Has Quality Improvement Really Improved Outcomes for Babies in the Neonatal Intensive Care Unit?

During the past decade, the emergence of outcome measurement and quality improvement in the neonatal intensive care unit, far more than the introduction of new research approaches or novel therapies, has had a profound effect on improving outcomes for premature neonates. Collection of outcome data, review of those data, and strategies to identify and resolve problems using continuous quality improvement methods can dramatically improve patient outcomes. It is likely that further initiatives in quality improvement will continue to have additional beneficial effects for the neonate.

Prevalence of Hypoalbuminemia and Elevated Bilirubin/Albumin Ratios in a Large Cohort of Infants in the Neonatal Intensive Care Unit.

OBJECTIVE: To provide descriptive data on serum albumin levels and the bilirubin to albumin (B/A) ratio in neonates admitted to the neonatal intensive care unit, assess the effect of gestational and chronological age on serum albumin and the B/A ratio, and evaluate the association between extreme values and mortality. STUDY DESIGN: Using a retrospective cohort design, we queried the Pediatrix clinical data warehouse for all infants born between 23 and 41 weeks of gestation from 1997 to 2014 who had a report of both a serum albumin and total serum bilirubin (TSB) level on the same day between birth and 14 days of life. RESULTS: There were 382 190 paired albumin and bilirubin levels across 164 401 neonates (15% of the 1 072 682 infants in the clinical data warehouse). Both gestational age and postnatal age were independent factors that influenced the values for serum albumin, TSB, and B/A ratio (ANOVA; P < .0001). TSB and B/A ratios values above birth weight-specific thresholds for exchange transfusions were uncommon (<6% of infants). Hypoalbuminemia (<2.5 mg/dL) was common (29% of infants). Neonates with serum albumin levels <2.5 g/dL or with B/A ratio levels exceeding exchange thresholds were at higher risk of death compared with infants who did not exceed these levels. This association was independent of other risk factors (estimated gestational age, birth weight, sex, and the presence of a major anomaly). CONCLUSION: Both gestational age and postnatal age influence TSB, albumin, and B/A ratios; hypoalbuminemia and extreme B/A ratios are associated with an increased risk of death.

Exposure to any antenatal corticosteroids and outcomes in preterm infants by gestational age: prospective cohort study.

Objective To determine whether exposure to any antenatal corticosteroids is associated with a lower rate of death at each gestational age at which administration is currently recommended.Design Prospective cohort study.Settings 300 participating neonatal intensive care units of the Pediatrix Medical Group in the United States.Participants 117 941 infants 23 0/7 to 34 6/7 weeks' gestational age born between 1 January 2009 and 31 December 2013.Exposure Any antenatal corticosteroids.Main outcomes measures Death or major hospital morbidities analyzed by gestational age and exposure to antenatal corticosteroids with models adjusted for birth weight, sex, mode of delivery, and multiple births.Results Infants exposed to antenatal corticosteroids (n=81 832) had a significantly lower rate of death before discharge at each gestation 29 weeks or less, 31 weeks, and 33-34 weeks compared with infants without exposure (range of adjusted odds ratios 0.32 to 0.55). The number needed to treat with antenatal corticosteroids to prevent one death before discharge increased from six at 23 and 24 weeks' gestation to 798 at 34 weeks' gestation. The rate of survival without major hospital morbidity was higher among infants exposed to antenatal corticosteroids at the lowest gestations. Infants exposed to antenatal corticosteroids had lower rates of severe intracranial hemorrhage or death, necrotizing enterocolitis stage 2 or above or death, and severe retinopathy of prematurity or death compared with infants without exposure at all gestations less than 30 weeks and most gestations for infants born at 30 weeks' gestation or later.Conclusion Among infants born from 23 to 34 weeks' gestation, antenatal exposure to corticosteroids compared with no exposure was associated with lower mortality and morbidity at most gestations. The effect size of exposure to antenatal corticosteroids on mortality seems to be larger in infants born at the lowest gestations.

Stronger and More Vulnerable: A Balanced View of the Impacts of the NICU Experience on Parents.

For parents, the experience of having an infant in the NICU is often psychologically traumatic. No parent can be fully prepared for the extreme stress and range of emotions of caring for a critically ill newborn. As health care providers familiar with the NICU, we thought that we understood the impact of the NICU on parents. But we were not prepared to see the children in our own families as NICU patients. Here are some of the lessons our NICU experience has taught us. We offer these lessons in the hope of helping health professionals consider a balanced view of the NICU's impact on families.

Ventriculomegaly in very-low-birthweight infants with Down syndrome.

AIM: The prevalence of Down syndrome in infants with fetal ventriculomegaly is 5% to 10%; however, the converse, the prevalence of cerebral ventriculomegaly in live-born infants with Down syndrome, is not well established. Because cranial ultrasounds are performed on most very-low-birthweight (VLBW) infants (birthweight <1500g), our aim was to examine ultrasound abnormalities of VLBW infants to determine prevalence of ventriculomegaly and intraventricular hemorrhage (IVH) in VLBW infants with Down syndrome, and whether VLBW infants with Down syndrome are at higher risk for cranial ultrasound abnormalities, compared with the already elevated risk in other VLBW infants. METHOD: This study comprised retrospective analysis of data from Pediatrix BabySteps Clinical Data Warehouse. The study population consisted of 121 736 VLBW infants (61 869 males, 59 867 females), born between 1996 and 2013, of whom 441 had Down syndrome (233 males, 208 females; mean gestational age 30wks, standard deviation [SD] 2.8wks). Logistic regression was used to calculate odds of ventriculomegaly and IVH for Down syndrome. RESULTS: Prevalence of ventriculomegaly in Down syndrome was 5.2% compared with 0.8% in other VLBW infants. Multivariate analysis indicated 5.8× odds (95% confidence interval [CI] 3.4-9.7) of ventriculomegaly in Down syndrome and 0.9× odds (95% CI 0.7-1.1) of IVH for Down syndrome. INTERPRETATION: Very preterm infants with Down syndrome are at increased risk for ventriculomegaly (but not for IVH) compared with other infants born very preterm.

Postnatal corticosteroids and risk of retinopathy of prematurity.

PURPOSE: To investigate the association between postnatal steroids and retinopathy of prematurity (ROP) in neonates born with birth weights at the limit of viability (<500 g). METHODS: Data from the Pediatrix BabySteps Clinical Warehouse were retrospectively reviewed. The study population consisted of 1,472 neonates with birth weights of <500 g who were discharged alive from 167 NICUs between 1996 and 2013. Statistical significance for unadjusted comparisons between groups was determined using the χ(2) or t test. Logistic regression was used to calculate odds of ROP. RESULTS: In multivariate analysis, the odds of any ROP for steroid treated infants was 1.6 (95% CI, 1.2-2.2) compared to nontreated infants; the odds of advanced ROP was 1.7 (95% CI, 1.3-2.3). CONCLUSIONS: In our large study cohort of critically low birth weight infants ROP was more common in neonates exposed to postnatal steroids.

A Multifaceted Approach to Improving Outcomes in the NICU: The Pediatrix 100 000 Babies Campaign.

BACKGROUND AND OBJECTIVE: Despite advances in neonatal medicine, infants requiring neonatal intensive care continue to experience substantial morbidity and mortality. The purpose of this initiative was to generate large-scale simultaneous improvements in multiple domains of care in a large neonatal network through a program called the "100,000 Babies Campaign." METHODS: Key drivers of neonatal morbidity and mortality were identified. A system for retrospective morbidity and mortality review was used to identify problem areas for project prioritization. NICU system analysis and staff surveys were used to facilitate reengineering of NICU systems in 5 key driver areas. Electronic health record-based automated data collection and reporting were used. A quality improvement infrastructure using the Kotter organizational change model was developed to support the program. RESULTS: From 2007 to 2013, data on 422 877 infants, including a subset with birth weight of 501 to 1500 g (n = 58 555) were analyzed. Key driver processes (human milk feeding, medication use, ventilator days, admission temperature) all improved (P < .0001). Mortality, necrotizing enterocolitis, retinopathy of prematurity, bacteremia after 3 days of life, and catheter-associated infection decreased. Survival without significant morbidity (necrotizing enterocolitis, severe intraventricular hemorrhage, severe retinopathy of prematurity, oxygen use at 36 weeks' gestation) improved. CONCLUSIONS: Implementation of a multifaceted quality improvement program that incorporated organizational change theory and automated electronic health record-based data collection and reporting program resulted in major simultaneous improvements in key neonatal processes and outcomes.

Trisomy 21 and Risk of Retinopathy of Prematurity.

BACKGROUND AND OBJECTIVES: Trisomy 21 is known to decrease the risk of several (nonocular) angiogenic-mediated diseases. The objective of this study was to determine whether trisomy 21 can also be shown to be significantly protective against ocular angiogenic-mediated disorders such as retinopathy of prematurity (ROP). METHODS: A retrospective analysis of deidentified data from the Pediatrix BabySteps Clinical Warehouse. This large repository of neonatal data is approved for use in research studies by the Western Institutional Review Board. The study population consisted of 99,080 infants with very low birth weights (BWs; BW <1500 g), born between 1996 and 2013, cared for at >300 US NICUs, and who had been discharged alive from hospital. Statistical significance for unadjusted comparisons between groups was determined with Pearson's χ(2) test or Student's t test. Logistic regression models were used to calculate the odds of ROP (of any stage) and advanced ROP (stage 3 or greater) for infants with trisomy 21 compared with all other infants. RESULTS: The prevalence of trisomy 21 was 0.3% in the study population (321 of 99,080). After adjustment for BW, gestational age, oxygen exposure, and other potential confounders, there was an odds ratio of 0.6 (95% confidence interval: 0.5-0.8) for ROP in infants with trisomy 21compared with other infants and an odds ratio of 0.4 (95% confidence interval: 0.1-0.9) for advanced-stage ROP. CONCLUSIONS: Trisomy 21 significantly decreases the odds for ROP in very low BW infant survivors. This study unmasks a potentially identifiable genetic component to ROP risk, paving the way for the development of a laboratory-based ROP screening tool.

Increasing incidence of the neonatal abstinence syndrome in U.S. neonatal ICUs.

BACKGROUND: The incidence of the neonatal abstinence syndrome, a drug-withdrawal syndrome that most commonly occurs after in utero exposure to opioids, is known to have increased during the past decade. However, recent trends in the incidence of the syndrome and changes in demographic characteristics and hospital treatment of these infants have not been well characterized. METHODS: Using multiple cross-sectional analyses and a deidentified data set, we analyzed data from infants with the neonatal abstinence syndrome from 2004 through 2013 in 299 neonatal intensive care units (NICUs) across the United States. We evaluated trends in incidence and health care utilization and changes in infant and maternal clinical characteristics. RESULTS: Among 674,845 infants admitted to NICUs, we identified 10,327 with the neonatal abstinence syndrome. From 2004 through 2013, the rate of NICU admissions for the neonatal abstinence syndrome increased from 7 cases per 1000 admissions to 27 cases per 1000 admissions; the median length of stay increased from 13 days to 19 days (P<0.001 for both trends). The total percentage of NICU days nationwide that were attributed to the neonatal abstinence syndrome increased from 0.6% to 4.0% (P<0.001 for trend), with eight centers reporting that more than 20% of all NICU days were attributed to the care of these infants in 2013. Infants increasingly received pharmacotherapy (74% in 2004-2005 vs. 87% in 2012-2013, P<0.001 for trend), with morphine the most commonly used drug (49% in 2004 vs. 72% in 2013, P<0.001 for trend). CONCLUSIONS: From 2004 through 2013, the neonatal abstinence syndrome was responsible for a substantial and growing portion of resources dedicated to critically ill neonates in NICUs nationwide.

Off-label use of inhaled nitric oxide after release of NIH consensus statement.

BACKGROUND: Inhaled nitric oxide (iNO) therapy is an off-label medication in infants <34 weeks' gestational age. In 2011, the National Institutes of Health released a statement discouraging routine iNO use in premature infants. The objective of this study was to describe utilization patterns of iNO in American NICUs in the years surrounding the release of the National Institutes of Health statement. We hypothesized that iNO prescription rates in premature infants have remained unchanged since 2011. METHODS: The Pediatrix Medical Group Clinical Data Warehouse was queried for the years 2009-2013 to describe first exposure iNO use among all admitted neonates stratified by gestational age. RESULTS: Between 2009 and 2013, the rate of iNO utilization in 23- to 29-week neonates increased from 5.03% to 6.19%, a relative increase of 23% (confidence interval: 8%-40%; P = .003). Of all neonates who received iNO therapy in 2013, nearly half were <34 weeks' gestation, with these infants accounting for more than half of all first exposure iNO days each year of the study period. CONCLUSIONS: The rates of off-label iNO use in preterm infants continue to rise despite evidence revealing no clear benefit in this population. This pattern of iNO prescription is not benign and comes with economic consequences.

The Pediatrix BabySteps® Data Warehouse--a unique national resource for improving outcomes for neonates.

The Pediatrix Medical Group Clinical Data Warehouse represents a unique electronic data capture system for the assessment of outcomes, the management of quality improvement (CQI) initiatives, and the resolution of important research questions in the neonatal intensive care unit (NICU). This system is described in detail and the manner in which the Data Warehouse has been used to measure and improve patient outcomes through CQI projects and research is outlined. The Pediatrix Data Warehouse now contains more than 1 million patients, serving as an exceptional tool for evaluating NICU care. Examples are provided of how significant outcome improvement has been achieved and several papers are cited that have used the "Big Data" contained in the Data Warehouse for novel observations that could not be made otherwise.

Etiologies of NICU deaths.

BACKGROUND AND OBJECTIVES: Infant mortality is an indicator of overall societal health, and a significant proportion of infant deaths occur in NICUs. The objectives were to identify causes of death and to define potentially preventable factors associated with death as areas for quality improvement efforts in the NICU. METHODS: In a prospectively defined study, the principal investigator in 46 level III NICUs agreed to review health care records of infants who died. For each infant, the principal investigator reviewed the medical record to identify the primary cause of death and to look for preventable factors associated with the infant's death. Infants born at ≥22 weeks estimated gestational age who were born alive were included. Stillborn infants were excluded. RESULTS: Data were collected on 641 infants who died. At lower gestational ages, mortality was most commonly due to extreme prematurity and the complications of premature birth (respiratory distress progressing to respiratory failure, intraventricular hemorrhage, necrotizing enterocolitis, and sepsis). With increasing gestational age, the etiology of mortality shifted to hypoxic-ischemic encephalopathy and genetic or structural anomalies. Reviewers of clinical care identified 197 (31%) infants with potentially modifiable factors that may have contributed to their deaths. CONCLUSIONS: The factors associated with death in infants admitted for intensive care are multifactorial and diverse, and they change with gestational age. In 31% of the deaths, potentially modifiable factors were identified, and these factors suggest important targets for reducing infant mortality.

Gestational age and age at sampling influence metabolic profiles in premature infants.

OBJECTIVE: To describe the influence that gestational age and chronological age have on amino acid and acylcarnitine profiles in an at-risk population of premature infants. METHODS: Metabolic profiles (15 amino acids and 35 acylcarnitines) were obtained by using standard newborn techniques on infants born between 23 and 31 completed weeks of gestation. The profiles were drawn within the first 24 hours after birth and on approximately days 7, 28, and 42 of life or at discharge. A single, central, contract laboratory analyzed and managed the samples. RESULTS: We studied 995 patients; none was subsequently diagnosed with an inborn error of metabolism. Of the 3579 samples, there were 257 (7.2%) amino acid or acylcarnitine alerts reported in 214 infants (21.5% of infants studied). Both gestational age and postbirth chronological age significantly influenced the metabolic profile. Twenty-nine percent of infants at 23 to 26 weeks' gestational age had an abnormal metabolic profile compared with 17% of infants at 29 to 31 weeks' gestational age (P < .01). On the day of birth, 12% of the profiles were abnormal compared with 2% on day 28 (P < .01). The highest rate of abnormal values occurred on day 7 in the infants 23 to 26 weeks' gestational age (21%). CONCLUSIONS: These results demonstrate the complexity of understanding the impact of immaturity and disease on metabolic profiles used to screen for inborn errors of metabolism. Our data provide reference values for studies aimed at better understanding metabolism in preterm infants.

Assessment of neonatal growth in prematurely born infants.

The concept that adequate nutritional status and normal growth are important is well-accepted. How to assess the adequacy of nutrition and how to define appropriate growth remains an area of active debate. Our goal is to review how growth is assessed at birth and during the hospital stay of prematurely born infants, and to offer a standardized approach.

Utility of genetic testing for the detection of late-onset hearing loss in neonates.

PURPOSE: The purpose of this study was to demonstrate the utility of molecular testing in the detection of potentially important causes of delayed hearing loss missed by current audiometric screening at birth. METHOD: We enrolled infants who had received a newborn audiometric hearing screen and a filter paper blood collection for state newborn screening. A central laboratory ran the SoundGene® panel. RESULTS: Of 3,681 infants studied, 35 (0.95%) had a positive SoundGene panel, 16 had mitochondrial mutations, 9 had Pendred mutations, 5 were cytomegalovirus (CMV) DNA positive, 2 had connexin mutations, and 3 had a combination of different mutations. Infants with an abnormal SoundGene panel were at increased risk for hearing loss compared to neonates without mutations. Three (8.6%) of the 35 subjects had persistent hearing loss compared to 5 (0.21%) of 2,398 subjects with no report of mutation (p < .01). Of 3,681 infants studied, 8 (0.22%) had persistent hearing loss: 5 (62.5%) had abnormal newborn audiometric screens, 2 (25%) had an abnormal SoundGene panel (1 was CMV positive, 1 had a mitochondrial mutation), and 1 (12.5%) had no identifiable risk factors. CONCLUSION: A positive SoundGene panel identifies infants who are not identified by audiometric testing and may be at risk for hearing loss.

Varying patterns of home oxygen use in infants at 23-43 weeks' gestation discharged from United States neonatal intensive care units.

OBJECTIVES: To compare proportions of infants at different gestational ages discharged from the neonatal intensive care unit (NICU) on home oxygen, to determine how many were classified with chronic lung disease based on timing of discharge on home oxygen, and to determine the percentage discharged on home oxygen who received mechanical ventilation. STUDY DESIGN: We evaluated a retrospective cohort of infants of 23-43 weeks' gestational age discharged from 228 NICUs in 2009, using the Pediatrix Clinical Data Warehouse. Multilevel logistic regression analysis identified predictors of home oxygen use among extremely preterm, early-moderate preterm, late preterm, and term infants. Duration of mechanical ventilation and median length of stay were calculated for infants discharged on home oxygen. RESULTS: For the 48877 infants studied, the rate of home oxygen use ranged from 28% (722 of 2621) in extremely preterm infants to 0.7% (246 of 34 934) in late preterm and term infants. Extremely preterm infants composed 56% (722 of 1286) of the infants discharged on home oxygen; late preterm and term infants, 19% (246 of 1286). After gestational age, mechanical ventilation was the main predictor of home oxygen use; however, 61% of the late preterm and term infants discharged on home oxygen did not receive ventilation. The median length of hospital stay was 95 days (IQR, 76-114 days) for extremely preterm infants discharged on home oxygen, but only 15 days (IQR, 10-22 days) for late preterm and term ventilated infants discharged on home oxygen. CONCLUSION: Although home oxygen use is uncommon in later-gestation infants, the greater overall numbers of later-gestation infants contribute significantly to the increased need for home oxygen for infants at NICU discharge. Neither respiratory failure nor lengthy hospitalization is a prerequisite for home oxygen use at later gestational age.