# TRUFFLE trial (timing of birth in early fetal growth restriction) Study · id `maternal:truffle-trial` · Maternal & Newborn Atlas · release `fc5a600ec7387e71` (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. Browse, life stage: Pregnancy; Infant follow-up Browse, care area: The baby before birth ## In plain language A European trial in women whose babies had severe growth restriction between 26 and 32 weeks of pregnancy. It tested three plans for deciding when to deliver, based on heart-rate tracing or on blood flow in a vein in the baby. The main result at 2 years of age was not clearly different between plans. ## Technical summary Prospective, European, multicentre, unblinded, randomised study (ISRCTN 56204499; Lancet 2015). 503 of 542 eligible women were randomly allocated 1:1:1 to delivery plans based on reduced cardiotocography short-term variation, early ductus venosus Doppler changes (pulsatility index above the 95th percentile) or late ductus venosus changes. Primary outcome: survival without cerebral palsy, neurosensory impairment or Bayley III score below 85 at 2 years. The primary result was not significant (p trend 0.09); the authors describe a survivor-only difference and a non-significant increase in mortality. This trial tested ductus venosus Doppler against cardiotocography, not umbilical artery Doppler (a high umbilical artery pulsatility index was an entry criterion). Funded by ZonMw and the Dr Hans Ludwig Geisenhofer Foundation. ## Key facts - Design: Prospective, European multicentre, unblinded, randomised study of women with singleton fetuses at 26 to 32 weeks with very preterm fetal growth restriction, allocated 1:1:1 (randomly sized blocks, stratified by centre and by gestational age below or at least 29 weeks) to three timing-of-delivery plans that differed in antenatal monitoring strategy. Intention to treat for the primary outcome. - Phase: Not reported - Enrolled: 503 women (randomly allocated from 542 eligible) (randomized count; 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial, snapshot `maternal:pubmed-25747582-2026-10-14`, retrieved 2026-10-14) - Started: Not reported - Primary completion: Not reported - Completion: Not reported - Countries: United Kingdom; Austria; Germany; Italy; Netherlands (Trial of Umbilical and Foetal Flow in Europe: TRUFFLE study (ISRCTN record), snapshot `maternal:truffle-isrctn-2026-10-14`, retrieved 2026-10-14) - Care setting: Not reported - Registry status: Not reported ## Claims, with the population each applies to ## Context: Surviving infants at 2 years after very preterm fetal growth restriction (TRUFFLE) Recipient: Child; Population: Surviving infants of women with a singleton fetus at 26 to 32 weeks of gestation and very preterm fetal growth restriction (abdominal circumference below the 10th percentile and umbilical artery Doppler pulsatility index above the 95th percentile), assessed at 2 years of age. The mothers were randomly allocated; outcomes are counted in the infants who survived and had known outcome.; Care setting: European multicentre trial; setting type not stated in the abstract; Geography: Europe (countries not named in the abstract); Life stage: Infant follow-up at 2 years of age; mothers were enrolled at 26 to 32 weeks of gestation; Gestational age: 26 weeks 0 days (182 days) to 32 weeks 0 days (224 days), measured at enrolment; Postnatal age: Not reported; Follow-up: Survival without cerebral palsy, neurosensory impairment or a Bayley III developmental score below 85, at 2 years of age ### TRUFFLE randomly allocated 503 of 542 eligible women (singleton fetus at 26 to 32 weeks with very preterm growth restriction) to three delivery-timing plans based on reduced cardiotocography short-term variation, early ductus venosus Doppler changes, or late ductus venosus Doppler changes. The primary outcome, survival without cerebral palsy, neurosensory impairment or a Bayley III score below 85 at 2 years, did not differ between groups: 111 of 144 infants with known outcome (77%) in the cardiotocography group, 119 of 142 (84%) in the early ductus group and 133 of 157 (85%) in the late ductus group (p trend 0.09). The authors call the difference non-significant at the primary endpoint. - Category: Effect - Evidence stage: Interventional - Certainty: Certainty not assessed - Applies to: Recipient: Child; Population: Surviving infants of women with a singleton fetus at 26 to 32 weeks of gestation and very preterm fetal growth restriction (abdominal circumference below the 10th percentile and umbilical artery Doppler pulsatility index above the 95th percentile), assessed at 2 years of age. The mothers were randomly allocated; outcomes are counted in the infants who survived and had known outcome.; Care setting: European multicentre trial; setting type not stated in the abstract; Geography: Europe (countries not named in the abstract); Life stage: Infant follow-up at 2 years of age; mothers were enrolled at 26 to 32 weeks of gestation; Gestational age: 26 weeks 0 days (182 days) to 32 weeks 0 days (224 days), measured at enrolment; Postnatal age: Not reported; Follow-up: Survival without cerebral palsy, neurosensory impairment or a Bayley III developmental score below 85, at 2 years of age - Limitations: The trial was unblinded and in a narrow group (singleton fetuses, 26 to 32 weeks, severe early growth restriction). A comparison among survivors only found more infants free of neuroimpairment when delivery followed late ductus changes (133 of 140, 95%) than when it followed cardiotocography (111 of 131, 85%; p=0.005), but it was accompanied by a non-significant increase in perinatal and infant mortality, and it is not the primary result. The authors say delivery timed by late ductus changes might improve developmental outcomes at 2 years, which is a hypothesis, not a finding. The linked erratum (PMID 26068267) is a short Department of Error notice whose PubMed record carries no text, so what it corrected is not known. Only the abstract was read. A published correction exists; whether it changes this claim is not known. - Last checked: 2026-10-14 - Source problem: a cited source is corrected. Check the sources before relying on this claim. - Sources: 1. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, METHODS, sentence 1, fragment 1 of 2. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. 2. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, METHODS, sentence 1, fragment 2 of 2. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. 3. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, METHODS, sentence 2, fragment 1 of 4. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. 4. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, METHODS, sentence 2, fragment 2 of 4. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. 5. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, METHODS, sentence 2, fragment 3 of 4. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. 6. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, METHODS, sentence 2, fragment 4 of 4. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. 7. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, METHODS, sentence 3, fragment 1 of 2. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. 8. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, METHODS, sentence 3, fragment 2 of 2. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. 9. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, FINDINGS, sentence 1, fragment 1 of 2. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. 10. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, FINDINGS, sentence 3, fragment 1 of 2. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. 11. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, FINDINGS, sentence 3, fragment 2 of 2. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. 12. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, INTERPRETATION, sentence 1, fragment 1 of 3. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. 13. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, INTERPRETATION, sentence 1, fragment 2 of 3. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. 14. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, INTERPRETATION, sentence 1, fragment 3 of 3. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. 15. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, FINDINGS, sentence 5, fragment 1 of 3. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. 16. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, FINDINGS, sentence 5, fragment 2 of 3. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. 17. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, FINDINGS, sentence 5, fragment 3 of 3. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. ## Context: Fetuses and neonates of women with very preterm growth restriction, all women randomly allocated (TRUFFLE) Recipient: Mixed recipients; Population: Fetuses of the 503 women randomly allocated in TRUFFLE (singleton fetus at 26 to 32 weeks with abdominal circumference below the 10th percentile and umbilical artery Doppler pulsatility index above the 95th percentile). Safety outcomes (deaths in utero, a fetal outcome, and neonatal deaths, a newborn outcome) were assessed in all randomly allocated women.; Care setting: European multicentre trial; setting type not stated in the abstract; Geography: Europe (countries not named in the abstract); Life stage: Pregnancy at 26 to 32 weeks of gestation at enrolment; neonatal period; Gestational age: 26 weeks 0 days (182 days) to 32 weeks 0 days (224 days), measured at enrolment; Postnatal age: Not reported; Follow-up: Deaths in utero and neonatal deaths ### Among all randomly allocated women in TRUFFLE, 12 fetuses (2%) died in utero and 27 (6%) neonatal deaths occurred. The authors note that delivery timed by late ductus venosus changes was accompanied by a non-significant increase in perinatal and infant mortality compared with timing by cardiotocography. - Category: Safety - Evidence stage: Interventional - Certainty: Certainty not assessed - Applies to: Recipient: Mixed recipients; Population: Fetuses of the 503 women randomly allocated in TRUFFLE (singleton fetus at 26 to 32 weeks with abdominal circumference below the 10th percentile and umbilical artery Doppler pulsatility index above the 95th percentile). Safety outcomes (deaths in utero, a fetal outcome, and neonatal deaths, a newborn outcome) were assessed in all randomly allocated women.; Care setting: European multicentre trial; setting type not stated in the abstract; Geography: Europe (countries not named in the abstract); Life stage: Pregnancy at 26 to 32 weeks of gestation at enrolment; neonatal period; Gestational age: 26 weeks 0 days (182 days) to 32 weeks 0 days (224 days), measured at enrolment; Postnatal age: Not reported; Follow-up: Deaths in utero and neonatal deaths - Limitations: The abstract gives the totals for all groups together and calls the mortality difference non-significant; it gives no group-by-group counts in the parts read. Safety outcomes were assessed in all randomly allocated women. Only the abstract was read. A published correction exists; whether it changes this claim is not known. - Last checked: 2026-10-14 - Source problem: a cited source is corrected. Check the sources before relying on this claim. - Sources: 1. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, METHODS, sentence 6. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. 2. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, FINDINGS, sentence 4. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. 3. Supports: 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial (Publication, edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read.) Locator: Abstract, FINDINGS, sentence 5, fragment 3 of 3. Retrieved 2026-10-14T18:18:28Z. Source state: Corrected. Snapshot hash: 9d6dd73d9507de5c16f996b3c7557f0b87aafbf0f68e54474481274105191ca2. How it applies: PubMed abstract. ## Connected pages - Women with very preterm fetal growth restriction: Fetal growth restriction (fetus) (`maternal:fetal-growth-restriction`) - Delivery timed by cardiotocography short-term variation is one arm: Electronic fetal heart-rate monitoring (cardiotocography) (`maternal:electronic-fetal-monitoring`) - Delivery timed by ductus venosus Doppler changes is two arms: Pregnancy ultrasound (`maternal:obstetric-ultrasound`) ## Provenance Content hash: 161b8532544afeb5b3b9c6f04671f57bbdcb468023503e2885f5721a630a5b21 Last substantive edit: 2026-10-14 Evidence last checked: 2026-10-14