{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:30:36Z","timestamp":1786354236522,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: Prostaglandin E2 (PGE2) suppresses perinatal breathing. Reducing antenatal PGE2 concentrations with paracetamol could stimulate spontaneous breathing in premature infants at birth. We aimed to assess feasibility and potential effects of antenatal paracetamol. Methods: In this randomised, placebo-controlled, triple-blind feasibility trial, pregnant women &lt;31 weeks\u2019 gestation were randomised to receive either intravenous paracetamol (intervention) or placebo (control). Multiple pregnancies were also eligible, and the number of infants could exceed the number of enrolled women. The primary outcome was feasibility of administering study medication within 30\u2013120 min prior to birth. Secondary exploratory outcomes included measures of breathing and other physiological parameters of infants during the first 1\u201310 min after birth and were compared between infants from mothers who received paracetamol and infants from mothers who received a placebo irrespective of timing of administration. Planned enrolment was 40 women. Results: The trial enrolled 23 women before termination due to low recruitment. Five women did not receive study medication, while 18 did (9 per group). Overall, 11 of the 23 enrolled women (48%) received study medication within the specified timeframe. The nine women in the intervention group gave birth to 13 infants, while the nine women in the control group gave birth to 12 infants. Among infants, average minute volume did not differ significantly between groups (intervention (n = 13) vs. control (n = 12); mean \u00b1 SEM; 147 \u00b1 12 vs. 114 \u00b1 14 mL\/kg\/min, p = 0.093). However, the intervention group had a significantly higher area under the curve for minute volume, greater inspiratory drive, and a higher heart rate (1120 \u00b1 410 vs. 707 \u00b1 346 mL\/kg, p = 0.020; 11.8 \u00b1 1.0 vs. 8.4 \u00b1 1.3 mL\/kg\/breath\/s, p = 0.046; 137 \u00b1 5 vs. 121 \u00b1 5 beats\/min, p = 0.037). Conclusions: Antenatal paracetamol administration 30\u2013120 min prior to birth was feasible in only half of the women, below the pre-specified threshold of 80%, but the exploratory findings suggest that it may improve the breathing effort of premature infants.<\/jats:p>","DOI":"10.3390\/children13081061","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T08:08:53Z","timestamp":1786349333000},"page":"1061","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effect of Antenatal Paracetamol on Breathing Effort of Premature Infants at Birth: A Feasibility Trial"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8987-3323","authenticated-orcid":false,"given":"Timothy J. R.","family":"Panneflek","sequence":"first","affiliation":[{"name":"Division of Neonatology, Department of Paediatrics, Willem-Alexander Children\u2019s Hospital, Leiden University Medical Centre, 2333 ZA\u00a0Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6710-3587","authenticated-orcid":false,"given":"Janneke","family":"Dekker","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Paediatrics, Willem-Alexander Children\u2019s Hospital, Leiden University Medical Centre, 2333 ZA\u00a0Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristel L. A. M.","family":"Kuypers","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Paediatrics, Willem-Alexander Children\u2019s Hospital, Leiden University Medical Centre, 2333 ZA\u00a0Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas P.","family":"Derleth","sequence":"additional","affiliation":[{"name":"Department of Paediatric and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN\u00a055905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme R.","family":"Polglase","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC\u00a03168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Melbourne, VIC\u00a03168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotte E.","family":"van der Meeren","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical Centre, 2333 ZA\u00a0Leiden, The Netherlands"},{"name":"Department of Pathology, Erasmus Medical Centre, 3000 CA\u00a0Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merlijn","family":"Wind","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Leiden University Medical Centre, 2333 ZA\u00a0Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remco","family":"Visser","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Paediatrics, Willem-Alexander Children\u2019s Hospital, Leiden University Medical Centre, 2333 ZA\u00a0Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart B.","family":"Hooper","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC\u00a03168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Melbourne, VIC\u00a03168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"van den Akker","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Leiden University Medical Centre, 2333 ZA\u00a0Leiden, The Netherlands"},{"name":"Athena Institute, VU University, 1081 HV\u00a0Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjan B.","family":"te Pas","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Paediatrics, Willem-Alexander Children\u2019s Hospital, Leiden University Medical Centre, 2333 ZA\u00a0Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/s41390-019-0468-7","article-title":"Stimulating and maintaining spontaneous breathing during transition of preterm infants","volume":"90","author":"Dekker","year":"2021","journal-title":"Pediatr. 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