Prolonged use of antibiotics after birth is associated with increased morbidity in preterm infants with negative cultures.

Background: Most preterm infants are exposed to a variable duration of antibiotic therapy after birth despite negative cultures. Data is emerging about the risks of prolonged antibiotics. We sought to assess the association between length of initial antibiotic course and neonatal outcomes in a cohort from a single large perinatal center.Methods: Retrospective cohort study of prospectively collected data on all infants with a birth weight of less than 1250 g hospitalized in our NICU in a 4 year window and who had negative blood and CSF cultures in the first 2 days of life. The primary outcome is a composite of necrotizing enterocolitis (NEC), late onset sepsis (LOS) and death evaluated using multivariable regression analysis.Results: A total of 620 infants less than 1250 g with negative cultures were eligible for study over a 4 year period. The 238 infants with more than 5 days initial antibiotic use were significantly smaller and of lower gestational age than the 382 infants who received up to 5 days of antibiotics. Their mothers had more clinical chorioamnionitis, less maternal hypertension and greater perinatal use of antibiotics. On multivariate analysis, infants who received empiric antibiotics for longer than 5 days had higher rates of neonatal morbidities after adjusting for gestational age, SNAP II, small-for-gestational age status, gender, maternal hypertension, prenatal steroid treatment, clinical chorioamnionitis, intrapartum antibiotic treatment, and multiple births. Composite outcome OR: 1.83 (1.15 to 2.92), LOS OR: 2.02 (1.20 to 3.39), bronchopulmonary dysplasia OR: 1.58 (1.04 to 2.29). Mortality and NEC were not significantly different.Conclusion: More than 5 days of antibiotic treatment in very preterm infants with negative cultures was associated with increased morbidity in our population, and that included BPD. It is of note that patterns of increased morbidity and/or mortality differ between studies. Prospective trials of clinical protocols for starting and stopping antibiotics in the very preterm infants are required.

Risk factors and outcomes of early pulmonary hypertension in preterm infants.

PURPOSE: Data on early pulmonary arterial hypertension (PAH) in preterm infants is limited and outcomes are conflicting. Our objectives are to examine the risk factors and neonatal outcomes of early onset PAH (EOPAH) diagnosed in the first 2 weeks of age in preterm infants in a large perinatal center. METHODS: We performed a case-control study to assess the risk factors and clinical outcomes of preterm infants with EOPAH. Preterm infants (<34 weeks) admitted to NICU between 2009 and 2013 with a diagnosis of PAH in the first 2 weeks of age were matched to two consecutive controls for gestational age, birth weight, and year of birth. We performed univariate and multivariate analyses. RESULTS: Of 1798 eligible infants, 60 (3.3%) had EOPAH with 57/60 (95%) diagnosed in the first 7 d of age. Infants with early PAH had higher incidence of prolonged rupture of membrane (47% versus 29%), oligohydramnios (37% versus 16%) and received less antenatal steroids (78% versus 91%). Fifty-one infants received inhaled nitric oxide (iNO) and all responded well. The overall mortality rate was not significantly different between two groups (13.3% versus 8%). After adjusting for potential confounding variables, early PAH is associated with bronchopulmonary dysplasia (BPD) (aOR 3.06, 95% CI 1.43, 6.54) and BPD/death (aOR 2.65, 95% CI 1.25, 5.64) and severe intraventricular hemorrhage (aOR 3.08, 95% CI 1.28, 7.39). CONCLUSION: Early onset pulmonary arterial hypertension in preterm is not uncommon and is associated with bronchopulmonary dysplasia and severe intraventricular hemorrhage. Inhaled nitric oxide was used to treat in majority of cases with good response and survival is high.

Ultrasound assessment of umbilical venous catheter migration in preterm infants: a prospective study.

OBJECTIVES: To evaluate the umbilical venous catheter (UVC) tip position by ultrasound and compare it with standard radiograph findings and to examine the catheter tip migration rates during the first week of life. DESIGN: Prospective observational study of inborn preterm infants who had an UVC placed and its position radiographically confirmed. The first ultrasound was done on UVC placement at median (IQR) age of 2 hours (1-4) and follow-up scans at a median (IQR) age of 34 hours (27-44 hours), 77 hours (70-94 hours) and 6 days (5-7 days) after insertion. Catheter tip was considered in optimum position if tip was lying in the inferior vena cava up to the right atrium opening. RESULTS: We studied 65 infants at a mean (±SD) gestational age and birth weight of 26.4 (±2.1) weeks and 808 (±289) g, respectively. Ultrasound confirmed optimum position of UVC tip in 25/65 (38.5%) infants. Majority (38/40) of the malpositioned catheters were located inside the heart with 15 reaching the left atrium. Catheter tip migration occurred in 29 of 58 infants (50%) at any time during the first week. The proportions of UVC migration were found to be 17%, 31% and 29% on subsequent ultrasound with a trend to outward movement over time. CONCLUSION: UVC tip localisation by standard radiography is very imprecise, and catheter tip migration occurs in a significant proportion of infants during first weeks of age. We suggest ultrasound as the best modality to assist localisation and follow-up of UVC tip in preterm infants.

Trends and Variations in the Use of Inhaled Nitric Oxide in Preterm Infants in Canadian Neonatal Intensive Care Units.

Objective To determine the proportion of infants who receive inhaled nitric oxide (iNO), and to characterize the variations in its use by gestational age (GA) and center in infants <34 weeks' gestation. Design Retrospective analysis was performed in infants born at <34 weeks' gestation and admitted to neonatal intensive care units participating in the Canadian Neonatal Network between January 2010 and December 2013. Results Of 19,525 infants, 831 (4.2%) received iNO. A total of 369 infants (44%) received iNO during the first 2 days after birth. The proportion of neonates who received iNO in the 22 to 25, 26 to 29, and 30 to 33 weeks' GA groups was 16.1, 6.0, and 1.3%, respectively. Infants in whom iNO was initiated in the first 2 days of age received it for a shorter duration (median, 3 days; interquartile range [IQR], 2-5) as compared with those who started after 2 days (median, 5 days; IQR, 2-11). The use of iNO varied by center, ranging from 0 to 15.5% (p < 0.001). Conclusion Out of every 25 infants born at <34 weeks' gestation in Canada received iNO, with the highest rate of use in infants born at lower gestation. Further research to identify reasoning, efficacy, and safety of iNO in preterm infants is warranted.

A Patent Ductus Arteriosus Severity Score Predicts Chronic Lung Disease or Death before Discharge.

OBJECTIVES: To test the hypothesis that a patent ductus arteriosus (PDA) severity score (PDAsc) incorporating markers of pulmonary overcirculation and left ventricular (LV) diastolic function can predict chronic lung disease or death before discharge (CLD/death). STUDY DESIGN: A multicenter prospective observational study was conducted for infants <29 weeks gestation. An echocardiogram was carried out on day 2 to measure PDA diameter and maximum flow velocity, LV output, diastolic flow in the descending aorta and celiac trunk, and variables of LV function using tissue Doppler imaging. Predictors of CLD/death were identified using logistic regression methods. A PDAsc was created and a receiver operating characteristic curve was constructed to assess its ability to predict CLD/death. RESULTS: We studied 141 infants at a mean (SD) gestation and birthweight of 26 (1.4) weeks and 952 (235) g, respectively. Five variables were identified that were independently associated with CLD/death (gestation at birth, PDA diameter, maximum flow velocity, LV output, and LV a' wave). The PDAsc had a range from 0 (low risk) to 13 (high risk). Infants who developed CLD/death had a higher score than those who did not (7.3 [1.8] vs 3.8 [2.0], P < .001). PDAsc had an area under the curve of 0.92 (95% CI 0.86-0.97, P < .001) for the ability to predict CLD/death. A PDAsc cut-off of 5 has sensitivity and specificity of 92% and 87%, and positive and negative predictive values of 92% and 82%, respectively. CONCLUSIONS: A PDAsc on day 2 can predict the later occurrence of CLD/death further highlighting the association between PDA significance and morbidity.

Utility of Targeted Neonatal Echocardiography in the Management of Neonatal Illness.

OBJECTIVES: To describe the impact of targeted neonatal echocardiography on management of neonatal illness in a tertiary perinatal center neonatal intensive care unit (NICU). METHODS: We conducted a retrospective analysis of consecutive targeted neonatal echocardiographic studies that were performed over an 18-month period in a regional perinatal center NICU in Canada. All studies were performed with a cardiovascular ultrasound machine and transducer and read on a workstation with storage and analysis software. Reporting was done on a standardized document, and any management change resulting from targeted neonatal echocardiography was documented. RESULTS: A total of 303 consecutive targeted neonatal echocardiographic studies were performed on 129 neonates. The mean gestational age ± SD was 27.8 ± 4.3 weeks (range, 23-41 weeks), and the mean birth weight ± SD was 1196 ± 197 g (range, 490- 4500 g). The median number of studies per neonate was 2 (range, 1-8), with most repeated studies for a patent ductus arteriosus (PDA). The most common indication for echocardiography was assessment of a PDA (52.1%), followed by early global hemodynamic assessment of very low birth weight (16.2%) and pulmonary hypertension (12.2%). Of the 303 studies, 126 (41.5%) resulted in management changes. The contribution to management was significantly related to the timing of echocardiography. Around half of the echocardiographic examinations during first the week of life resulted in management changes, compared to 22% of studies after 1 week of age (P = .002). Patent ductus arteriosus management accounted for almost half of the interventions. CONCLUSIONS: Targeted neonatal echocardiography is a valuable tool in the NICU and can contribute substantially to hemodynamic management in the first week of life, PDA management in the first 2 weeks of life, and cases of hypotension or shock at any time during the hospital stay.

Rates of intracardiac umbilical venous catheter placement in neonates.

OBJECTIVES: To review umbilical venous catheter (UVC) placement in neonates who underwent targeted neonatal echocardiography (TNE) and to correlate catheter tip placement on TNE and anteroposterior thoracoabdominal radiography. METHODS: We conducted a retrospective analysis of 51 neonates who had UVC positions assessed by TNE and radiography in a neonatal intensive care unit (NICU). A single operator performed all TNE examinations. The final radiographic catheter placement was taken from the image closest to the time of echocardiography. Fisher exact, χ(2), and t tests were used as appropriate. RESULTS: Among the 51 neonates who had catheters placed for 24 hours or more, TNE was performed on 48 in the first 48 hours, 2 at day 6, and 1 at day 9. Thirty-six neonates were extremely low birth weight (ELBW; <1000 g). Twenty-nine had good catheter tip positions, and 22 had catheters inside the heart (10 in the right atrium [RA], 3 at the foramen ovale, and 9 in the left atrium [LA]). Twenty neonates with catheter tips in the heart were ELBW, including 8 with catheters in the LA. The ELBW neonates were more likely to have catheters in the heart than non-ELBW neonates (20 of 36 versus 2 of 15; P= .01; odds ratio [OR], 8.1; confidence interval [CI], 1.59-41.3). Good placement on TNE varied widely in relation to thoracic vertebral landmarks on radiography: from the T7-8 interspace to T11. When radiography showed a catheter tip at T9-T10, there was no difference in the proportion of neonates with a good catheter position versus malposition (8 of 22 versus 8 of 29; P = .55; OR, 0.67; CI, 0.20-2.19). CONCLUSIONS: A high proportion of ELBW neonates in a busy NICU had UVCs placed with the tips in the RA or LA despite common placement practices. We recommend adding TNE to radiography to position UVCs, especially in ELBW neonates.

Effectiveness and safety of indomethacin versus ibuprofen for the treatment of patent ductus arteriosus in preterm infants.

OBJECTIVE: To compare the incidence of medical closure of patent ductus arteriosus (PDA) and adverse events (acute renal dysfunction, necrotizing enterocolitis, spontaneous intestinal perforation, and gastrointestinal bleeding) between preterm infants who received indomethacin and ibuprofen for the treatment of PDA. STUDY DESIGN: A retrospective comparative effectiveness evaluation study was conducted on preterm infants (≤32 weeks) who received indomethacin or ibuprofen for treatment of symptomatic PDA. RESULTS: Of the 124 eligible infants, 54 received indomethacin and 70 received ibuprofen. The overall incidence of medical PDA closure with indomethacin was 37/54 (68.5%) as compared with 42/70 (60%) in the ibuprofen group (p = 0.32). The proportion of infants with surgical PDA ligation was similar between the two groups (18.5% in both the groups). There was no difference in the incidences of acute renal dysfunction, necrotizing enterocolitis stage ≥ 2, spontaneous intestinal perforation, and gastrointestinal bleeding between indomethacin and ibuprofen groups. CONCLUSION: Ibuprofen is as effective as indomethacin in the treatment of symptomatic PDA in preterm infants. This study also shows that both agents have similar adverse effects and the choice of one agent over the other should be based on local availability and dosing preference.

Comparison between a suprasternal or high parasternal approach and an abdominal approach for measuring superior vena cava Doppler velocity in neonates.

OBJECTIVES: Superior vena cava (SVC) flow is becoming an important hemodynamic measurement in neonates through its use in targeted neonatal echocardiography. Previous studies measured the flow velocity in the SVC through an abdominal approach. In adults and children, the abdominal and the suprasternal or high parasternal window are considered equivalent. We compared the two approaches in neonates. Our hypothesis was that the two echocardiographic approaches would yield similar results. METHODS: We conducted a prospective observational study of 40 neonates with gestational ages of 23 to 40 weeks and weights of 540 to 3805 g. Interventions included measurements of SVC flow velocity from an abdominal approach and a suprasternal or high parasternal approach. The main outcome measure was the SVC velocity time integral. RESULTS: The SVC velocity time integral was able to be measured from both approaches in all patients. The abdominal velocity time integral yielded on average slightly higher values by 5.1% (95% confidence interval, 0.6% to 9.8%). This finding was statistically significant for the whole sample (P = .025). The median of the absolute percent difference between measurements was 9.7% (range, 1.6% to 28.8%). The individual results were within the 95% confidence interval for intraobserver variability of the thoracic velocity time integral in 36 of 40 neonates. Times to completion were similar in both groups, with a slight advantage for the thoracic approach in larger neonates. CONCLUSIONS: The suprasternal or high parasternal approach is feasible and an acceptable alternative to the abdominal approach for measuring SVC flow velocity in the context of targeted neonatal echocardiography. Angle correction is usually necessary.