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.

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.

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.

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.

The dreaded desaturating baby: a difficult problem in clinical management.

There are various causes for frequent desaturations in infants. Frequent hypoxemia is a significant change in clinical status and must be investigated carefully for possible etiology. When common extra-airway causes for desaturation are ruled out, one should attempt to distinguish between central apnea and obstructive events. The most commonly overlooked obstructive event is tracheobronchomalacia, and steps should be initiated to understand the scope of the problem through pulmonary function testing and bronchoscopy. Adequate respiratory support for the infant should be provided until adequate time passes to enable airway growth and improved cartilaginous deposition to occur. Parents must be carefully supported during this time; the stress of having an infant who requires prolonged hospitalization and care for tracheobronchomalacia is substantial.

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.

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.

Partial truncation of the NH2-terminus affects physical characteristics and membrane binding, aggregation, and fusion properties of annexin A7.

Annexin A7 (synexin, annexin VII), a member of the annexin family of proteins, causes aggregation of membranes in a Ca2+-dependent manner and has been suggested to promote membrane fusion during exocytosis of lung surfactant, catecholamines, and insulin. Although annexin A7 (A7) was one of the first annexin proteins described, limited studies of its physical characteristics or of structural domains affecting any of its proposed functions have been conducted. As postulated for other annexin proteins, the unique NH2-domain possibly determines the functional specificity of A7. Therefore, we evaluated the effects of segmental deletions in the NH2-terminus on several characteristics associated with the COOH-terminus of A7. The COOH-terminus contains the only tryptophan residue, and all potential trypsin sites, and the Ca2+ and phospholipid binding sites. Recombinant rat A7 and its deletion mutants were expressed using constructs based on the cDNA sequence obtained by screening a rat lung cDNA library. Ca2+ increased the tryptophan fluorescence of A7 and caused a small red shift in the emission maximum (lambdamax), which was further increased in presence of phospholipid vesicles (PLV). NH2-terminal deletions of 29, 51, and 109 residues affected the peak width of fluorescence and lambdamax, surface-exposure of tryptophan residue, and caused a smaller Ca2+-dependent red shift in lambdamax of membrane-bound protein in comparison to A7. Limited proteolysis with trypsin showed that Ca2+ increased the proteolysis of all proteins, but the deletions also affected the pattern of proteolysis. The presence of PLV protected against Ca2+-dependent increase in proteolysis of all proteins. The deletion of first 29 residues also caused decreased membrane binding, aggregation, and fusion, when compared with A7. Collectively, these results suggest that specific NH2-terminus domains can alter those properties of A7 that are normally associated with the COOH-terminus. We speculate that interactions between the NH2- and COOH-termini are required for membrane binding, and aggregation and fusion properties of annexin A7.

Mass spectrometry in neonatal medicine and clinical diagnosis--the [corrected] potential use of mass spectrometry in neonatal brain [corrected] monitoring.

This article discusses the application of mass spectroscopy, a technology that may have great potential for screening neonatal brain injury. This approach is anticipated to become increasingly important in neonatal and perinatal research and newborn care during the next few years.

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.

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.

Practice variation in suspected neonatal sepsis: a costly problem in neonatal intensive care.

OBJECTIVE: The most common admission to intensive care nurseries is the infant with suspected neonatal sepsis. To determine the clinical practice of neonatologists with respect to this diagnosis, we examined a large neonatal database during a 2-year period of time. The goal of this study was to define whether there were optimal practice strategies that could identify a "benchmark" clinical approach for this diagnosis. DESIGN: The PROACT database of ParadigmHealth was examined for all term infants with an admitting ICD - 9 code for suspected neonatal sepsis between January 1, 2001 and December 31, 2002. Infants had to be asymptomatic by 24 hours of life with no significant respiratory signs and receiving oral feedings. All infants had negative blood cultures. Maternal risk factors were examined to determine if they influenced the duration of therapy. The impact of treatment upon subsequent length of stay was also evaluated. Several areas of the country were individually examined to see if possible regional variations existed with respect to treatment of suspected sepsis. RESULTS: There were no significant differences noted in the management when maternal risk factors for suspected sepsis were assessed. In general, neonates were treated for 3.3+/-1.8 to 3.5+/-2.1 days, regardless of the number of maternal risk factors present at birth (p=NS). Length of stay ranged from 4.2+/-2.1 to 4.4+/-1.9 days in these groups (p=NS). The duration of treatment ranged from 1 to 10 days, even though all infants were clinically well and feeding by 24 hours of life. A total of 170 infants (17.0%) were treated for 4 to 6 days and 116 (11.6%) neonates received antibiotics for 7 to 10 days, even with negative blood cultures. One region of the country appeared to treat infants for a longer period of time than the other four regions examined, increasing the mean length of stay by 1.8 days (p<0.05). CONCLUSIONS: Treatment of neonates with suspected sepsis appears to be influenced by considerations other than maternal risk factors or the infant's clinical condition beyond the first day of life. There appears to be a great deal of practice variation among neonatologists confronted by patients with suspected sepsis. Awareness of this unnecessary variation may be of great value in reducing the duration of antibiotic therapy in the NICU and shortening the length of stay.

Histological chorioamnionitis and the risk of early intraventricular hemorrhage in infants born < or =28 weeks gestation.

OBJECTIVE: To test the hypothesis that histological chorioamnionitis (CA) is not associated with increased risk of early onset intraventricular hemorrhage (IVH). STUDY DESIGN: Clinical data were prospectively collected for 62 consecutive neonates born before 28 weeks of gestation. Placental histology for CA was performed by a pathologist unaware of the head ultrasound scan (HUS) results. The first HUS was obtained by 30 minutes of life. Follow-up HUS were performed before 24 hours and again at 48 to 72 postnatal hours of life. An IVH (grade I to IV) at less than 72 hours of life was deemed an early hemorrhage. RESULTS: Nine of the 62 (14.5%) infants had early onset IVH. In all, 29 infants were born to women with histological evidence of CA; 33 infants did not have CA. Infants did not differ in birth weight, gestational age, sex, cord blood pH, 5-minute Apgar score of <7, cesarean delivery, prenatal use of steroids, administration of tocolytics, need for resuscitation, presence of pneumothorax, platelet count at birth, or use of surfactant. Early IVH rates (3/29 in CA vs 6/33 in non-CA) were similar (p=0.48). Two infants in each group with early IVH died before 2 weeks of age. Five additional infants from the CA group developed IVH at more than 72 postnatal hours of life (late onset IVH), and two of those infants progressed to develop periventricular leukomalacia (PVL). In contrast, only three non-CA infants had late IVH and none developed PVL. Logistic regression confirmed that no perinatal variables including CA were associated with early onset IVH. CONCLUSION: Chorioamnionitis is not associated with increased risk of early IVH.

The influence of genetic counselors on the acceptance of mid-trimester amniocentesis.

OBJECTIVE: To determine the effect of the genetic counselor on the acceptance of genetic amniocentesis. METHODS: We studied women with singleton pregnancies who would be at least 35 years of age at the estimated date of delivery without fetal structural anomalies or family history of chromosomal abnormalities. The acceptance rate of genetic amniocentesis among women evaluated by each counselor was compared with the average acceptance rate for our population. Chi-square test, Fisher exact test and ANOVA were used for analysis. RESULTS: Of the 2,180 women met our inclusion criteria, 1,719 (78.9%) accepted genetic amniocentesis. The maternal age at estimated date of delivery, the proportion of women who conceived by in vitro fertilization, and the proportion with history of miscarriage were similar among women evaluated by each of the six genetic counselors. However, the acceptance rate of genetic amniocentesis was significantly lower in women evaluated by counselor C [115/170 (67.6%), P=0.001] and significantly higher in the group evaluated by counselor D [138/154 (89.6%), P=0.002] compared with the overall study population rate [1719/2180 (78.9%)]. The acceptance rate of 80.4% (210/261, P=0.52), 75.6 % (232/307, P=0.23), 80.9% (443/547, P=0.30] and 78.4% (581/741, P=0.83) for Counselors A, B, E and F respectively did not differ from the overall study population rate. CONCLUSIONS: Considerable variation exists in the acceptance rate of genetic amniocentesis among women based on the genetic counselor.

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.

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.

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.