Erythropoietin improves neurodevelopmental outcome of extremely preterm infants.

OBJECTIVE: Erythropoietin has been reported to possess neuroprotective properties in animal studies. No previous studies have investigated the neurodevelopmental outcome of extremely low birth weight (ELBW) infants treated with recombinant human erythropoietin (rEpo) and evaluated it at school age. METHODS: Of 200 ELBW infants treated from 1993 to 1998, 171 (86%) survived, and 148 (87%) were followed up to the age of 10 to 13 years. The neurodevelopmental and school outcome of the ELBW infants receiving rEpo treatment for stimulation of erythropoiesis in the first weeks of life (n = 89) was compared to that of untreated children (n = 57). To test for a neuroprotective effect of erythropoietin therapy, analyses of variance (ANOVAs) were conducted with erythropoietin treatment and intraventricular hemorrhage (IVH) as independent variables and Hamburg-Wechsler Intelligence Test for Children-III (HAWIK-III) intelligence quotient (IQ) scores as dependent variables. RESULTS: The rEpo group scored significantly better than untreated children in the overall developmental assessment (55% vs 39% normally developed, p < 0.05) as well as in the psychological examination (mean composite HAWIK-III IQ score, 90.8 vs 81.3, p < 0.005). The results of ANOVAs show that these differences were ascribable to children with IVH. Whereas those children with IVH treated with rEpo scored significantly better than untreated children (52% vs 6% normally developed, composite HAWIK-III IQ score, 90.3 vs 67.0), treated and untreated children without IVH did not differ in their outcome. The treatment and control groups were comparable in perinatal parameters relevant to prognosis. INTERPRETATION: The results of our observational study confirm the hypothesis of a neuroprotective effect of rEpo in ELBW infants with IVH. This offers a promising preventative therapeutic option for the treatment of these high-risk infants.

Outcome of extremely low birth weight survivors at school age: the influence of perinatal parameters on neurodevelopment.

Extremely low birth weight (ELBW) is associated with impaired neurodevelopmental outcome in infancy. Information on the long-term cognitive and neurological consequences of ELBW is scarce. We aimed to identify the perinatal and neonatal factors of ELBW infants associated with adverse cognitive and neurological outcome at school age. A regional cohort of 135 ELBW infants born between 1993 and 1998 was prospectively evaluated at 3, 6, 12, and 18 months postmenstrual age and at yearly intervals up to age 10 years. The comprehensive follow-up programme for high-risk infants included neurological examinations and psychometric evaluations. According to the overall results of these tests, children were classified as either being normal or having minor or major impairment. At a mean age of 8.4 (SD: 1.6) years, 43% of children had survived without any impairment. Minor impairment was diagnosed in 39% and major impairment in 18% of assessed children. The proportion of disabled school children rose with decreasing gestational age. The following neonatal complications were significant risk factors for developing major or minor impairment at school age: an increase in head circumference < 6 mm per week (OR 4.0, 95% CI: 1.1-14.8), parenteral nutrition > or = 6 weeks (OR 2.5, 95% CI: 1.1-6.0), and mechanical ventilation > 14 days (OR 2.3, 95% CI: 1.0-5.1). High-grade intraventricular haemorrhage (IVH) and/or PVL (OR 13.3, 95% CI: 4.0-44.9), neonatal seizures (OR 5.2, 95% CI: 1.2-22.4) and bowel perforation, and/or necrotizing enterocolitis (OR 4.4, 95% CI: 1.1-17.0) were significant risk factors for developing major impairment. In spite of the relatively large proportion of normal children, ELBW remains an important risk factor for neurodevelopmental impairment at school age. Thus, measures to prevent complications such as necrotizing enterocolitis, cerebral haemorrhage, and undernutrition remain important goals for neonatal intensive care.

Neurodevelopmental outcome in extremely low birth weight infants: what is the minimum age for reliable developmental prognosis?

AIM: We present a longitudinal study on the neurodevelopmental outcome in preterm infants with extremely low birth weight <1000 g (ELBW) to answer the question at which age a developmental prognosis can be given. METHODS: A group of 129 ELBW, median birth weight: 794 g (SD 123 g), gestational age: 27.0 weeks (SD 2.0 weeks), born between 1993 and 1998, were followed up to the age between 6 and 10 years (mean 8.5 years [SD 1.7 years]) and evaluated by neurodevelopmental and psychometric tests. The status of children without cerebral palsy was ranked into categories of major, minor and no developmental impairments. RESULTS: At the time of the last follow-up examination 17% of the children showed a major impairment including 9% cerebral palsy, 42% a minor impairment and 41% were normally developed. The longitudinal analysis of cases without cerebral palsy reveals that an assessment 'at term' can only give the correct developmental prognosis in 49% of the cases. At the corrected age of 12 months the prognosis is correct in 59% of the cases, whereas at the corrected age of 3 years 70% proves to be right. Diagnosis of cerebral palsy could be confirmed at the corrected age of 2 years with sufficient reliability. CONCLUSION: The neurodevelopmental evaluation of former preterm infants with a birth weight <1000 g demands a follow-up period of at least 6 years in order to make reliable statements. We are doubtful that follow-up testing completed prior to this age can yield reliable results.