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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.
("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])

Search Outcome

A total of 7 articles were identified for critical appraisal.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
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]

References

1. 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. American Journal of Perinatology April 10, 2017; pp.1185-1189
2. 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? Journal of Perinatology Journal of Perinatology (2021) 41:2519-2525