Alona Bin-Nun

Managing the Patent Ductus Arteriosus in the Premature Neonate: A New Look at What We Thought We Knew

Over recent years, the clinical approach to patency of the ductus arteriosus in the premature neonate has been the subject of intensive reevaluation. What had once been considered inherently obvious is no longer to be taken for granted. In this review we will focus on some of the controversies surrounding various aspects of the pharmacologic treatment regimens for patent ductus arteriosus closure. The pros and cons of prophylactic vs therapeutic indomethacin, of early vs late therapy, of high- vs low-dose indomethacin, of single vs multiple courses of treatment, and of ibuprofen vs indomethacin will be considered. In addition, the possibility that patency of the ductus arteriosus is merely a physiological manifestation of extreme prematurity, and thus does not necessarily need to be therapeutically closed, has become a viable approach in some cases. As such, we will examine echocardiographic and biochemical criteria aimed at determining the clinical and hemodynamic significance of ductal shunting, and thereby of the need to treat. Finally, we speculate on potential therapeutic directions for the future, including individualized treatment regimens and multidrug treatment cocktails for those who fail initial monodrug therapy.

Rapid Fecal Calprotectin (FC) Analysis: Point of Care Testing for Diagnosing Early Necrotizing Enterocolitis

OBJECTIVE The aim of this study is to compare fecal calprotectin (FC) levels as measured by a rapid FC assay with those measured by enzyme-linked immunosorbent assay (ELISA) from concurrent stool samples. We also attempted to demonstrate a correlation between elevated rapid assay FC levels and the presence of necrotizing enterocolitis (NEC) and to define a cutoff FC value which could serve as a basis for diagnosing NEC in the future. STUDY DESIGN Stool samples were collected for FC analysis at 1 and 3 weeks postnatally and whenever there was clinical suspicion of NEC. RESULTS Rapid assay FC levels were elevated with NEC (3,000 µg/g stool [2075,7875] vs. without (195 µg/g stool [110,440] p < 0.001); and were well correlated with ELISA FC levels (r(2) = 0.89). CONCLUSION We present the first data showing that rapid assay FC levels are potentially useful in the bedside diagnosis of NEC.

Neonatal Hyperbilirubinemia in the Low-Intermediate–Risk Category on the Bilirubin Nomogram

OBJECTIVE: Predischarge bilirubin screening predicts neonatal hyperbilirubinemia. We evaluated the incidence of false-negative bilirubin screening among readmissions for hyperbilirubinemia. METHODS: In healthy term and late preterm, predominantly breastfeeding newborns, predischarge transcutaneous bilirubin values were plotted on the hour of life–specific bilirubin nomogram and confirmed with plasma total bilirubin in those with a transcutaneous reading ≥75th percentile, or between the 41st and 75th percentiles in the presence of predictive icterogenic risk factors. False-negative bilirubin screen was defined as a predischarge bilirubin value ≤75th percentile in a newborn who was subsequently readmitted for phototherapy. RESULTS: Of a total of 25 439 neonates born between 2008 and 2009, 143 (0.56%) were readmitted with a mean plasma total bilirubin of 18.7 ± 1.7 mg/dL at 125 ± 54 hours. False-negative predischarge bilirubin screen was identified in 46 (32.2%). Of these, 6 (4.2%) were in the low-risk zone (≤40th percentile, relative risk [RR] = 1) and 40 (28%) in the intermediate-low–risk zone (41st–75th percentile, RR 7.62 [95% confidence interval 3.23–17.96]). Of those in the high-risk zones, 76 (53.1%) were in the intermediate-high–risk zone (76th–95th percentile, RR 25.32 [11.03–58.10]) and 21 (14.7%) in the high-risk zone (>95th percentile, RR 27.78 [11.23–68.70]). CONCLUSIONS: Predischarge bilirubin levels in newborns classified as low risk did not eliminate the risk of readmission for hyperbilirubinemia. All newborns including those at low risk must be vigilantly observed for subsequent hyperbilirubinemia.

Elevated Nucleated Red Blood Cells at Birth Predict Hemodynamically Significant Patent Ductus Arteriosus

We hypothesized that postnatal absolute nucleated red blood cell (aNRBC) counts would be elevated in premature infants with hemodynamically significant patent ductus arteriosus (PDA), reflecting intrauterine hypoxia. PDA severity was assessed and categorized echocardiographically. aNRBC counts were significantly correlated with ductal severity (Pearson correlation: P = .007). At the extremes, aNRBC levels were 3770 (728, 6015) hemodynamically significant PDA vs 865 (483, 2528) closed ductus.

Paracetamol Serum Concentrations in Neonates Treated Enterally for Ductal Closure: A Pilot Study

&NA; We determined serum paracetamol concentrations 4 hours after the eighth dose in infants treated enterally for ductal closure. Serum paracetamol concentrations correlated (P = .0026) with ductal response. No patent ductus arteriosus in a baby with paracetamol levels <20 mg/L closed in response to treatment. Paracetamol levels also correlated (P = .046) with postnatal age.

Ductus arteriosus outcome with focus on the initially patent but hemodynamically insignificant ductus in preterm neonates

Background/objectivesThe hemodynamically insignificant (hisPDA) ductus arteriosus often progresses to hemodynamic significance. In this review, we sought risk factors predictive of progression.MethodsEarly hisPDAs were subdivided into those that closed spontaneously vs. those that progressed to hsPDA.ResultsSixty percent of early hisPDAs subsequently progressed to hsPDAs. In all but one, the ductus never closed, but rather became progressively more significant over time. The echocardiographic parameters best associated with subsequent progression were an increased transductal diameter (1.81 ± 0.77 vs. 1.21 ± 0.44 mm; p < 0.001) and the presence of diastolic flow reversal. ROC curve analysis showed that the best ductal diameter criterion for predicting the progression to hsPDA was >1.4 (sensitivity = 91; specificity = 81). The combined morbidity score was higher in those infants who progressed to hsPDA as compared with those who did not (p = 0.0038).ConclusionsIncreased ductal diameter and diastolic flow reversal on the first echocardiogram were best correlated with progression of hisPDA to hsPDA.

Might Bilirubin Serve as a Natural Antioxidant in Response to Neonatal Encephalopathy

Background Neonatal asphyxia is often associated with hepatic injury. We hypothesized that this might lead to increased bilirubin concentrations. Study Design Term neonates admitted between January 2015 and April 2017 who remained hospitalized for ≥ 4 days and who had serial serum bilirubin concentrations recorded were divided into those with neonatal encephalopathy (NE) and controls. Serial serum bilirubin concentrations during the first days of life were compared between groups. Results Twenty‐nine neonates with NE and 84 age‐matched controls were identified. Mean total serum bilirubin concentrations of NE babies were significantly lower than those controls throughout the first days of life. At 96 hours of age, NE serum bilirubin concentrations were 4.5 (3.2, 5.8) versus controls of 10.5 (9.4, 11.5) mg/dL (p < 0.0001). The mean area under the curve (AUC) for the NE group was 268 (215, 321) versus 663 (608, 718), p < 0.0001, for the control group. All of the NE babies remained below the 40th percentile of the Bhutani curve and none required phototherapy. Conclusion Contrary to our hypothesis, bilirubin concentrations in NE infants are significantly lower than expected during the first 4 days postnatally. We speculate that, under conditions of severe oxidative stress, bilirubin is consumed as an antioxidant.