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.

In recent years, neonatal abstinence syndrome (NAS), which commonly occurs after opioid use in pregnant women, has increased, nearly tripling in the United States between 2000 and 2009. There are limited data on the treatment of infants with NAS or changes in neonatal intensive care units. Previous studies have focused on specific geographic areas or used hospital billing records, not infant-specific clinical information, to identify cohorts. This study aims to analyze changes in incidence as well as treatment of infants with NAS in neonatal intensive care units (NICUs) across the United States from 2004 to 2013.Data were collected from Pediatrix Clinical Data Warehouse, which includes information from NICUs in 33 states and Puerto Rico. Infants were excluded if they had major congenital anomalies, if they were born before 34 weeks, if they were admitted only for suspected cases or to rule out NAS, or if they had exposure to narcotics but were not diagnosed with NAS. Infants were grouped by year of discharge in 1-year periods. Multiple cross-sectional analyses were performed using general linear regression.A total of 10,327 infants from 299 centers met diagnostic criteria for NAS. The frequency of infants with NAS admitted to NICUs increased from 7 cases per 1000 admissions to 27 cases per 1000 admissions between 2004 and 2013 and increased more rapidly between 2009 and 2013 than between 2004 and 2008. The length of hospital stay also increased from 13 to 19 days between 2004 and 2013, and the number of NICU hospital days attributed to NAS increased from 0.6% in 2004 to 4.0% in 2013 (P < 0.001 for trend). The proportion of infants treated for NAS with pharmacotherapy increased from 74% to 87% (P < 0.001 for trend), and the mean duration of therapy increased (P < 0.001 for trend). Whereas the ratio of days of therapy to NICU days increased (P = 0.004 for trend), the proportion of infants discharged while receiving medications decreased (4% in 2004-2005 vs 2% in 2012-2013, P < 0.001 for trend). The most commonly used medication was morphine, and the proportion of infants on morphine increased from 49% in 2004 to 72% in 2013 (P < 0.001 for trend). Between 2004Between and 2013Between , clonidine use increased, and between 2011Between and 2013 The study found that between 2012 and 2013, many mothers of affected infants used opioid pain relievers rather than illicit drugs, which is consistent with reports suggesting that increased opioid use in pregnant women is in part causing the increase in the incidence of NAS. The study also found increases in the utilization of resources for infants with NAS in NICUs between 2004 and 2013, and effective strategies for antenatal prevention and postnatal treatment of NAS are needed. These findings also support the need to address the current opioid use and abuse epidemic in the United States. 551Newborn Medicine

Background Gastroschisis and omphalocele are the most common anterior abdominal wall defects affecting infants. There are few large cohort studies describing the frequency of associated anomalies in infants with these 2 conditions. We describe associated anomalies and outcomes in infants with these defects using a large, multi-center clinical database. Methods We identified all infants with gastroschisis or omphalocele from a prospectively collected database of infants discharged from 348 neonatal intensive care units in North America from 1997–2012. Maternal and patient demographic data, associated anomalies, and outcome data were compared between infants with gastroschisis and omphalocele. Results A total of 4687 infants with gastroschisis and 1448 infants with omphalocele were identified. Infants with omphalocele were more likely to be diagnosed with at least 1 other anomaly compared with infants with gastroschisis (35% vs. 8%, p<0.001). Infants with omphalocele were more likely to develop pulmonary hypertension compared with those with gastroschisis (odds ratio [OR] 7.78; 95% confidence interval 5.81, 10.41) and had higher overall mortality (OR 6.81 [5.33, 8.71]). Conclusion Infants with omphalocele were more likely to have other anomalies, be diagnosed with pulmonary hypertension, and have higher mortality than infants with gastroschisis.

Background: Human milk reduces morbidities in extremely low birth weight (ELBW) infants. However, clinical instability often precludes ELBW infants from receiving early enteral feeds. This study compared clinical outcomes before and after implementing an oropharyngeal colostrum (COL) protocol in a cohort of inborn (born at our facility) ELBW infants. Study Design: This is a retrospective cohort study of inborn ELBW infants admitted to the Duke Intensive Care Nursery from January 2007 to September 2011. In November 2010, we initiated a COL protocol for infants not enterally fed whose mothers were providing breastmilk. Infants received 0.1 mL of fresh COL to each cheek every 4 hours for 5 days beginning in the first 48 postnatal hours. We assessed demographics, diagnoses, feeding history, and mortality and for the presence of medical necrotizing enterocolitis (NEC), surgical NEC, and spontaneous perforation. Between-group comparisons were made using Fisher's exact test or Wilcoxon rank sum testing where appropriate. Results: Of the 369 infants included, 280 (76%) were born prior to the COL protocol (Pre-COL Cohort [PCC]), and 89 (24%) were born after (COL Cohort [CC]). Mortality and the percentage of infants with surgical NEC and spontaneous perforations were statistically similar between the groups. The CC weighed an average (interquartile range) of 1,666 (1,399, 1,940) g at 36 weeks versus 1,380 (1,190, 1,650) g for the PCC ( p < 0.001). In a multivariable analysis with birth weight as a covariable, weight at 36 weeks was significantly greater (37 g; p < 0.01). Conclusions: Initiating oropharyngeal COL in ELBW infants in the first 2 postnatal days appears feasible and safe and may be nutritionally beneficial. Further research is needed to determine if early COL administration reduces neonatal morbidity and mortality.

Background: Calprotectin is a cytosolic component of neutrophils. Fecal calprotectin (FC) level is a useful marker for exacerbation of inflammatory bowel disease in children. FC may be a useful marker for necrotizing enterocolitis (NEC). Objective: To determine normal baseline levels of FC and observe dynamic changes of FC levels over the first postnatal month in very low birth weight (VLBW) infants. Methods: FC levels of 14 VLBW infants (gestational age 23–30 weeks, birth weight ≤1,500 g) were serially measured in the first postnatal month. Demographics, feeding regimens, antibiotic use, laboratory and x-ray results, and maternal information were recorded. We assessed how FC levels changed over time, varied with nutritional source and differed between sick versus well infants. Results: FC levels were not related to gestational age or feedings regimen. FC levels tended to decrease with increasing age (p = 0.121) and feeding volumes (p = 0.179). FC levels differed between ‘well’ and ‘sick’ infants (122.8 ± 98.9 vs. 380.4 ± 246.3 µg/g stool, p < 0.001). FC >350 µg/g stool was noted with signs of gastrointestinal injury, such as bloody stool and bowel perforation. FC levels decreased after initiation of treatments in sick infants who recovered. Conclusions: FC levels may be a marker for early diagnosis and resolution of gastrointestinal illnesses in VLBW infants. Its utility for early diagnosis and assessment of resolution of NEC should be studied in a larger cohort of VLBW infants.

Background Coagulase-negative staphylococci (CoNS) are the most commonly isolated pathogens in the neonatal intensive care unit (NICU). CoNS infections are associated with increased morbidity including neurodevelopmental impairment. Objective Describe the epidemiology of CoNS infections in the NICU. Determine mortality among infants with definite, probable, or possible CoNS infections. Methods We performed a retrospective cohort study of all blood, urine, and cerebrospinal fluid cultures from infants <121 postnatal days. Setting 248 NICUs managed by the Pediatrix Medical Group from 1997 to 2009. Results We identified 16,629 infants with 17,624 episodes of CoNS infection: 1734 (10%) definite, 3093 (17%) probable, and 12,797 (73%) possible infections. Infants with lower gestational age and birth weight had a higher incidence of CoNS infection. Controlling for gestational age, birth weight, and 5-minute Apgar score, infants with definite, probable, or possible CoNS infection had lower mortality—OR=0.74 (95% confidence interval; 0.61, 0.89), OR= 0.68 (0.59, 0.79), and OR=0.69 (0.63, 0.76)—compared to infants with negative cultures (P<0.001). No significant difference in overall mortality was found in infants with definite CoNS infection compared to those with probable or possible CoNS infection—OR=0.93 (0.75, 1.16) and OR=0.85 (0.70, 1.03), respectively. Conclusions CoNS infection was strongly related to lower gestational age and birth weight. Infants with clinical sepsis and culture-positive CoNS infection had lower mortality rates than infants with clinical sepsis and negative blood culture results. No difference in mortality between infants diagnosed with definite, probable, or possible CoNS infection was observed.

Background The impact of age and weight on outcomes following the Fontan operation is unclear. Previous analyses have suggested that lower weight-for-age z-score is an important predictor of poor outcome in patients undergoing bidirectional Glenn. We evaluated variation in age, weight, and weight-for-age z-score at Fontan across institutions, and the impact of these variables on post-operative morbidity and mortality. Methods Patients in the Society of Thoracic Surgeons Congenital Heart Surgery Database undergoing the Fontan operation (2000–2009) were included. Center variation in age, weight, and weight-for-age z-score were described. Multivariable analysis was performed to evaluate the impact of age, weight, and weight-for-age z-score on in-hospital mortality, Fontan failure (combined in-hospital mortality and Fontan takedown/revision), post-operative length of stay, and complications, adjusting for other patient and center factors. Results A total of 2747 patients (68 centers) were included: 61% male; 45% right dominant lesions (38% left dominant, 17% undifferentiated). An extracardiac conduit Fontan (vs. lateral tunnel) was performed in 63%; 65% were fenestrated. Median age and weight at Fontan operation and proportion with weight-for-age z-score <−2 varied across centers ranging from 1.7–4.8 yrs, 10.5–16.1 kg, and 0%–30%, respectively. In multivariable analysis, age and weight were not significantly associated with outcome. Weight-for-age z-score <−2 was associated with increased in-hospital mortality (OR 2.73, 95%CI 1.09–6.86), Fontan failure (OR 2.59, 95%CI 1.24–5.40), and longer length of stay (+1.2 days, 95%CI 0.1–2.4). Conclusions Weight-for-age z-score <−2 is associated with significant morbidity and mortality following the Fontan operation independent of other patient and center characteristics.

NCT00621192.