933ef4083442a3a46c7af8f85b02df3088bf83ebc48 Last substantive edit: 2026-10-12 Evidence last checked: Not recorded