The current clinical approach to a patent ductus arteriosus (PDA) in the preterm infant is varied and controversial and range from treating prophylactically, treating when mild signs present within a few days after birth or taking an ‘‘expectant’’ approach and allow for possible spontaneous closure, treating at a later time, only when signs indicate haemodynamic significance. This variation in practice is caused by the lack of definitive data on the optimal time to treat for immediate clinical response and long-term complications, such as bronchopulmonary dysplasia and pulmonary hypertension. There are risks and benefits with either approach: early treatment may be beneficial by eliminating both early and later morbidity. However, because a substantial percentage of PDAs will close without therapy, or may remain open without producing significant symptoms, initiating early treatment may expose many infants to unnecessary cyclo-oxygenase inhibitors or surgical ligation, both of which are associated with adverse effects. This situation might be avoided by delaying PDA treatment and allowing for the possibility of spontaneous closure without exposure to these interventions.

This randomised double-blind controlled trial aimed to determine whether ‘‘early’’ ibuprofen treatment, at the onset of subtle PDA symptoms, would improve respiratory outcome in premature infants compared with ‘‘expectant’’ management, with ibuprofen treatment only if and when the PDA became HS (pulmonary haemorrhage, hypotension, respiratory deterioration). The researchers hypothesised that ‘‘early’’ pharmacological treatment of the PDA with ibuprofen would improve respiratory course (as reflected by a reduction in duration of supplemental O2 during the first 28 days) compared with ‘‘expectant’’ PDA treatment.

The study involved infants with gestational ages 23 to 32 weeks and birth weights 500g to 1250g who had echocardiography for subtle PDA symptoms. They were randomised to ‘‘early’’ treatment (blinded ibuprofen; n = 54) or ‘‘expectant management’’ (blinded placebo, n = 51). If the PDA became HS, infants received open label ibuprofen. Respiratory outcomes and mortality and major morbidities were determined.

The following findings were reported:

• ‘‘Early’’ treatment infants received ibuprofen at median age of 3 days; infants in the ‘‘expectant group’’ in whom HS symptoms developed (20%) received ibuprofen at median of 11 days.

• 49% of ‘‘expectant’’ infants never required ibuprofen or ligation.

• No significant differences were found in the primary outcome (days on O2 during first 28 days), death, O2 at 36 weeks, death or O2 at 36 weeks, intestinal perforation, surgical necrotising enterocolitis, grades III and IV intracranial haemorrhage, periventricular leukomalacia, sepsis or retinopathy of prematurity.

The researchers conclude that “taking the strengths and weaknesses in account, the study results suggest a lack of benefit from early PDA treatment at the onset of mild clinical signs compared with delay of PDA treatment until the onset of clear hemodynamic signs. On the basis of these results, plus the finding of a high spontaneous PDA closure rate, delaying therapy until a HS PDA is present could prevent unnecessary and potentially toxic intervention for PDA in critically ill premature infants.”