Chronic physiologic instability is associated with neurodevelopmental morbidity at one and two years in extremely premature infants.
OBJECTIVE
The objective of this study was to evaluate the relationships between chronic physiologic instability, as assessed by the cumulative daily Score for Neonatal Acute Physiology (SNAP), and neurodevelopmental morbidity in premature infants at 1 year and at 2 to 3 years of age.


METHODS
The subjects of this retrospective study were extremely premature (</=30 weeks' gestational age [GA]) infants born in 1993 and 1994 who were seen in follow-up at least once between 1 and 3 years of age. Cumulative daily SNAP scores were calculated over the entire neonatal intensive care unit course for 96 infants (mean GA, 27.3 +/- 1.6 weeks; mean birth weight, 1065 +/- 270 g). The Mental and Psychomotor Developmental (MDI and PDI) of the Bayley Scales of Infant Development (II) were administered at 1 year and at 2 to 3 years of age; the Receptive-Expressive Emergent Language Scale (REEL) was administered at 2 to 3 years of age. To compare the most stable infants with the most unstable infants, the subjects were divided into three quartile groups based on their cumulative SNAP scores (<25th percentile, 25 to 75th percentile, and >75th percentile). MDI, PDI, and REEL scores were compared for the three groups using analysis of variance. To evaluate the relative contributions of physiologic stability, intracranial abnormalities, GA, and early postnatal nutritional intakes, multiple regression analyses were performed using cumulative SNAP score, an intraventricular hemorrhage (IVH) score (incorporating IVH and periventricular leukomalacia), GA, and a weight-change score for the first month as independent variables, and MDI, PDI, and REEL quotients as dependent variables. Regression analyses were repeated, with cumulative SNAP subscores for oxygenation, hypotension, acidosis, and hypoxia/ischemia included with IVH score, GA, and first month weight z score change as independent variables, and MDI, PDI, and REEL quotients as dependent variables.


RESULTS
The infants with the highest degree of physiologic instability (cumulative SNAP scores greater than the 75th percentile) had significantly lower MDI scores at 1 year of age and lower PDI scores at 1 year and at 2 to 3 years of age than did infants who were more physiologically stable. Sixty-seven percent of infants with cumulative SNAP scores greater than the 75th percentile had neurodevelopmental abnormalities at 2 to 3 years of age (cerebral palsy or delayed mental, motor, or language development). Using multiple regression analyses, higher cumulative SNAP scores, IVH scores, and GA were associated with lower 1-year MDI scores. Higher cumulative SNAP scores and IVH scores were associated with lower 1-year PDI scores. By 2 years, only higher cumulative SNAP scores were significantly associated with lower MDI and PDI scores. With respect to language development, only lower weight-change scores over the first month were significantly associated with poorer receptive language development. Lower weight-change scores over the first month and higher hypotension scores were significantly associated with poorer expressive language development. In the secondary regression analyses, higher IVH score, higher cumulative oxygenation scores, and higher hypoxia/ischemia scores all were significantly associated with lower 1-year MDI scores. By 2 to 3 years of age, only higher oxygenation scores were significantly associated with lower MDI scores.


CONCLUSIONS
Prolonged physiologic instability was associated with deleterious neurodevelopmental consequences for extremely premature infants through 2 to 3 years of age, independent of effects of intracranial abnormalities and GA.
Mattia
F R
FR
Division of Neonatology, Department of Pediatrics, University of Minnesota and Children's Hospitals and Clinics-St Paul, St Paul, Minnesota, USA.
deRegnier
R A
RA
D000704:Analysis of Variance; D001835:Body Weight; D002547:Cerebral Palsy / Q000175:diagnosis / Q000453:epidemiology; D016009:Chi-Square Distribution; D002908:Chronic Disease; D005500:Follow-Up Studies; D006801:Humans; D007230:Infant, Low Birth Weight / Q000502:physiology; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology*; D007235:Infant, Premature, Diseases / Q000145:classification* / Q000453:epidemiology*; D008991:Monitoring, Physiologic; D009420:Nervous System / Q000254:growth & development*; D009422:Nervous System Diseases / Q000145:classification* / Q000453:epidemiology*; D010100:Oxygen / Q000097:blood; D012044:Regression Analysis; D012189:Retrospective Studies; D012720:Severity of Illness Index
D010100:Oxygen