Korean J Pediatr 2010;53(6):694-700 • DOI: 10.3345/kjp.2010.53.6.694 695 Introduction With advances in perinatal and neonatal intensive care, the survival rate of extremely low birthweight (ELBW) infants has increased remarkably. The estimated survival rate of ELBW infants was higher than 70% in Japan, America and other countries in early 20001-3), and 62.4% in Korea and 89% in Severance Hospital in 20071). The long term quality of life in ELBW infants therefore needs much consideration; survivors remain at high risk of late death and neurodevelopmental impairments, such as cerebral palsy (CP), cognitive delay, deafness and blindness4-6). However, predicting the long term outcome of ELBW infants is still difficult7, 8). Current risk scoring systems such as the Score for Neonatal Acute Physiology (SNAP) and Clinical Risk Index for Babies (CRIP)9-12) are limited during the first few days and weeks after birth because their predictability is compounded by the ongoing influence of neonatal morbidities and adverse events due to prolonged hospitalization8,13). Bronchopulmonary dysplasia (BPD) is one of the major neonatal morbidities which have an impact on poor outcome, such as cerebral palsy, blindness and late death14,15). Severe intraventricular hemorrhage (IVH), extensive periventricular leukomalasia (PVL), and posthemorrhagic hydrocephalus requiring shunt insertion are also related to poor cognitive outcomes15,16). Retinopathy of prematurity (ROP) is associated with later visual impairment17). Additionally, recent reports have mentioned the association between undernutrition during brain growth and neurodevelopmental outcome18,19). Since most ELBW infants are affected with several morbidities in the same period7, 8), it may not be possible to predict poor long term outcomes from individual neonatal morbidities. So Schmidt et al.7) made attempts to predict long term outcomes by the combination of 3 neonatal morbidities. They reported that 3 neonatal morbidities (severe BPD, severe brain injury and severe ROP) are individually or collectively correlated with poor outcomes such as late death or survival with CP, delayed development, hearing loss, and blindness at 18 months of corrected age. They showed that the higher the morbidity count, the higher the risk of poor outcome. Consequently they were able to establish a simple logistic model that predicts poor outcome using the morbidity count. Bassler et al.8) went on to report the mediated effects of neonatal infection on this logistic model. This model suggested by Schmidt et al.7) is unique in that it applies a combination of neonatal morbidities to long term prognosis prediction. Such analysis has yet to be reported in Korea. In our study, severe parenteral nutrition associated cholestasis (PNAC) that reflects undernutrition was added to the three major neonatal morbidities. We undertook this study to examine the individual and combined prognostic impact of severe BPD, severe brain injury, severe ROP, and severe PNAC on the long term outcome of ELBW infants hospitalized at the Severance Neonatal Intensive Care Unit (NICU). Materials and methods 1. Subjects Two hundred and seventy-two ELBW infants weighing less than 1,000 g were hospitalized at the NCIU of Severance Children’s Hospital, Yonsei University College of Medicine between January 1, 1997 and December 31, 2007. The medical records of 111 patients surviving longer than a postmenstrual age of 36 weeks were examined retrospectively. Of these, follow-up observation records were available for 80 patients. These 80 patients were enrolled in the study. 2. Methods 1) Examination of neonatal morbidities The neonatal morbidities of ELBW infants were examined by dividing them to 4 categories: (1) BPD more than moderate severity, (2) severe brain injury such as PVL or IVH higher than grade 3, (3) severe ROP, and (4) severe PNAC. BPD was defined as the need for supplemental oxygen at a postmenstrual age of 36 weeks. According to severity based classification20), severe BPD was defined as requiring either 28 days of supplemental oxygen therapy with more than 30% oxygen, or nasal continuous positive airway pressure (CPAP) or positive pressure ventilation at 36 weeks’ postmenstrual age or discharge, whichever came first, in infants whose gestational age was younger than 32 weeks, or at 56 days’ postnatal age or discharge, whichever came first, in infants whose gestational age was older than 32 weeks. Severe brain injury was defined as confirmed PVL by brain magnetic resonance imaging (cases only suspected by brain ultrasonography were excluded). Cases with IVH higher than grade 3 confirmed by brain ultrasonography or brain magnetic resonance imaging were included. ROP was diagnosed and classified according to the International Classification of Acute Retinopathy of Prematurity (ICROP)21). ROP cases showing the plus sign or those which underwent surgical treatment such as cryotherapy or laser photocoagulation were defined as severe ROP. Severe PNAC was defined as cholestasis development secondary to total parenteral nutrition, with a direct bilirubin value higher than 5.0 mg/dL and persistent for longer than one month, in association with increased liver enzyme values (>70 IU/L).