Jaana Leipälä

Atypical auditory event-related potentials in preterm infants during the first year of life: a possible sign of cognitive dysfunction?

We assessed auditory event-related potentials in small-for-gestational-age (SGA; 850 ± 258 g, 28.9 ± 3.3 gestational wk; n = 15) and appropriate for gestational age (AGA; 1014 ± 231 g, 26.9 ± 1.9 gestational wk; n = 20) preterm infants and healthy term infants (n = 22). An oddball paradigm was used with a harmonic tone of 500-Hz frequency as the standard and of 750-Hz frequency as the deviant stimulus. The preterm infants were studied at 40 gestational wk and at 6 and 12 mo of corrected age, and the control subjects were studied at 2–4 d and at 3, 6, 9, 12, and 15 mo of age. The peaks of interest were the main positive peak (P350), the negative peaks at 250 ms (N250) and 650 ms (Nc), and the mismatch negativity at 200 ms (MMN). At term, the P350 in the preterm infants was similar to that of the newborn control subjects. In response to the deviant, the Nc was smaller in the SGA than in the AGA (P < 0.02) and control (P < 0.005) infants. The N250 amplitude was also lower in the SGA infants. At 12 mo, the MMN was observed in the control but not in the preterm infants, whose broad difference positivity correlated with the Bayley developmental index. The decreased Nc and N250 peaks in the SGA infants may suggest an increased risk for cognitive dysfunction. The broad difference positivity at 1 y of age may indicate atypical cortical auditory processing. Whether cognitive dysfunction can be predicted by these findings needs to be assessed in a study with extended follow-up.

Auditory event-related potentials and cognitive function of preterm children at five years of age

OBJECTIVE In our previous study, auditory event-related potentials (AERPs) in preterm 1-year-old children had a positive deflection at 150-350 ms that correlated positively with their 2-year neurodevelopmental outcome. In a study of the same subjects at age 5, our aim was to assess AERPs and their relationship to neuropsychological test results. METHODS Preterm small (SGA, n=13), appropriate for gestational age (AGA, n=15), and control (n=13) children were assessed with an Easy paradigm presenting a large frequency change accompanied with occasional novel sounds, and a Challenging paradigm presenting small frequency and duration changes with a rapid rate. The preterm children underwent neurocognitive tests. RESULTS Easy paradigm. The P1 response to frequency deviant was smaller and MMN larger in the preterm than in the control children. Challenging paradigm. The P1 response to standard, frequency, and duration deviants was smaller in the preterm than in the control children. The N2 response to frequency deviant was larger in the preterm than in the control children. AGA and SGA children had similar AERPs. The P1, N2, and MMN amplitudes correlated with verbal IQ and NEPSY language subtests. CONCLUSIONS Small P1 response(s) appears to be typical for preterm children. SIGNIFICANCE Small P1 response in preterm children may suggest altered primary auditory processing.

The Effect of Birth in Secondary- or Tertiary-Level Hospitals in Finland on Mortality in Very Preterm Infants: A Birth-Register Study

OBJECTIVE. Our goal was to test the hypothesis that the level of the delivery hospital affects 1-year mortality of very preterm infants in Finland. PATIENTS AND METHODS. This retrospective national medical birth-register study included 2291 very preterm infants (gestational age of <32 weeks at birth or birth weight of ≤1500 g) born in 14 level II (central) and 5 level III (university) hospitals in 2000–2003. The main outcome measures were adjusted total mortality (including stillbirths) and mortality of live-born infants until the age of 1 year. RESULTS. Both the total 1-year mortality and the 1-year mortality of live-born infants were higher in level II hospitals compared with level III hospitals. Total mortality was higher in very preterm infants who were not born during office hours. In theory, delivery of all very preterm infants in level III instead of level II hospitals translates into an annual prevention of 69 of the 170 total deaths and prevention of 18 of the 45 deaths of live-born infants. CONCLUSIONS. Resources in neonatal intensive care should be increased, especially during non–office hours, to have an equally distributed service through the 24-hour day. More efficient regionalization of very preterm deliveries may improve 1-year survival of very preterm infants in Finland.

Cardiac Hypertrophy and Altered Hemodynamic Adaptation in Growth-Restricted Preterm Infants

The objective was to elucidate hemodynamic adaptation in very low birth weight (<1500 g) infants after intrauterine growth retardation. 31 growth-retarded (SGA, birth weight <-2 SD) and 32 appropriate for gestational age (AGA, birth weight within ± 1 SD range) infants were enrolled. In SGA infants, the diastolic diameters of the interventricular septum and the left ventricle were increased, and serum brain natriuretic peptide (BNP) was elevated. Left ventricular output (LVO) of the AGA infants increased from 150 ± 28 to 283 ± 82 mL/kg/min during the study (p < 0.01). The SGA infants had a higher initial LVO than the AGA infants (243 ± 47 versus 150 ± 28 mL/kg/min, p < 0.05), but did not show further LVO increase during the study period. Red cell (RCV) and blood (BV) volume were assessed by Hb subtype analysis, when packed donor red cells were transfused. RCV and BV did not differ between the groups initially, but RCV increased by 18% and BV by 29% in the AGA group during the first 3 d. On day 3, AGA infants had larger BV than the SGA infants (88 ± 5 versus 73 ± 12 mL/kg, p < 0.05). In conclusion, cardiac hypertrophy, elevated initial LVO and BNP of the SGA infants suggest increased cardiac workload after intrauterine growth retardation. Based on the BV and RCV data, blood volume regulation may also be impaired. The data suggest that SGA preterm infants may be exposed to an increased risk of circulatory failure during early adaptation.

Morbidities and Hospital Resource Use During the First 3 Years of Life Among Very Preterm Infants

OBJECTIVE: The objective of this study was to determine how the use of hospital resources during the first 3 years of life was associated with prematurity-related morbidity in very preterm infants (gestational age of <32 weeks or birth weight of <1501 g). METHODS: The study was a retrospective, national register study including all very preterm infants born alive in Finland between 2000 and 2003 (N = 2148). Infants who died before the age of 3 years (n = 264) or who had missing register data (n = 88) were excluded from the study. The relationship between 6 morbidity groups and the need for hospital care during the first 3 years of life was studied by using a negative binomial model. RESULTS: A total of 66.2% of the infants did not have any of the morbidities studied. Infants who were subsequently diagnosed as having cerebral palsy (6.1% of the study group), later obstructive airway disease (20.0%), hearing loss (2.5%), visual disturbances or blindness (3.8%), or other ophthalmologic problems (13.4%) had initial hospital stays that were a mean of 7, 8, 12, 17, and 3 days longer, respectively, than those for infants without these conditions. All morbidity groups were associated with increased numbers of hospital visits during either the second or third year of life, compared with infants without these morbidities. The need for hospitalizations and outpatient hospital care decreased with postnatal age for infants with later morbidities and for infants without later morbidities. CONCLUSIONS: Most very preterm infants born in Finland survived without severe morbidities and required relatively little hospital care after the initial discharge. However, those with later morbidities had a long initial length of stay and more readmissions and outpatient visits during the 3-year follow-up period.

Impact of Very Preterm Birth on Health Care Costs at Five Years of Age

OBJECTIVE: We assessed the effects of very preterm birth (gestational age <32 weeks or birth weight <1501 g) and prematurity-related morbidities on health care costs during the fifth year of life. METHODS: The study population consisted of 588 very preterm children and 176 term control subjects born in 2001–2002. Costs of hospitalizations, visits to health care professionals and therapists, and the use of other social welfare services were assessed during the fifth year of life. Hospital visits were derived from register data and other health care contacts, and the use of social welfare services were derived from parental reports. The effects of 6 prematurity-related morbidities (cerebral palsy [CP], seizure disorder, obstructive airway disease, hearing loss, visual disturbances or blindness, and other ophthalmologic problems) on the costs of health care were studied. RESULTS: The average health care costs during the fifth year of life were 749€ in the term control subjects, 1023€ in the very preterm children without morbidities, and 3265€ in those with morbidities. The costs of social welfare services and therapies exceeded the hospitalization costs in all groups. Among children who were born preterm, CP was associated with 5125€ higher costs, whereas later obstructive airway diseases increased the costs by 819€ compared with individuals without these morbidities. CONCLUSIONS: The health care costs during the fifth year of life in very preterm children with morbidities were 4.4-fold and in those without morbidities 1.4-fold compared with those of term control subjects. This emphasizes the importance of prevention of morbidities, especially CP, to reduce the long-term costs of prematurity.

Health-Related Quality of Life in 5-Year-Old Very Low Birth Weight Infants

OBJECTIVE To investigate the effect of preterm birth, the time of birth, and birth hospital level and district on health-related quality of life (HRQoL) and quality-adjusted life years (QALYs). STUDY DESIGN This national study included all very low birth weight infants (VLBWIs; birth weight <or= 1500 g or gestational age < 32 weeks) born in Finland between 2000 and 2003 (n = 1169; live-born, n = 900) and full-term controls (n = 368). Register data and parental questionnaires were used. The relationships among HRQoL and QALYs at age 5 years and preterm birth, time of birth, and the level and district of the birth hospital were studied. RESULTS HRQoL at age 5 years was lower and 1.3 QALYs were lost in VLBWIs compared with controls. Regional differences in the QALYs of VLBWIs were found among the 5 university hospital districts. Birth hospital level or birth outside office hours had no effect on the QALYs of live-born VLBWIs. The adjusted HRQoL total score was not affected by birth outside office hours or by the birth hospital level or district. CONCLUSIONS Differences in QALYs related to hospital district suggest variation in the care of VLBWIs that needs to be addressed.

Hospital costs and quality of life during 4 years after very preterm birth.

OBJECTIVE To evaluate the effect of gestational age and prematurity-related morbidities on hospital costs and cost per quality-adjusted life-year (QALY) during the first 4 years of life. DESIGN Population-based study using national register data and parental questionnaires. SETTING Finland. PARTICIPANTS All 2064 very preterm children (gestational age <32 weeks or birth weight <1501 g) and all 200 609 full-term control individuals (mean [SD] gestational age, 37 [0] to 41 [6] weeks) born from January 1, 2000, through December 31, 2003. MAIN EXPOSURE Prematurity. MAIN OUTCOME MEASURES Costs of hospital care and cost per QALY at 4 years of age according to gestational age and prematurity-related morbidities. RESULTS By 4 years of age, the cost per QALY for full-term controls (in 2008 currency) was euro1181 (US

Exhaled nitric oxide levels in infants with chronic lung disease

1736). In very preterm children, the average cost per QALY was euro19 245 (

Health and the use of health care services in 5-year-old very-low-birth-weight infants

28 290), ranging from euro11 824 to euro54 324 (