The systematic review protocol was approved by the Cochrane Neonatal Review Group (CNRG). The selection criteria included studies that were randomized or quasi- randomized clinical trials, and the participants were preterm infants with less than 28 weeks gestation or less than 1000 g at birth who were on assisted ventilation and/or supplemental oxygen without clinical signs of a hemodynamically significant PDA.
The intervention was prophylactic surgical ligation of the PDA (i.e. procedure done during the first 72 hours of life in asymptomatic ELBW infants) versus no prophylactic intervention or medical prophylaxis (cyclooxygenase inhibitors) without dose specification.
The criteria for an asymptomatic or “silent ductus” include echocardiographic demonstration of a left to right shunt across the PDA, presence of a ductal size greater than 1.5 mm, left atrial: Aortic root ratio over 1.3 or end diastolic reversal of aortic blood flow in the absence of clinical signs such as a murmur, bounding pulses, overactive precordium and hemodynamic or respiratory compromise attributable to the PDA. The outcome measures were all causes of neonatal mortality at 36 weeks postmenstrual age and BPD defined as oxygen requirement at 36 weeks postmenstrual age. Other secondary outcomes were IVH; severe grade III-IV, IVH as per Papile criteria,[28
] severe NEC (stage II or more) as per Bell’s criteria[29
] periventricular leukomalacia (PVL) defined as cystic changes in the periventricular area, retinopathy of prematurity (ROP) (defined by ICORP classification, any ROP and severe ROP stage 3 or worse), nosocomial sepsis, defined as positive bacterial blood or cerebrospinal fluid cultures taken beyond five days of age, time to establish full enteral feeds (days), duration of ventilation and supplemental oxygen, duration of hospital stay, neurodevelopment impairment i.e. rates of cerebral palsy, cognitive delay defined as a Mental Development Index score of less than 70 (2 SD below the mean of 100) on the Bayley Scales of Infant Development II,[30
] deafness, blindness or their composite reported at 18 months corrected age or later, pneumothorax and vocal cord palsy.
The following databases were used for identification of studies: OVID MEDLINE-National Library of Medicine (1966 to December 2008) using the following subject headings (MeSH) and text word terms: “Neonate(s), newborn(s), infant(s), PDA, ligation, indomethacin, ibuprofen, cyclooxygenase inhibitors and publication type ‘controlled trial’. No language restrictions were applied. Other databases including EMBASE (1980 to December 2008), the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library, Issue 4, 2008) were searched. Two review authors conducted the electronic database search independently. A manual search of the abstract books published from the Society of Pediatric Research (SPR) and the European Society of Pediatric Research (ESPR) for the period of 1985-2008 was performed. Additional citations were sought using references in articles retrieved from searches. Subject experts were contacted to identify the unpublished and ongoing studies. Two review authors independently screened candidate articles to check the eligibility for inclusion in the review.
Standard methods of Cochrane collaboration and its neonatal group were used to assess the methodological quality (validity criteria) of the trials. For each trial, information was sought regarding the method of randomization, blinding and reporting of all outcomes of all infants enrolled in the trial. Each criteria was assessed as yes, no, can’t tell. Retrieved articles were assessed for eligibility and data abstracted independently by two review authors. Discrepancies were resolved by discussion and consensus.