Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low-birth-weight infants

11 March 2015, Updat­ed Chocrane review



In preterm new­borns, the duc­tus arte­rio­sus fre­quent­ly fails to close and the infants require med­ical or sur­gi­cal clo­sure of the patent duc­tus arte­rio­sus (PDA). A PDA can be treat­ed sur­gi­cal­ly or med­ical­ly with one of two prostaglandin inhibitors, indomethacin or ibupro­fen. Case reports sug­gest that parac­eta­mol may be an alter­na­tive for the clo­sure of a PDA. Con­cerns have been raised that in neona­tal mice parac­eta­mol may cause adverse effects on the devel­op­ing brain, and an asso­ci­a­tion between pre­na­tal expo­sure to parac­eta­mol and lat­er devel­op­ment of autism or autism spec­trum dis­or­der has been report­ed.


To deter­mine the effi­ca­cy and safe­ty of intra­venous or oral parac­eta­mol com­pared with place­bo or no inter­ven­tion, intra­venous indomethacin, intra­venous or oral ibupro­fen, or with oth­er cyclo-oxy­ge­nase inhibitors for clo­sure of a PDA in preterm or low-birth-weight infants.

Authors’ con­clu­sions

Although a lim­it­ed num­ber of infants with a PDA have been stud­ied in ran­domised tri­als of low to mod­er­ate qual­i­ty accord­ing to GRADE, oral parac­eta­mol appears to be as effec­tive in clos­ing a PDA as oral ibupro­fen. In view of a recent report in mice of adverse effects on the devel­op­ing brain from parac­eta­mol, and anoth­er report of an asso­ci­a­tion between pre­na­tal parac­eta­mol and the devel­op­ment of autism or autism spec­trum dis­or­der in child­hood, long-term fol­low-up to at least 18 to 24 months post­na­tal age must be incor­po­rat­ed in any stud­ies of parac­eta­mol in the new­born pop­u­la­tion. Such tri­als are required before any rec­om­men­da­tions for the use of parac­eta­mol in the new­born pop­u­la­tion can be made.