Does paracetamol use to close patent ductus arteriosus in neonates result in adverse neurodevelopmental outcomes?
Date First Published:
August 20, 2023
Last Updated:
June 27, 2024
Report by:
Dr Adam Pearce/Dr Asad Abbas/Dr Lewis Saunders, Clinical teaching Fellow/Consultant Neonatologist/Paediatric Trainee (University Hospital Coventry and Warwickshire)
Three-Part Question:
In [preterm neonates], does the use of [paracetamol for closure of patent ductus arteriosus] result in [adverse neurodevelopmental outcomes]?
Clinical Scenario:
Following a failed extubation on day 3 of life on a neonate born at 25 weeks gestation, an echocardiogram was performed that showed a hemodynamically significant patent ductus arteriosus (PDA). A clinical decision was made to treat the PDA with intravenous paracetamol. A recent review article showed an association between prenatal and neonatal use of paracetamol with adverse neurodevelopmental outcomes. Can this be true for paracetamol use for PDA closure?
Search Strategy:
A literature search was performed via Medline, Ovid Embase, CINAHL
Relevant articles were identified by their abstracts. References and citing articles were identified for each of the articles identified from the initial search.
Relevant articles were identified by their abstracts. References and citing articles were identified for each of the articles identified from the initial search.
Search Details:
("Infant, Newborn" [MeSH] OR "neonate*" [Title/Abstract]) AND ("Paracetamol" [MeSH] OR "Acetaminophen" [Title/Abstract]) AND ("Ductus Arteriosus, Patent/drug therapy" [MeSH] OR "patent ductus arteriosus" [Title/Abstract]) AND ("Neurodevelopmental Disorders" [MeSH] OR "neurodevelopment*" [Title/Abstract] OR "Child Development" [MeSH] OR "Developmental Disabilities" [MeSH])
Outcome:
A total of 7 articles were identified for critical appraisal.
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Neurodevelopmental Outcomes of Preterm Infants Treated with Oral Paracetamol Versus Ibuprofen for Patent Ductus Arteriosus. Oncel MY, Eras Z, Uras N, Canpolat FE, Erdeve O, Oguz SS 2017 Turkey | Neonates born at <= 30 weeks gestation, with a haemodynamically-significant PDA at 48-96 hrs after birth. | Follow-up of randomised controlled trial. Randomised to oral paracetamol or oral ibuprofen for paracetamol closure. At 18-24 months corrected gestational age: Neurodevelopmental outcome using Bayley Scales of Infant Development (BSID II), which includes the Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) Neurodevelopmental impairment (NDI) was diagnosed if either MDI or PDI <70 OR if there was moderate-severe cerebral palsy, OR if there were visual/hearing problems |
Bayley Scales Psychomotor Development Index (PDI) [Paracetamol vs Ibuprofen (Mean), p] | [81.7 vs 81.9, 0.96] | Study was not powered to detect this outcome. Relatively small size and 75% of enrolled neonates evaluated for the outcome due to dropout. Did not evaluate autism spectrum disorder. |
| Bayley Scales Mental Development Index (MDI) [Paracetamol vs Ibuprofen (Mean), p] | [81.7 vs 82.1, 0.92] | ||||
| Neurodevelopmental Impairment (PDI or MDI <0.7 or mod/severe CP or visual/hearing problems [Paracetamol vs Ibuprofen (Mean), p] | [30% vs 32.3%, 0.84] | ||||
| Is late treatment with acetaminophen safe and effective in avoiding surgical ligation among extremely preterm neonates with persistent patent ductus arteriosus? Mashally, S; Banihani, R; Jasani, B; Nield, L; Martins, F; Jain, A; Weisz, D. 27/08/2021 Canada, Brazil | 92 neonates born <28 weeks (ELGANs) with persistent PDA (pPDA) despite COX inhibitor treatment or conservative management. | Is late treatment with acetaminophen safe and effective in avoiding surgical ligation among extremely preterm neonates with persistent patent ductus arteriosus? | Epoch design has a lot of possible confounders. Epoch 2 group significantly more likely to have received magnesium sulphate and delivery room CPAP due to shift in neonatal management. Follow up at 18-24 months likely too early to be able to confidently exclude major concerns for autism spectrum disorder or attention deficit hyperactivity disorder. |
References:
- Oncel MY, Eras Z, Uras N, Canpolat FE, Erdeve O, Oguz SS. Neurodevelopmental Outcomes of Preterm Infants Treated with Oral Paracetamol Versus Ibuprofen for Patent Ductus Arteriosus.
- Mashally, S; Banihani, R; Jasani, B; Nield, L; Martins, F; Jain, A; Weisz, D.. Is late treatment with acetaminophen safe and effective in avoiding surgical ligation among extremely preterm neonates with persistent patent ductus arteriosus?