Multivariable Predictive Models of Death or Neurodevelopmental Impairment Among Extremely Low Birth Weight Infants Using Heart Rate Characteristics.

OBJECTIVE: We hypothesized that a cumulative heart rate characteristics (HRC) index in real-time throughout the neonatal intensive care unit (NICU) hospitalization, alone or combined with birth demographics and clinical characteristics, can predict a composite outcome of death or neurodevelopmental impairment (NDI). STUDY DESIGN: We performed a retrospective analysis using data from extremely low birth weight infants who were monitored for HRC during neonatal intensive care. Surviving infants were assessed for NDI at 18-22 months of age. Multivariable predictive modeling of subsequent death or NDI using logistic regression, cross-validation with repeats, and step-wise feature elimination was performed each postnatal day through day 60. RESULTS: Among the 598 study participants, infants with the composite outcome of death or moderate-to-severe NDI had higher mean HRC scores during their stay in the NICU (3.1 ± 1.8 vs 1.3 ± 0.8; P < .001). Predictive models for subsequent death or NDI were consistently higher when the cumulative mean HRC score was included as a predictor variable. A parsimonious model including birth weight, sex, ventilatory status, and cumulative mean HRC score had a cross-validated receiver-operator characteristic curve as high as 0.84 on days 4, 5, 6, and 8 and as low as 0.78 on days 50-52 and 56-58 to predict subsequent death or NDI. CONCLUSIONS: In extremely low birth weight infants, higher mean HRC scores throughout their stay in the NICU were associated with a higher risk of the composite outcome of death or NDI. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00307333.

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.

High Flow Nasal Cannula Use Is Associated with Increased Morbidity and Length of Hospitalization in Extremely Low Birth Weight Infants.

OBJECTIVE: To determine differences in the incidence of bronchopulmonary dysplasia (BPD) or death in extremely low birth weight infants managed on high flow nasal cannula (HFNC) vs continuous positive airway pressure (CPAP). STUDY DESIGN: This is a retrospective data analysis from the Alere Neonatal Database for infants born between January 2008 and July 2013, weighing ≤1000 g at birth, and received HFNC or CPAP. Baseline demographics, clinical characteristics, and neonatal outcomes were compared between the infants who received CPAP and HFNC, or HFNC ± CPAP. Multivariable regression analysis was performed to control for the variables that differ in bivariate analysis. RESULTS: A total of 2487 infants met the inclusion criteria (941 CPAP group, 333 HFNC group, and 1546 HFNC ± CPAP group). The primary outcome of BPD or death was significantly higher in the HFNC group (56.8%) compared with the CPAP group (50.4%, P < .05). Similarly, adjusted odds of developing BPD or death was greater in the HFNC ± CPAP group compared with the CPAP group (OR 1.085, 95% CI 1.035-1.137, P = .001). The number of ventilator days, postnatal steroid use, days to room air, days to initiate or reach full oral feeds, and length of hospitalization were significantly higher in the HFNC and HFNC ± CPAP groups compared with the CPAP group. CONCLUSIONS: In this retrospective study, use of HFNC in extremely low birth weight infants is associated with a higher risk of death or BPD, increased respiratory morbidities, delayed oral feeding, and prolonged hospitalization. A large clinical trial is needed to evaluate long-term safety and efficacy of HFNC in preterm infants.

Death or neurodevelopmental impairment at 18 to 22 months corrected age in a randomized trial of early dexamethasone to prevent death or chronic lung disease in extremely low birth weight infants.

OBJECTIVE: To evaluate the incidence of death or neurodevelopmental impairment (NDI) at 18-22 months corrected age in subjects enrolled in a trial of early dexamethasone treatment to prevent death or chronic lung disease in extremely low birth weight infants. STUDY DESIGN: Evaluation of infants at 18-22 months corrected age included anthropomorphic measurements, a standard neurological examination, and the Bayley Scales of Infant Development-II, including the Mental Developmental Index and the Psychomotor Developmental Index. NDI was defined as moderate or severe cerebral palsy, Mental Developmental Index or Psychomotor Developmental Index <70, blindness, or hearing impairment. RESULTS: Death or NDI at 18-22 months corrected age was similar in the dexamethasone and placebo groups (65% vs 66%, P = .99 among those with known outcome). The proportion of survivors with NDI was also similar, as were mean values for weight, length, and head circumference and the proportion of infants with poor growth (50% vs 41%, P = .42 for weight less than 10th percentile); 49% of infants in the placebo group received treatment with corticosteroid compared with 32% in the dexamethasone group (P = .02). CONCLUSION: The risk of death or NDI and rate of poor growth were high but similar in the dexamethasone and placebo groups. The lack of a discernible effect of early dexamethasone on neurodevelopmental outcome may be due to frequent clinical corticosteroid use in the placebo group.

Quality of life at age 18 years after extremely preterm birth in the post-surfactant era.

OBJECTIVES: To assess the self-reported quality of life, health status, self-esteem, and functional outcomes at age 18 years of extremely preterm (EP; <28 weeks gestation) or extremely low birth weight (ELBW; birth weight <1000 g) adolescents born in 1991-1992 compared with normal birth weight (birth weight >2499 g) controls, and, within the EP/ELBW cohort, to assess whether these outcomes are related to gestational age or birth weight. STUDY DESIGN: Self-reported measures of quality of life, health status, self-esteem, and functional outcomes were obtained at age 18 years from a geographic cohort of all survivors born EP/ELBW in 1991-1992 in the state of Victoria, Australia, along with matched normal birth weight controls. RESULTS: Data were available from 194 EP/ELBW and 148 control adolescents. EP/ELBW adolescents reported similar overall quality of life, health status, and self-esteem as controls (P > .05). Birth at younger gestational age or lower birth weight were not related to poorer quality of life within the EP/ELBW cohort (P > .05). EP/ELBW adolescents reported less physical activity (OR, 0.5; 95% CI, 0.3-0.8; P < .01), sexual activity (OR, 0.6; 95% CI, 0.4-0.9; P = .01), and alcohol intake (OR, 0.5; 95% CI, 0.3-0.8; P = .01) compared with controls. Other aspects of risk-taking behavior were similar in the 2 groups (P > .05). CONCLUSION: EP/ELBW individuals born after the introduction of exogenous surfactant are transitioning well into young adulthood, despite the fact that more of the tiniest and most immature infants survive than ever before. They report similar quality of life, self-esteem, and social and risk-taking behaviors as controls.

Neurodevelopmental outcome of extremely low birth weight infants with Candida infection.

OBJECTIVE: Candida remains an important cause of late-onset infection in preterm infants. Mortality and neurodevelopmental outcome of extremely low birth weight (ELBW) infants enrolled in the Candida study were evaluated based on infection status. STUDY DESIGN: ELBW infants born at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) centers between March 2004 and July 2007 who were screened for suspected sepsis were eligible for inclusion in the Candida study. Primary outcome data for neurodevelopmental impairment (NDI) or death were available for 1317 of the 1515 infants (87%) enrolled in the Candida study. The Bayley Scales of Infant Development-II or -III was administered at 18 months' adjusted age. A secondary comparison was performed with 864 infants enrolled in the NRN Generic Database during the same cohort who were never screened for sepsis and therefore not eligible for the Candida study. RESULTS: Among ELBW infants enrolled in the Candida study, 31% with Candida and 31% with late-onset non-Candida sepsis had NDI at 18 months. Infants with Candida sepsis and/or meningitis had an increased risk of death and were more likely to have the composite outcome of death and/or NDI compared with uninfected infants in adjusted analysis. Compared with infants in the NRN registry never screened for sepsis, overall risk for death were similar but those with Candida infection were more likely to have NDI (OR 1.83, 95% CI 1.01-3.33, P = .047). CONCLUSIONS: In this cohort of ELBW infants, those with infection and/or meningitis were at increased risk for death and/or NDI. This risk was highest among those with Candida sepsis and/or meningitis.

Association between feeding difficulties and language delay in preterm infants using Bayley Scales of Infant Development-Third Edition.

OBJECTIVE: To evaluate the relationship between abnormal feeding patterns and language performance on the Bayley Scales of Infant Development-Third Edition at 18-22 months adjusted age among a cohort of extremely premature infants. STUDY DESIGN: This is a descriptive analysis of 1477 preterm infants born ≤ 26 weeks gestation or enrolled in a clinical trial between January 1, 2006 and March 18, 2008 at a National Institute of Child Health and Human Development Neonatal Research Network center who completed the 18-month neurodevelopmental follow-up assessment. At 18-22 months adjusted age, a comprehensive neurodevelopmental evaluation was performed by certified examiners including the Receptive and Expressive Language Subscales of the Bayley Scales of Infant Development-Third Edition and a standardized adjusted age feeding behaviors and nutritional intake. Data were analyzed using bivariate and multilevel linear and logistic regression modeling. RESULTS: Abnormal feeding behaviors were reported in 193 (13%) of these infants at 18-22 months adjusted age. Abnormal feeding patterns, days of mechanical ventilation, hearing impairment, and Gross Motor Functional Classification System level ≥ 2 each independently predicted lower composite language scores. CONCLUSIONS: At 18 months adjusted age, premature infants with a history of feeding difficulties are more likely to have language delay. Neuromotor impairment and days of mechanical ventilation are both important risk factors associated with these outcomes.