Growth Outcomes of Preterm Infants Exposed to Different Oxygen Saturation Target Ranges from Birth.

OBJECTIVE: To test whether infants randomized to a lower oxygen saturation (peripheral capillary oxygen saturation [SpO2]) target range while on supplemental oxygen from birth will have better growth velocity from birth to 36 weeks postmenstrual age (PMA) and less growth failure at 36 weeks PMA and 18-22 months corrected age. STUDY DESIGN: We evaluated a subgroup of 810 preterm infants from the Surfactant, Positive Pressure, and Oxygenation Randomized Trial, randomized at birth to lower (85%-89%, n = 402, PMA 26 ± 1 weeks, birth weight 839 ± 186 g) or higher (91%-95%, n = 408, PMA 26 ± 1 weeks, birth weight 840 ± 191 g) SpO2 target ranges. Anthropometric measures were obtained at birth, postnatal days 7, 14, 21, and 28; then at 32 and 36 weeks PMA; and 18-22 months corrected age. Growth velocities were estimated with the exponential method and analyzed with linear mixed models. Poor growth outcome, defined as weight <10th percentile at 36 weeks PMA and 18-22 months corrected age, was compared across the 2 treatment groups by the use of robust Poisson regression. RESULTS: Growth outcomes including growth at 36 weeks PMA and 18-22 months corrected age, as well as growth velocity were similar in the lower and higher SpO2 target groups. CONCLUSION: Targeting different oxygen saturation ranges between 85% and 95% from birth did not impact growth velocity or reduce growth failure in preterm infants.

The effects of aggressive vs. conservative phototherapy on the brainstem auditory evoked responses of extremely-low-birth-weight infants.

INTRODUCTION: This study was a two-center, stratified, parallel-group randomized trial comparing the effects of aggressive vs. conservative phototherapy on brainstem auditory evoked response (BAER) latencies in infants with extremely low birth weight (ELBW, ≤ 1,000 g). RESULTS: BAER latencies of 751-1,000 g birth-weight infants were shorter by 0.37 ms (95% confidence interval (CI) = 0.02, 0.73) for wave V, 0.39 ms (0.08, 0.70) for wave III, and 0.33 ms (0.01, 0.65) for wave I after aggressive phototherapy at one center. Interwave intervals did not differ significantly. Similar nonsignificant trends were recorded for 501-750 g birth-weight infants. At the other participating center, no significant differences were recorded, cautioning against overgeneralizing these results. DISCUSSION: The effects of bilirubin on the auditory pathway in ELBW infants depend on a complex interaction of bilirubin exposure, newborn characteristics, and clinical management. METHODS: Aggressive phototherapy was initiated sooner and continued at lower bilirubin levels than conservative phototherapy. A total of 174 ELBW infants were enrolled in the study; 111 infants were successfully tested at 35 weeks postmenstrual age (PMA); 57 died; and 6 were not successfully tested.

Is phototherapy exposure associated with better or worse outcomes in 501- to 1000-g-birth-weight infants?

AIM: To compare risk-adjusted outcomes at 18- to 22-month-corrected age for extremely low birth weight (ELBW) infants who never received phototherapy (NoPTx) to those who received any phototherapy (PTx) in the NICHD Neonatal Research Network randomized trial of Aggressive vs. Conservative Phototherapy. METHODS: Outcomes at 18 to 22-month-corrected age included death, neurodevelopmental impairment (NDI) and Bayley Scales Mental Developmental Index (MDI). Regression models evaluated the independent association of PTx with adverse outcomes controlling for centre and other potentially confounding variables. RESULTS: Of 1972 infants, 216 were NoPTx and 1756 were PTx. For the entire 501- to 1000-g-BW cohort, PTx was not independently associated with death or NDI (OR 0.85, 95% CI: 0.60-1.20), death or adverse neurodevelopmental endpoints. However, among infants 501-750 g BW, the rate of significant developmental impairment with MDI < 50 was significantly higher for NoPTx (29%) than PTx (12%) (p = 0.004). CONCLUSIONS: Phototherapy did not appear to be independently associated with death or NDI for the overall ELBW group. Whether PTx increases mortality could not be excluded because of bias from deaths before reaching conservative treatment threshold. The higher rate of MDI < 50 in the 501- to 750-g-BW NoPTx group is concerning and consistent with NRN Trial results.

Target ranges of oxygen saturation in extremely preterm infants.

BACKGROUND: Previous studies have suggested that the incidence of retinopathy is lower in preterm infants with exposure to reduced levels of oxygenation than in those exposed to higher levels of oxygenation. However, it is unclear what range of oxygen saturation is appropriate to minimize retinopathy without increasing adverse outcomes. METHODS: We performed a randomized trial with a 2-by-2 factorial design to compare target ranges of oxygen saturation of 85 to 89% or 91 to 95% among 1316 infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. The primary outcome was a composite of severe retinopathy of prematurity (defined as the presence of threshold retinopathy, the need for surgical ophthalmologic intervention, or the use of bevacizumab), death before discharge from the hospital, or both. All infants were also randomly assigned to continuous positive airway pressure or intubation and surfactant. RESULTS: The rates of severe retinopathy or death did not differ significantly between the lower-oxygen-saturation group and the higher-oxygen-saturation group (28.3% and 32.1%, respectively; relative risk with lower oxygen saturation, 0.90; 95% confidence interval [CI], 0.76 to 1.06; P=0.21). Death before discharge occurred more frequently in the lower-oxygen-saturation group (in 19.9% of infants vs. 16.2%; relative risk, 1.27; 95% CI, 1.01 to 1.60; P=0.04), whereas severe retinopathy among survivors occurred less often in this group (8.6% vs. 17.9%; relative risk, 0.52; 95% CI, 0.37 to 0.73; P<0.001). There were no significant differences in the rates of other adverse events. CONCLUSIONS: A lower target range of oxygenation (85 to 89%), as compared with a higher range (91 to 95%), did not significantly decrease the composite outcome of severe retinopathy or death, but it resulted in an increase in mortality and a substantial decrease in severe retinopathy among survivors. The increase in mortality is a major concern, since a lower target range of oxygen saturation is increasingly being advocated to prevent retinopathy of prematurity. (ClinicalTrials.gov number, NCT00233324.)

Aggressive vs. conservative phototherapy for infants with extremely low birth weight.

BACKGROUND: It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less). METHODS: We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments. RESULTS: Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 micromol per liter], P<0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P=0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g. CONCLUSIONS: Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials.gov number, NCT00114543.)

Effects of sample dilution, peroxidase concentration, and chloride ion on the measurement of unbound bilirubin in premature newborns.

OBJECTIVES: To assess the effects of sample dilution, peroxidase concentration, and chloride ion (Cl(-)) on plasma unbound bilirubin (B(f)) measurements made using a commercial peroxidase methodology (UB Analyzer) in a study population of ill, premature newborns. DESIGN AND METHODS: B(f) was measured with a UB Analyzer in 74 samples at the standard 42-fold sample dilution and compared with B(f) measured at a 2-fold sample dilution using a FloPro Analyzer. B(f) was measured at two peroxidase concentrations to determine whether the peroxidase steady state B(f) (B(fss)) measurements were significantly less than the equilibrium B(f) (B(feq)), in which case it was necessary to calculate B(feq) from the two B(fss) measurements. B(f) was also measured before and after adding 100 mmol/L Cl(-) to the UB Analyzer assay buffer. RESULTS: B(feq) at the 42-fold dilution was nearly 10-fold less than but it correlated significantly with B(feq) at the 2-fold dilution (mean 8.2+/-5.2 nmol/L versus 73.5+/-70 nmol/L, respectively, p<0.0001; correlation r=0.6). The two UB Analyzer B(fss) measurements were significantly less than B(feq) in 42 of 74 (57%) samples, and Cl(-) increased B(feq) in 66 of 74 (89%) samples by a mean of 82+/-67%. CONCLUSIONS: B(fss) measured by the UB Analyzer at the standard 42-fold sample dilution using assay buffer without Cl(-) and a single peroxidase concentration is significantly less than the B(feq) in undiluted plasma. Accurate B(f) measurements can be made only in minimally diluted serum or plasma.

Do former preterm infants remember and respond to neonatal intensive care unit noise?

BACKGROUND: Previous studies have shown that 4-month-old infants have a decrease in heart rate, a component of the orienting reflex, in response to interesting auditory stimuli and an increase in heart rate to aversive auditory stimuli. OBJECTIVE: To compare the heart rate responses of former preterm and term infants at 4-5 months corrected age to a recording of NICU noises. METHODS: 13 former preterm infants and 17 full-term infants were presented NICU noise and another noise of similar level and frequency content in random order. Heart rate 10s prior to the stimulus and for 20s during the stimulus was analyzed. Group differences in second by second heart rate changes in response to the two noise stimuli were compared by analysis of covariance. RESULTS: Both the preterm and term newborns responded similarly to the NICU noise and the control noise. The preterm infants did not alter their heart rate in response to either stimulus. In contrast, the term infants displayed an orienting response to the second stimulus presented regardless of whether it was the NICU or control noise. CONCLUSIONS: Former preterm infants at 4-5 months corrected age have reduced responsiveness to auditory stimulation in comparison to 4- to 5-month-old term infants. Furthermore, they did not respond to the NICU noise as an aversive stimulus.

Rehospitalization of extremely low birth weight (ELBW) infants: are there racial/ethnic disparities?

BACKGROUND: Premature infants are at increased risk for rehospitalization after discharge from the hospital. Racial disparities are known to exist in pediatric health care. OBJECTIVE: To evaluate whether racial disparities exist in the proportion of extremely low birth weight (ELBW) infants rehospitalized prior to 18 months corrected age and the causes of rehospitalization. METHODS: The National Institute of Child Health and Human Development Neonatal Research Network database was used to identify all ELBW infants (n=2446) who were born between November 1, 1998 and May 31, 2000 at the 14 participating centers and discharged alive (n=1591). Infants were seen at 18-22 months corrected age for followup. Data related to maternal variables, race, socioeconomic status, medical morbidities, insurance, and rehospitalizations were recorded from the medical record and parent interview. Logistic regression analyses were used to examine the relationship of race/ethnicity and rehospitalization while controlling for gestational age, gender, center, maternal education, family income, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis, ventriculoperitoneal (VP) shunt, respiratory syncytial virus (RSV) prophylaxis, and insurance type. RESULTS: In all, 1405 (88%) infants were evaluated at followup. The racial distribution of infants admitted, discharged, seen at followup, and rehospitalized were similar. Rehospitalization occurred at least once in 49% of the infants. In the logistic regression analyses, race was not a significant predictor for rehospitalization. The odds of rehospitalization were related to low family income, type of insurance, BPD, VP shunt, RSV prophylaxis, and center. CONCLUSION: Race was not a predominant variable in the risk of rehospitalization in this cohort of ELBW infants. Medical morbidities and low family income appear to be the major risk factors for rehospitalization.

Sterile water gastric drip in extremely low birthweight premature infants: a randomized trial.

This study was performed to test the hypothesis that sterile water gavage drip (SWGD) used in the fluid management of extremely low birthweight (ELBW) infants will decrease the incidence of hypernatremia. Secondary hypotheses included decreased hyperkalemia, hyperglycemia, and hyperbilirubinemia. Sixty ELBW infants were randomized before 36 hours of age to receive SWGD (up to 30 mL/kg/d) and intravenous fluid or conventional intravenous fluid management. SWGD was well tolerated in 89% of the infants. No difference was seen in the incidence of hypernatremia, hyperkalemia, hyperglycemia, or hyperbilirubinemia. A significant reduction in the incidence of treated patent ductus arteriosus (PDA) was noted in the study group (36% versus 69%; relative risk, 0.52; 95% confidence interval, 0.30 to 0.90; p = 0.02). SWGD may provide an alternative means of safely administering free water to the ELBW infant. The observed reduction in treated PDA requires further investigation.

Extremely low birthweight neonates with protracted ventilation: mortality and 18-month neurodevelopmental outcomes.

OBJECTIVE: To compare duration of ventilation to mortality and adverse neurodevelopmental outcomes among extremely low birth weight (ELBW; 501-1000 g) infants. STUDY DESIGN: Retrospective analysis of prospectively collected data from 5364 infants with a birthweight of 501 to 1000 g born at National Institute of Child Health and Human Development (NICHD) Neonatal Research Network centers from 1995 to 1998. The main outcome measures were: survival, duration of mechanical ventilation, and neurodevelopmental outcome. RESULTS: Overall survival was 71%. The median duration of ventilation for survivors was 23 days; 75% were free of mechanical ventilation by 39 days, and 7% were ventilated for > or = 60 days. Of those ventilated for > or = 60 days, 24% survived without impairment. Of those ventilated for > or = 90 days, only 7% survived without impairment. Of those ventilated > or = 120 days, all survivors were impaired. CONCLUSIONS: The prognosis for ELBW with protracted ventilation remains grim. The cohort who remain intubated have diminished survival and high rates of impairment. Parents of these infants should be informed of changes in prognosis as the time of ventilation increases.

Patterns of physical and neurologic development in preterm children.

OBJECTIVE: To evaluate the influence of medical complications, gestational age, gender, ethnicity, and socioeconomic status on the changes in anthropometric measures and severity of neurologic impairment from 6 to 54 months of age in premature and term infants. STUDY DESIGN: This study was a prospective longitudinal study to determine predictors of patterns of growth and neurologic outcome in low-risk (n=137) and high-risk (n=96) preterm infants compared to full-term infants (n=136). Growth modeling analyses were used to evaluate factors that might influence patterns of physical growth and changes in neurologic status. RESULTS: Medical risk level was a predictor of height and head circumference at 30 months and neurologic outcome. Gender was a predictor of weight gain. Medical risk level and gender predicted 13.8% and 32% of the variance in head circumference and neurologic scores, respectively. CONCLUSION: Medical complications after birth and gender are stronger influences than gestational age on patterns of growth and neurologic outcome.