Jen-Fu Hsu

Incidence, clinical characteristics and risk factors for adverse outcome in neonates with late-onset sepsis.

Background: Late-onset sepsis (LOS) is a common complication in the neonatal intensive care unit. We aimed to describe the epidemiology, clinical characteristics and risk factors for adverse outcome in neonates with LOS. Methods: We conducted a cohort study of all neonates with LOS at the neonatal intensive care unit of a Tertiary Taiwan Medical Center from January 2004 through December 2011 and used multivariate logistic regression to identify risk factors for final adverse outcome. Results: Among 5010 neonates over 253,644 neonate-days, 713 (14.2%) experienced a total of 942 episodes of LOS (incidence rate, 3.71 episodes per 1000 neonate-days). Although the rates of LOS were inversely proportional to birth weight and gestational age, the incidence rates were comparable among extremely preterm, late preterm and full term neonates. Fungemia was found to have significantly higher rate of infectious complication (30.8%), persistent bloodstream infection (19.2%) and sepsis attributable mortality (23.1%). The overall mortality rate was 12.6% (90/713), and sepsis attributable mortality rate was 7.2% (68/942 episodes). Independent predictors of in-hospital mortality were Pseudomonas LOS (adjusted odds ratio [OR], 14.31; 95% confidence interval [CI]: 3.87–53.0), fungemia (OR, 5.69; 95% CI: 2.48–13.01), presence of congenital anomalies (OR, 4.12; 95% CI: 1.60–10.60), neuromuscular comorbidities (OR, 3.34; 95% CI: 1.66–6.73) and secondary pulmonary hypertension with/without cor pulmonale (OR, 23.48; 95% CI: 5.96–92.49). Conclusions: LOS predisposes hospitalized neonates to increased risk of mortality or morbidity, especially caused by Pseudomonas aeruginosa or Candida spp. More aggressive treatment strategy is worth consideration in neonates with presumed LOS, particularly those with certain underlying chronic conditions.

Risk Factors of Catheter-related Bloodstream Infection With Percutaneously Inserted Central Venous Catheters in Very Low Birth Weight Infants: A Center's Experience in Taiwan

BACKGROUND Infected percutaneously inserted central venous catheters (PICCs) are a problem in hospitalized patients, especially in the neonatal intensive care unit. The objective of this study was to assess the risk of infection and other PICC-associated complications in very low birth weight infants. METHODS Between January 2005 and December 2006, we studied 412 PICCs inserted in 267 neonates with a birth body weight ≤ 1500g. PICC-related bloodstream infections and other complications were recorded and analyzed. RESULTS These 412 PICCs were inserted for a mean duration of 16.6 ± 9.9 (SD) days. The most common catheter-related complications were catheter-related blood-stream infection (CRBSI; incidence: 8.3 per 1000 catheter days), followed by catheter occlusion (4.0 per 1000 catheter days), catheter site inflammation (3.5 per 1000 catheter days), and phlebitis (3.1 per 1000 catheter days). The most common pathogen of CRBSI was coagulase-negative staphylococcus (40.1%). Significant risk factors of CRBSI included catheters inserted at femoral sites (increased risk of CRBSI compared with nonfemoral catheters: 1.76; 95% confidence interval, 1.01-3.07, p = 0.045) and a longer duration of PICC placement (p < 0.001). A low birth body weight and gestational age were not found to significantly affect the risk of CRBSI. CONCLUSION It is important to avoid inserting a PICC at the femoral site. Strict catheter care protocol should also be applied to reduce local site bacterial colonization and removal of PICCs as soon as they are no longer essential for patient care to reduce the incidence of infection.

Complication Rates With Central Venous Catheters Inserted at Femoral and Non-femoral Sites in Very Low Birth Weight Infants

Objective: To compare the complication rates of femoral versus nonfemoral sites of percutaneously inserted central venous catheters (PICCs) in very low birth weight infants. Methods: Between 2004 and 2006, 518 PICCs inserted in 334 neonates with a birth body weight ≥1500 g were studied. 278 catheters were inserted at nonfemoral sites, and 240 catheters at a femoral site. All catheter-related complications were recorded and analyzed. Results: The infants with femoral PICCs had a significantly higher rate of catheter-related sepsis (CRS) than those with nonfemoral PICCs (22.5% vs. 12.2%, P = 0.002) and the incidence rate was also significantly higher (10.9 vs. 6.8 episodes per 1000 catheter days, P = 0.012). The infants with nonfemoral PICCs had significantly higher rates of phlebitis, catheter site inflammation, and need for early removal than those with femoral PICCs. Multiple logistic regression analysis showed that the significant contributors to CRS were duration of the PICC placement (P < 0.001) and insertion of the PICC at a femoral site (P = 0.010). Conclusions: Because of a higher rate of CRS, the femoral site should not be considered for the placement of PICCs in VLBW infants, when possible.

The relationship between attention deficit hyperactivity disorder and premature infants in Taiwanese: a case control study

BackgroundPreterm survivors from the neonatal intensive care unit (NICU) are considered to be at risk for some neurobehavioral disorders such as attention-deficit/hyperactivity disorder (ADHD). The current study aimed to explore the relationship between ADHD and premature infants in Taiwan.MethodsA total of 195 children (157 males and 38 females) diagnosed with ADHD based on DSM-IV and aged between 6 to 12 years and a control group of 212 (164 males, 48 females) age- and sex-matched healthy children were enrolled. The ADHD-Rating scale and CGI severity were performed by child psychiatrists. Demographic data of the children, including birth history, perinatal neurological and respiratory problems were collected to facilitate the investigation of whether a correlation exists between ADHD and prematurity.ResultsThe ADHD group had a significantly higher rate of prematurity and significantly higher rate of low birth body weight (defined as <2500 g) than the control group (both P = 0.003). Pearson correlation showed a significantly negative correlation between gestational age and ADHD-RS score, inattentive score, hyperactivity and CGI-S score (P = 0.004, 0.013, 0.015 and 0.002, respectively). However, only a CGI-S score (P = 0.018) showed a significantly correlation between low birth weight and ADHD.ConclusionsPremature infants have significantly more severe symptoms of ADHD at school age and they were highly correlated. Further study is necessary to determine the main effect and pathogenesis of moderate as well as extreme preterm birth on the development of ADHD.

Recurrent late-onset sepsis in the neonatal intensive care unit: incidence, clinical characteristics and risk factors

We aimed to characterize the incidence, clinical features, risk factors and outcomes of recurrent late-onset sepsis (LOS) in the neonatal intensive care unit (NICU). All neonates with LOS from the NICU of a tertiary-level teaching hospital in northern Taiwan between 2004 and 2011 were enrolled for analyses. A case-control study was performed to determine risk factors for recurrence. Of 713 neonates with LOS, 150 (21.0%) experienced recurrence and 48 (6.7%) had >1 recurrences; c. two-thirds of recurrent LOS occurred in infants with birth weight (BW)≦1500 g or gestational age (GA)≦30 weeks. The recurrent LOS episodes were significantly more severe and had a higher sepsis-attributable mortality rate than the first episodes. The overall in-hospital mortality rate was 30.7% for neonates with recurrent LOS and 7.8% for those with single LOS (odds ratio (OR), 5.22; 95% CI, 3.28-8.30). When both BW and GA were controlled, neonates with recurrent LOS had a significantly prolonged hospitalization compared with the controls (median 109 vs. 84 days, p<0.001). After multivariate logistic regression, longer duration of total parenteral nutrition (TPN; OR, 1.30; 95% CI, 1.10-1.52 for every 10-day increment), presence of congenital anomalies (OR, 2.64; 95% CI, 1.10-6.35) and neurological co-morbidities (OR, 4.14; 95% CI, 1.14-15.10) were identified as the independent risk factors for LOS recurrence. We concluded that c. one-fifth of neonates with LOS had recurrence, which significantly resulted in prolonged hospitalization and increased mortality. Longer TPN administration, presence of congenital anomalies and neurological co-morbidities are independently associated with recurrent LOS.

Serum Lactate, Brain Magnetic Resonance Imaging and Outcome of Neonatal Hypoxic Ischemic Encephalopathy after Therapeutic Hypothermia

BACKGROUND Serum lactate was used to predict the severity and outcome of neonatal hypoxic ischemic encephalopathy (HIE) before the era of therapeutic hypothermia (TH). There is no report on neurodevelopment (ND) outcome of neonates with HIE treated with TH in Taiwan. METHODS Between April 2011 and December 2012, newborn infants admitted to Chang Gung Memorial Hospital (CGMH), with gestational age > 35 weeks and birth weight ≥ 1800 g, who had acute perinatal events, evidence of significant fetal compromise, and ongoing clinical encephalopathy were prospectively enrolled for TH. Whole body cooling method was used to maintain the affected neonates esophageal temperature at 33.5 ± 0.5 °C for 72 hours. Demographic data were recorded and hemogram, biochemical parameters, serum lactate, and creatine kinase (CK) were measured as well. Brain magnetic resonance imaging (MRI) was performed between 7 and 14 days of life. ND outcome of infants was evaluated by Bayley Scales of Infant Development, third edition (BSID-III) at 24 months of corrected age. Poor ND (PND) outcome was defined as infants surviving with either disability or ND delay. RESULTS Seventeen patients were enrolled. Fifty-nine percent of babies (10/17) were born through cesarean section and 77% of babies (13/17) were transferred from outside hospitals. Six babies were moderate HIE and 11 babies were severe HIE. Among the 14 surviving patients, eight infants had PND outcome. There was no difference in demographic data between infants with and without PND. Serum level of lactate (mg/dL) after 72 hours of TH was higher (35.6 vs. 13.8, p = 0.042) in infants with PND. Neonates with abnormal brain MRI findings were also associated with PND (p = 0.01). CONCLUSION This is the first report on ND outcome of neonates with HIE treated with TH in Taiwan. Higher serum level of lactate following TH and abnormal results of brain MRI are associated with poor ND outcome.

Neurological Complications after Neonatal Bacteremia: The Clinical Characteristics, Risk Factors, and Outcomes

Background Neonates with bacteremia are at risk of neurologic complications. Relevant information warrants further elucidation. Study Design This was a retrospective cohort study of neonates with bacteremia-related neurologic complications (BNCs) in a tertiary-level neonatal intensive care unit (NICU). A systemic chart review was performed conducted to identify clinical characteristics and outcomes. A cohort of related conditions was constructed as the control group. Logistic regression analysis was used to identify independent risk factors for BNC. Results Of 1037 bacteremia episodes, 36 (3.5%) had BNCs. Twenty-four cases of BNCs were related to meningitis, five were presumed meningitis, and seven occurred after septic shock. The most common causative pathogens were Group B streptococcus (41.7%) and E. coli (16.7%). The major BNCs consisted of seizures (28), hydrocephalus (20), encephalomalacia (11), cerebral infarction (7), subdural empyema (6), ventriculitis (8), and abscess (4). Eight (22.8%) neonates died and six (16.7%) were discharged in critical condition when the family withdrew life-sustaining treatment. Among the 22 survivors, eight had neurologic sequelae upon discharge. After multivariate logistic regression analysis, neonates with meningitis caused by Group B streptococcus (adjusted odds ratio [OR]: 8.90, 95% confidence interval [CI]: 2.20–36.08; p = 0.002) and combined meningitis and septic shock (OR, 5.94; 95% CI: 1.53–23.15; p = 0.010) were independently associated with BNCs. Conclusions Neonates with bacteremia-related neurologic complications are associated with adverse outcomes or sequelae. Better strategies aimed at early detection and reducing the emergence of neurologic complications and aggressive treatment of Group B streptococcus sepsis are needed in neonates with meningitis and septic shock.

Predictors of clinical and microbiological treatment failure in neonatal bloodstream infections

This study aimed to identify independent predictors of clinical and microbiological treatment failure and develop a predictive model for neonates with bloodstream infection (BSI). This study included 1087 episodes of BSIs in 793 neonates in a tertiary-level neonatal intensive care unit of northern Taiwan between 2004 and 2012. Patient demographics, underlying chronic comorbidities, clinical features, antimicrobial treatment and microbiological characteristics were evaluated. The presence of underlying congenital anomalies (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.09 to 4.10) and pulmonary hypertension (OR 3.63, 95% CI 1.70 to 7.74), infections caused by multidrug-resistant gram-negative bacteria (OR 2.89, 95% CI 1.23 to 6.79), group B Streptococcus (OR 3.15, 95% CI 1.33 to 7.46), and fungi (OR 4.13, 95% CI 2.02 to 8.46), a Neonatal Therapeutic Intervention Scoring System score of ≥ 23 (OR 6.96, 95% CI 2.55 to 28.58), inappropriate antibiotics (OR 2.13, 95% CI 1.41 to 3.23), and concomitant meningitis (OR 4.25, 95% CI 2.08 to 8.69) and ventilator-associated pneumonia (OR 2.73, 95% CI 1.22 to 6.13) were identified as independent risk factors for 28-day treatment failure in neonatal BSI. A risk score model was created by adding the points for each independent risk factor, and had a c-statistic of 0.83. Patients with risk scores of 0, 4, 8, 12 and 15 had estimated 28-day treatment failure rates of approximately 3.5%, 17.0%, 53.5%, 86.6% and 95.9%, respectively. This predictive model, calculated after documentation of a BSI, reflects a spectrum of BSI severity and was associated with subsequent treatment failure through illness severity score and case mix variables. This simple score could prove useful in clinical and research settings, and practical in estimating the prognosis.

Early detection of minor neurodevelopmental dysfunctions at age 6 months in prematurely born neonates

OBJECTIVE To investigate the 6-month neurodevelopmental outcomes of prematurely born neonates and find the determining neonatal factors of minor neurological dysfunctions (MNDs). STUDY DESIGN We examined data collected prospectively on 151 infants born before 37th week of gestation in 2009-2010 who were assessed at 6 months corrected age with the Bayley Scales of Infant Development-2nd Edition (BSID-II) and the Denver Developmental Screening Test (DDST). RESULTS Of 151 neonates born before 37 weeks, 20 (13.2%) had MNDs at 6 months corrected age. These proportions were 21.6%, 13.2%, and 8.2% for neonates born before 28 weeks, 29 weeks to 32 weeks, and 33 weeks to 36 weeks, respectively. Half of neonates with MNDs have a birth body weight of less than 1000g. BSID-II and DDST are highly correlated in assessing the MNDs of premature neonates at 6 months corrected age. MND was independently associated with postnatal corticosteroid use (odds ratio [OR], 11.2; 95% confidence interval [CI], 1.9-66.0, P=0.008) and cholestasis (OR, 6.2; 95% CI, 1.16-33.1, P=0.033). CONCLUSIONS Premature neonates, even those born at 33 to 36 weeks, are found to have MNDs as early as 6 months corrected age by BSID-II and DDST, with risk increasing as gestation decreases.

Polymicrobial Bloodstream Infection in Neonates: Microbiology, Clinical Characteristics, and Risk Factors

Background Polymicrobial bloodstream infections (PBSIs) have been associated with complex underlying medical conditions and a high incidence of specific microorganisms in several settings, but the relevant data are scarce in neonates. Methods Positive blood cultures from January 2004 to December 2011 in the neonatal intensive care unit (NICU) of Chang Gung Memorial Hospital (CGMH) were reviewed. Each neonate with PBSI (case episode) was matched to two episodes of monomicrobial BSI (control episode) by birth weight, gestational age and gender. Records were reviewed to compare their underlying medical conditions, organisms isolated, adequacy of therapy, clinical characteristics and outcomes. Results Forty-five episodes of PBSI (4.4% of all neonatal BSIs) were identified in 43 neonates. Gram-negative organisms constituted 59.8% of all PBSI pathogens, and 33 (73.3%) of PBSIs were caused by at least one Gram-negative organism. PBSIs were significantly more likely to be the recurrent episode and have endotracheal tube in place. No significant difference was found between PBSIs and controls in terms of demographics and most chronic conditions. PBSIs were significantly associated with a higher severity of illness, a longer duration of septic symptoms, and a higher rate of modification of antimicrobial regimens than monomicrobial BSIs. However, the sepsis-attributable mortality rates were comparable between these two groups. Conclusions In the NICU, PBSIs were more often caused by Gram-negative bacilli, and often occurred in neonates without any chronic conditions. The clinical significance of PBSIs included a more severe illness, longer duration of septic symptoms and a higher rate of modification of antimicrobial regimens.